clinical - Journal of the International AIDS Society

Transcription

PE
PEER-REVIEWD
OPEN ACCESS
HIV/AIDS JOURNAL
ONLINE
ONLINE
HIV/AIDS JOURNAL
HIV/AIDS JOURNAL PEER-REVIEWD
HIV/AIDS JOURNAL PO
ONLI
ONLINE HIV/AIDS JOURNAL
ONLI
OPEN ACCESS
PEER-REVIEWDHIV/AIDS JOURNAL
N ACCESS
ACCESS
ONLINE
PEER-REVIEWD
/AIDS JOURNAL
EN ACCESS
OPEN A
ONLINE
R-REVIEWD
PEER-REVIEWD
ONLINE
PEER-REVIEWD
IDS JOURNAL OPEN ACCESS HIV/AIDS
JOURNAL
HIV/AIDS JOUR
ONLINE HIV/A
HIV/AIDS JOUR
OPEN ACC
HIV/AIDS JOUR
-REVIEWD
PEER-REVIEW
URNAL
HIV/AIDS JOURNAL HIV/AIDS JOURNAL
PEER-REVIEW
Abstract supplement
OPEN ACCESS
OPEN ACCESS
PEER-REVIEWD
ONLINE
NEW TREATMENTS AND TARGETS
AEs
MOTHER-TO - CHILD
TR ANSMISSION
HIV ANDVULNERABLE POPULATIONS
HIV-RELATED
INFECTIONS
AS PREVENTION
HEPATITIS
TREATMENT AS PREVENTION
CLINICAL
PHARMACOLOGY
ENDEMIC
DISEASES
LABORATORY
MONITORING
OF DISEASE
AND THERAPY
TREATMENT
HIV Drug Therapy in the Americas Congress
13–15 June 2013, São Paulo, Brazil
ADHERENCE
Volume 16, Supplement 1
June 2013
RESISTANCE
NON‑AIDS MORBIDITIES
AND M O R TA L I T Y,
TUBERCULOSIS A N D A G E I N G
TREATMENT
STRATEGIES
PRE‑ AND POST‑EXPOSURE PROPHYLAXIS
Scan this QR code with
your mobile device to view
the supplement online
Abstract supplement
HIV Drug Therapy in the Americas Congress
13 – 15 June 2013
Contents
Keynote Lectures
Oral Abstracts
Update on Antiretrovirals and Treatment Strategies
Hepatitis and HIV
Living Longer with HAART and Non-communicable Diseases and HIV
Epidemiology and Clinical Issues for Women and Implementing Treatment as Prevention
Treatment Guidelines
HIV and Endemic Diseases
HIV and Vulnerable Populations
Access and Treatment, Policy Issues
Tuberculosis and HIV
Update from the 20th Conference on Retroviruses and Opportunistic Infections (CROI)
1
3
5
6
7
8
8
9
9
10
10
Poster Abstracts
Adherence12
Adverse Events
12
HIV and Endemic Diseases
15
HIV-related Infections, Co-infections and Cancers
16
Laboratory Monitoring of Disease and Therapy
17
Mother-to-child Transmission
17
Non-AIDS Morbidities and Mortality, and Ageing
18
Treatment as Prevention
20
Resistance21
Treatment Strategies
22
Author Index
June 2013
http://www.jiasociety.org/index.php/jias/issue/view/1463
25
Abstracts of the HIV Drug Therapy in the Americas Congress
Journal of the International AIDS Society 2013, 16 (Suppl 1)
http://www.jiasociety.org/index.php/jias/article/view/18720
KEYNOTE LECTURES
KL1
Research on persistence and pathogenesis under ART
M Stevenson
Miller School of Medicine, University of Miami, Miami, USA.
Introduction: Antiretroviral therapy (ART) can sustain suppression of
plasma viremia for years. However, if therapy is interrupted, there is
a rapid resumption in viremia. Therefore, HIV-1 has the ability to
persist in the face of potent ART. Identifying the mechanism through
which HIV-1 persists in infected individuals on suppressive therapy is
central to the goal of curing infection in these individuals. For this
reason, research is focused on establishing tools with which to probe
the reservoirs that persist in aviremic individuals as well as clinical
protocols with which to perturb those reservoirs. How we measure
viral reservoirs in aviremic patients and, as a consequence, how we
gauge the impact of treatments on those reservoirs is a contentious
issue. Most attention has focused on the role of latently infected
T-cells in viral persistence and clinical strategies are geared towards
purging of these reservoirs. However, other factors may be
contributing to viral persistence including residual viral replication
and establishment of non-T-cell reservoirs. In addition, although ART
significantly improves health outcomes for the patient, several
markers of immunopathogenicity persist in the face of effective
viral suppression and drive comorbidities. The underlying cause of
ongoing pathogenicity in the face of effective ART is unclear. Studies
examining the impact of treatment intensification on markers of viral
pathogenicity will be discussed.
http://dx.doi.org/10.7448/IAS.16.2.18687
KL2
Prevention of HIV-1 infection 2013: glimmers of hope
M Cohen
University of North Carolina School of Medicine, Chapel Hill, USA.
The efficiency of transmission of HIV depends on the infectiousness of
the index case and the susceptibility of those exposed. Infectiousness
is dictated by the concentration of HIV-1 in relevant fluids (regardless
of route of transmission) and the viral genotype and phenotype.
People newly infected with HIV-1 (i.e. acute infection) and those with
STD co-infections excrete such a large concentration of virus as to be
‘‘hyperinfectious’’. The actual transmission of HIV likely occurs in the
first few hours after exposure. The probability of transmission may be
as low as 1/10,000 episodes of intercourse or 1/10 sexual exposures
when anal intercourse is practiced. The transmission of HIV is generally
limited to one or a small number of founder variants which themselves
may be ‘‘hyperinfectious’’. Synergistic behavioural and biologic HIV
prevention strategies have been developed and implemented. Safer
sex includes limiting the number of sexual partners, use of male latex
condoms, and structural interventions to reduce exposure. These
strategies appear to have contributed to reduced HIV incidence in
many countries. Biological interventions have proven catalytic: these
include treatment of inflammatory cofactors, voluntary male circumcision, and use of antiviral agents either for infected people (who can
be rendered remarkably less contagious) or as pre- and post-exposure
prophylaxis (PrEP and PEP). Ecologic evidence suggests that broader,
earlier antiviral treatment of HIV may be reducing incidence in some
(but not all) populations. However, maximal benefit of HIV ‘‘treatment
for prevention’’ and application of PrEP will likely require a program of
universal ‘‘test and treat’’, where many more infected patients are
identified, linked to care, and treated very early in disease and for life.
Community randomized trials designed to support this approach are
underway in Africa. The ‘‘test and treat’’ prevention strategy is
resource intensive and serves to emphasize research that searches
for a cure for HIV infection, so that HIV infected people can eventually
reduce or stop treatment. Likewise, success in HIV prevention emphasizes the importance of development of an HIV vaccine,
which remains focused on agents that may evoke CTL responses,
antibody-dependent cytotoxicity, and (perhaps most important) broad
neutralizing antibodies. A human clinical trial (RV144) and animal
experiments have provided hope, excitement, and a roadmap for
development of an HIV vaccine.
KL3
From HIV to global health: economic issues in the region
S Bautista
Instituto National de Salud Publica, Mexico City, Mexico.
Latin America is globally recognized for achieving high coverage of
antiretroviral treatment. Virtually all countries in the region have been
able to achieve this important goal by offering universal access to
antiretroviral drugs through their public health systems, despite the
fact that antiretrovirals are available for these countries at relatively
high prices, compared to other low- and middle-income countries.
However, even though it would be fair to say that the access problem
has been solved in the region, there are other important challenges
that need to be strategically addressed. Both treatment and prevention programmes in our countries urgently need to be optimized,
which means that although the infrastructure and capacity to
implement highly effective programmes already exist, but the
challenge now is to increase quality and efficiency. During this
presentation, I will address some of the aspects, both programmatic
and economic, that appear to be the most pressing ones requiring our
attention, and also discuss some of the alternatives available to us
toward improving the performance of our programmes. On the
treatment side, I propose that there are likely large potential gains in
improving timeliness of treatment initiation and efficiency of treatment regimes. On the prevention side, significantly improving testing
efforts and increasing their coverage is probably a good measure
toward increasing the health gains of our efforts. Using evidence to
address these issues is key, and I wish to put to you that not only have
we not done it enough in the past but that we also urgently need to
generate evidence upon which to base our decisions. Most of the
scientific evidence on the prevention realm comes from Africa. We
need to be more creative and innovative and rigorously evaluate
approaches to improve access, quality and efficiency.
KL4
HIV eradication: virological chances and clinical perspectives
C-F Perno
University of Rome ‘Tor Vergata’, Rome, Italy.
Once a retrovirus infects a eukaryotic cell and integrates within
chromosomal DNA, it becomes part of its genome and can be
1
activated/transcribed/translated to produce viral proteins and/or
new viral particles. Over the years, some of these retroviruses may
lose their pathogenicity and become adapted to the new host. Under
these conditions, retroviruses can paradoxically ameliorate the
functional portfolio of the infected cell, thus potentially increasing
its functionality and/or chances of survival in a difficult environment.
Individuals whose cells are infected by retroviruses have acquired, in
the last millions of years, innovative functions that, once transmitted
to the new generation through germinal cells, have become essential
for their homeostasis, or even for their survival. This is the case of
some endogenous retroviruses, whose products are mandatory for
the proper vascularization of human placenta. To our knowledge,
there are no natural means able to selectively eliminate retroviral
genes from an infected cell or an individual. Therefore, chances of
getting naturally cured by retroviruses, once infection is set and viral
genomes are spread into the body, are minimal or absent. HIV is a
retrovirus that behaves as all other retroviruses that interacted with
humans in the past millennia. Its fate is to remain forever within
the infected body. For these reasons, chances of getting rid of
Keynote Lectures
HIV infection and being biologically cured (that is, eliminating all
viral genomes from the body) are very limited if we consider
current knowledge, biotechnology, and available medical tools (yet it
cannot be fully excluded in very peculiar cases). The option offered
by the so called ‘‘functional cure’’ is different. In this case, medical
manipulation may create conditions whereby viral genomes, decreased in number and function by proper therapies/vaccines, are no
longer able to harm the host for an indefinite period of time. Patients
do remain infected, but viral replicative cycles are absent, and
progression of the disease is interrupted. This latter clinical approach
may be suitable, and this is where the clinical research is directing its
efforts. If achievable, infected persons should cope with the virus
and keep it under control for decades, without support of chronic
antiviral therapy. In conclusion, the proper knowledge of the
biological characteristics of HIV helps in selecting the best strategies
aimed at obtaining the maximum achievable clinical result.
2
Oral Abstracts
ORAL ABSTRACTS
O11 UPDATE ON ANTIRETROVIRALS
AND TREATMENT STRATEGIES
O111
Treatment optimisation in low- and middle-income
countries
I Weller
University College London, London, UK.
The collaborative international effort to provide universal access to
HIV care and effective antiretroviral therapy (ART) has reached a
critical time point. The global economic downturn, changing donor
priorities and competing priorities in the health sector threaten the
capacity of various agencies to maintain support for the continued
scale-up of access toward the UN General Assembly-agreed target of
15 million people with HIV/AIDS receiving ART by 2015. We now
know that treatment acts as prevention by reducing the infectiousness of treated individuals. It is now necessary to review the
elements of the successes and challenges to date, in order to be able
to best use finite resources. These elements include efforts to
optimize the delivery of HIV care, including ART, in low- and middleincome countries (LMIC) and the emergence of new agents and drug
classes, which have simplified HIV treatment and made broader
successful management more achievable. Recent studies have
indicated that earlier commencement of HIV therapy is beneficial,
leading to changes in the recommended ART initiation threshold in
LMIC to B350 CD4 T cells. Forthcoming revised WHO guidelines are
anticipated to raise this threshold. Studies currently under way are
investigating approaches to second-line ART in LMIC. The results
from these studies will better inform the roll-out of effective secondline therapy. In addition, the financial cost of ART makes optimization
of dosing an important consideration in LMIC, in order to maximize
effectiveness while limiting costs. ART monitoring is also an
important priority in LMIC. Efforts to develop simple and reliable
technologies that can provide rapid results in the field are underway.
In the meantime, a number of recent studies in adults and children
point to the way forward and the best use of resources. The final
priority is operational optimization, to ensure adequate service
delivery. Although the challenges in LMIC are substantial and
evolving, considerable inroads have been and are being made into
optimizing HIV treatment and its delivery, which is crucial in reducing
the global impact of the disease. This abstract is modified from an
abstract provided by David Cooper, University of New South Wales,
Sydney, Australia, when presented as the Lock Lecture at HIV Drug
Therapy in Glasgow, November 2012.
O112
Initiation and sequencing of ART
R Gulick
Weill Medical College of Cornell University, New York, USA.
There currently are 27 antiretroviral drugs approved for the
treatment of HIV infection. In choosing the optimal initial regimen,
a number of factors should be considered: antiretroviral activity (HIV
RNA, CD4 cell, and clinical responses); durability of responses;
baseline drug resistance; tolerability and both acute and chronic
side effects; convenience (number of pills, dosing interval, food/
fasting requirements); preserving future treatment options; patient’s
stage of HIV disease, concomitant illnesses and medications (and
drug-drug interactions); access; and cost. The optimal initial regimen
is one that is individualized to the specific patient’s situation.
Current preferred initial regimens include two nucleoside analogues
(NRTI) combined with either a non-nucleoside analogue (NNRTI),
a boosted protease inhibitor (PI), or an integrase inhibitor (II). Onepill, once-daily combination regimens have proven particularly
popular with patients and providers alike. The most common initial
regimen worldwide is two NRTI an NNRTI. In the event of virologic
failure of an initial regimen, multiple causes of failure should be
assessed, including: adherence; drug resistance; use of less potent
antiretroviral regimens; drug levels and drug-drug interactions; and
theoretically, tissue reservoir penetration (central nervous system,
genital tract). Of course, any or all of these reasons may be important and the challenge is to address the probable cause(s) of
failure and address them in choosing the next regimen, to ensure
success. Genotypic drug resistance testing is indicated in the
assessment of first (or second) virologic failure and can help optimize the selection of the next regimen. Genotypic and phenotypic
testing is recommended following failure of multiple regimens.
A common sequence of regimens is two NRTI and an NNRTI,
changing to two NRTI a boosted PI. The availability of drugs with
activity against drug-resistant viruses (e.g. newer NNRTIs and PIs)
and new classes of drugs (e.g. integrase inhibitors, CCR5 antagonists)
offers additional options for constructing successful subsequent
ART regimens.
O113
Resistance in Latin America, is anything different?
L Soto-Ramirez
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran,
Mexico City, Mexico.
HIV resistance to ARV therapy is an unwanted consequence of
HAART as it limits future options. The emergence and spread of high
levels of HIV-1 drug resistance in resource-limited settings where
combination antiretroviral treatment has been scaled up, without
proper treatment monitoring and drug availability, could compromise the effectiveness of national HIV treatment programmes.
Compared to developed countries, most of Latin America do not
perform resistance assays before starting ARV treatment and after
first line failure, having more resistance as a consequence in some
cases and the need for more expensive salvage treatments. Some
countries in the region do not have access to resistance tests due to
cost and lack of infrastructure. The presentation will include data on
the limited increase of transmitted resistance over time in the region
compared to other developing countries, especially in Africa, as well
as the prevalence of secondary resistance in first line failure and
multiexperienced patients, with remark on specific issues with non-B
subtypes. The elevated cross-resistance to the entire nucleoside
analogue group in countries still using thymidine compounds in first
line treatment will be stressed. Moreover, it will include the big
limitations for resistance assay interpretations and performance in
low level viraemia in Latin America as well as the excellent results of
using resistance committees in the optimization of available assays as
in the prescription of newer drugs.
3
O114
Clinical and virologic outcomes after changing first
antiretroviral regimen at 7 sites in the Caribbean, Central,
and South America Network (CCASAnet)
M Wolff1; C Cortes1; B Crabtree-Ramirez2; J Pape3; D Padget4;
B Grinsztejn5; E Gotuzzo6; C Cesar7; J Sierra-Madero2; M Bacon8;
K Jayathilake9 and B Shepherd10
1
Internal Medicine, University of Chile School of Medicine, Santiago,
Chile. 2Infectologı́a, Instituto Nacional de Ciencias Médicas y
Nutrición Salvador Zubirán, Mexico City, Mexico. 3Les Centres,
GHESKIO, Port au Prince, Haiti. 4Instituto Hondureño de Seguro
Social y Hospital Escuela, Tegucigalpa, Honduras. 5Instituto de
Pesquisa Clinica Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil.
6
Instituto de Medicina Tropical Alexander von Humboldt, Universidad
Peruana Cayetano Heredia, Enfermedades Infecciosas y Tropicales,
Lima, Peru. 7Fundación Huesped, Buenos Aires, Argentina. 8Division
of AIDS, National Institute of Health, Bethesda, USA. 9School of
Medicine, Vanderbilt University Medical, Nashville, USA.
10
Department of Biostatistics, Vanderbilt University, Nashville, USA.
Introduction: Access to highly active antiretroviral therapy (ART) is
expanding in resource limited settings (RLS), and ART regimens are
frequently changed. Outcomes after changes in the first regimen
(ART-1) have not been well studied in RLS. CCASAnet is a consortium
of adult HIV clinics from seven countries (Argentina, Brazil, Chile,
Haiti, Honduras, Mexico, and Peru).
Methods: Retrospective observational cohort study, assessing
rates of death, virologic failure (VF), and change in second ART
regimen (ART-2) after modification/changes of ART-1. Rates were
computed using Kaplan-Meier methods and hazard ratios (HR)*
adjusted for sex, age, CD4, clinical stage, calendar year, time between
starting regimens, reasons for changing ART-1, and type of regimen
change*were computed using Cox models stratified by site.
Results: A total of 3,384 patients (25% of total initiating HAART)
changed ART-1 by at least one drug and were included in this study,
with a median follow-up of 2.8 years from start of ART-2. Median age
at start of ART-2 was 37 years, 60% were male, and median CD4 was
181 cells/mL; toxicity was the most common reason for changing ART1 (48%) and the median time from start of ART-1 was 275 days. After
starting ART-2, 319 patients (9.4%) died; the probability of death at
years 1, 3, and 5 after ART-2 was 0.06, 0.10, and 0.12, respectively.
Risk factors for death were older age (HR 1.24 for 50 vs. 40
years; p 0.052), clinical AIDS at first visit (HR 1.30; p0.027), and
lower CD4 at start of ART-2 (HR 1.67 for 200 vs. 350 cells/mL;
p B0.001). While on ART-2, 366 (18%) of patients experienced VF;
the cumulative incidences of VF after 1, 3, and 5 years were 0.11,
0.22, and 0.28, respectively. Risk factors for virologic failure were
younger age (HR 1.41 for 20 vs. 40 years; p0.003), lower CD4
(HR 1.47 for 200 vs. 350 cells/mL; p B0.001), starting ART in an
earlier year (HR 1.20 for 2004 vs. 2007; p0.006), and changing
to ART-2 due to failure (HR 2.05 compared to toxicity; p B0.001)
or for some other non-toxicity reason (HR 1.57; p 0.001). The
cumulative incidence of changing ART-2 after 1, 3, and 5 years was
0.30, 0.51, and 0.64 respectively.
Conclusions: In a multi-centre resource-limited setting cohort of
patients modifying their first ART regimen, rates of subsequent ART
regimen modifications, mortality, and virologic failure were high.
Access to expanded ART formularies, especially with newer, saferprofile drugs, is needed.
O115
Next-generation drugs inclusion to the South’s HIV/AIDS
programs: the Brazilian experience on third-line drugs
Oral Abstracts
C Zaire1,2; L Hasenclever2 and B Coriat1
1
CEPN/Université Paris 13, France. 2Instituto de Economia/UFRJ,
Rio de Janeiro, Brazil.
Introduction: Third-line antiretroviral drugs (ARV) are now indicated
for the treatment of multi-resistant HIV/AIDS patients in virological
treatment failure. Although being the last and highly effective line of
defence, they are almost not present in the South because of their
prohibitive cost. Therefore, Brazil, where these drugs have been
adopted since 2005, constitutes an ideal laboratory to study nextgeneration drugs inclusion.
Materials and methods: Study the Brazilian Program focusing on
costs of this new treatment strategy. We monitored the purchases
between 2007 and 2009 looking for unitary costs of drugs and the
total costs for the Ministry of Health. This research was based on
the review of official documents from the Ministry of Health and
statistical work on National Health Bank (BPS) and Ministry of Health
budget databases.
Results: The National Program HIV/AIDS now distributes five third-line
ARV: Darunavir (introduced in 2007), enfuvirtide (2005), etravirine
(2010), raltegravir (2008), tipranavir (2010), all patented and imported
at very high prices. Over time, however, a lower purchase price is
observable (see Table 1). Thus, the price of darunavir (300 mg
tablet) decreased by 19.6% between 2007 and 2009; enfuvirtide
(108 mg vial) by 19.3% between 2007 and 2009; raltegravir (400 mg
tablet) by 12.8% between 2008 and 2009.
In 2008, only three third-line ARVs consumed together approximately 26% of the total budget for the acquisition and distribution
of National HIV/AIDS Program (see graphic 1). In 2009, the situation
becomes even more significant: almost 40% of the total budget were
spent with these three ARVs (see graphic 2).
Discussion and conclusion: Brazil is considered a middle-income
country and therefore cannot be benefited with the low prices
offered to low-income countries. However, as ARVs purchases are
performed centrally, we expected a greater bargaining power by the
Ministry of Health. In practice, there are price reductions when
increasing quantity purchases, but this does not seem sufficient to
ensure financial sustainability of the rising third-line ARV Program.
Today, third-line ARVs are distributed to 5,000 patients (from the
universe of 190,000 patients that are currently receiving antiretroviral therapy) and consume 40% of the total ARV procurement. This
scenario seems daunting given the strategies of ARV treatment,
which already consumes two percent of the total ministerial budget.
In fact, it is essential to continue negotiations with the pharmaceutical industry; furthermore, we must not forget the investment in
Table 1.
Informations for third-line ARV in Brazil
Average
Total cost (dollar) annual price
Daily dose
Quantity
price
purchased
Darunavir 300 mg tablet
2007
$ 11 357 243,05
$ 4,95
$ 19,81
2 293 200
2008
$ 16 768 434,62
$ 4,98
$ 19,92
3 366 490
2009
$ 51 648 122,75
$ 3,98
$ 15,94
5 659 680
Enfuvirtide 108 mg vial
2007
$ 24 836 274,11
$ 25,87
$ 51,74
960 000
2008
$ 61 612 677,02
$ 24,65
$ 49,31
2 499 000
2009 $ 27 234 536,44
Raltegravir 400 mg tablet
$ 20,87
$ 41,74
1 305 000
2008
$ 7 771 986,41
$ 10,65
$ 21,30
729 600
2009
$ 67 394 879,46
$ 9,29
$ 18,58
7 254 160
4
Expenditure in 2008
Oral Abstracts
Expenditure in 2009
5%
14%
19%
7%
2%
61%
18%
74%
Darunavir
Darunavir
Enfuvirtide
Enfuvirtide
Raltegravir
Raltegravir
Expenditure remains on the
programme HIV/AIDS
Expenditure remains on the
programme HIV/AIDS
Graphics 1 and 2. Total budget of acquisition and distribution of
the National HIV/AIDS Programme (ARVs and other drugs).
Source: Data from Brasil (2011b) and BPS (2011).
infrastructure and human resources for national production. In the
future, Brazil can be benefited by voluntary licenses granted by
the patent-pool strategies, but it is necessary to be able to absorb
the new technologies involved in the production of third-line drugs.
O21 HEPATITIS AND HIV
O211
Overview of HIV and hepatitis B and C co-infection
M Nelson
Chelsea and Westminster Hospital, London, UK.
Although co-infection with both hepatitis B and hepatitis C in HIV is a
common phenomenon, it should be remembered that the livers with
those living with HIV are under attack from various other areas as
well. These include the HIV virus itself which may infect stellate cells
leading to the generation of fibrosis, antiretroviral therapy, other
clinical medications, recreational drug use, other infections as well as
traditional risk factors, principally alcohol. Approximately four million
individuals are estimated to be co-infected with HIV and hepatitis
B. Fortunately, there are agents which are active against both HIV
and hepatitis B infection. The majority of individuals will have
suppressed hepatitis B replication through receiving HAART containing tenofovir with either lamivudine or entricitabine. Alternative
therapeutic options for individuals who are co-infected include
pegylated interferon, entecavir, telbivudine and adefovir. Entecavir
and telbivudine also have potential anti-HIV activity and therefore
should only be administered with highly active antiviral therapy
against HIV. Adefovir may be prescribed as monotherapy for hepatitis
B alone, although it is less potent than other but at the dose utilised
there is no activity against HIV. It is essential that all individuals with
hepatitis B are monitored for the development of hepatoma due
to an increased frequency of development and progression of this
tumour type in those co-infected with hepatitis B. HIV and hepatitis
C co-infection is common due to shared routes of transmission and
similar geographical distributions. Although hepatitis C does not
impact on the prognosis of HIV disease, HIV is associated with more
rapid progression of fibrosis and hence hepatic complications
associated with hepatitis C infection. Globally there is an epidemic
of acute hepatitis C in HIV-infected homosexual men, which is
fuelling the numbers who are co-infected. Hepatitis C infection is
associated with complications associated with HIV disease including
a higher risk of cardiovascular disease, diabetes, renal dysfunction,
and osteoporosis with bone fractures. The development of the
protease inhibitors telaprevir and boceprevir for the treatment of
hepatitis C has translated into improvements in the outcome of
therapy in the hepatitis C mono-infected population; although only
small studies are available, the results in the co-infected population appear to be similar. In addition, second generation protease
inhibitors have been associated with early response rates, even
higher than with telaprevir and boceprevir in the co-infected
populations. The generation of interferon-sparing regimens is also
of great promise, and clinical studies have recently commenced in
the HIV-infected population. It is essential that individuals with HIV
are tested for hepatitis B and for hepatitis C and vice-a-versa, and
that these are repeated frequently, so that individuals who are or
do become co-infected can benefit from the positive outcomes
associated with these new treatments.
O213
Pharmacokinetic data supporting the potential use of
sofosbuvir with antiretrovirals in HIV/HCV co-infected
patients
B Kirby; A Mathias; C Moyer; G Shen and B Kearney
Clinical Pharmacology, Gilead Sciences, Foster City, USA.
Introduction: Recently approved HCV protease inhibitors (PIs)
have drug interaction liabilities with key HIV antiretrovirals (ARVs),
specifically, ritonavir-boosted PIs. Sofosbuvir (SOF, formerly GS7977), a NS5B nucleotide inhibitor, is in Phase 3 clinical development
for the treatment of chronic HCV infection. We conducted a study
to evaluate potential interactions between SOF and common HIV
ARVs of varying 3rd agent classes (NNRTI, PI/r and integrase
inhibitor-based).
Methods: In a Phase 1, fixed sequence, 4-cohort study, healthy
volunteers received a single dose of SOF 400 mg before and after 14
days of Atripla (ATR, EFV/FTC/TDF 600/200/300 mg QD; n 17,
fasted), or 10 days of rilpivirine (RPV, 25 mg QD, n 17, fed),
darunavir/ritonavir (DRV/r, 800/100 mg QD, n 19, fed), or raltegravir (RAL, 400 mg BID, n 19, fasted). Geometric means ratio%
(GMR%, combination vs alone) of PK parameters AUCinf and Cmax
for SOF and GS-331007 (circulating nucleoside metabolite of SOF), or
AUCtau, Cmax, and Ctau for TFV, FTC, EFV, RPV, DRV/r, or RAL were
evaluated against a predetermined 70143% equivalence boundary.
Safety assessments were conducted throughout the study.
Results: A total of 16 and 17 subjects completed the ATR and RPV
cohorts, respectively, and 18 subjects completed the DRV/r and RAL
cohorts. The most frequent adverse events were dizziness, headache,
diarrhea, nausea, and constipation, predominantly during ATR
dosing. All but one event were mild and most were consistent with
known EFV adverse events. Overall, SOF was well tolerated with very
few treatment-emergent events during the administration of SOF
with ARVs. Co-administration of HIV ARVs and SOF did not result in
clinically significant changes in SOF and/or GS-331007 exposure. ATR
slightly decreased SOF and GS-331007 Cmax (2023%), RPV, DRV/
r, and RAL modestly increased SOF exposure by 21 to 45% with no
effect on GS-331007. SOF slightly increased TFV Cmax (25%),
modestly decreased RAL AUCtau (27%) and Cmax ( 43%), but did
not affect RAL Ctau, and had no other effect on PK parameters of
FTC, TFV, EFV, RPV, or DRV/r.
Conclusions: No clinically significant DDIs were observed between
SOF and EFV, RPV, DRV/r, RAL or the standard-of-care backbone of
5
FTC/TDF. These data support potential use of SOF with a variety of
ARV regimens in the HIV/HCV co-infected population.
O22 LIVING LONGER WITH HAART AND
NON-COMMUNICABLE DISEASES AND HIV
O221
Review of life expectancy in people with HIV in settings
with optimal ART access: what we know and what
we don’t
C Sabin
University College London, London, UK.
Life expectancy (LE) is an important indicator of health used widely
by government and healthcare agencies to monitor trends over time
and to determine resource allocation, as well as by insurance
companies and pension providers. LE of the HIV-positive population
has increased dramatically since the introduction of combination
antiretroviral therapy (cART); indeed, it is now believed that LE may
be similar to that of the general population in some subgroups.
There are, however, specific subgroups in which LE remains
substantially impaired. The impact of HIV and of cART on mortality
may be expressed in several ways. LE itself provides an estimate of
the average additional number of years that an individual would be
expected to live beyond a particular age. However, the detrimental
impact of HIV may also be described in terms of the number of years
of life lost or the gains in LE if HIV were to be eliminated as a cause
of morbidity in the population. My presentation will start with a
description of the different methods that researchers have used to
describe the mortality outcomes of those with HIV, and the impact of
cART on these. I will then consider how LE in the HIV-positive
population has changed over time, and will describe the impact of
demographic factors (e.g., gender, age, ethnic group) on LE. To
investigate the circumstances under which LE may return to normal
levels, I will also consider the potential impact of timely diagnosis
and linkage into care, continued engagement with care, optimal
initiation of cART, and maintenance of viral suppression on LE.
Finally, I will discuss some of the limitations of the approaches used
to estimate LE, with particular emphasis on the confounding effects
of lifestyle and behavioural factors when making any comparison
with LE in the general population.
O222
Renal dysfunction: real and apparent on HAART
A Pozniak
Chelsea and Westminster Hospital, London, UK.
Human immunodeficiency virus (HIV) infection has become a chronic
long-term manageable condition. Subsequently with ageing of this
population, comorbidities such as renal impairment are becoming
more prevalent. Kidney diseases are emerging as significant causes of
morbidity and mortality with older age, black ethnicity, hypertension,
diabetes, low CD4 cell count, HCV co-infection and high viral load
remaining important risk factors for kidney disease in the HIVinfected population. HIV-associated nephropathy (HIVAN) is an
uncommon but important cause of renal disease whose outcome
can be improved by HAART. Having started treatment, HIV-infected
individuals require lifelong antiretroviral medication but longterm data on the renal toxicity of HAART are limited. HIV affects
Oral Abstracts
the kidney directly or indirectly by drug-related effects that are
directly nephrotoxic or lead to changes in renal function by inducing
metabolic vaculopathy and renal damage. Historically, indinavir,
mainly through renal crystal and stone formation, affected renal
function but more recently cohort data have implied that atazanavir
and lopinavir are also linked to renal dysfunction through a similar
mechanism. Randomized clinical trials and post-marketing data
supported the renal safety of tenofovir in relatively healthy HIVpositive individuals. However, overall tenofovir use is associated
with 0.52.5% risk of acute kidney injury (AKI). The most frequent
mechanism of tenofovir-induced kidney failure is thought to be
tubular necrosis due to mitochondrial toxicity. Other mechanisms by
which antiretroviral drugs cause renal impairment are complex and
not completely understood. Effects on drug transporters leading to
unfavourable drug interactions have been proposed. The increase in
drug levels of tenofovir when given with ritonavir may be part of the
reason why regimens of boosted PIs and tenofovir are associated
with abnormalities in eGFR. Calculations estimating clearance of
creatinine are widely accepted as the best measure of kidney
function when using a 24-hour collection of urine. As urine
collections are rarely performed, formulae to calculate eGFR using
serum creatinine, demographic, and other factors have been
developed. Interpretation of these formulae is complicated, and
distinguishing normal from abnormal function in the individual
patient is inherently difficult. The most used formulae are the
CockcroftGault formula, the Modification of Diet in Renal Disease
(MDRD) formula, or The Chronic Kidney Disease Epidemiology
Collaboration (CKD-EPI) formula. All use serum creatinine as the
basis of their calculation and hence any tubular contribution to
plasma creatinine levels are included in their estimation of GFR.
None of these equations have been systematically validated in HIVinfected patients. The evaluation of glomerular filtration using these
formulae which include plasma creatinine to estimate GFR do not
take into account that 1020% of creatine is secreted through the
tubules and the proportion rises with worsening glomerular function.
The actual or real glomerular filtration rate (aGFR) is difficult to
measure requiring isotopic or intravenous infusions such as iohexol
or detailed imaging. Another reason for the eGFR to become
abnormal when the aGFR remains unaffected is the inhibition of
tubular enzymes. Blocking enzymes responsible for the tubular
secretion of creatinine will lead to rises in serum creatinine and a
fall in eGFR. This can lead to physicians believing that drugs have
caused renal impairment but actually there is no change in aGFR.
Dolutegravir by inhibiting OCT 2 and ritonavir and cobicistat by
inhibiting MATE-1 renal transporters can all show this phenomenon
with median falls in eGFR after starting these compounds of around
10-15 ml/min. These effects usually reach a steady state by two
to four weeks. Physicians need to be aware of this and be able
to differentiate between the expected changes in eGFR due to any
enzyme inhibition and any changes due to true renal disease.
Measuring tubular dysfunction is problematic and rely on increases
in urine creatinine protein ratios, normoglycemic glycosuria, the
presence of increased amounts of low-molecular-weight proteins
such as b2-microglobulin or light chains, aminoaciduria, and
inappropriate amounts of uric acid or phosphorus, coupled with a
reduced phosphate re-absorption rate. It has been suggested
that urine dipstick for glucose and protein and serum phosphate be used as monitoring tools to trigger further investigation of tubular dysfunction. With the ageing of the HIV population
and the use of co-medications that could alter renal function, the
issue of monitoring and interpreting and understanding laboratory
data to safely prescribe antiretrovirals will come even more into
focus.
6
O223
HIV, cardiovascular disease, and ageing
O Sued
Huésped Foundation, Buenos Aires, Argentina.
The introduction of highly active antiretroviral therapy resulted
in the dramatic reduction of HIV/AIDS-associated mortality and the
redefinition of HIV infection as a chronic condition. Nowadays,
life expectancy of new diagnosed HIV individuals is approaching that
of the uninfected population. Therefore, HIV management is now
faced by challenges associated with age-related comorbidities, in
particular cardiovascular disease (CVD). It was suggested that HIV
individuals are at higher risk of developing CVD compared with the
general population, which can be explained by several factors: a) HIV
individuals have a higher prevalence of smoking and other unhealthy
lifestyle behaviours, b) some antiretroviral drugs have been linked
to direct cardiovascular risk due to their effect on lipids or other
not well-understood effects, and c) HIV might additionally contribute
both directly or indirectly to a higher cardiovascular risk. Uncontrolled HIV viraemia is usually associated with chronic inflammation,
chronic immune activation and immunosenescence, which some
authors have defined as an ‘‘accelerated ageing’’ status. As the HIVpositive population continues to age, and HIV infection among older
people is not an uncommon phenomenon, the risk of CVD will
continue to increase. However, opportunities for preventive care
and screening for and treatment of CVD are frequently missed.
Case management and integrated care can help them confront
the physical and psychosocial aspects of the disease and reduce
marginalization and the dual stigma of both ageing and HIV.
O23 EPIDEMIOLOGY AND CLINICAL
ISSUES FOR WOMEN AND
I M P L E M E N T I N G T R E AT M E N T A S
PREVENTION
O231
Epidemiology and clinical issues of HIV positive women in
the Americas
P Volkow
National Institute of Cancer, Mexico City, Mexico.
Within the last decade, the HIV epidemic amongst women has been
steadily growing in the Americas, representing in some areas almost
half of HIV-infected individuals. Although biological factors determine
a higher vulnerability to HIV infection in women other elements seem
to play as major determinants in this increasing dynamic of the HIV
women’s epidemic. There are epidemiological factors that are shared
among HIV-infected women in different countries: belonging to
minority groups, being less educated, exposed to domestic violence,
high rates of poverty and difficult access to health care. These same
factors hinder diagnosis and HIV care, even in countries where access
to treatment is universal. Opportunities for early HIV-diagnosis are also
limited; only during pregnancies in countries with MTCT prevention
programmes; for most women HIV serology is performed when a
partner or a child has been diagnosed, or when they arrive severely ill
to a hospital. Care of HIV-infected women needs to address genderrelated health problems, particularly HPV co-infection. As patients
survive longer with HAART, other health problems of ageing women
need also to be surveyed and screened: osteoporosis, other gynecologic malignancies and metabolic disturbances among them. MTCT
Oral Abstracts
programmes have achieved enormous success in high-income countries. Although enormous efforts have been made to extend this
success to low- and middle-income countries, there is still a wide lag
in many countries, and children born HIV-positive are still counted
in their hundreds in Latin-America. This field needs further advocacy
to achieve universal MTCT prevention.
O232
Implementing treatment as prevention: the key to an AIDSand HIV-free generation
J Montaner
British Columbia Centre for Excellence in HIV/AIDS, St Paul’s Hospital,
Providence Health Care, and Division of AIDS, University of British
Columbia, Vancouver, Canada
Treatment of HIV/AIDS: While an outright cure or a preventive vaccine
for HIV/AIDS remains elusive, remarkable advances in HIV treatment
have been achieved over the past two decades. Most significant
among these advances is the development of highly active antiretroviral therapy (HAART). Two international clinical trials presented at
the 1996 International AIDS Conference in Vancouver, served as the
cornerstone for the emergence of triple therapy regimens based on
the use of two nucleosides plus either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor (aka highly active antiretroviral therapy or HAART) as the new standard of care [13]. In each
case the novel triple therapy regimen used among treatment-naı̈ve
individuals fully suppressed HIV replication and, therefore, rendered
the number of viral copies present in a patient’s blood undetectable.
As a result, the CD4 cell counts recovered and the disease was placed
into a long-term remission. In the province of British Columbia (BC),
within three years of the implementation of HAART, the BC Centre for
Excellence in HIV/AIDS (BC-CfE) documented an 85% reduction in HIV/
AIDS mortality among patients engaged in treatment. Similar results
have been observed in other resource-rich environments, and more
recently in resource-limited settings, where HAART has become
available.
Treatment as prevention: More recently, evidence has accumulated
that the viral load suppression achieved by HAART has a marked
impact on decreasing HIV transmission. Already in August 2006, we
proposed in a viewpoint article in The Lancet that the expansion of
HAART coverage to all those in medical need would represent a key
strategy to dramatically curb HIV/AIDS morbidity and mortality, as well
as HIV transmission [4]. We further suggested that such strategy would
be potentially cost-averting [5]. Evidence to support the impact of
HAART on HIV transmission can be readily found in vertical transmission studies where it has led to the near complete prevention of
transmission of HIV from the infected mother to the newborn.
Similarly, among sero-discordant couples (one infected and one
uninfected partner) transmission is a direct function of the level of
plasma HIV viral load in the infected member of the couple: the more
HIV is present in blood, the more virus is present in sexual fluids and
therefore the greater the risk of HIV transmission [6]. HIV viral load in
plasma and consequently in sexual fluids are effectively decreased to
undetectable levels with HAART, thereby HAART dramatically reduces
the risk of sexual HIV transmission. We have also shown that HAART
can similarly prevent HIV transmission among injection drug users [7].
These results have now been independently validated within the ALIVE
Cohort in the US [8]. More recently, at the population level, we have
documented that expansion of HAART uptake between 1996 and 2010
has been associated with a greater than 65% decrease in HIV new
diagnoses in BC [9]. Of note, this has taken place against a background
of stable or rising sexually and blood-borne infections in the province.
As a result, the provincial government has committed to further
7
expand outreach efforts to maximize HIV testing and facilitated HAART
access in BC, this initiative is known as Seek and Treat for Optimal
Prevention of HIV/AIDS in BC (STOP HIV/AIDS in BC). The BC-CfE’s
proposal in support of ‘‘Treatment as Prevention’’ was initially
regarded as controversial; however, this notion has gained the support
of the international community, including the International AIDS
Society and President Clinton in 2008 and Michel Sidibé, the Executive
Director of the Joint United Nations Programme on HIV/AIDS
(UNAIDS), shortly thereafter. In January 2009, investigators based at
the World Health Organization (WHO) AIDS programme published a
paper in The Lancet, which independently verified the potentially
critical role of ‘‘Treatment as Prevention’’ in the control of the
epidemic [10]. More recently, HPTN 052 - a prospective randomized
trial - provided definitive and compelling confirmatory evidence of the
efficacy of ‘‘Treatment as Prevention’’ among sero-discordant couples
[11]. HPTN 052 showed an impressive 96.3% decrease in the risk of HIV
transmission with immediate HAART. Of note, immediate HAART was
also associated with a 30% decrease in the combined endpoint of
disease progression and death, and an 83% reduction in the incidence
of extra-pulmonary tuberculosis. The latter results further galvanized
international attention towards the key role of ‘‘Treatment as
Prevention’’ for the control of the HIV epidemic. Indeed, US Secretary
of State Hilary Clinton pledged the support of the US administration
towards re-profiling PEPFAR efforts to emphasize the role of ‘‘Treatment as Prevention’’ and this was echoed by US President Obama
during his speech on 1 December 2011, and on 23 December 2011,
Science Magazine named ‘‘Treatment as Prevention’’ as the scientific
breakthrough of 2011. It is clear that expanding access to HAART is
highly effective in preventing morbidity and mortality among HIVinfected individuals, and secondarily it prevents HIV transmission. The
data is conclusive and compelling. The anticipated release of the
revised 2013 WHO treatment guidelines in July 2013 will markedly
expand HAART eligibility globally [12]. The challenge remains to secure
the necessary political will to fully renew WHO guidelines and, thus,
implement the ‘‘Treatment as Prevention’’ strategy. An AIDS & HIVfree generation is within reach, however, this will not be attained if we
fail to fully capitalize on the promise of ‘‘Treatment as Prevention’’.
References
1. Carpenter CC, Fischl MA, Hammer SM, Hirsch MS, Jacobsen DM,
Katzenstein DA, et al. Antiretroviral therapy for HIV infection in
1996. Recommendations of an international panel. International
AIDS Society-USA. JAMA. 1996 Jul 10;276(2):14654.
2. Gulick RM, Mellors JW, Havlir D, Eron JJ, Gonzalez C, McMahon D,
et al. Treatment with indinavir, zidovudine, and lamivudine in adults
with human immunodeficiency virus infection and prior antiretroviral
therapy. N Engl J Med. 1997;337:7349.
3. Carpenter CC, Fischl MA, Hammer SM, Hirsch MS, Jacobsen DM,
Katzenstein DA, et al. Antiretroviral therapy for HIV infection in 1998:
updated recommendations of the International AIDS Society-USA
Panel. JAMA. 1998 Jul 1;280(1):7886.
4. Montaner JS, Hogg R, Wood E, Kerr T, Tyndall M, Levy AR,
et al. The case for expanding access to highly active antiretroviral
therapy to curb the growth of the HIV epidemic. Lancet. 2006 Aug
5;368(9534):5316.
5. Lima VD, Johnston K, Hogg RS, Levy AR, Harrigan PR, Anema A,
et al. Expanded access to highly active antiretroviral therapy: a
potentially powerful strategy to curb the growth of the HIV epidemic.
J Infect Dis. 2008 Jul 1;198(1):5967.
6. Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li C, WabwireMangen F, et al. Viral load and heterosexual transmission of human
immunodeficiency virus type 1. Rakai Project Study Group. N Engl J
Med. 2000 Mar 30;342(13):9219.
7. Wood E, Kerr T, Marshall BD, Li K, Zhang R, Hogg RS, et al.
Longitudinal community plasma HIV-1 RNA concentrations and
incidence of HIV-1 among injecting drug users: prospective cohort
study. BMJ. 2009 Apr 30;338:b1649.
Oral Abstracts
8. Kirk G, Galai N, Astemborski J, Linas B, Celentano D, Mehta S, et al.
Decline in Community Viral Load Strongly Associated with Declining
HIV Incidence among IDU, Abstract #484, CROI 2011.
9. Montaner JS, Lima VD, Barrios R, Yip B, Wood E, Kerr T, et al. Association of highly active antiretroviral therapy coverage, population
viral load, and yearly new HIV diagnoses in British Columbia, Canada:
a population-based study. Lancet. 2010 Aug 14;376(9740):5329.
10. Granich RM, Gilks CF, Dye C, De Cock KM, Williams BG. Universal
voluntary HIV testing with immediate antiretroviral therapy as
a strategy for elimination of HIV transmission: a mathematical
model. Lancet. 2009 Jan 3;373(9657):4857. doi: 10.1016/S01406736(08)61697-9. Epub 2008 Nov 27.
11. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC,
Kumarasamy N, et al. Prevention of HIV-1 infection with early
antiretroviral therapy. N Engl J Med. 2011 Aug 11;365(6):493505.
doi: 10.1056/NEJMoa1105243. Epub 2011 Jul 18.
12. Doherty M, et al. Maximizing the prevention benefits of ARVs:
WHO’s Global Guidelines. Presented at the 3rd International HIV
Treatment as Prevention Workshop. April 2225, 2013. Vancouver,
BC, Canada. Available from: http://www.treatmentasprevention
workshop.org.
O24 TREATMENT GUIDELINES
O241
One world, but how many standards of care?
P Cahn
Huésped Foundation, Buenos Aires, Argentina.
The International AIDS conference held in Vancouver in 1996, where
modern HAART was born, was held under the motto ‘‘One world, one
hope’’. Unfortunately, the world is falling short of this goal. Albeit it is
encouraging that eight million people living with HIV in low- and
middle-income countries have started antiretroviral treatment since
2001 people that would probably have died otherwise millions of
people living with HIV still lack access to treatment and care. Many
thousands of women, men and children continue to die as a consequence of our failure as a global community. Therefore, we need to
plan aiming to honour the commitments and keep the promises made
several times in different high level meetings, conferences and in an
incredible number of declarations, papers and documents. As of today,
ARV guidelines in so-called rich countries are not matched by WHO
guidelines and several local countries recommendations. Of note these
differences are not limited to the ‘‘When to start’’ question, but also
include the list of preferred drugs, the recommended monitoring tools
and the management of co-morbidities. In the era of treatment as
prevention, the benefits of HAART expansion are no longer limited to
the individual and has become a strategic public health tool in the
struggle against HIV/AIDS. So, the gap between rich and poor countries’
guidelines becomes even more unfair and painful. The world needs to
move ahead and make the goal of ‘‘One world, one hope’’ a reality.
O31 HIV AND ENDEMIC DISEASES
O311
HIV and endemic diseases
J Sierra-Madero
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran,
Mexico City, Mexico.
8
Infectious agents that are endemic to specific geographic regions
provide the clinical syndrome of AIDS with unique clinical and
epidemiologic characteristics often not well recognized in different
publications. In Latin America and the Caribbean, the infectious agents
that play significant roles in the HIV epidemic in certain geographic
areas are Histoplasma capsulatum, Leishmania sp, Trypanosoma cruzi,
Coccidiodes imitis, Paracoccidioides brasilensis, Mycobacterium bovis,
and some intestinal parasitic infections. Even though these infections
are well known locally, there are significant knowledge gaps regarding
the clinical presentation and epidemiology of these infections when
present in HIV-infected patients. A review of the existing information
on the topic will be presented. Implications for clinical management,
research questions, and the challenge they represent to the health
systems in the region will be discussed. Occurrence of these infections
in the context of the immunosuppression associated with HIV infection
accounts for the most widely recognized clinical and epidemiologic
consequences. However, the increasing importance of chronic noncommunicable diseases in HIV-infected patients may also contribute to
the unique challenges posed by these infections. Such may be the case
of chronic Trypanosoma cruzi infection and cardiovascular diseases
present in HIV-infected individuals.
Oral Abstracts
the health outcomes in diverse populations and groups. This framework provides to explain health inequities and the impact of social
injustice in health. In this presentation, the social determinants of
health framework will be used to describe the impact of the socioeconomic and political contexts on HIV transmission risks in different
populations. Particular attention will be placed to the impact of these
social determinants in framing HIV-related inequities and vulnerability.
Examples from prisoners and other populations in Caribbean Region
will be used to describe the impact of social determinants of health on
selected HIV-related outcomes including access and retention in care.
Strategies and interventions to reduce inequities and address
vulnerabilities associated with HIV/AIDS will be discussed.
O33 ACCESS AND TREATMENT, POLICY
ISSUES
O331
Overview of barriers to diagnosis/treatment and retention
in care, to include late presenters
O32 HIVAND VULNERABLE POPULATIONS
J Pape1,2
1
Division of Infectious Diseases, Center for Global Health, Weill
Cornell Medical College, Cornell University, New York, USA. 2Les
Centres, GHESKIO, Port au Prince, Haiti.
O321
Alcohol and non-injected drugs
No abstract available.
O322
Transgender medicine
A Radix
Callen-Lorde Clinic, New York, USA.
Transgender women are disproportionately affected by HIV, with
prevalence and incidence rates consistently found to exceed those of
men who have sex with men (MSM). Of particular concern are
prevalence rates of over 50% found among young transgender
women of colour. Despite this, the medical and psychosocial needs
of transgender persons remain largely unmet, and few culturally
appropriate and targeted HIV-prevention interventions exist for this
population. This presentation will review the structural factors,
including stigma, discrimination, and criminalization, as well as
individual level factors, that lead to elevated HIV risk. These factors
also negatively impact on access to medical care and affect all points
of the HIV treatment cascade. Innovative evidence-based strategies
that have been successfully implemented among transgender women,
resulting in greater uptake of HIV testing, engagement, and retention
in care will be described.
By 2010, Latin America and the Caribbean achieved 63% antiretroviral
therapy (ART) coverage for HIV-infected patients although continuing
barriers to HIV testing, ART initiation, and adherence remain.
The region has a high rate of late ART initiation (LAI) associated with
increase in early mortality, cost of care, and risk for HIV transmission.
LAI is linked to high rate of both late HIV testing (LHT) and late
presenters (LP), defined as starting ART ]6 months after HIV
diagnosis. Barriers to HIV testing include lack of access to testing
centres and poor service quality. Stigma plays a significant role for LHT
and LP. Even with significant dissemination efforts in the public realm
about HIV, individuals continue to underestimate their vulnerability
to risk. Male gender, older age, lower socio-economic status, and
external locus of control are characteristics of LP. Once patients are
diagnosed with HIV, they face high rates of attrition prior to ART
initiation. Absence of linkage of HIV testing centres to ART facilities,
cost and logistics, such as clinic co-payments, transportation expenses, lack of nutritional support, and long waiting times are
significant barriers to ART initiation and ongoing care. There is
evidence that waived clinic fees, nutritional supplement, faster ART
initiation, transportation subsidies, and early tracking for patients
who miss visits may significantly decrease the rate of LP and LAI,
improve retention in care, and adherence to ART. Further efforts to
decrease barriers to HIV testing, ART initiation, and adherence will be
critical to reach the goal of HIV universal treatment.
O332
O323
Missed opportunities and late diagnosis in HIV infected
Mexican women
Social determinants of health and HIV: the experience of
prisoners and other populations made vulnerable
C Rodriguez-Diaz
School of Public Health, University of Puerto Rico, Aguas Buenas,
Puerto Rico.
Social determinants of health are factors which can be changed and
controlled by policy and are largely responsible for the differences in
A Martin Onraet1; A Gonzalez2; M Guerrero-Almeida1; C MagisRodriguez3; P Volkow-Fernandez4; V Alvarez-Wyssmann5 and J SierraMadero1
1
Infectious Diseases, Instituto Nacional de Ciencias Medicas y
Nutricion Salvador Zubiran, Mexico City, Mexico. 2Coordination,
Clinica Especializada Condesa, Mexico City, Mexico. 3Clinical
Research, Clinica Especializada Condesa, Mexico City, Mexico.
9
4
Infectious Diseases, Instituto Nacional de Cancerologia, Mexico City,
Mexico. 5Infectious Diseases, Clinica Especializada Condesa, Mexico
City, Mexico.
Introduction: Social factors increasing vulnerability to HIV in women
hinder healthcare and early HIV diagnosis. Prevention efforts in
countries with concentrated epidemics focus mainly in MSM and do
not reach women at risk. We evaluated a sample of recently diagnosed
HIV Mexican women to describe diagnosis circumstances, frequency
of late diagnosis and factors associated with vulnerability.
Materials and methods: Interviews were conducted on Mexican
women from 2 large HIV care centers in Mexico City between
January 2009 and November 2012. Information on sociodemographic data, partners, risk behaviour, history of physical/
sexual violence, HIV diagnosis circumstances and access to medical
and prenatal care was obtained. Clinical information was taken from
medical records.
Results: 152 women were included (24% of total diagnosed in the
period in both centers). Interviews were done to 122 women.
Median age at diagnosis was 33 (1775). Maximum level of
education was primary school in 42 (30%), 14(9%) were illiterate.
A median of 3 lifetime sexual partners (1300) was reported. A third
had their first pregnancy as teenagers. History of physical violence
and sexual abuse was reported by 52% & 38%, respectively. In 85
(70%), likely source of infection was a stable partner. HIV diagnosis
was made after a partner/child diagnosis in 40%; in 37% because
women were symptomatic. Only 15% were diagnosed by screening,
including during pregnancy (7.5%). 39% had sought medical care a
median of 4 times because of symptoms related to HIV without
being offered an HIV test. Median CD4 count at diagnosis was
154 (11341). CD4 B200 at diagnosis was present in 58%, and
B100 CD4 in 34%. Lower CD4 were found in women with lower
education levels, women diagnosed with symptoms, and those
who sought medical care before being diagnosed. 87% of women
with previous pregnancies reported never being offered an HIV
test.
Conclusions: Women living with HIV in this sample had low socioeconomic background, high prevalence of physical/sexual violence,
and late stage disease at diagnosis. Missed opportunities for early
testing (prenatal/primary care) were identified. In Mexico, HIV
screening strategies are focused on selected groups that do not
include women, unless they are pregnant. Women are diagnosed
mostly when they become sick or after a family member is detected.
Preventive policies should also address women; screening strategies
need to be reinforced in primary care to increase early HIV detection
in women.
Oral Abstracts
patients, 45% initiated HAART in AIDS stage and 50% had baseline
CD4 count B 100 cell/mL, (earlier treatment is more frequent
lately). In this treatment, naı̈ve population 5-year survival and
AIDS-free survival were 90% and 70%, respectively. Three-year
mortality decreased from 20.8% for those initiating HAART in
2001 to 3.4% in those doing it from 2008 onward. Cross-sectional
study showed 73% of patients with undetectable viral load; median
CD4 count increased from baseline of 164 to 358 cell/mL at
last count. The expanded access to HAART guaranteed by law
and the Chilean AIDS Cohort has been a successful synergistic
initiative for the implementation of treatment and its evaluation in
Chile.
O34 TUBERCULOSIS AND HIV
O341
An overview of TB and its treatment
No abstract available.
O342
Tuberculosis and immune response inflammatory syndrome
M Lederman
Case Western Reserve University School of Medicine and University
Hospitals of Cleveland, Cleveland, USA.
In persons with advanced HIV infection, the initiation of antiretroviral
therapy occasionally provokes an inflammatory illness called immune
response inflammatory syndrome (IRIS). In some instances, this is
manifested as deterioration of an already recognized opportunistic
illness (paradoxical IRIS) and in others, the inflammatory response
allows recognition of an opportunistic illness that was sub-clinical
before ART initiation (unmasking IRIS). In either setting, the
occurrence of IRIS underscores the two edged nature of the immune
response at the same time both responsible for defence against
microbial pathogens and also responsible for the signs and
symptoms of infection. While IRIS is clearly an inflammatory disorder,
the precise mechanisms responsible for its appearance as viral
replication are attenuated and systemic immunity restored remain
incompletely defined.
O333
The Chilean experience in the treatment of AIDS
M Wolff
University of Chile School of Medicine, Santiago, Chile.
Chile, a 16.6 million-people upper middle-income country has a
0.3 105 rate of HIV infection in adults, mostly cared by the Public
Health System (PHS) through 34 AIDS care centers (ACC). Expanded
access program (EAP) to HAART was begun in 2001 and there is now
guaranteed free access to antiretrovirals and monitoring (CD4 count,
viral load, and genotype) in the PHS (with low co-payment, also
guaranteed for the privately insured). First-line HAART are assigned
at the ACC but rescue therapies are approved centrally. Standards for
professional staffing at ACC are based by norm on patient load. 32/
34 ACC have enrolled their patient on HAART without exclusions
in the Chilean AIDS Cohort ( 15,000 patients) for homogeneous
management and evaluation of the EAP. In 5,000 treatment naı̈ve
O35 UPDATE FROM THE 20TH
CONFERENCE ON RETROVIRUSES AND
OPPORTUNISTIC INFECTIONS (CROI)
O351
Update from the 20th CROI: Pathogenesis, Prevention and
Treatment
R Diaz1 and D Kuritzkes2
1
Paulista School of Medicine, Federal University of São Paulo, São
Paulo, Brazil. 2Brigham and Women’s Hospital, Harvard Medical
School, Boston, USA.
The 20th Conference on Retroviruses and Opportunistic Infections
was held in Atlanta, Georgia, in March 2013. Important new data on
10
the pathogenesis, prevention, and treatment of HIV were presented
and are reviewed here. In the realm of pathogenesis and HIV
eradication, a study of patients with acute HIV infection showed that
those treated with combination antiretroviral therapy (cART) during
Fiebig Stage I had undetectable proviral DNA and negative viral
outgrowth assays when tested after a year on therapy. Immediate
treatment of an infant with evidence for maternal transmission
of HIV led to apparent cure of the infant. A randomized study
confirmed previous observations that intensification of cART with
raltegravir leads to a transient increase in 2-LTR circles, strongly
suggesting ongoing viral replication in at least some patients. Studies
in HIV prevention included the disappointing results of the VOICE
trial, which failed to show evidence of protection against HIV
infection in women given oral or topical pre-exposure prophylaxis;
poor adherence appears to explain this result. By contrast, studies in
Oral Abstracts
the macaque model demonstrated high rates of protection against
vaginal SHIV challenge using a rilpivirine-containing vaginal ring, and
against rectal challenge using a long-acting (monthly) injectable
formulation of a novel integrase inhibitor. A study of the investigational integrase inhibitor dolutegravir in cART-experienced, integrase
inhibitor-naı̈ve patients showed that dolutegravir was superior to
raltegravir when combined with ritonavir-boosted darunavir. The
Second Line study of lopinavir/ritonavir (LPV/r) plus two nucleoside
reverse transcriptase inhibitors (NRTI) versus LPV/r plus raltegravir as
second-line cART showed the two regimens to be similar in overall
efficacy. Lastly, the OPTIONS study showed that NRTI do not add
significantly to the activity of salvage cART regimens that include
more than two active agents from other classes.
11
Poster Abstracts
POSTER ABSTRACTS
ADHERENCE
ADVERSE EVENTS
P1
P2
Self-reported cART adherence and alcohol, tobacco, and
illicit drug use in a cohort of HIV-infected patients in
Buenos Aires
Cardiovascular risk assessment In HIV patients of an
outpatient HIV clinic in Mexico City
C Cesar1; V Fink1; M Socias1; G Vigo2; S. Jimenez1; O Sued1;
C McGowan3 and P Cahn1
1
Clinical Research, Fundacion Huesped, Buenos Aires, Argentina.
2
Infectious Diseases Division, Hospital Juan A Fernandez, Buenos
Aires, Argentina. 3School of Medicine, Vanderbilt University School of
Medicine, Nashville, USA.
Introduction: Substance use is frequently encountered in HIV-infected
individuals. The introduction of effective cART has led to a significant
decrease in AIDS-related mortality and morbidity. However, these
benefits may be less pronounced in drug users who may have reduced
access to, or be less adherent with, cART. The objective of this study
was to evaluate the frequency of self-reported substance use and
its relationship to cART adherence using a questionnaire administered
to outpatients attending an HIV clinic in Buenos Aires.
Materials and methods: A rapid clinical screening tool was adapted
from a previously validated questionnaire [1] and translated into
Spanish for use in CCASAnet (Caribbean, Central and South America
network for HIV epidemiology). The questionnaire was administered
to all patients presenting for laboratory testing at Hospital Juan A.
Fernandez, the CCASAnet site in Buenos Aires, between 15 Feb 2013
and 15 Mar 2013. Univariate comparisons of demographics and substance use were made between those patients on cART with and without missed doses. Chi-square tests were used for categorical variables.
Results: The questionnaire was administered to 228 HIV-infected
patients in care during a one-month period: 159 (69.7%) were male
and median age was 41.4 years (IQR: 3348.8). Among 173 patients
receiving cART, 33 (14.5%) reported missed ART doses in the previous
seven days (median missed doses 2 [IQR: 211]). Use of marijuana,
cocaine, alcohol, and cigarettes within the previous seven days
was self-reported by 11.4%, 6.6%, 36.8%, and 39.9% of patients,
respectively. Compared to non-use, cocaine and alcohol use were
associated with missed ART doses (cocaine use in those who missed/
did not miss doses: 18.2% vs. 2.8%, P:0.04; alcohol use 48.5% vs.
29.6% p:0.043). Marijuana use was not associated with missed doses.
Conclusions: This pilot study confirms previous reports showing the
linkage between substance abuse and lack of adherence. The point of
care questionnaire was easily implemented and widely accepted and
may be useful for identifying patients with increased risk for suboptimal adherence. Specific and culturally appropriate interventions
are required to address this important barrier. Further analyses will
assess the association of substance use and virologic suppression. This
study was partially supported by CCASAnet/IeDEA, Grant awarded
number UO1AI069923.
Reference
1. Rasbach DA, Desruisseau AJ, Kipp AM, Stinnette S, Kheshti A,
Shepherd BE, et al. Active cocaine use is associated with lack of HIV-1
virologic suppression independent of nonadherence to antiretroviral
therapy: use of a rapid screening tool during routine clinic visits. AIDS
Care. 2013;25(1):10917.
C Magis-Rodrı́guez1; J Casillas2; V Alvarez-Wyssmann1; M CarreteZúñiga1; E Rodrı́guez-Nolasco3; R Niño-Vargas3; T Escobedo4 and
A Rodrı́guez5
1
Research and Education, Clinica Especializada Condesa, Mexico City,
Mexico. 2Clinical, Clinica Especializada Condesa, Mexico City, Mexico.
3
Clinica Especializada Condesa, Informatics, Mexico City, Mexico.
4
Clinica Especializada Condesa, Laboratory, Mexico City, Mexico.
5
Program of HIV/AIDS, Clinica Especializada Condesa, Mexico City,
Mexico.
Introduction: Several studies conclude that patients with HIV on
antiretroviral treatment have higher risk of cardiovascular disease.
The objective of this study was to assess cardiovascular risk in
patients from Clinica Condesa, an HIV clinic in Mexico.
Material and methods: This retrospective study included HIVinfected patients from Clinica Condesa with initial visit between
2009 and 2011 and had a complete lipid profile. The smoking
status and systolic blood pressure were obtained from the patient’s
clinical file. General demographic information, total cholesterol, HDL
cholesterol, and antiretroviral treatment were obtained from an
integrated clinical and laboratorial database. The Framingham group
assessment charts were used to evaluate cardiovascular risk, which
was then categorized in high ( 20), medium (10 to 20) and low
( B10). Hypertriglyceridemia was defined as triglycerides 150
mg/dL, total hypercholesterolemia as 200 mg/dL, and low HDL
cholesterol as B45 mg/dL. For statistical analysis, the 20.0 SPSS
software was used.
Results: Out of 399 patients included, 19 (5%) were women and 380
(95%) men. The total mean age was 37.7; 41.1 for women and 37.5 for
men. Current smokers were 5 (1.25%) women and 200 (50%) men. The
average systolic blood pressure was 110 SD98, HDL cholesterol 37.7
SD910.7, and total cholesterol 164 SD991. Only 4 (1%) men had high
risk, 1 (0.3%) woman and 20 (5%) men were in medium, while 18
women (5%) and 354 men (89%) showed low risk. Comparisons of low
group vs. medium and high group and found no differences in gender
(95 vs. 96%), smokers (57 vs. 68%), low HDL cholesterol (79 vs. 88%),
or antiretroviral therapy (85 vs. 60% on EFV/FTC/TDF). Differences
were found in age, low-risk group had on average 36.7 while high and
medium group had 54, prevalence of hypertriglyceridemia 55% (ICI
50% ICS 60%) vs. 96%(ICI 82% ICS 99%) and total hypercholesterolemia 12% (ICI 9% ICS15%) vs. 64% (ICI 44% vs. 81%).
Conclusions: Although a low prevalence of high cardiovascular risk
was found in Clinica Condesa, the prevalent metabolic alterations
related to medium and high risk should be specially regarded. As the
patients are predominantly young, growing older increases the risk
factors for cardiovascular disease.
P3
Analysis of glucose, insulin, HOMA-IR, and triglycerides
after 48 weeks of LPV/r therapy among subjects in 3
prospective randomized clinical trials
12
Poster Abstracts
R D’Amico1; C Wegzyn1; W Richter2; C Lin1; J Beron3; Y Hu1;
L Fredrick1; B Saget1; M Guion1 and M Norton1
1
AbbVie Inc., Global Pharmaceutical Research and
Development, North Chicago, USA. 2Research Institute for Lipid
Metabolism and Hemorrheology, Windbach, Germany. 3Medical
Department, Abbott AG, Baar, Switzerland.
Conclusions: In this analysis, there was no evidence for the
development of insulin resistance in HIV-infected subjects receiving
LPV/r-based regimens. These findings challenge hypotheses associating LPV/r therapy and insulin resistance. Median Changes From
Baseline to Week 48 in Insulin Resistance Parameters and Triglyceride Levels (Total Population).
Introduction: The potential for development of insulin resistance
(IR) in patients receiving LPV/r was raised in HIV treatment
guidelines including the 2011 DHHS and 2010 IAS-USA versions.
There are conflicting data for this association. Studies in healthy
volunteers demonstrate a transient effect of LPV/r on IR, whereas
studies in HIV-infected individuals demonstrate minimal impact of
LPV/r on insulin, glucose, or HOMA-IR levels after 48 weeks of
antiretroviral therapy (ART). This retrospective analysis compared
baseline (BL) and week 48 (WK48) insulin resistance parameters
and triglyceride levels in subjects receiving LPV/r either as mono,
dual, or triple ART.
Materials and methods: Fasting glucose, insulin, HOMA-IR, and
triglyceride (TG) levels were measured from plasma samples of 529
antiretroviral-naı̈ve subjects in three randomized, prospective, multicentre studies (FRAN-03-001, M05-730, and M10-336). Of the 529
subjects, 486 subjects with BL and WK48 data were included: LPV/r
monotherapy (n 70), LPV/r AZT/3TC (n 40), LPV/r FTC/TDF
(n 280), LPV/r RAL (n 96). Within-group median changes from
BL to WK48 were evaluated using the Wilcoxon signed-rank test.
Results: Eighty percent of subjects were male, 77% were white,
and 9% were Hispanic. At BL, 37% of subjects had CD4 T-cell
counts B 200 cells/mL and 33% of subjects had plasma HIV-1 RNA ]
100,000 copies/mL. There was no significant increase in fasting
glucose, insulin, or HOMA-IR levels from BL to WK48 for any
treatment group. However, a significant increase in TG was observed
from BL to WK48 in all treatment groups. Results were similar when
66 additional subjects receiving lipid-lowering or anti-glycaemic
agents pre- or post-BL were excluded. Using regression analysis,
LPV/r associated increases in TG did not appear to be associated with
increased insulin resistance.
P4
Week 96 renal safety update of Elvitegravir/Cobicistat/
Emtricitabine/Tenofovir DF from two phase 3 randomized
controlled trials
F Post1; J Winston2; B Hendry1; B Gazzard3; J Molina4; H Liu5;
D Piontkowsky6; A Cheng6; M Rhee5 and J Szwarcberg6
1
King’s College London School of Medicine, London, UK. 2Mount
Sinai School of Medicine, New York, USA. 3Chelsea and Westminster
Hospital, London, UK. 4Saint-Louis Hospital and University of Paris
Diderot, Paris, France. 5HIV Clinical Research, Gilead Sciences, Foster
City, USA. 6Gilead Sciences, Foster City, USA.
Introduction: Cobicistat increases serum creatinine (Cr) by inhibiting
tubule Cr secretion, and tenofovir DF (TDF) may cause renal toxicity.
We examined the renal safety profile of elvitegravir/cobicistat/emtricitabine (FTC)/TDF (STB) through week 96 in two phase 3, randomized,
double-blind studies to determine whether co-administration of
COBI and TDF increases the rate of TDF-associated renal toxicity.
Methods: Pooled data from Study 103 (STB vs. ritonavir-boosted
atazanavir [ATV/r] FTC/TDF [TVD]) and Study 102 (STB vs. FTC/TDF/
efavirenz [ATR]) were analyzed for renal safety including renal
discontinuations through week 96, and for subclinical renal toxicity
defined as having abnormalities in at least two out of four renal
laboratory parameters (tubular abnormalities [hypophosphatemia,
proteinuria or normoglycemic glycosuria] or increases in serum Cr).
Results: Median exposures to STB (n 701), ATV/r TVD (n355),
and ATR (n 352) were 97, 96 and 108 weeks. Median (IQR) changes
from baseline in serum Cr (mg/dL) at week 96 were 0.13 [0.040.20]
Abstract P3Table 1.
LPV/r
monotherapy
LPV/r AZT/3TC
LPV/r RAL
LPV/r FTC/TDF
LPV/r total
Median BL (IQR)
83.8 (77.5-95.5)
86.5 (79.3-93.7)
86.8 (81.1-97.0)
88.3 (81.1-95.5)
88.0 (81.1-95.5)
Median WK48 (IQR)
82.0 (77.5-93.7)
85.6 (75.7-91.9)
88.7 (83.0-97.0)
90.1 (82.9-98.5)
Glucose, mg/dL
Median D from BL
1.8
0.9
1.9
1.8
88.3 (81.1-97.3)
0.3
Insulin, mU/mL
Median BL (IQR)
7.2 (6.2-12.4)
8.2 (6.2-12.4)
4.7 (2.6-8.6)
7.8 (5.2-13.0)
Median WK48 (IQR)
8.2 (5.2-12.4)
7.2 (4.2-14.4)
4.9 (2.3-11.0)
7.8 (6.0-11.2)
Median D from BL
HOMA-IR, mmol/L mU/mL
1.0
1.0
0.3
0.0
Median BL (IQR)
1.6 (1.2-2.7)
1.7 (1.2-2.4)
1.0 (0.5-1.9)
1.7 (1.1-3.1)
Median WK48 (IQR)
1.4 (0.9-2.5)
1.6 (0.9-2.8)
1.1 (0.5-2.8)
1.9 (1.2-2.7)
Median D from BL
0.2*
0.1
7.2 (4.3-12.1)
7.6 (4.3-11.4)
0.4
1.6 (1.0-2.7)
1.6 (0.9-2.7)
0.1
0.2
0.1
104.0 (77.0-157.0)
Triglycerides, mg/dL
Median BL (IQR)
Median WK48 (IQR)
Median D from BL
*P B0.05 for median change
83.0 (62.0-122.0)
92.0 (71.0-145.0)
111.0 (81.0-165.0)
110.0 (81.0-160.0)
136.0 (92.0-221.0)
164.5 (101.0-235.0)
175.0 (115.0-287.0)
172.0 (117.0-239.0)
53.0*
72.5*
64.0*
62.0*
169.0 (112.0-241.0)
65.0*
from BL to WK48
13
vs. 0.08 [0.000.16] vs. 0.01 [ 0.070.09], and were similar to
those observed at week 48. In STB patients, serum Cr changes did
not differ by age, sex, race, HIV-1 RNA, CD4 cell count or presence of
hypertension, diabetes. The number of renal discontinuations was
STB 11 (1.6%) vs. ATV/r TVD 7 (2.0%) vs. ATR 0; of which 4 vs. 4 vs.
0 had evidence of proximal renal tubulopathy (PRT); all 4 STB PRT
cases occurred before week 24; all 4 ATV/r TVD PRT cases occurred
after week 48. All PRT cases improved after study drug discontinuation. All other renal discontinuations were due to serum Cr increases
without tubular function abnormalities. In STB patients, the
occurrence of tubular abnormalities was similar regardless of baseline Cr clearance ( 5 vs. 80 mL/min) or on-treatment Cr clearance
( 5 vs. 70 mL/min). No subclinical renal toxicity was identified
among the 697 STB patients without PRT.
Conclusions: The rate and type of renal discontinuations in the STB
group were similar to those in the ATV/r TVD group and consistent
with published historical rates. No STB patient developed PRT after
week 24. The risk of PRT with STB is low, monitorable and reversible
upon discontinuation, which is similar to a regimen containing TDF
and boosted ATV.
P5
Diabetes prevalence and factors associated among patients
at an outpatient HIV clinic in Mexico City
V Alvarez-Wyssmann1; M Carrete-Zúñiga1; J Casillas2; E Rodrı́guezNolasco3; R Niño-Vargas3; T Escobedo4; A Rodrı́guez5 and
C Magis-Rodrı́guez1
1
Clinica Especializada Condesa, Research and Education, Mexico City,
Mexico. 2Clinical, Clinica Especializada Condesa, Mexico City, Mexico.
3
Clinica Especializada Condesa, Informatics, Mexico City, Mexico.
4
Laboratory, Clinica Especializada Condesa, Mexico City, Mexico.
5
Program of HIV/AIDS, Clinica Especializada Condesa, Mexico City,
Mexico.
Introduction: Studies about the prevalence of diabetes mellitus in
HIV-positive patients on HAART therapy show contradictory conclusions. This study aimed to find the prevalence of diabetes and
whether specific antiretroviral treatment is associated with an
increment amongst HIV patients on treatment.
Methods: A retrospective study was performed. HIV-positive
patients on HAART whose first visit to Clı́nica Condesa was in 2009
to 2011 and are still active (last clinical visit within 2012) were
included. General demographic information, antiretroviral therapy,
CD4 and viral load were obtained from a clinical database; the
general lab database provided fasting glucose levels. Diabetes
mellitus was defined as doctor reported in the lab request and/or
fasting glucose levels above 126 mg/dL. For analysis, SPSS 20
package was used.
Results: In this study, 4,950 patients were included; the population
was composed of 542 (11%) women, 4,288 (87%) men and 127 (3%)
transgender men. The mean age was 39 years and average glucose was
90 mg/dL SD923. Diabetes was found in 2.5% (ICI 2% ICS 3%) of the
patients; of this, 15% were women, 83% men, and 2% transgender
men.
Conclusions: The prevalence of diabetes mellitus in Clı́nica Condesa
was low relative to general Mexican population (7.34%).[1] There are
several factors yet to be studied that may influence this prevalence,
but this result is a hint that Mexican HIV population behaves
differently.
Reference
1. Villalpando S, Rojas R, Shamah-Levy T, Ávila MA, Gaona B, De la
Cruz V, et al. Prevalence and distribution of type 2 Diabetes mellitus
Poster Abstracts
in Mexican adult population. A probabilistic survey. Salud Publica
Mex. 2010;52(Suppl 1):S19S26.
P6
Renal safety profile of Lopinavir/ritonavir (LPV/r)-based
regimens in the PROGRESS study
B Renjifo; C Argyropoulos; R Stubbs; D Arikan; R Trinh and A Nilius
AbbVie Inc., Global Pharmaceutical Research and Development,
North Chicago, USA.
Introduction: There is an increasing need to identify alternative
antiretroviral (ARV) combinations for HIV () patients that avoid
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTI) to
minimize long-term organ toxicity. The PROGRESS study (Reynes J,
et al. AIDS Research and Human Retroviruses 2013; 29:256)
compared the novel NRTI-sparing regimen LPV/r raltegravir (RAL)
to LPV/r TDF and emtricitabine (FTC) in ARV-naı̈ve patients.
Through 48 weeks of follow up, LPV/r RAL was noninferior in
efficacy and exhibited comparable safety and tolerability profiles
compared to LPV/r TDF/FTC. As a component of a secondary
endpoint, we evaluated the renal safety profile associated with each
ARV regimen during the 96 weeks of follow up time.
Materials and methods: Creatinine clearance (CrCl) was estimated
by the CockroftGault equation, and changes from baseline (BL)
were assessed by one way ANOVA. Subjects were followed through
96 weeks or until discontinuation from the study based on the
investigator’s best clinical judgment.
Results: Study participants (n 172, LPV/r TDF/FTC 90) were
39.9910.7 years old, 88.4% White, 11.6% women, BL CrCl of
120.3934.9 ml/min, and 28.9% had a diagnosis of hypertension.
There were no differences in BL demographics between arms. Mean
change from BL to week 96 in CrCl was statistically significantly
greater with LPV/r TDF/FTC compared to LPV/r RAL (D 7.3
versus 1.5 ml/min, p 0.035). Four subjects experienced a renal
serious adverse event (SAE) for which clinical course, renal biopsies,
laboratory abnormalities, concomitant comorbidities, and medications will be presented.
Conclusions: At week 96, the majority of patients had a CrCl in the
normal range. Decline in CrCl was larger with LPV/r TDF/FTC. Renal
SAEs were temporally related to exposure to non ARV meds, except
for one Fanconi case considered by the investigator to be related to
LPV/r TDF/FTC exposure.
Abstract P6Table 1.
Age in years
33
42
52
55
M
Gender
M
F
M
Race
W
B
W
B
ARV regimen
LT
LR
LT
LT
Renal
diagnosis
Obstructive
Acute
Fanconi
stone
kidney
syndrome injury with
injury
Acute kidney
tubulointerstitial
nephritis
(biopsy)
Outcome
Ureteral
Dialysis
Persistent Persistent
stent placed dependent
MMale, FFemale, W White, BBlack, LR: LPV/rRAL, LT:
LPV/rTDF/FTC
14
P7
Chronic diarrhoea: a current reality? DIACRO study
J Sanz1; M Palazuelos2; H Hevia2 and F Ledesma2
1
Hospital Universitario La Princesa, Enfermedades Infecciosas,
Madrid, Spain. 2Janssen Spain, Medical Affairs, Madrid, Spain.
Introduction: Chronic diarrhoea has been historically a common
problem within the HIV-infected population. Currently, we do not
know the accurate prevalence in the clinical setting. The objective of
the DIACRO study is to identify the presence of chronic diarrhoea
within the HIV-infected patients and to outline its characteristics, as
well as to profile its cause and to know the clinician perception about
its frequency and repercussion.
Materials and methods: A cross-sectional study was undertaken in
40 Spanish hospitals. HIV-infected patients that attended the HIV
clinic during the study period (10 consecutive days from 7 May 2012)
and signed informed consent went through a five question screening
test. Those patients who marked positively having ]2 stools/day
and bowel movement disturbance 1 month plus another positive
question of five (increase in bowel volume/frequency within the
last month, weakness faeces or to abandon activities urgently to
defecate within the last 15 days) were considered as chronic
diarrhoea patients. These patients went on further evaluation and
their socio-demographic and clinical characteristics were registered.
Results: The analysis included 2,658 patients that fulfilled inclusion
criteria. Eight hundred ninety-four (34%) of them had ]2 stools/day.
According to the study, chronic diarrhoea definition, the prevalence of
these symptoms was 10.3% (273 patients). Within this population,
62.3% (170) of the patients did not report it proactively to their
physicians. Of the patients, 28.8% (77) had sometimes self-medicated
to try to mitigate it. Seventy-two percent (196) of them had to
abandon urgently their activities to defecate in the last 15 days. Of
the chronic diarrhoea patients, 17.6% declared having ]4 stools/day
and 76.2% (208) suffered from bowel movement disturbance 6
months. Physicians related the appearance of these symptoms to the
ARV therapy in 50% of the cases. Regarding investigators perception,
47.5% of them believed that chronic diarrhoea is frequent within the
HIV-infected population. Of them, 72.5% stated to ask proactively to
patients about this disorder in their clinical practice.
Conclusions: Chronic diarrhoea is still a current reality in our HIVinfected patient setting. A lot of them do not communicate
proactively its presence to the clinicians. A simple medical/case
history could help to identify the underlying chronic diarrhoea,
although there is not an established criteria about its cut-off point or
definition.
References
1. Mertz HR, Beck K, Dixon W, Esquivel A, Hays RD, Shapiro MF.
Validation of a New Measure of Diarrhea. Dig Dis Sci. 1995;40:
187382.
2. MacArthur RD, DuPont HL. Etiology and pharmacologic management of noninfectious diarrhea in HIV-infected individuals in the
highly active antiretroviral therapy era. Clin Infect Dis. 2012;55:
8607.
HIV AND ENDEMIC DISEASES
P8
HIV and neglected infectious diseases in Latin America and
the Caribbean: issues and challenges for knowing the
burden of co-infection
Poster Abstracts
M Socı́as1,2; M Saboyá3 and O Sued1
1
Investigaciones Clı́nicas, Fundación Huésped, Buenos Aires,
Argentina. 2Programas y Proyectos, Fundación Mundo Sano,
Buenos Aires, Argentina. 3Neglected Infectious Diseases Program, Pan
American Health Organization, Washington DC, USA.
Introduction: Neglected infectious diseases (NID) overlap geographically and epidemiologically with HIV. There is growing interest about
the mutual impact of the biological and clinical interactions and the
potential for integrate the control of these diseases. The objective of
this study was to describe the burden of co-infection of HIV and NID
in Latin America and the Caribbean (LAC).
Materials and methods: A systematic bibliographic review from
Pubmed, Lilacs, and available conferences proceedings from relevant
scientific meetings (ASTMH, IAS, CROI) between 1980 and 1 May
2011 was performed.
Results: One hundred and forty-seven eligible articles were identified. The majority addressed co-infection between HIV and either
Chagas’ disease, soil-transmitted helminthes (STH) or leishmaniasis,
with little information about other NID (n 18) and most of them
were case-series (n 113). Prevalence of co-infection ranges between 1.2 and 9.9% for T. cruzi, and 044% for STH and S. stercoralis
with significant variation between regions.
Conclusions: Despite the relevance of these diseases, information
about prevalence, incidence, and interactions between specific NID
and HIV is very limited and the possibility of integrating the control
of these diseases is difficult. Prospective prevalence studies of coinfection in endemic areas for NID should be encouraged to better
describe the current situation. This bibliographic review was started
during an internship at Pan American Health Organization in May/
June 2011, with support of a scholarship of HIV Research Trust to
MES.
P9
Yellow fever vaccination in HIV-infected patients
M Carvalho1; L de Franceschi1; L Clementino1; S Santos1 and P Costa2
1
Departamento de Medicina, Universidade Federal de São Carlos,
São Carlos, Brazil. 2Department of Clinical and Toxicological Analyses,
São Paulo State University, São Paulo, Brazil.
Introduction: Yellow fever (YF) is prevalent from northwest to
southeast of São Paulo State. YF vaccine is a live attenuated virus
vaccine with an efficacy of 99% in one month. It is reasonably safe,
with an incidence of mild adverse effects of 2 to 5%. More severe
adverse events (encephalitis, immediate hypersensitivity reactions,
viscerotropic disease) are rare (4.7 cases per 100,000 doses of
vaccine administered) [1] but they are potentially more frequent in
immunocompromised patients. There is a report of fatal encephalitis
in a HIV-infected patient who received YF vaccine without knowing
his serological status or his severe immunological condition (CD4 Tlymphocyte count of 108 cells/mm3 [2]. YF vaccine is contraindicated
for people with AIDS or other clinical HIV infection manifestations,
including people with CD4 T-lymphocyte count B200 cells/mm3.
Data on safety and efficacy of YF vaccine in the population infected
with HIV/AIDS are scarce. Current available data on the subject are
only based on retrospective studies.
Material and methods: Clinical trial of vaccination against YF in
HIV-infected patients. Participants were HIV-infected adults followed
at the Centro Municipal de Especialidades de São Carlos (CEME),
without severe immunosuppression (CD4 T-lymphocyte count 200
cells/mm3) living in São Carlos city, area where there is a risk of YF
transmission. Data were collected on age, gender, mode of HIV
transmission, CDC/08 classification, antiretroviral drugs, comorbities,
15
Poster Abstracts
coinfections and immunization charts. Patients received YF vaccine if
not vaccinated in the past 10 years. Blood samples were taken
before, one week and one month after vaccination. Clinical adverse
events, liver enzymes and HIV infection markers were monitored.
Partial results: Up to now, 35 HIV-infected patients were invited to
the study. We excluded six subjects who presented CD4 count B 200
cells/mm3, seven patients who have recently received YF vaccine,
and three individuals who have refused informed consent. The
remaining 19 patients formed the basis for this study, 57.9%
male, mean age 45.5 years (2963). In relation to the mode of
HIV transmission, 26.3% were MSM, 63.2% heterosexual, 5.26% IDU
and 5.26% unknown. CDC classification: 47.4% A, 36.8% B and 15.8%
C. HCV coinfection was found in three patients (15.8%). Most
patients were on use of antiretroviral schemes including protease
inhibitors (63.2%), with median CD4 count of 693 cells/mm3 and
undetectable HIV plasmatic load (63.2%). Mild local side effects were
referred by 10.5% of patients. No patient presented increase in
serum transaminase values after vaccination.
Conclusions: YF vaccine seems to be safe in HIV-infected patients.
References
1. Staples JE, Gershman M, Fischer M, CDC. Yellow fever vaccine:
recommendations of the Advisory Committee on Immunization
Practices (ACIP). MMWR Recomm Rep. 2010,59:127.
2. Kengsakul K, Sathirapongsasuti K, Punyagupta S. Fatal myeloencephalitis following yellow fever vaccination in a case with HIV
infection. J Med Assoc Thai. 2002;85:1314.
Materials and methods: Retrospective, chart review study was
conducted in two large HIV treatment centres in Mexico. We
included all patients treated with a 4 NUCS combination comprised
by Abacavir, Tenofovir, zidovudine and 3TC/FTC while receiving RIF
anti-TB for active tuberculosis.
Results: From 1998 to 2012, 12 patients were included. Eleven (92%)
were male. Median CD4 nadir cell count at baseline was 65 cell/
mm3 (IQR 43-105). Only two (17%) patients were naive to ART.
The median time of ART exposure before TB diagnosis was 23 (IQR
13.523) months. Seven patients (58%) had used protease inhibitors
before, and one patient (8.3%) used lopinavir ritonavir 800/ mg/d
during RIF anti-TB before the 4 NUCS regimen. Three patients (25%)
had history of liver disease at baseline. The reason for not using EFV
was previous failure in nine (75%), and intolerance or contraindications for its use in the rest. Four of 10 treatment-experienced
subjects had a genotype before the ARV change was made. Median
time of 4 NUCS treatment was 6.5 (IQR 517.5) months. Viral load
B400 copies/ml was achieved in 58% of the patients. There was
a median increase in CD4 cells of 81 cell/mm3 (IQR 41-250) during
the 4 NUCS treatment. One subject (8.3%) discontinued treatment
because of intolerance. GIII-IV alkaline phosphatase elevation
occurred in three (25%) subjects. Eight (67%) patients are alive
and continue in follow-up.
Conclusions: Selection of ART remains a challenge for ART-experienced and EFV-intolerant patients who receive RIF anti-TB. In this
case series a four nucleoside regimen, used mostly in patients with
previous virological failure, was well tolerated and the majority of
the patients achieved virological suppression.
H I V - R E L AT E D I N F E C T I O N S , C O INFECTIONS AND CANCERS
P11
P10
V Fink1; S Figurelli2; H Concetti2; L Daniel3; C Marı́a Pı́a3; D Zurita4;
R Bun5; L Svidler5; P Gisela5; N Tokumoto6; M Socias1; C Cesar1;
P Patterson1; M Figueroa1; E Rodriguez6; M Fischer7; H Perez6;
O Sued1 and P Cahn6
1
Department of Clinical Research, Fundacion Huesped, Buenos Aires,
Argentina. 2Department of Pathology, Hospital Fernandez, Buenos
Aires, Argentina. 3Department of Oncology, Hospital Fernandez,
Buenos Aires, Argentina. 4Department of Gynaecology, Hospital
Fernandez, Buenos Aires, Argentina. 5Department of Proctology,
Hospital Fernandez, Buenos Aires, Argentina. 6Department of
Infectious Diseases, Hospital Fernandez, Buenos Aires, Argentina.
7
Department of Hematology, Hospital Fernandez, Buenos Aires,
Argentina.
Introduction: The profile of cancer in HIV patients has changed with
the widespread use of HAART. Non-AIDS-defining tumours have
become more frequent. Data about cancer and HIV in Argentina are
scarce. Hospital Fernandez Infectious Diseases Unit is a reference
centre with 4,000 HIV-positive patients in follow-up.
Methods: Retrospective data collection on cancers diagnosed in HIV
patients between January 2004 and October 2012 was performed
from different hospital units: Infectious Diseases, Oncology, Pathology,
ARV treatment with four nucleosides in HIVtuberculosis
co-infected subjects when efavirenz (EFV) is not an option
A Piñeirua-Menendez1; A Meraz-Muñoz2; A Campos-Loza3;
F Badial-Hernández4; B Crabtree-Ramirez1; J Andrade-Villanueva3 and
J Sierra-Madero1
1
Department of Infectious Diseases, Instituto Nacional de Ciencias
Medicas y Nutrición Salvador Zubiran, Mexico City, Mexico.
2
Department of Internal Medicine, Instituto Nacional de Ciencias
Medicas y Nutrición Salvador Zubiran, Mexico City, Mexico. 3HIV
Unit, Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara,
Jal, Mexico. 4HIV Clinic, Clı́nica Especializada Condesa, Mexico City,
Mexico.
Introduction: Options for antiretroviral therapy (ART) in patients
receiving rifampin-containing anti-tuberculosis treatment (RIF antiTB) are limited to EFV and more recently Raltegravir-containing
regimens. In ART experienced subjects, few alternatives exist. The
aim of this study was to describe a case series of co-infected patients
who were treated with four nucleosides (4 NUCS) while on RIF antiTB because of EFV resistance or intolerance.
Abstract P11Table 1.
Cancer profile in HIV patients from a reference centre in
Argentina
Shows the characteristics of AIDS and non-AIDS-defining cancers
AIDS-defining cancers (n 163)
Female, n (%)
Non-AIDS-defining cancers (n 95)
p
28 (17.2%)
31 (32.6%)
0.004
Age at diagnosis, median (IQR) (years)
37.2 (3244.4)
42 (36.652.7)
B0.0001
Time from HIV diagnosis, median (IQR) (years)
CD4 at cancer diagnosis, median (IQR) (cells/ml)
2.7 (0.27.2)
68 (26186.5)
7.8 (2.97.1)
206 (106.8391.3)
B0.0001
B0.0001
16
Proctology, Gynaecology, and Dermatology. Demographic, HIV, and
cancer data were collected. Preliminary results are presented.
Results: Two hundred and fifty-eight cancers were diagnosed in 257
patients. Most frequent cancers were Kaposi sarcoma (KS) (43%); NonHodgkin lymphoma (NHL) (19.4%); skin cancer (5.8%), two-thirds
basocellular epithelioma; anal (5.8%); lung (4.7%),-two-thirds adenocarcinoma; cervix (3.5%); and Hodgkin’s lymphoma (9, 3.5%). Fiftyeight patients (22.6%) had their cancer diagnosis concomitant or
within six months of the HIV diagnosis (36 were KS and 14 were NHL).
AIDS-defining cancers corresponded to 69% of total cancers reported
in the period 2004 to 2006 and 65% in the period 2010 to 2012. Among
those with survival data, 29% died (42% NHL y 23.4% KS).
Conclusions: Opportunistic cancers are still the most frequent
tumours. There is no evidence of decline in the frequency of
opportunistic cancers along time. Patients with non-AIDS-defining
cancers were older, had a longer time since HIV diagnosis, and had a
higher CD4 cell count. Late HIV diagnosis continues to be a problem
in our population. Access to early HIV diagnosis should be granted.
(Partially funded by NIH Cooperative agreement 2 U01 AI069923).
LABORATORY MONITORING OF DISEASE
AND THERAPY
P12
Evaluation of residual HIV-1 replication among individuals
receiving different antiretroviral treatment regimens
L Giron; S Tenore; R Gabriel; L Janini; M Sucupira and R Diaz
Infectious Diseases Division, Paulista School of Medicine, Federal
University of São Paulo, São Paulo, Brazil.
Introduction: Residual HIV-1 replication among individuals under
antiretroviral therapy is an obstacle towards reduction of chronic HIV
related micro-inflammation. To determine the levels of residual viral
replication of HIV-1 in distinct subgroups of patients inferred by
quantification of episomal HIV DNA, quantification of total HIV DNA,
and quantification of HIV-1 specific antibodies.
Materials and methods: A total of 109 patients with undetectable
viral load were divided into five groups: first suppressive therapy
with efavirenz (26), first suppressive therapy with boosted protease
inhibitors (PI) (25), salvage therapy using boosted PI (27), salvage
therapy with raltegravir (15) and virological failure (16). Quantification of episomal and total DNA was performed by real-time PCR.
Specific antibody quantification was performed using enzyme
immunoassay capture.
Results: Episomal DNA amplification was positive in 36 out of 109
patients’ samples (33%) and quantification of total DNA was obtained
in 94 patients’ samples (86.3%). Individuals on salvage therapy using
Raltegravir presented lower prevalence and lower quantitation of
epissomal DNA as compared to other treatment groups (p 0.03).
There was no differences between groups in quantification of total
DNA (p 0.298) or antibodies (p 0.126). The HIV-1 proviral load was
higher among individuals with positive epissomal DNA (p 0.01).
There was a negative correlation between the episomal DNA
quantification and (i) duration of treatment with undetectable viral
load, (ii) CD4 counts, and (iii) CD8 counts. There was a higher
prevalence of episomal DNA and a higher quantification of total
DNA in virologic failure group (p 0.009 and 0.06, respectively).
The antibody quantitation was higher among individuals on initial
treatment using efavirenz compared to initial treatment with PIs
(p 0.027).
Conclusions: Duration of treatment, CD4, CD8 counts, and raltegravir-based regimens relate to decreased residual viral replication
Poster Abstracts
(epissomal DNA). The relationship between episomal DNA and total
DNA suggests replenishment of proviral reservoir with potential
impact on HIV persistence. Lower antibodies levels among patients
with PI-based initial treatment may suggest a more effective HIV
suppression of these regimens, with higher capacity of decreasing
the HIV antigenic component.
P13
Prevalence of recombinant forms and non-syncytiuminducing strains in Cuban patients HIV-1 recently infected
E Noa1; L Navea1; Y Sánchez1; L Machado2; M Dubed1; A Duran1;
M Blanco2; D Romay2 and H Dı́az3
1
AIDS Research Laboratory, Microbiology, San José de las Lajas, Cuba.
2
AIDS Research Laboratory, Molecular Biologic, San José de las Lajas,
Cuba. 3AIDS Research Laboratory, Diagnostic, San José de las Lajas,
Cuba.
Introduction: The determination of biological characteristics of the
HIV strains is essential for the clinical handling in recently infected
patients and to optimize your selection before starting treatment.
The aim of this study was to relate the viral genotype and phenotype
of the isolation from recently infected patient without treatment
with the clinical-epidemiologic characteristics.
Methods: Peripheral blood mononuclear cells and plasma of Cuban
patients HIV-1 recently infected, obtained at least eight months from
the diagnostic date, were used for the isolation and capacity of
syncytium-inducing (SI) and determination the subtype and resistance-associated mutations (RAMs) by sequence and analysis of the
pol gene. The viral genotype and phenotype were related with the
gender, sexual conduct, age, clinical status and count of CD4 cells
of the patients at the moment of the diagnosis.
Summary of results: We included in the study 38 treatment-naive HIV1 infected patients, five women and 33 men. In male patients, 25 are
men who have sex with men (MSM). The means values (range) of age
and CD4 cells were 36.7 years (1868) and 386.8 cells/mm3 (53
1260), prevailing the clinical status from A1 to A3 (31/38). We detected
13 subtypes B, 15 circulating recombinant forms (CRF) (9 CRF 20-2324_BG, 6 CRF_19cpx and 2 CRF_18cpx), 3 unique recombinant forms
(URF) (2 URF B/18cpx and 1 URF B/19cpx) and five non-amplified. Five
viruses (13.2%) presented RAMs, one with multiresistance (subtype B)
and other 4 for protease inhibitors (one subtype B and three
recombinant forms). The virus was isolated from 63.2% (24/38) of
the patients, who were related with the conditions MSM, 4050 years,
clinical status A3 or superior, CD4 5250 cells/mm3 and infection
with CRF; but not with the presence of RAMs. Only 25% of the strains
were IS. Recombinant forms without RAMs were detected in all
women, while in men there was no relation between sexual conduct
and viral genotype. The presence of recombinant form was also
associated with CD4 counts less than 500 cells/mm3.
Conclusions: The results show that in Cuban patients HIV-1 recently
infected treatment-naı̈ve predominate non-SI strains and recombinant forms with RAMs.
MOTHER-TO-CHILD TRANSMISSION
P14
Systematic review of the safety and efficacy of Lopinavir/
ritonavir-based antiretroviral therapy in pregnant women
M Pasley; M Martinez; R Stubbs; R D’Amico; A Hermes and
A Nilius
17
Poster Abstracts
North Chicago, USA.
Introduction: The protease inhibitor, lopinavir, co-formulated with
ritonavir (LPV/r) plus two nucleoside reverse transcriptase inhibitors
is recommended by the U.S. Department of Health and Human
Services Perinatal Guidelines as a preferred regimen for HIV treatment in pregnant women. Pharmacokinetic studies suggest that the
LPV/r standard dose of 400/100 mg twice-daily during pregnancy
results in reduced plasma LPV exposure in the third trimester;
however, these declines do not appear to impact maternal clinical
outcomes or MTCT rates. Pharmacokinetic studies are not designed
nor powered to assess clinical outcomes.
Materials and methods: We conducted a systematic review to assess
maternal and infant clinical and safety outcomes in pregnant women
treated with LPV/r-based regimens. PubMed, EMBASE, and HIV
congresses were searched for studies published through 31 May,
2012. Studies were selected if they included HIV-1-infected pregnant
women treated with LPV/r-based therapy and reported maternal and
infant outcomes as a primary objective. Data were extracted from
publications and tabulated for analysis.
Results: A total of 13 publications/presentations describing 9 studies
were identified. These studies included 2,675 women treated with
LPV/r: 1,618 received LPV/r 800/200 mg/day, 70 received 800/200
mg/day, and 987 received an unknown LPV/r dose. Overall, 80% of
women (6497%) achieved viral suppression below the threshold for
the study in which they enrolled. There was no significant difference in
the number of women with HIV-1 RNA ]1000 copies/mL in the one
study evaluating both standard and high doses of LPV/r. Eight studies
reported MTCT, measured at times ranging from birth to 18 months.
MTCT rates ranged from 0 to 2.8%. In the one trial comparing standard
to higher-dose, MTCT rate was 0.6% and 0.0%, respectively. Maternal
serious adverse events (SAE) were reported in four studies and
occurred in 036% of subjects. Grade 34 laboratory events were
reported in three studies and occurred in 3.411.6% of women.
Discontinuation rates were reported in two studies and were 0.4
1.7%. Reasons for discontinuation were not reported.
Conclusions: This systematic review of 2,675 pregnant women
suggests no unique safety or efficacy concerns with the use of
standard dose LPV/r-based ART in pregnant women. Although high
dose LPV/r use was limited to one study in this analysis, the safety
and efficacy outcomes reported, including MTCT rates, were similar
to those obtained with standard dose.
P15
Abstract withdrawn.
NON-AIDS MORBIDITIES
MORTALITY, AND AGEING
AND
P16
Diagnosis of HIV infection over 50 years. Clinical and
epidemiological implications
D Beltran Santiago; Y Caro Vega; J Sierra-Madero and B CrabtreeRamirez
Medicas y Nutrición Salvador Zubiran (INCMSZ), Mexico City, Mexico.
Introduction: Elderly HIV-infected subjects are being cared for
because of increased survival with ART and because of new HIV
infections in this population. The purpose of this study was to
describe the clinical and epidemiological characteristics of patients
diagnosed with HIV infection over 50 years.
Methods: Single centre, cohort study evaluating all HIV-infected
subjects admitted to the HIV clinic at INCMNSZ between 2002 and
2012. Patients diagnosed with HIV infection 50 years were compared to those diagnosed B50 years in demographic, clinical characteristics and laboratory markers at diagnosis. Changes in retention
in care over time, prevalent and new cases were assessed using the
trend test.
Results: A total of 2,554 patients were admitted to the clinic in the
study period. Two-thousand three sixty-two (92%) were diagnosed
at B 50 years of age, and 192 (8%) at 50. In younger adults 67%
were MSM, 18% were heterosexual men and 11% heterosexual
women. In contrast, in elderly adults 33% were MSM, 39%
heterosexual men and 19% heterosexual women (p B0.001 for all
comparisons). CD4 cell count at diagnosis was significantly lower
in the group of 50 years (112 cell/mm3 vs. 184 cell/mm3,
p 0.008), whereas the proportion of patients with HIV viral load
75 000 c/ml was higher in the groupB50 years of age (63 vs. 27%,
p B0.001) (Table 1). The number of accumulated and new cases of
HIV infection in patients 50 years of age remained stable over
time. Retention in care significantly increased over time in the
group 50 years (p 0.03) (see Figures 1 and 2).
Conclusions: The trend in the proportion of diagnosis in HIV-infected
subjects with B50 and 50 years of age in our population has
remained stable over the last 10 years. HIV infections in patients
diagnosed over 50 years are mainly heterosexually transmitted both
in men and women. More advanced stage of HIV infection in elderly
subjects was found at diagnosis, emphasizing the need to target this
population in HIV detection efforts.
Abstract P16Table 1. General characteristics of HIV-infected
patients receiving medical care at the INCMNSZ
Age at HIV diagnosis
General characteristics
(n 2554)
Age at diagnosis, median
(IQR)
Male (%)
Female (%)
Transmission categories
MSM (%)
Heterosexual men (%)
Heterosexual women (%)
Transfusion (%)
IDU (%)
Other (%)
Unknown (%)
CD4 cell count at diagnosis
(n 1551)
CD4 cell/ml, median (IQR)
CD4 350 cell/ml (%)
CD4 200349 cell/ml (%)
CD4 51199 cell/ml (%)
CD4 B 50 cell/ml (%)
HIV viral load at diagnosis
(n 1337)
VL B 75 000 copies/ml (%)
VL 75 000 copies/ml (%)
B50 years
30 (2536)
2080 (88)
282 (12)
1577 (67)
413 (18)
262 (11)
20 (1)
2 (B1)
34 (1)
54 (2)
(n 1431)
50 years
55 (5261) B0.001
153 (80)
39 (20)
0.001
63 (33) B0.001
75 (39)
37 (19)
6 (3)
0
1 (1)
10 (5)
(n 120)
184 (61349) 112 (30250)
355 (25)
24 (20)
329 (23)
19 (16)
431 (30)
40 (33)
316 (22)
37 (31)
(n 1235)
(n 102)
452 (37)
783 (63)
P
0.008
0.05
74 (73%) B0.001
28 (27%)
18
Poster Abstracts
Abstract P16Figure 1. Accumulated cases of HIV-infected pateients
by age group.
Baseline characteristics
Age, years (mean)***
Black race (%)***
Hispanic/Latino ethnicity (%)***
Baseline CD4 T-cell count, cells/mm3
B200 cells/mm3 (%)*
B50 cells/mm3 (%)*
Baseline laboratory values
Amylase (U/L)**
Aspartate aminotransferase (U/L)*
Cholesterol (mg/dL)***
Creatinine clearance (mL/min)$,***
Glucose (mg/dL)***
Lipase (U/L)***
Triglycerides (mg/dL)***
Uric acid (mg/dL)**
Efficacy (at Week 48)
Plasma HIV-1 RNA B50 copies/mL (%)$
CD4 T-cell count mean change from
baseline (cells/mm3)%
*,**,***p B0.05, p B0.01, and
$
Abstract P16Figure 2. New cases of HIV-infected pateients by
age group.
P17
Meta-analysis comparing safety, tolerability, and efficacy of
LPV/r-containing ART in women agedB50 versus]50
years in randomized clinical trials
A Hermes; L Fredrick; M Martinez; R Rode; M Pasley; M Norton and
A Nilius
North Chicago, USA.
Introduction: Health and Human Services Guidelines state that
treatment of older HIV-positive patients requires management of
aging-related comorbidities in addition to HIV-infection, and that HIV
itself may affect the biology of aging. This meta-analysis compared
women aged B50 and]50 years receiving lopinavir/ritonavir (LPV/
r)-containing antiretroviral therapy (ART) to evaluate potential
effects of age on safety, tolerability, and efficacy in women.
Materials and methods: Meta-analysis included AbbVie or AbbViesupported AIDS Clinical Trials Group (ACTG) randomized clinical trials
(RCTs) in adult subjects including women, LPV/r 800/200 mg/day as
part of a 3-drug regimen, and follow-up duration]48 weeks. Virologic
efficacy was evaluated using a random-effects meta-analysis; other
endpoints were analyzed using pooled subject-level data.
Results: A total of 992 women from 11 RCTs (7 AbbVie, 4 ACTG) were
included, with 889 women B50 and 103 women ]50 years old.
79.6% and 75.7% of women were ART-naı̈ve in the B50 and]50 age
groups, respectively. Baseline HIV-1 RNA level was similar between
age groups. Baseline characteristics that differed by age group, and
virologic and immunologic response by age group are summarized in
the Table 1.
Overall discontinuation rates were similar; however, a smaller
proportion of women B50 years discontinued due to adverse events
(AEs)/HIV-related events (3.5% vs. 10.7%, p 0.002). Overall, 18.9%
B50 Years
]50 Years
Old
Old
34.7
71.5
13.2
55.2
51.5
29.1
66.2
12.2
52.9
20.6
87.3
32.4
152.1
117.0
85.2
37.1
112.8
4.5
105.8
37.7
166.7
96.7
96.6
56.9
164.0
5.0
59.2
193
69.2
176
(from 182)
(from 199)
pB0.001, respectively
Meta-analysis: 95% CI ( B50 minus
]50 age group) ( 28.7%, 0.5%);
p0.058
%
p 0.278
reported ]1 moderate-to-severe AE possibly related to study drug
(16.6% vs. 37.9% in women B50 vs.]50 years, pB0.001). Significant differences (p B0.05) were observed between women B50
and ]50 years, respectively, in the proportion of subjects with postbaseline grade 3 laboratory abnormalities for amylase (1.6% vs.
6.8%), lipase (0.6% vs. 6.4%), creatinine clearance (2.0% vs. 12.1%),
and cholesterol (3.2% vs. 14.9%).
Conclusions: Women aged B50 and ]50 years had similar virologic
and immunologic response, and overall discontinuation rates. Women
]50 had a higher incidence of moderate-to-severe treatment-related
AEs and abnormalities in amylase, lipase, creatinine clearance, and
cholesterol. These observations are consistent with baseline comorbidities and laboratory measures. Interactions between ART agents
and other medications, differences in baseline laboratory values,
additional comorbidities, and differences in baseline CD4 T-cells
counts could contribute to these findings.
P18
Virological and immunological response to highly active
antiretroviral therapy in patients over 50 years of age in
a cohort of patients in Mexico
D Beltran Santiago; Y Caro Vega; B Crabtree-Ramirez and
J Sierra-Madero
Medicas y Nutrición Salvador Zubiran (INCMSZ), Mexico City,
Mexico.
19
Poster Abstracts
1
Introduction: The number of HIV-infected adults over the age of
50 years is increasing. Recent studies of responses to HAART
among elderly patients conducted in high-resource settings have
demonstrated a CD4 cell reconstitution significantly slower
despite a better virological response in this age group. We compared
the virological and immunological response to first-line HAART in
subjects 50 years old compared to younger patients in Mexico.
Methods: Retrospective cohort study of patients with HIV infection
receiving medical care at INCMNSZ in Mexico City. All treatmentnaive patients who started HAART between 2007 and 2012 were
evaluated for CD4 recovery and virologic response. Immunological
response (IR) (increase of CD4 cell count 100/mm3 and virological
response (HIV RNA B400 copies/ml) at one year were compared
in subjects initiating treatment at 50 years of age with those
initiating at a younger age. Patients lost to follow-up (LTFU) and
incomplete data were included in an intention to treat analysis (ITT).
Results: Eight-hundred thirty-six patients started HAART between
2007 and 2012; 742 (89%) with B50 years and 94 (11%) 50 years
of age. Only 723 (86%) patients completed at least 12 months followup. Demographic and clinical baseline characteristics are presented
in Table 1.
By 12 months after starting HAART, 75% of patients B50 years of age
experienced IR, compared with 63% in ]50 years (p 0.09); the
median gain in the CD4 cell count was 173 cell/mm3 in B50 years
and 144 cell/mm3 in ]50 years of age (p 0.08). VR was similar in
both age groups, 97% in B50 years and 98% in ]50 years of age (p
0.71) (Table 2).In the ITT analysis, 46% of patients B50 years achieved
IR, whereas in the group ]50 years only 35% (p 0.05) (Table 3).
Conclusions: Among HIV-infected elderly population, the immunological response after 12 months of HAART was lower in the group of
patients who started HAART at or after 50 years of age, with a trend
toward statistical significance. We found no significant difference in
virologic response between the two groups.
Gynecology, Clinica Especializada Condesa, Mexico City, Mexico.
Dermatology, Clinica Especializada Condesa, Mexico City, Mexico.
3
Coordination, Clinica Especializada Condesa, Mexico City, Mexico.
2
Introduction: The Specialized Condesa Clinic of Mexico City is a
detection, treatment and follow up centre for people with HIV/AIDS
and sexually transmitted infections (STI), with a care program of HIV
and STI for victims of sexual violence since 2008. According to research,
almost one in four women can be a victim of sexual violence and one in
three female adolescents informs that her first sexual experience was
forced. Sexual violence is associated with sexual health problems later
on and thus, considered a public health problem.
Materials and methods: Cross-sectional study of data from female
patients who attended the sexual violence program. The data
collection tool used was a seroepidemiologic questionnaire which
collected the clinical history along with blood tests from January 2,
2012 through December 31, 2012. The study sample was of 1,071
female patients, all received antibody HIV 1-2, surface antigen HBV,
antibodies for HCV and Syphilis antibodies testing. All tests were
performed during the initial visit and during each follow up visit at
three and six months. All patients who procured services within 72
hours from the event received post exposure prophylaxis treatment
for HIV, Gonorrhea, Syphilis, Trychomoniasis, Chlamydia and emergency contraception.
Results: Of the 1,071 patients 44 were under 12 years (4.1% of
total); 150 were 1214 year olds and 354 were 1519 year olds;
for a total of 504 adolescent patients (47% of total). The average
age of patients was 22.2 years (range of 8 to 82). Four-hundred and
one patients (37.4%) accessed the service within 72 hours after the
sexual violence event, while 670 patients (62.5%) accessed services
afterwards. Five-hundred and thirty six patients received emergency
contraception. Four-hundred one patients received HIV PEP for 28
days. They also received prophylaxis for STI. During initial screening
two patients (0.18%) had a positive HIV result, and two (0.18%) had
a positive HCV result. These infections were not acquired during
the sexual violence event. Nine patients had pregnancies related to
the sexual violence event, six terminated their pregnancies legally,
two refused interruption and one was too late to perform the
interruption. During the follow-up visits, no patients showed with
HIV or STI infection.
Conclusions: Medical care to victims of sexual violence is a priority
since it prevents HIV, STI and unwanted pregnancies. The time after
the sexual violence event is crucial since if care is not rendered in
time it could result in negative lasting consequences.
TREATMENT AS PREVENTION
P19
Model of care for HIV. STI, and pregnancy prevention for
female sexual violence victims in Mexico City
T De Jesus1; U Ramos1; C Cruz2 and A Gonzalez3
Baseline Characteristics of HIV-infected adults who Initiated HAART
Age at start HAART
Variable
Age at HIV diagnosis, median (IQR)
Age at start HAART, median (IQR)
Male (%)
Female (%)
Baseline CD4 count, median (IQR)*
Baseline HIV-1 viral load (VL), copies/ml*
B75 000 (%)
75 000 (%)
Follow-up, months, median (IQR)
B50
50
n 647 (89%)
n 76 (11%)
30 (2536)
33 (2839)
52.5 (5058)
55 (5259.5)
580 (90)
63 (83)
67 (10)
13 (17)
153 (52284)
156 (36)
274 (64)
29 (1444)
150 (28295.5)
9 (21)
34 (79)
27.5 (1247)
p
B 0.001
B0.001
0.08
0.88
B0.001
0.72
* Considering only subjects with CD4 (B50: 501, 50: 55) value and VL ( B50: 430, 50:43) available.
20
References
1. Alamillo U, Pedroza Islas L. Guı́a de Atención Médica a Personas
Violadas. Centro Nacional de Equidad de Género y Salud Reproductiva. Secretaria de Salud. 2007.
2. Cruz Palacios C, Ramos Alamillo U, González Rodrı́guez A. Guı́a de
prevención, diagnóstico y tratamiento de ITS. Dirigida a personal de
servicios de salud. Fundación Mexicana para la Salud A.C. México,
D.F. 2011.
3. Informe Mundial sobre la Violencia y la Salud. 2003. Organización
Panamericana de la Salud. Capı́tulo 6. La violencia sexual.
RESISTANCE
P20
Emergent drug resistance in patients with pre-existing
mutations in HIV-1 phase 3 elvitegravir/cobicistat/
emtricitabine/tenofovir DF studies through W96
K White1; R Quercia2; M Abram1; R Kulkarni1; J Szwarcberg3 and
M Miller1
1
Department of Virology, Gilead Sciences, Foster City, USA.
2
Department of Public Health and Education, Gilead Sciences, Foster
City, USA. 3Department of Clinical Research, Gilead Sciences, Foster
City, USA.
Introduction: Two phase 3 studies of elvitegravir/cobicistat/emtricitabine/tenofovir DF (STB) in treatment-naive subjects are ongoing
(GS-US-236-0102 and -0103). The W96 responses were high, durable
and comparable for STB vs. efavirenz (EFV/FTC/TDF [ATR]) (84 vs.
82%) and STB vs. ritonavir-boosted atazanavir (ATV/r) FTC/TDF
(ATV/r Truvada [TVD])(83 vs. 82%). Resistance analyses through
week 96 are presented.
Methods: HIV-1 genotypes (protease and reverse transcriptase [RT])
were analyzed at screening (GeneSeq, Monogram Biosciences);
subjects with resistance to study drugs were excluded. Retrospective
integrase (IN) genotyping was conducted on a large set of STB
baseline samples. The resistance analysis population had genotypic/
phenotypic analyses at failure confirmation and baseline for PR, RT,
and IN using PhenoSenseGT, IN GeneSeq, IN PhenoSense, PRIme
(Monogram) or IN GenoSure (Labcorp).
Results: STB-treated subjects with baseline PI (N 18) and NNRTI
mutations (N 95) had high treatment responses through W96. Of
the 95 subjects that had pre-existing NNRTI-associated mutations,
including 27 with K103N, 87 and 85% maintained virological suppression (VS) at W96, respectively; among those with viral rebound in this
group, none developed STB resistance. Eighteen subjects with preexisting PI mutations had a VS rate of 89%. Fifty-two subjects with
primary NRTI mutations had a VS rate of 85%. Baseline primary INSTI
mutations were rare (N 4/337; T97A [N 3] and Y143H [N 1])
and interestingly, all four subjects carrying these pre-existing INSTI
mutations had VS. HIV-1 subtype B was the predominant subtype and
all STB virologic failures (VF) occurred in subtype B. In the STB group
through W96, 16 subjects (2.3%; 16/701) developed primary INSTI
and/or NRTI resistance mutations and had phenotypic resistance to
STB: 13 subjects in year 1 and 3 subjects in year 2. Emergent mutations
were E92Q (N 9), N155H (N 5), Q148R (N 3) and T66I (N 2)
in IN in combination with M184V/I (N 15) and K65R (N 5) in RT.
STB VF retained susceptibility against NNRTIs, PIs and many NRTIs. In
the ATR group, 10 subjects (2.9%; 10/352) developed RT resistance to
ATR: 8 subjects in year 1 and 2 subjects in year 2. Resistance was most
commonly K103N (N 9) with M184V/I plus K65R (N 3). In the
Poster Abstracts
ATV/r TVD group, 16 subjects were analyzed and none developed
resistance.
Conclusions: STB achieved durable high rates of VS in HIV-1
treatment-naive subjects, including subjects with pre-existing NNRTI,
PI and NRTI resistance.
P21
Characterization of protease resistance-associated
mutations in HIV-1 drug-naive patients following the
increased prevalence of the CRF strain in Cuba
M Dubed1; L Machado2; H Dı́az3; N Ruiz2; D Romay2 and M Blanco2
1
AIDS Research Laboratory, Microbiology, San José de las Lajas, Cuba.
2
AIDS Research Laboratory, Molecular Biologic, San José de las Lajas,
Cuba. 3AIDS Research Laboratory, Diagnostic, San José de las Lajas,
Cuba.
Introduction: The selection of resistance mutations is a major
complication during antiretroviral therapy (ART) for HIV-infected
patients. There are 17 major mutations associated with the protease
(PR) that confer resistance to inhibitors PR (PI), allowing the virus to
replicate in the presence of drugs, in addition, some minor mutations
have been shown to compensate the loss in fitness of viruses
harbouring major mutations. Mutations at position 10 occur at much
higher frequencies in treated patients than in naive patients,
suggesting that these minor mutations may play a role in conferring
resistance to PIs. In Cuba, the prevalence of resistance to PI was low
among treatment-naive subjects (3.2%). The objective of this study
is to evaluate the prevalence of resistance-associated mutations
(RAMs) to PR and determine if the emergence of RAMs could have a
significant correlation with the increasing prevalence of CRFs strains
in Cuba.
Methods: A total of 288 PR gene sequences were amplified
from drug-naive HIV-1-infected individuals. Plasma HIV RNA was
quantified using the COBAS Ampliprep/COBAS Taqman HIV-1 Test
(Roche Diagnostics GmbH, Mannheim, Germany). The mutations
associated with reduced susceptibility to IP were detected by means
of the Stanford University calibrated population resistance tool.
Results: The prevalence of associated mutations to the transmission
of drug-resistant HIV among treatment-naive patients was 9.7%.
The subtype analysis reported that subtype B, the recombinant
forms CRF 19_cpx, CRF BG, CRF 18_cpx, URF, and CRF05_DF and
subtypes G, H, and C are included. Frequency of occurrence of
changes L10I/R and K20I was 15.9 and 44.8% respectively (p B0.05).
L10I substitution was associated significantly with subtype B, 19 CPX
and BG. The proportion of substitution K20I/R in the FRC 18 cpx
and BG was considerably higher than others. In the latter was
detected more frequently the combination of the two substitutions.
A low level of resistance to nelfinavir was found in 83% of samples,
related to the presence of changes at positions 10 and 20 of the PR.
Conclusions: Significant differences in the prevalence of resistance to
PI were not detected among the most frequent genetic forms from
naive-treated patients, but differences between some amino acids
changes should be taken into account. The presence of transmitted
resistance mutations supports the study of resistance at the baseline
of treatment.
P22
Transmitted HIV type-1 drug resistance in newly diagnosed
patients from Havana City: 20092012
L Machado1; H Diaz1; M Dubed1; N Ruiz1; M Blanco1; L Martı́nez2;
D Romay1 and E Silva1
21
1
AIDS Research Laboratory, Molecular Biology, San José de las Lajas,
Cuba. 2Outpatients Department, Hermanos Ameijeiras, Havana,
Cuba.
Introduction: The pre-existence of antiretroviral (ARV) drug resistant virus is strongly associated with treatment failure in naive
treatment patients, for that the knowledge of transmitted drug
resistance (TDR) in newly diagnosed patients constitutes a fundamental premise in the epidemiological surveillance. The aim of this
study was to analyze the profile of TDR in newly diagnosed patients
from Havana city.
Methods: One hundred and twenty-seven HIV-1 infected patients
from Havana and diagnosed between 2009 and 2012 were included
in the study. The viral RNA was isolated from plasma and used as
target to amplify the pol gene by RT-nested PCR. PCR products were
sequenced and the data generated used to determine the viral
subtype by phylogenetic analysis. The TDR were detected by HIVdb
v6.1.1 and CPR tool v 6.0, according the 2009 surveillance drug
resistance mutations list.
Results: The majority of patient was male (87.4%), 72.4% of the
infections was acquired by homosexual transmission and 13.4% were
recent infection. As high as 39.4% of the analyzed samples corresponded to the subtype B, followed by CRF19_cpx (26%), CRF 20-2324_BG (18.9%), CRF18_cpx (7.9%), URF (5.5%), C (0.8%), G (0.8%),
CRF05_DF (0.8%). Overall, 22.8% (29/127) had evidences of TDR.
6.3% presented mutations to NRTI, 4.7% to NNRTI and 3.1% to PI.
Drug resistance mutations against both NRTI and NNRTI were
observed in 7.9%, whereas triple class resistance was found in only
0.8% of the studied samples. The most common mutations were
M184V (34.5%) and G190A (31%) for the NRTIs and NNRTIs,
respectively. In patients with TDR virus, the first line HAART may
be effective in 17.2%, partially effective in 44.8% and ineffective
in 38%.
Conclusions: This study confirmed the high HIV-1 genetic diversity
in newly diagnosed patients from Havana. The increment of TDR
in the HIV-infected people from Havana indicates the importance
of maintaining the epidemiological surveillance in the patients of
recently diagnosed due to its possible implications in the effectiveness the first- line regimens prescribed in Cuba.
P23
Antiretroviral drug resistance in HIV-1 patients failing
antiretroviral therapy in an outpatients department from
Havana City during 2012
H Diaz1; L Machado1; L Martı́nez2; N Ruiz1; D Romay1; M Dubed1 and
M Blanco1
1
AIDS Research Laboratory, Molecular Biology, San José de las Lajas,
Cuba. 2Outpatients Department, Hermanos Ameijeiras, Havana,
Cuba.
Introduction: Since 2001, Cuba achieved universal antiretroviral
therapy with domestically manufactured antiretroviral (ARV) for
patients meeting international clinical criteria and has resulted in a
decrease in AIDS mortality rate and incidence of opportunistic
infections. However, the emergency of HIV-1 drug resistance is
strongly associated with treatment failure. The aim of this study was
to analyze the associated mutations to ARV resistance and the
resistance levels in a group of patients that attended to the
infectious diseases outpatients department of Hermanos Ameijeiras
Hospital, Havana City with treatment failure during the year 2012.
Methods: During 2012, were collected 25 plasma samples from HIV1 patients with treatment failure of 157 HIV patients that attended
Poster Abstracts
to the infectious diseases outpatients department of Hermanos
Ameijeiras Hospital. The viral RNA was used as target to amplified
and sequenced pol gene. The viral subtype and the drug resistance
mutations and levels were determined. The time between the
appearance of resistance and the beginning the last therapy was
considered.
Results: Most of the patients were MSM (96%) and 52% had only
received first-line HAART. Subtype B was the most prevalent subtype
(52%) followed by non-B subtypes (CRF19_cpx, CRF 20-23-24_BG,
URF and CRF18_cpx). Drug-resistant mutations were detected in 21
patients (84%). Of them, 61.9% presented mutations against both
NRTI and NNRTI, 19.1% to the combination PI NRTI, 9.5% to NRTI,
and 9.5% to NNRTI. The most frequent mutation for NRTI was M184V
(56%), while for NNRTI were Y181C/I/V (24%) and K103N (20%). As
high as 64% presented high resistance to all or some of the drugs
used as first-line HAART in Cuba (AZT/D4T 3TC NVP). The
average of years in the appearance of resistance after beginning
the last therapy was of 2.3 years. The therapeutic failure of 16% of
the patients that presented susceptible virus was due to the poor
adherence to HAART.
Conclusions: This study evidenced the high resistance levels to the
first-line regimens prescribed in Cuba, as well as the fast appearance
of resistant variants after beginning the therapy. These results
emphasize the necessity of the monitoring of the resistance in those
patients that will begin a new therapeutic regimen.
TREATMENT STRATEGIES
P24
STAR: Rilpivirine/Emtricitabine/TenofovirDF is non-inferior
to Efavirenz/Emtricitabine/TenofovirDF in naive adult
Latino, black & white subpopulations
C Cohen1; D Wohl2; J Arribas3; K Henry4; M Bloch5; W Towner6;
R Ebrahimi7; D Porter8; S De-oertel9; R Quercia10 and T Fralich9
1
Department of Infectious Diseases, Brigham and Women’s Hospital,
Boston, USA. 2Department of Infectious Diseases, University of North
Carolina, Chapel Hill, USA. 3Department of Infectious Diseases,
Hospital de la Paz, Madrid, Spain. 4Department of HIV Research,
Hennepin County Medical Center, Minneapolis, USA. 5HIV Clinical
Research, Holdsworth House Medical Practice, Sydney, Australia.
6
Kaiser Permanente, Los Angeles, USA. 7Department of Biostatistics,
Gilead Sciences, Foster City, USA. 8Department of Clinical Virology,
Gilead Sciences, Foster City, USA. 9Department of Medical Affairs,
Gilead Sciences, Foster City, USA. 10Department of Public Health and
Education, Gilead Sciences, Foster City, USA.
Introduction: Rilpivirine/Emtricitabine/Tenofovir DF (RPV/FTC/TDF)
is a once-daily single-tablet regimen (STR) HIV-1 treatment option.
This is the first study to directly compare safety and efficacy of the
two STRs, RPV/FTC/TDF and Efavirenz/Emtricitabine/Tenofovir DF
(EFV/FTC/TDF) in treatment-naive adults. Since virologic response
to ART can vary by ethnicity or race, it is of interest to evaluate
outcomes within these subpopulations.
Objective: Evaluate safety and efficacy in the overall study population and subpopulations by ethnicity and race.
Methods: STaR is an ongoing, open-label, international, 96-week
study evaluating safety and efficacy of the STR RPV/FTC/TDF vs. the
STR EFV/FTC/TDF in ARV-naive, HIV-1 infected subjects. Subjects
were randomized 1:1 to RPV/FTC/TDF or EFV/FTC/TDF. Eligibility
criteria included screening HIV-1 RNA ]2,500 c/mL, genotypic
22
sensitivity to EFV, FTC, TDF and RPV and no prior ARV therapy. The
primary endpoint was proportion of subjects with HIV-1 RNA B50 c/
mL at week 48 (12% non-inferiority margin).
Results: RPV/FTC/TDF was non-inferior to EFV/FTC/TDF (86%
[n 394] vs. 82% [n 392]) respectively, at week 48 for HIV RNA
B50 c/mL (difference 4.1%, 95% CI [ 1.1%, 9.2%]) per FDA snapshot
analysis. In the Hispanic/Latino ethnicity subgroup, RPV/FTC/TDF
(n 59) reached virologic suppression (VS) levels of 90 vs. 81% for
EFV/FTC/TDF (n 75) (difference 7.9%, 95% CI [4.3%, 20.1%]). VS in
Black subgroup was 79% for RPV/FTC/TDF (n 98) vs. 83% for EFV/
FTC/TDF (n 94) (difference3.6%, 95% CI [14.6%, 7.4%]);
whereas the White subgroup (RPV/FTC/TDF [n 266], EFV/FTC/TDF
[n 262]) had VS of 88 vs. 81% respectively (difference 6.2%, 95% CI
[ 0.1%, 12.5%]). Overall the virologic failure (VF) rate was 8 and 6%,
respectively. VF was 5% RPV/FTC/TDF vs. 9% EFV/FTC/TDF for Latinos
(p 0.37), 12 vs. 7% (p 0.37) for Black race and 7 vs. 5% (p 0.28) in
the White race subpopulation, respectively.
Conclusions: In treatment-naive HIV-1-infected patients, RPV/FTC/
TDF was non-inferior to EFV/FTC/TDF for VS in the overall study
population at week 48, showing similar VS levels for Latino, Black
and White subpopulations.
Poster Abstracts
Results: Four hundred seventy-six subjects were randomized. At W24
virologic suppression (VS) was achieved by 94% of subjects in the
RPV/FTC/TDF arm vs.90% in the PI RTV 2NRTI arm; (difference
3.8%, 95% CI: [1.69.1]). Through W48, 89% of subjects switching
to RPV/FTC/TDF at baseline maintained VS. The rate of VS at W48
for the 152 subjects who switched to RPV/FTC/TDF at W24 was
comparable to the rate of VS at W24 for those who switched to
RPV/FTC/TDF at baseline (Delayed Switch to RPV/FTC/TDF 92%). VF
was lower in the switch arm (0.9%) compared to remaining on
PI RTV 2NRTIs (5%) at W24. VF was also lower in the delayed
switch arm (1.3% from W24-48). At week 48, patients in the
immediate switch arm had few VFs (1.1%; 4/317) and resistance
development was infrequent after switching to RPV/FTC/TDF. There
were 24 subjects with pre-existing K103N mutations: 18 in the
immediate switch arm and six in the delayed switch arm. Twenty
three out of twenty four subjects successfully maintained suppression after switching to RPV/FTC/TDF. One patient had viral rebound
with resistance: showing pre-existing K103N and V179I with
emergent M184V, E138K and V108V/I mutations in the RT.
Conclusions: In the W48 analysis, VS was maintained regardless of
whether subjects switched to RPV/FTC/TDF at baseline or at W24.
RPV/FTC/TDF-treated subjects with pre-existing K103N mutations
had a high response rate.
References
P25
Efficacy of switching to rilpivirine/emtricitabine/tenofovir
DF from boosted PI in HIV-1 virologically suppressed
patients with or without the K103N
F Pallela1; P Tebas2; M Fisher3; B Gazzard4; P Ruane5; J Van Lunzen6;
D Shamblaw7; J Flamm8; R Ebrahimi9; D Porter10; K White10;
S De-Oertel11; T Fralich11 and R Quercia12
1
Center for AIDS Research, Northwestern University, Chicago, USA.
2
AIDS Clinical Trials Unit, University of Pennsylvania, Philadelphia,
USA. 3Department of Infectious Diseases, Brighton & Sussex
University Hospital NHS Trust, Brighton, UK. 4HIV/GUM Clinical
Research & Education, Chelsea & Westminister Hospital Foundation
Trust, London, UK. 5Peter J Ruane, MD, Inc., HIV Clinic, Los Angeles,
USA. 6Infectious Diseases Unit, Hamburg University Medical Center,
Hamburg, Germany. 7HIV Clinic, La Playa Medical Group, San Diego,
USA. 8HIV Clinic, Kaiser Permanente, Los Angeles, USA. 9Department
of Biostatistics, Gilead Sciences, Foster City, USA. 10Department of
Clinical Virology, Gilead Sciences, Foster City, USA. 11Department of
Medical Affairs, Gilead Sciences, Foster City, USA. 12Department of
Public Health and Education, Gilead Sciences, Foster City, USA.
Introduction: Antiretroviral simplification improves quality of life
and adherence while reducing the risk of HIV virologic failure (VF).
Carrying a transmitted K103N RT mutation is not rare [1,2] and could
be particularly important in the case of virologically suppressed
patients with a boosted PI-based regimen switching to a NNRTIbased regimen.
Methods: SPIRIT is a phase 3b, randomized, open-label, multicentre,
international, 48-week study to evaluate the safety and efficacy of
switching from PI RTV 2NRTI regimens to RPV/FTC/TDF in
virologically suppressed HIV-1 infected subjects. Subjects were
randomized 2:1 to switch to RPV/FTC/TDF at baseline or maintain
their current PI RTV 2NRTI regimen with a delayed switch to
RPV/FTC/TDF at W24. The primary endpoint was non-inferiority (12%
margin) of RPV/FTC/TDF relative to PI RTV 2NRTI regimens in
maintaining plasma HIV-1 RNA B50 c/mL at W24 by FDA snapshot
analysis. Inclusion criteria allowed enrolment of patients with
evidence of a K103N mutation in their historical genotype obtained
prior to first line therapy.
1. Castor D, Low A, Evering T, Karmon S, Davis B, Figueroa A, et al.
Transmitted drug resistance and phylogenetic relationships among
acute and early HIV-1-infected individuals in New York City. J Acquir
Immune Defic Syndr. 2012;61(1):18.
2. Machado LY, Dubed M, Dı́az H, Ruiz N, Romay D, Váldes N, et al.
Transmitted HIV type 1 drug resistance in newly diagnosed Cuban
patients. AIDS Res Hum Retroviruses. 2013;29(2):4114.
P26
Evaluation of HIV-1 genotypic tropism among HIV-1 infected
patients failing HAART in Santos and São Paulo cities, Brazil
M Cicero1; N Mantovani1; L Santana1; R Azevedo1; R Arnold1;
M Caseiro2; R Diaz1 and S Komninakis3
1
Department of Infectology, Federal University of São Paulo,
São Paulo, Brazil. 2Department of Parasitology, Lusı́ada Foundation,
Santos, Brazil. 3Department of Molecular Biology, Lusı́ada
Foundation, Santos, Brazil.
Introduction: New antiretroviral agents have been introduced for
treatment-experienced patients; one of them is Maraviroc (MVC).
MVC is an efficacious entry inhibitor and well-tolerated, but it is
restricted to patients infected by CCR5 tropic virus. As HIV-1 enters T
CD4 cells using either CCR5 or CXCR4 co-receptors, a tropism test
must be performed before prescribing MVC. The aim of the study
was to analyze the HIV-1 genotypic tropism among 36 HIV-1 infected
patients failing HAART, receiving multiples regimens and naive to
MVC.
Materials and methods: Thirty-six treatment-experienced patients
were enrolled in the study. The average age was 39 years old, the
average T CD4 count was 216 cells/mm3 and the median viral load
was 4.63 log copies/mL. Nineteen patients live in São Paulo city and
17 live in Santos city. The V3 region of gp120 region was amplified
using nested PCR, sequenced and analyzed using the geno2pheno/
coreceptor tool (false positive rate cutoff of 10%).
Results: Of the 36 patients, 75% (27) were infected with CCR5 tropic
variants, while 25% (9) of the patients were infected with CXCR4
variants. Analyzing cities separately, 79% (15) of the patients from
23
São Paulo were infected with the CCR5 tropic virus, while 70% (12) of
the patients from Santos city were infected with the CCR5 variants.
We have not detected any dual tropic HIV-1 variants.
Conclusions: The genotypic tropism assay is the standard assay for
tropism testing and improves the management of treatment in
clinical practise. It is known that the use of the CXCR4 co-receptor
leads to a rapid disease progression. A high frequency of CCR5 tropic
virus was observed among patients on a failing HAART, which
Poster Abstracts
indicate that MVC is a good option for treating heavily treatmentexperienced patients. The tropism test continues to be a feasible and
low cost method to evaluate the tropism of HIV-1. However, a
phenotypic test is more accurate and should be indicated to detect
dual tropic virus and improve the treatment response.
24
AUTHOR INDEX
A
Abram, M
Alvarez-Wyssmann, V
Andrade-Villanueva, J
Argyropoulos, C
Arikan, D
Arnold, R
Arribas, J
Azevedo, R
P20
O332, P2, P5
P10
P6
P6
P26
P24
P26
B
Bacon, M
Badial-Hernández, F
Bautista, S
Beltran Santiago, D
Beron, J
Blanco, M
Bloch, M
Bun, R
O114
P10
KL3*
P16*, P18*
P3
P13, P21, P22, P23
P24
P11
C
Cahn, p
Campos-Loza, A
Caro Vega, Y
Carrete-Zúñiga, M
Carvalho, M
Caseiro, M
Casillas, J
Cesar, C
Cheng, A
Cicero, M
Clementino, L
Cohen, C
Cohen, M
Concetti, H
Coriat, B
Cortes, C
Costa, P
Crabtree-Ramirez, B
Cruz, C
O241*, P1, P11
P10
P16, P18
P2, P5
P9*
P26
P2, P5
O114, P1, P11
P4
P26*
P9
P24
KL2*
P11
O115
O114
P9
P10, P16, P18, O114
P19
Ebrahimi, R
Escobedo, T
M
P11
P11
P1, P11
P11
P25
P25
P24, P25
P3, P17
Machado, L
P13*, P21, P22*, P23*
Magis-RodrÍguez, C
P2*, P5*, O332
Mantovani, N
P26
Marı́a Pı́a, C
P11
Martı́nez, L
P22, P23
Martin Onraet, A
O332*
Martinez, M
P14*, P17*
Mathias, A
O213
McGowan, C
P1
Meraz-Muñoz, A
P10
Molina, J
P4
Montaner, J
O232*
Moyer, C
O213
F
Figueroa, M
Figurelli, V
Fink, V
Fischer, M
Fisher, M
Flamm, J
Fralich, T
Fredrick, L
G
Gabriel, R
Gazzard, B
Giron, L
Gisela, P
Gonzalez-Rodriguez, A
Gonzalez, A
Gotuzzo, E
Grinsztejn, B
Guerrero-Almeida, M
Guion, M
Gulick, R
P12
P4, P25
P12*
P11
O332
P19
O114
O114
O332
P3
O112*
H
Hasenclever, L
Hendry, B
Henry, K
Hermes, J
Hevia, H
Hu, Y
O115
P4
P24
P14, P17
P7
P3
J
Janini, L
Jayathilake, K
Jimenez, S
P3*, P14
P11
P9
P19*
P24, P25
P13, P21, P22, P23
P12, P26, O351*
P13, P21*, P22, P23
P13
P3
P4
P24, P25
P2, P5
P12
O114
P1
N
Navea, L
Nelson, M
Nilius, A
Niño-Vargas, R
Noa, E
Norton, M
P13
O211*
P6, P14, P17
P2, P5
P13
P3, P17
P
Padget, D
Palazuelos, M
Pallela, F
Pape, J
Pasley, M
Patterson, P
Perez, H
Perno, C-F
Piñeirua-Menendez, A
Piontkowsky, D
Porter, D
Post, F
Pozniak, A
O114
P7
P25
O114, O331*
P14, P17
P11
P11
KL4*
P10*
P4
P24, P25
P4
O222*
Q
K
D
D’Amico, R
Daniel, L
de Franceschi, L
De Jesus, T
De-oertel, S
Diaz, H
Diaz, R
Dubed, M
Duran, A
Lin, C
Liu, H
E
Kearney, B
Kirby, B
Komninakis, S
Kulkarni, R
Kuritzkes, D
Quercia, R
O213
O213*
P26
P20
O351*
L
Lederman, M
Ledesma, F
O342*
P7
P20*, P24*, P25*
R
Radix, A
Ramos, U
Renjifo, B
Rhee, M
Richter, W
Rode, R
Rodrı́guez, A
O322*
P19
P6*
P4
P3
P17
P2, P5
25
Rodrı́guez-Nolasco, E
Rodriguez, E
Rodriguez-Diaz, C
Romay, D
Ruane, P
Ruiz, N
P2, P5
P11
O323*
P13, P21, P22, P23
P25
P21, P22, P23
S
Sánchez, Y
Sabin, C
Saboyá, M
Saget, B
Santana, L
Santos, S
Sanz, J
Shamblaw, D
Shen, G
Shepherd, B
Sierra-Madero, J
Silva, E
P13
O221*
P8
P3
P26
P9
P7*
P25
O213
O114
P10, P16, P18, O114,
O311*, O332
P22
Socı́as, M
Soto-Ramirez, L
Speaker, TBC
Stevenson, M
Stubbs, R
Sucupira, M
Sued, O
Svidler, L
Szwarcberg, J
P1*, P8*, P11*
O113*
O321*, O341*
KL1*
P6, P14
P12
O223*, P1, P8, P11
P11
P4*, P20
T
Tebas, P
Tenore, S
Tokumoto, N
Towner, W
Trinh, R
P25
P12
P11
P24
P6
Volkow, P
Volkow-Fernandez, P
O231*
O332
W
Wegzyn, C
Weller, I
White, K
Winston, J
Wohl, D
Wolff, M
P3
O111*
P20, P25
P4
P24
O114*, O333*
Z
Zaire, C
Zurita, D
O115*
P11
V
Van Lunzen, J
Vigo, G
P25
P1
26
Journal Information
About the journal
The Journal of the International AIDS Society, an official journal of
the Society, provides a peer-reviewed, open access forum for
essential and innovative HIV research, across all disciplines.
All articles published by the Journal of the International AIDS
Society are freely accessible online. The editorial decisions are
made independently by the journal’s editors-in-chief.
Email: editorial@jiasociety.org
Website: http://www.jiasociety.org
eISSN: 1758-2652
Editorial board
Editors-in-Chief: Susan Kippax (Australia),
Papa Salif Sow (Senegal), Mark Wainberg (Canada)
Executive Editor: Shirin Heidari (Switzerland)
Managing Editor: Mirjam Curno (Switzerland)
Editorial Assistant: Helen Etya’Ale (Switzerland)
Editorial Board:
Quarraisha Abdool Karim (South Africa)
Dennis Altman (Australia)
Joe Amon (United States)
Judith Auerbach (United States)
Francoise Barré-Sinoussi (France)
Chris Beyrer (United States)
Nomita Chandhiok (India)
Mark Cotton (South Africa)
Mary Crewe (South Africa)
John N. Erni (China)
Alex Ezeh (Kenya)
Nathan Ford (South Africa)
Diane Havlir (United States)
Kuan-Teh Jeang (United States)
Fatima Juarez (Mexico)
Elly Katabira (Uganda)
Sukhontha Kongsin (Thailand)
Ivette Lorenzana de Rivera (Honduras)
Kathleen MacQueen (United States)
Julio Montaner (Canada)
Hector Perez (Argentina)
Deborah Posel (South Africa)
Subhasree Raghavan (India)
Naomi Rutenberg (United States)
Seema Sahay (India)
Gabrielle Scarlatti (Italy)
Amalio Telenti (Switzerland)
Marco Vittória (Switzerland)
Ian Weller (United Kingdom)
Alan Whiteside (South Africa)
Yazdan Yazdanpanah (France)
Publisher
International AIDS Society
Avenue de France 23
1202 Geneva, Switzerland
Tel: +41 (0) 22 710 0800
Email: info@iasociety.org
Website: http://www.iasociety.org
Indexing/abstracting
The Journal of the International AIDS Society is indexed in a
variety of databases including PubMed, PubMed Central,
MEDLINE, Science Citation Index Expanded and Google Scholar.
Advertising, sponsorship and donations
Please contact the editorial office if you are interested in
advertising on our journal’s website.We also gladly receive
inquiries on sponsorship and donations to support open access
publications from authors in low- and middle-income countries.
Supplements
The Journal of the International AIDS Society publishes
supplements, special issues and thematic series on own initiative
or based on proposals by external organizations or authors.
Inquiries can be sent to the editorial office at editorial@
jiasociety.org. All articles submitted for publication in supplements
are subject to peer review. Published supplements are fully
searchable and freely accessible online and can also be produced
in print.
Disclaimer
The authors of the articles in this supplement carry the
responsibility for the content and opinions expressed therein.
The editors have made every effort to ensure that no
inaccurate or misleading content or statements appear in this
supplement. However, in all cases, the publisher, the editors and
editorial board, and employees involved accept no liability for
the consequences of any inaccurate or misleading content or
statement.
Copyright
The content in this supplement is published under the Creative
Commons Attribution-NonCommercial 3.0 Unported
(http://creativecommons.org/licenses/by-nc/3.0/) license.
The license allows third parties to share the published work
(copy, distribute, transmit) and to adapt it, under the condition
that the authors are given credit, that the work is not used
for commercial purposes, and that in the event of reuse or
distribution, the terms of this license are made clear. Authors
retain the copyright of their articles, with first publication rights
granted to the Journal of the International AIDS Society.
June 2013
http://www.jiasociety.org/index.php/jias/issue/view/1463

clinical - Journal of the International AIDS Society

Transcription

Similar documents

INDBX NUMBER: SUPERVISOR: INSTITUTIOI{:

Babies born from HIV/AIDS positive mothers

Reach Out brochure - Reach Out Nkokonjeru Parish Reach Out

B U CA I

View the presentation

Lecture 11: HIV

Omorebokhae

Balancing fear with Efficacy: The case of Intersexions

April 15 express proof - Hotchkiss K-8