the e

Identifying Opportunities to Intervene in Reducing
Risk of Sexual Transmission of Antiretroviral Drug
Resistance among HIV-Infected Patients in Care
Heidi M. Soeters , Christopher B. Hurt , Sonia Napravnik
1
2
1,2,3
, Oksana M. Zakharova , Joseph J. Eron, Jr.
2,3
2,3
Department of Epidemiology, 2Division of Infectious Diseases, and 3Center for AIDS Research
University of North Carolina at Chapel Hill, Chapel Hill, NC USA
1
INTRODUCTION
METHODS
•Primary acquisition of drug-resistant HIV, called transmitted drug resistance (TDR), is
detected in 10-15% of newly diagnosed individuals in the United States1-2 and Europe.3-4
•A subject was included if s/he was a participant in the UCHCC and had completed a
comprehensive, standardized, face-to-face interview exploring HIV-related behaviors.
•“Donors” for TDR may have been infected with drug-resistant HIV themselves,5 or have
acquired drug resistance through suboptimal adherence to antiretroviral (ARV) therapy.6
•Clinical variables were obtained from medical records, and demographic and behavioral
data were obtained from the in-person interview.
•Patients who engage in ongoing risk behavior following their HIV diagnosis tend to be
less adherent to prescribed ARV regimens,7-8 providing a pathway for TDR to occur.
•Risk of TDR was defined as having unprotected sex in the 6 months prior to interview,
HIV RNA ≥400 copies/mL, and ≥1 surveillance drug resistance mutation (SDRM).10
•We sought to characterize opportunities for TDR using cross-sectional clinical and
behavioral data from the UNC CFAR HIV Clinical Cohort Study (UCHCC).9
•Multivariable log-linear binomial regression was used to identify predictors of TDR risk.
8.3 years 6.7 years
RESULTS
595
Interviews included in analyses, by year
482
21%
100
Interviews included
in analyses
2000
2005
2010
Median CD4 count at
interview (cells/µL)
Dual-class n=61
24%
10%
NRTI & NNRTI n=33 (54%)
NRTI & PI n=25 (41%)
NNRTI & PI n=3 (5%)
478
None
n=129
38%
62%
100%
38%
No
n=204
19%
0
n=194
<400
27%
58%
68%
42%
Yes
40%
Zero
One
≥2
68%
24%
One
2 to 4
Sexual Activity
8%
Condom Use
HIV RNA*
ARV Resistance†
n=353
n=239
Heterosexual
n=180
1500- >10,000
10,000
Risks for transmitting resistant HIV among 244 interviewees with genotyping
Number of partners
MSM
4001499
0
Unprotected sex
n=298
60%
50%
20%
Yes
Men
Missed ARV doses in prior 4 days
60%
Sexual activity in prior six months
Women
Range, 9-1998
Interquartile range, 256-704
HIV RNA (copies/mL) at time of interview
Range, 19-82
Interquartile range, 38-50
Gender & sexual orientation
n=118
n=85
n=290
78%
60%
Non-White
40%
n=377
Yes (n=30, 12%)
No (n=14, 6%)
Inconsistent
(n=94, 39%)
Yes (n=23, 9%)
Undetectable
(n=50, 20%)
≥1 partner
(n=172, 70%)
No (n=27, 11%)
Yes (n=13, 5%)
Detectable
(n=27, 11%)
No (n=14, 6%)
Always
(n=78, 32%)
Yes (n=30, 12%)
Undetectable
(n=51, 21%)
Yes, using
Other
90%
No (n=22, 9%)
Detectable
(n=44, 18%)
Cannabis n=107
Crack n=96
Alcohol n=50
Cocaine n=27
Opiates n=14
Other n=12
Injection n=3
None
Yes (n=22, 9%)
Undetectable
(n=44, 18%)
Active substance use
22%
No (n=15, 6%)
No partners
(n=72, 30%)
More than 4
Race & ethnicity
Yes (n=13, 5%)
Detectable
(n=28, 11%)
n=29
n=339
47%
of interviewees
were ARV-naïve
40%
Black
18%
0
43
n=105
NRTI n=28 (61%)
NNRTI n=15 (33%)
PI n=3 (7%)
Triple-class n=26
Interviewees had
genotypic resistance tests
White
n=117
7%
of interviewees had a
history of AIDS (n=101)
Single-class n=46
50
250
n=184
No SDRMs
Median time since first
ARV regimen initiated
150
Face-to-face interviews
between 2000-2011
Median age
Median time from HIV
diagnosis to interview
Surveillance drug resistance mutations
n=192
No (n=21, 9%)
n=16 (4.2%)
Hispanic
n=7 (1.9%)
Native American
* The cutoff for “detectable” RNA was defined as ≥400 copies/mL.
† Resistance was defined as having ≥1 surveillance drug resistance mutation (SDRM) from the 2009 WHO list.10
n=15 (4%)
Bivariate and multivariate associations between demographic and clinical characteristics and having a high risk for transmitting drug-resistant HIV
Race
Education
(Black = referent)
Male
Prevalence Ratio
1.95
Age (10Y)
1.00
White
1.05
Other
0.37
Years since HIV diagnosis
(High school grad = referent)
MSM
1.89
Substance
Use†
Depression
*
1.42
3.86
Some
College
2.03
(3-10 years = referent)
College or Homeless- History of Less than
Higher
ness‡
AIDS
3 years
0.63
2.82
1.50
0.20
11-15
years
1.54
16 years
or more
0.57
Adjusted Prevalence Ratios
MSM
1.75
Substance HomelessUse
ness
3.12
2.20
10
1
0.1
0.01
* Depression was defined as any diagnosis of depression in subject’s medical record prior to interview.
† Substance use was defined as drinking alcohol ≥4 days per week, or regular consumption of any illicit substances in the year prior to interview.
‡ Homeless at any time since HIV diagnosis.
LIMITATIONS
CONCLUSIONS
•Cohort members who participated in the interview represent a subset of the overall clinic
population. Generalizability to other clinical settings may be limited.
•A small but significant proportion (12%) of patients in the cohort are at risk of
transmitting drug-resistant HIV to sexual partners.
•Social desirability bias may have influenced subjects’ responses during the face-to-face
interview, which would tend to underestimate risk behaviors.
•Active substance use, a history of homelessness since HIV diagnosis, and being a man
who has sex with men had the strongest associations with risk of transmitting drugresistant virus to sexual partners.
•We did not quantitate the number of sexual encounters per partner, only the number of
partners. Low average per-encounter risk may be compounded with regular partner(s).
REFERENCES
•Improved efforts in secondary prevention may have an impact on TDR prevalence.
ACKNOWLEDGMENTS
1 Wheeler, et al. AIDS 2010;24(8):1203
6 Bangsberg, et al. Curr HIV/AIDS Rep 2007;4(2):65
2 Ross, et al. HIV Clin Trials 2007;8(1):1
7 Kozal, et al. AIDS 2004;18(16):2185
3 Wensing, et al. J Infect Dis 2005;192(6):958
8 Kalichman. Psychosom Med 2008;70(5):593
4 Masquelier, et al. JAIDS 2005;40(5):505
9 Howe, et al. AIDS Res Hum Retrov 2010;26(8):875
5 Brenner, et al. AIDS 2008;22(18):2509
10 Bennett, et al. PLoS ONE 2009;4(3):e4724
The authors thank Liz Yanik, Sam Stinnette, Brant Stalzer, and Luca Vernazza for their
assistance. Funding for this project was provided by the Social and Behavioral Science
Research Core of the University of North Carolina Center for AIDS Research (CFAR).
HMS (2 T32 AI070114 06), CBH (8 KL2 TR000084 05), SN (5 R01 HS018731 03), and JJE
(2 P30 AI50410 14) are supported by funding from the National Institutes of Health.
XIX INTERNATIONAL AIDS CONFERENCE – JULY 22-27, 2012 – WASHINGTON DC