PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (91)
 

Clipboard (0)
None

Select a Filter Below

Journals
more »
Year of Publication
1.  Risk of Drug Resistance Among Persons Acquiring HIV Within a Randomized Clinical Trial of Single- or Dual-Agent Preexposure Prophylaxis 
The Journal of Infectious Diseases  2015;211(8):1211-1218.
Background. Preexposure prophylaxis (PrEP) with emtricitabine plus tenofovir disoproxil fumarate (FTC/TDF) or TDF alone reduces the risk of human immunodeficiency virus (HIV) acquisition. Understanding the risk of antiretroviral resistance selected by PrEP during breakthrough infections is important because of the risk of treatment failure during subsequent antiretroviral use.
Methods. Within the largest randomized trial of FTC/TDF versus TDF as PrEP, plasma samples were tested for HIV with resistance mutations associated with FTC (K65R and M184IV) and TDF (K65R and K70E), using 454 sequencing.
Results. Of 121 HIV seroconverters, 25 received FTC/TDF, 38 received TDF, and 58 received placebo. Plasma drug levels in 26 individuals indicated PrEP use during or after HIV acquisition, of which 5 had virus with resistance mutations associated with their PrEP regimen. Among those with PrEP drug detected during infection, resistance was more frequent in the FTC/TDF arm (4 of 7 [57%]), compared with the TDF arm (1 of 19 [5.3%]; P = .01), owing to the FTC-associated mutation M184IV. Of these cases, 3 had unrecognized acute infection at PrEP randomization, and 2 were HIV negative at enrollment.
Conclusions. These results suggest that resistance selected by PrEP is rare but can occur both with PrEP initiation during acute seronegative HIV infection and in PrEP breakthrough infections and that FTC is associated with a greater frequency of resistance mutations than TDF.
doi:10.1093/infdis/jiu677
PMCID: PMC4402339  PMID: 25587020
HIV; pre-exposure prophylaxis; antiretroviral resistance; HIV prevention
2.  PrEP-selected Drug Resistance Decays Rapidly After Drug Cessation 
AIDS (London, England)  2016;30(1):31-35.
Objective
Resistance to emtricitabine plus tenofovir disoproxil fumarate (FTC/TDF) or TDF alone used as pre-exposure prophylaxis (PrEP) has been detected in individuals who initiated PrEP during unrecognized acute HIV infection and, rarely, in PrEP breakthrough infections. PrEP-selected resistance could alter future treatment options, and therefore we sought to determine how long resistance persisted after PrEP cessation.
Methods
The Partners PrEP Study was a randomized placebo-controlled trial of FTC/TDF or TDF as PrEP for HIV prevention. We previously reported that PrEP-related mutations (K65R, K70E or M184IV) were detected by 454 sequencing following seroconversion in 9 individuals who acquired HIV during the Partners PrEP Study. In the current study, we used 454 sequencing to detect and quantify PrEP-related mutations in HIV RNA-positive plasma samples prior to seroconversion, as well as in plasma from 6, 12, and 24 months after PrEP cessation from these 9 individuals.
Results
HIV RNA-positive, antibody-negative samples were available prior to seroconversion for 4 of 9 individuals with resistance detected at seroconversion. In all 4 cases, K65R, K70E and M184IV were not detected prior to seroconversion, suggesting PrEP-related resistance was selected and not transmitted. All PrEP-selected mutations were no longer detectable by 6 months after PrEP cessation and remained undetectable at 12 and 24 months in the absence of antiretroviral therapy.
Conclusion
Using highly sensitive assays, PrEP-selected resistance in plasma decays below detection by six months following drug cessation and remains undetectable for ≥24 months. Even high levels of resistance mutations during acute infection decay rapidly in the absence of ongoing PrEP exposure.
doi:10.1097/QAD.0000000000000915
PMCID: PMC4704103  PMID: 26731753
HIV; pre-exposure prophylaxis; HIV drug resistance; antiretroviral therapy; heterosexual transmission; HIV prevention
3.  Effect of Pregnancy on Response to Antiretroviral Therapy in HIV-Infected African Women 
Background:
While most recent evidence does not support a role for pregnancy in accelerating HIV disease progression, very little information is available on the effects of incident pregnancy in response to antiretroviral therapy (ART). Hormonal, immune, and behavioral changes during pregnancy may influence response to ART. We sought to explore the effects of incident pregnancy (after ART initiation) on virologic, immunologic, and clinical response to ART.
Methods:
Data were collected from HIV-infected women participating in 3 prospective studies (Partners in Prevention Herpes simplex virus/HIV Transmission Study, Couples Observational Study, and Partners Preexposure Prophylaxis Study) from 7 countries in Africa from 2004 to 2012. Women were included in this analysis if they were ≤45 years of age, were started on ART during the study and were not pregnant at ART initiation. Pregnancy was treated as a time-dependent exposure variable covering the duration of pregnancy, including all pregnancies occurring after ART initiation. Virologic failure was defined as a viral load (VL) greater than 400 copies per milliliter ≥6 months after ART initiation and viral suppression was defined as VL ≤400 copies per milliliter. Multivariable Cox proportional hazards models were used to assess the association between pregnancy and time to viral suppression, virologic failure, World Health Organization clinical stage III/IV, and death. Linear mixed-effects models were used to assess the association between pregnancy and CD4+ count and VL. All analyses were adjusted for confounders, including pre-ART CD4+ count and plasma VL.
Results:
A total of 1041 women were followed, contributing 1196.1 person-years of follow-up. Median CD4+ count before ART initiation was 276 cells per cubic millimeter (interquartile range, 209–375); median pre-ART VL was 17,511 copies per milliliter (interquartile range, 2480–69,286). One hundred ten women became pregnant after ART initiation. Pregnancy was not associated with time to viral suppression (adjusted hazard ratio [aHR], 1.20, 95% confidence interval [CI]: 0.82 to 1.77), time to virologic failure (aHR, 0.67, 95% CI: 0.37 to 1.22), time to World Health Organization clinical stage III or IV (aHR, 0.79, 95% CI: 0.19 to 3.30), or time to death (aHR, 2.04, 95% CI: 0.25 to 16.8). Incident pregnancy was associated with an adjusted mean decrease in CD4+ T-cell count of 47.3 cells per cubic millimeter (P < 0.001), but not with difference in VL (P = 0.06).
Conclusions:
For HIV-infected women on ART, incident pregnancy does not affect virologic control or clinical HIV disease progression. A modest decrease in CD4+ T-cell count could be due to physiologic effects of pregnancy.
doi:10.1097/QAI.0000000000001199
PMCID: PMC5147030  PMID: 27787340
pregnancy; HIV; antiretroviral therapy; response; African
4.  Estimating Efficacy in a Randomized Trial With Product Nonadherence: Application of Multiple Methods to a Trial of Preexposure Prophylaxis for HIV Prevention 
American Journal of Epidemiology  2015;182(10):848-856.
Antiretroviral preexposure prophylaxis (PrEP) for persons at high risk of human immunodeficiency virus infection is a promising new prevention strategy. Six randomized trials of oral PrEP were recently conducted and demonstrated efficacy estimates ranging from 75% to no effect, with nonadherence likely resulting in attenuated estimates of the protective effect of PrEP. In 1 of these trials, the Partners PrEP Study (Kenya and Uganda, 2008–2011), participants (4,747 serodiscordant heterosexual couples) were randomized to receipt of tenofovir (TDF), coformulated TDF/emtricitabine (FTC), or placebo. Intention-to-treat analyses found efficacy estimates of 67% for TDF and 75% for TDF/FTC. We applied multiple methods to data from that trial to estimate the efficacy of PrEP with high adherence, including principal stratification and inverse-probability-of-censoring (IPC) weights. Results were further from the null when correcting for nonadherence: 1) among the strata with an estimated 100% probability of high adherence (TDF hazard ratio (HR) = 0.19, 95% confidence interval (CI): 0.07, 0.56; TDF/FTC HR = 0.12, 95% CI: 0.03, 0.52); 2) with IPC weights used to approximate a continuously adherent population (TDF HR = 0.18, 95% CI: 0.06, 0.53; TDF/FTC HR = 0.15, 95% CI: 0.04, 0.52); and 3) in per-protocol analysis (TDF HR = 0.18, 95% CI: 0.06, 0.53; TDF/FTC HR = 0.16, 95% CI: 0.05, 0.53). Our results suggest that the efficacy of PrEP with high adherence is over 80%.
doi:10.1093/aje/kwv202
PMCID: PMC4634306  PMID: 26487343
HIV; HIV prevention; intention-to-treat analysis; medication adherence; randomized controlled trials
5.  Integrated Delivery of Antiretroviral Treatment and Pre-exposure Prophylaxis to HIV-1–Serodiscordant Couples: A Prospective Implementation Study in Kenya and Uganda 
PLoS Medicine  2016;13(8):e1002099.
Background
Antiretroviral-based interventions for HIV-1 prevention, including antiretroviral therapy (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) to reduce the susceptibility of HIV-1 uninfected persons, showed high efficacy for HIV-1 protection in randomized clinical trials. We conducted a prospective implementation study to understand the feasibility and effectiveness of these interventions in delivery settings.
Methods and Findings
Between November 5, 2012, and January 5, 2015, we enrolled and followed 1,013 heterosexual HIV-1-serodiscordant couples in Kenya and Uganda in a prospective implementation study. ART and PrEP were offered through a pragmatic strategy, with ART promoted for all couples and PrEP offered until 6 mo after ART initiation by the HIV-1 infected partner, permitting time to achieve virologic suppression. One thousand thirteen couples were enrolled, 78% of partnerships initiated ART, and 97% used PrEP, during a median follow-up of 0.9 years. Objective measures of adherence to both prevention strategies demonstrated high use (≥85%). Given the low HIV-1 incidence observed in the study, an additional analysis was added to compare observed incidence to incidence estimated under a simulated counterfactual model constructed using data from a prior prospective study of HIV-1-serodiscordant couples. Counterfactual simulations predicted 39.7 HIV-1 infections would be expected in the population at an incidence of 5.2 per 100 person-years (95% CI 3.7–6.9). However, only two incident HIV-1 infections were observed, at an incidence of 0.2 per 100 person-years (95% CI 0.0–0.9, p < 0.0001 versus predicted). The use of a non-concurrent comparison of HIV-1 incidence is a potential limitation of this approach; however, it would not have been ethical to enroll a contemporaneous population not provided access to ART and PrEP.
Conclusions
Integrated delivery of time-limited PrEP until sustained ART use in African HIV-1-serodiscordant couples was feasible, demonstrated high uptake and adherence, and resulted in near elimination of HIV-1 transmission, with an observed HIV incidence of <0.5% per year compared to an expected incidence of >5% per year.
In a prospective implementation study, Jared Baeten and colleagues investigate integrated delivery of antiretroviral treatment and pre-exposure prophylaxis to HIV-1–serodiscordant couples in Kenya and Uganda.
Author Summary
Why Was This Study Done?
Each year, approximately 2 million people become infected with HIV-1, most through sexual transmission and a majority in Africa.
Antiretroviral medications effectively treat HIV-1 infection, and, in the last 5 y, pivotal clinical trials demonstrated that such medications can be used to prevent new infections as well, through treatment of HIV-1 infected persons to reduce their infectiousness and use as pre-exposure prophylaxis by HIV-1 uninfected persons to reduce their susceptibility.
Models for effective delivery of antiretroviral medications for HIV-1 prevention in Africa have not been evaluated.
What Did We Do and Find?
We conducted a prospective study of a novel delivery model for use of antiretroviral medications for HIV-1 prevention among just over 1,000 HIV-1-serodiscordant couples (i.e., couples in which one member was HIV-1 infected and the other uninfected) in Kenya and Uganda; couples had behavioral and biologic characteristics that put them at particularly enhanced risk of HIV-1, even compared with HIV-1-serodiscordant couples in general.
Both members of all couples were offered antiretroviral medications, and they were counseled on their HIV-1 prevention benefits; the study took a pragmatic and cost-minimizing approach, discontinuing the use of pre-exposure prophylaxis for the uninfected partner 6 mo after the infected partner initiated antiretroviral treatment.
The primary goals of the project were to evaluate the implementation of the delivery model, including uptake, adherence, continuation, and safety.
Part-way through the anticipated delivery period, it became clear that the approach was highly successful and that HIV-1 transmission rates were considerably lower than would have been anticipated (a 96% reduction compared to expected rates in a simulated model).
What Do These Findings Mean?
Antiretroviral medications have proven to be a powerful tool for preventing HIV-1 spread in clinical research studies; the results of this study show that a practical delivery approach in an implementation setting is feasible with high uptake and adherence and can virtually eliminate HIV1- transmission.
Wide-scale roll-out of use of antiretroviral medications for HIV-1 prevention could have substantial effects in reducing the global burden of new HIV-1 infections.
doi:10.1371/journal.pmed.1002099
PMCID: PMC4995047  PMID: 27552090
6.  Antiretroviral drug use and HIV drug resistance among HIV-infected Black men who have sex with men: HIV Prevention Trials Network 061 
BACKGROUND
HPTN 061 enrolled Black men who have sex with men in the United States. Some men with low/undetectable HIV RNA had unusual patterns of antiretroviral (ARV) drug use or had drugs detected in the absence of viral suppression. This report includes a comprehensive analysis of ARV drug use and drug resistance among men in HPTN 061 who were not virally suppressed.
METHODS
The analysis included 169 men who had viral loads >400 copies/mL at enrollment, including three with acute infection and 13 with recent infection. By self-report, 88 were previously diagnosed, including 31 in care; 137 men reported no ARV drug use. Samples from these 169 men and 23 seroconverters were analyzed with HIV genotyping and ARV drug assays.
RESULTS
Forty-eight (28%) of the 169 men had ≥1 drug resistance mutation (DRM); 19 (11%) had multi-class resistance. Sixty men (36%) had ≥1 ARV drug detected, 42 (70%) of whom reported no ARV drug use. Nine (23%) of 39 newly-infected men had ≥1 DRM; 10 had ≥1 ARV drug detected. Unusual patterns of ARV drugs were detected more frequently in newly-diagnosed men than previously-diagnosed men. The rate of transmitted drug resistance (TDR) was 23% based on HIV genotyping and self-reported ARV drug use, but was 12% after adjusting for ARV drug detection.
CONCLUSIONS
Many men in HPTN 061 had drug-resistant HIV and many were at risk of acquiring additional DRMs. ARV drug testing revealed unusual patterns of ARV drug use and provided a more accurate estimate of TDR.
doi:10.1097/QAI.0000000000000633
PMCID: PMC4482803  PMID: 25861015
HIV; drug resistance; antiretroviral drug; Black; men who have sex with men
7.  Determination of HIV status in African adults with discordant HIV rapid tests 
Background
In resource-limited settings, HIV infection is often diagnosed using two rapid tests. If the results are discordant, a third tie-breaker test is often used to determine HIV status. This study characterized samples with discordant rapid tests and compared different testing strategies for determining HIV status in these cases.
Methods
Samples were previously collected from 173 African adults in a population-based survey who had discordant rapid test results. Samples were classified as HIV positive or HIV negative using a rigorous testing algorithm that included two fourth-generation tests, a discriminatory test, and two HIV RNA tests. Tie-breaker tests were evaluated, including: rapid tests (one performed in-country), a third-generation enzyme immunoassay (EIA), and two fourth-generation tests. Selected samples were further characterized using additional assays.
Results
Twenty-nine (16.8%) samples were classified as HIV positive; 24 (82.8%) of those samples had undetectable HIV RNA. Antiretroviral drugs were detected in one sample. Sensitivity was 8.3%–43% for the rapid tests; 24.1% for the third-generation EIA; 95.8% and 96.6% for the fourth-generation tests. Specificity was lower for the fourth-generation tests than the other tests. Accuracy ranged from 79.5–91.3%.
Conclusions
In this population-based survey, most HIV-infected adults with discordant rapid tests were virally suppressed without antiretroviral drugs. Use of individual assays as tie-breaker tests was not a reliable method for determining HIV status in these individuals. More extensive testing algorithms that use a fourth-generation screening test with a discriminatory test and HIV RNA test are preferable for determining HIV status in these cases.
doi:10.1097/QAI.0000000000000610
PMCID: PMC4483143  PMID: 25835607
HIV; rapid test; discordant; Africa
8.  Antiretroviral Pre-Exposure Prophylaxis Does Not Enhance Immune Responses to HIV in Exposed but Uninfected Persons 
The Journal of Infectious Diseases  2014;211(12):1943-1952.
Background. Antiretroviral preexposure prophylaxis (PrEP), using daily oral combination tenofovir disoproxil fumarate plus emtricitabine, is an effective human immunodeficiency virus (HIV) prevention strategy for populations at high risk of HIV acquisition. Although the primary mode of action for the protective effect of PrEP is probably direct antiviral activity, nonhuman primate studies suggest that PrEP may also allow for development of HIV-specific immune responses, hypothesized to result from aborted HIV infections providing a source of immunologic priming. We sought to evaluate whether PrEP affects the development of HIV-specific immune response in humans.
Methods and Results. Within a PrEP clinical trial among high-risk heterosexual African men and women, we detected HIV-specific CD4+ and CD8+ peripheral blood T-cell responses in 10%–20% of 247 subjects evaluated. The response rate and magnitude of T-cell responses did not vary significantly between those assigned PrEP versus placebo, and no significant difference between those assigned PrEP and placebo was observed in measures of innate immune function.
Conclusions. We found no evidence to support the hypothesis that PrEP alters either the frequency or magnitude of HIV-specific immune responses in HIV-1–exposed seronegative individuals. These results suggest that PrEP is unlikely to serve as an immunologic prime to aid protection by a putative HIV vaccine.
doi:10.1093/infdis/jiu815
PMCID: PMC4836720  PMID: 25520426
T-lymphocyte; HIV-1; cellular immunity; prevention of sexual transmission
9.  Plasma Cytokine Levels and Risk of HIV Type 1 (HIV-1) Transmission and Acquisition: A Nested Case-Control Study Among HIV-1–Serodiscordant Couples 
The Journal of Infectious Diseases  2014;211(9):1451-1460.
Background. A heightened proinflammatory state has been hypothesized to enhance human immunodeficiency virus type 1 (HIV-1) transmission – both susceptibility of HIV-1-exposed persons and infectiousness of HIV-1-infected persons.
Methods. Using prospective data from heterosexual African couples with HIV-1 serodiscordance, we conducted a nested case-control analysis to assess the relationship between cytokine concentrations and the risk of HIV-1 acquisition. Case couples (n = 120) were initially serodiscordant couples in which HIV-1 was transmitted to the seronegative partner during the study; control couples (n = 321) were serodiscordant couples in which HIV-1 was not transmitted to the seronegative partner. Differences in a panel of 30 cytokines were measured using plasma specimens from both HIV-1–susceptible and HIV-1–infected partners. Plasma was collected before seroconversion for cases.
Results. For both HIV-1–infected and HIV-1–susceptible partners, cases and controls had significantly different mean responses in cytokine panels (P < .001, by the Hotelling T2 test), suggesting a broadly different pattern of immune activation for couples in which HIV-1 was transmitted, compared with couples without transmission. Individually, log10 mean concentrations of interleukin 10 (IL-10) and CXCL10 were significantly higher for both HIV-1–susceptible and HIV-1–infected case partners, compared with HIV-1–susceptible and HIV-1–infected control partners (P < .01 for all comparisons). In multivariate analysis, HIV-1 transmission was significantly associated with elevated CXCL10 concentrations in HIV-1–susceptible partners (P = .001) and with elevated IL-10 concentrations in HIV-1–infected partners (P = .02).
Conclusions. Immune activation, as measured by levels of cytokine markers, particularly elevated levels of IL-10 and CXCL1, are associated with increased HIV-1 susceptibility and infectiousness.
doi:10.1093/infdis/jiu621
PMCID: PMC4447828  PMID: 25389306
HIV-1 acquisition; immune activation; Africa
10.  Expanding substance use treatment options for HIV prevention with Buprenorphine-Naloxone: HIV Prevention Trials Network 058 (HPTN 058) 
Background
Injection opioid use plays a significant role in the transmission of HIV infection in many communities and several regions of the world. Access to evidence-based treatments for opioid use disorders is extremely limited.
Methods
HPTN 058 was a randomized controlled trial designed to compare the impact of two medication assisted treatment (MAT) strategies on HIV incidence or death among opioid dependent people who inject drugs (PWID). HIV-negative opiate dependent PWID were recruited from four communities in Thailand and China with historically high prevalence of HIV among PWID. 1251 participants were randomly assigned to either; 1) a one year intervention consisting of two opportunities for a 15 day detoxification with buprenorphine/naloxone (BUP/NX) combined with up to 21 sessions of behavioral drug and risk counseling (Short Term Medication Assisted Treatment: ST-MAT) or, 2) thrice weekly dosing for 48 weeks with BUP/NX and up to 21 counseling sessions (Long Term Medication Assisted Treatment: LT-MAT) followed by dose tapering. All participants were followed for 52 weeks after treatment completion to assess durability of impact.
Results
While the study was stopped early due to lower than expected occurrence of the primary endpoints, sufficient data were available to assess the impact of the interventions on drug use and injection related risk behavior. At weeks 26, 22% of ST-MAT participants had negative urinalyses for opioids compared to 57% in the LT-MAT (p<0.001). Differences disappeared in the year following treatment: at week 78, 35% in ST-MAT and 32% in the LT-MAT had negative urinalyses. Injection related risk behaviors were significantly reduced in both groups following randomization.
Conclusions
Participants receiving BUP/NX three times weekly were more likely to reduce opioid injection while on active treatment. Both treatment strategies were considered safe and associated with reductions in injection related risk behavior. These data support the use of thrice weekly BUP/NX as a way to reduce exposure to HIV risk. Continued access to BUP/NX may be required to sustain reductions in opioid use.
doi:10.1097/QAI.0000000000000510
PMCID: PMC4382671  PMID: 25564105
11.  Assessment of contamination and misclassification biases in a randomized controlled trial of a social network peer education intervention to reduce HIV risk behaviors among drug users and risk partners in Philadelphia, PA and Chiang Mai, Thailand 
AIDS and behavior  2015;19(10):1818-1827.
Context
Controlled trials of educational interventions are susceptible to contamination.
Objectives
To test a contamination measure based on recall of terms.
Main study
A randomized controlled trial of a social network peer education intervention among 1,123 injection drug users and risk partners in Philadelphia, PA and Chiang Mai, Thailand.
Methods
We assessed the recall of test, negative and positive control terms by intervention and control arm participants and compared the relative odds (OR) of recall of test vs. negative control terms between study arms.
Results
The contamination measure showed good discriminant ability only among participants from Chiang Mai. In Philadelphia there was no evidence of contamination and little evidence of diffusion. In Chiang Mai there was evidence of diffusion and contamination of 4 of 5 terms tested.
Conclusions
Network structure and peer education in Chiang Mai likely led to contamination. Recall of intervention materials can be a useful method to detect contamination in trials of educational interventions.
doi:10.1007/s10461-015-1073-3
PMCID: PMC4567413  PMID: 25935214
Contamination; HIV; Prevention; Injection drug use; Social networks; Diffusion
12.  The effect of psychosocial syndemic production on 4-year HIV incidence and risk behavior in a large cohort of sexually active men who have sex with men 
Background
Cross-sectional studies have suggested that co-occurring epidemics or “syndemics” of psychosocial health problems may accelerate HIV transmission among men who have sex with men (MSM) in the United States. We aimed to assess how five syndemic conditions (depressive symptoms, heavy alcohol use, stimulant use, polydrug use, and childhood sexual abuse) affected HIV incidence and sexual risk behavior over time.
Methods
Eligible men in a large, prospective cohort of sexually active, HIV-uninfected MSM completed HIV testing and behavioral surveys at baseline and every 6 months for 48 months. We examined interrelationships between psychosocial problems and whether these interactions increased the odds of HIV risk behaviors and risk of seroconversion over study follow-up.
Results
Among 4295 men, prevalence of psychosocial conditions was substantial at baseline and was positively associated with each other. We identified a statistically significant positive dose-response relationship between numbers of syndemic conditions and HIV seroconversion for all comparisons (with the greatest hazard among those with 4-5 conditions, aHR=8.69; 95% CI: 4.78-15.44). The number of syndemic conditions also predicted increased HIV related risk behaviors over time, which mediated the syndemic-HIV seroconversion association.
Conclusions
The accumulation of “syndemic” psychosocial problems predicted HIV-related sexual risk behaviors and seroconversion in a large sample of U.S. MSM. Given the high prevalence of syndemic conditions among MSM and the moderate effect sizes attained by traditional brief behavioral interventions to date, the HIV prevention agenda requires a shift toward improved assessment of psychosocial comorbidities and stronger integration with mental health and substance abuse treatment services.
doi:10.1097/QAI.0000000000000475
PMCID: PMC4415161  PMID: 25501609
HIV; men who have sex with men; psychosocial conditions; prevention of sexual transmission; sexual behaviors
13.  Changing antiretroviral eligibility criteria: impact on the number and proportion of adults requiring treatment in Swaziland 
Objective
Early initiation of antiretroviral treatment (ART) at CD4+ cell count ≥ 500 cells/μL reduces morbidity and mortality in HIV-infected adults. We determined the proportion of HIV-infected people with high viral load (VL) for whom transmission prevention would be an additional benefit of early treatment.
Design
A randomly selected sub-set of a nationally representative sample of HIV-infected adults in Swaziland in 2012.
Methods
Eight to twelve months after a national survey to determine adult HIV prevalence, 1,067 of 5,802 individuals identified as HIV-infected were asked to participate in a follow-up cross-sectional assessment. CD4+ cell enumeration, VL measurements and ART status were obtained to estimate the proportion of currently untreated adults and of the entire HIV-infected population with high VL (≥1000 copies/mL) whose treatment under a test-and-treat or VL threshold eligibility strategy would reduce HIV transmission. .
Results
Of the 927 (87% of 1,067) participants enrolled, 466 (50%) reported no ART use. Among them, 424 (91%) had VL ≥1000 copies/mL; of these, 148 (35%) were eligible for ART at the then existing CD4+ count threshold of <350 cells/μL; an additional 107 (25%) were eligible with expanded CD4+ criterion of <500 cells/μ; and 169 (40%) remained ART-ineligible. Thus 36% of the 466 currently untreated and 18% of the total 927 had high VL yet remained ART-ineligible under a CD4+ criterion of <500 cells/μL.
Conclusions
A test-and-treat or VL threshold for treatment eligibility is necessary to maximize the HIV transmission prevention benefits of ART.
doi:10.1097/QAI.0000000000000846
PMCID: PMC4752404  PMID: 26361174
HIV; antiretroviral therapy; HIV treatment eligibility; CD4+ count; viral load; Swaziland
14.  Changing Antiretroviral Eligibility Criteria: Impact on the Number and Proportion of Adults Requiring Treatment in Swaziland 
Objective:
Early initiation of antiretroviral treatment (ART) at CD4+ cell count ≥500 cells per microliter reduces morbidity and mortality in HIV-infected adults. We determined the proportion of HIV-infected people with high viral load (VL) for whom transmission prevention would be an additional benefit of early treatment.
Design:
A randomly selected subset of a nationally representative sample of HIV-infected adults in Swaziland in 2012.
Methods:
Eight to 12 months after a national survey to determine adult HIV prevalence, 1067 of 5802 individuals identified as HIV-infected were asked to participate in a follow-up cross-sectional assessment. CD4+ cell enumeration, VL measurements, and ART status were obtained to estimate the proportion of currently untreated adults and of the entire HIV-infected population with high VL (≥1000 copies/mL) whose treatment under a test-and-treat or VL threshold eligibility strategy would reduce HIV transmission.
Results:
Of the 927 (87% of 1067) participants enrolled, 466 (50%) reported no ART use. Among them, 424 (91%) had VL ≥1000 copies per milliliter; of these, 148 (35%) were eligible for ART at the then existing CD4+ count threshold of <350 cells per microliter; an additional 107 (25%) were eligible with expanded CD4+ criterion of <500 cells per microliter; and 169 (40%) remained ART ineligible. Thus, 36% of the 466 currently untreated and 18% of the total 927 had high VL yet remained ART ineligible under a CD4+ criterion of <500 cells per microliter.
Conclusions:
A test-and-treat or VL threshold for treatment eligibility is necessary to maximize the HIV transmission prevention benefits of ART.
doi:10.1097/QAI.0000000000000846
PMCID: PMC4752404  PMID: 26361174
HIV; antiretroviral treatment; HIV treatment eligibility; CD4+ count; viral load; Swaziland
15.  Changes in Glomerular Kidney Function among HIV-1 Uninfected Men and Women Receiving Emtricitabine/Tenofovir Disoproxil Fumarate Pre-exposure Prophylaxis: A Randomized Placebo-controlled Trial 
JAMA internal medicine  2015;175(2):246-254.
Importance
Tenofovir disoproxil fumarate (TDF) use has been associated with declines in the estimated glomerular filtration rate (eGFR) when used as part of antiretroviral treatment by HIV-1 infected persons, but limited data are available for risk when used as pre-exposure prophylaxis (PrEP) for HIV-1 prevention.
Objective
To determine whether TDF-based PrEP causes eGFR decline in HIV-1 uninfected adults.
Design, Setting, and Participants
A per-protocol safety analysis of changes in eGFR in the Partners PrEP Study, a randomized, placebo-controlled trial of daily oral TDF and emtricitabine (FTC)-TDF PrEP among African heterosexual HIV-1 uninfected members of serodiscordant couples conducted from 2008 to 2012.
Main Outcomes and Measures
Pre-defined outcomes of this analysis were mean eGFR change and a ≥25% eGFR decline from baseline. eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration.
Results
Of 4640 subjects randomized and followed on either once daily TDF (n=1548), FTC-TDF (n=1545), or placebo (n=1547), 63% were male. At enrollment, median age was 35 years (range 18–64) and mean eGFR was 130 mL/min/1.73m2. During a median follow-up of 18 months (interquartile range 12–27), mean within-group eGFR change from baseline was +0.14 mL/min/1.73m2 for TDF, −0.22 mL/min/1.73m2 for FTC-TDF, and +1.37 mL/min/1.73m2 for placebo, translating into average declines in eGFR attributable to PrEP versus placebo of −1.23 mL/min/1.73m2 (95% CI −2.06, −0.40; p=0.004) for TDF and −1.59 mL/min/1.73m2 (95% CI −2.44, −0.74; p<0.001) for FTC-TDF. The difference in mean eGFR between PrEP and placebo appeared by one month after randomization, was stable through twelve months, and then appeared to wane thereafter. The proportion of persons who developed a confirmed ≥25% eGFR decline from baseline by 12 and 24 months was 1.3% and 1.8% for TDF and 1.2% and 2.5% for FTC-TDF, and these frequencies were not statistically different compared to placebo (0.9% and 1.3% by 12 and 24 months).
Conclusion and Relevance
In this large randomized, placebo-controlled trial among heterosexual persons, with median follow-up of 18 months and maximum follow-up of 36 months, daily oral TDF-based PrEP resulted in a small but non-progressive decline in eGFR that was not accompanied by a substantial increase in the risk of clinically relevant (≥25%) eGFR decline.
Trial Registration
Clinicaltrials.gov Identifier: NCT00557245
doi:10.1001/jamainternmed.2014.6786
PMCID: PMC4354899  PMID: 25531343
16.  Performance of the fourth-generation Bio-Rad GS HIV Combo Ag/Ab enzyme immunoassay for diagnosis of HIV infection in Southern Africa 
Background
Fourth-generation HIV assays detect both antigen and antibody, facilitating detection of acute/early HIV infection. The Bio-Rad GS HIV Combo Ag/Ab assay (Bio-Rad Combo) is an enzyme immunoassay that simultaneously detects HIV p24 antigen and antibodies to HIV-1 and HIV-2 in serum or plasma.
Objective
To evaluate the performance of the Bio-Rad Combo assay for detection of HIV infection in adults from Southern Africa.
Study design
Samples were obtained from adults in Soweto and Vulindlela, South Africa and Dar es Salaam, Tanzania (300 HIV-positive samples; 300 HIV-negative samples; 12 samples from individuals previously classified as having acute/early HIV infection). The samples were tested with the Bio-Rad Combo assay. Additional testing was performed to characterize the 12 acute/early samples.
Results
All 300 HIV-positive samples were reactive using the Bio-Rad Combo assay; false positive test results were obtained for 10 (3.3%) of the HIV-negative samples (sensitivity: 100%, 95% confidence interval [CI]: 98.8–100%); specificity: 96.7%, 95% CI: 94.0–98.4%). The assay detected 10 of the 12 infections classified as acute/early. The two infections that were not detected had viral loads < 400 copies/mL; one of those samples contained antiretroviral drugs consistent with antiretroviral therapy.
Conclusions
The Bio-Rad Combo assay correctly classified the majority of study specimens. The specificity reported here may be higher than that seen in other settings, since HIV-negative samples were pre-screened using a different fourth-generation test. The assay also had high sensitivity for detection of acute/early infection. False-negative test results may be obtained in individuals who are virally suppressed.
doi:10.1016/j.jcv.2014.11.023
PMCID: PMC4319362  PMID: 25542477
Fourth-generation; HIV; Diagnosis; Africa; Enzyme immunoassay
17.  Positive Social Impacts Related to Participation in an HIV Prevention Trial Involving People Who Inject Drugs 
IRB  2015;37(1):17-19.
Although attention has focused on whether participants actually derive better medical outcomes in research, the social benefits experienced in research have not been systematically examined. At regular follow-up visits during a phase III randomized trial assessing the safety and efficacy of a long-term versus a short-term drug treatment intervention in decreasing HIV transmission and mortality conducted in China and Thailand, participants identified research-related negative and positive social impacts (PSIs). Open-ended PSI responses were coded using standard qualitative techniques. Among 1025 participants, only 4 reported a negative social impact; however, 77% reported at least one PSI over the 104 week follow-up period. Given the high prevalence of PSIs we observed, future research should embed assessments of negative and positive social impacts experienced by participants in research not only to ensure their well-being, but also to inform policy and conceptual work related to research ethics.
PMCID: PMC4591048  PMID: 26247080
social impacts; benefits; HIV prevention; research ethics; injection drug use
18.  Single-Agent Tenofovir versus Combination Emtricitabine/Tenofovir for Pre-Exposure Prophylaxis against HIV-1 Acquisition: A Randomized Trial 
The Lancet. Infectious diseases  2014;14(11):1055-1064.
SUMMARY
Background
Antiretroviral pre-exposure prophylaxis (PrEP), using daily oral tenofovir disoproxil fumarate (TDF) or TDF in combination with emtricitabine (FTC/TDF), has been demonstrated to be efficacious for HIV-1 prevention. While the use of multiple antiretroviral agents is essential for effective HIV-1 treatment, multiple agents may not be required for effective prophylaxis. The relative efficacy of single-agent TDF versus combination FTC/TDF PrEP has not been directly assessed.
Methods
We conducted a randomized, double-blind, placebo-controlled three-arm trial of daily oral TDF and FTC/TDF PrEP among HIV-1 uninfected members of heterosexual HIV-1 serodiscordant couples from Kenya and Uganda. After an interim review, the trial’s placebo arm was discontinued due to demonstration of PrEP efficacy, and the results of each active PrEP agent compared to placebo were reported (TDF 67%, FTC/TDF 75%). Thereafter, the active arms were continued, and participants initially randomized to placebo were offered re-randomization to TDF or FTC/TDF PrEP.
Findings
4410 couples received TDF or FTC/TDF PrEP and were followed for HIV-1 acquisition. Of 52 incident HIV-1 infections, 31 were among those assigned TDF (incidence 0.71 per 100 person-years) and 21 were among those assigned FTC/TDF (incidence 0.48 per 100 person-years); for comparison, HIV-1 incidence in the placebo arm prior to its discontinuation was 2.00 per 100 person-years. HIV-1 prevention efficacy for FTC/TDF compared to TDF alone was not statistically significantly different: HR 0.67, 95% 0.39–1.17, p=0.16. Detection of tenofovir in plasma samples, compared to no detection and as measured in seroconverters and a subset of non-seroconverters, was associated with an 85% relative risk reduction in HIV-1 acquisition for the TDF arm and 93% for the FTC/TDF arm (both p<0.0001).
Interpretation
These results do not rule out the potential for a modest difference in HIV-1 protection for TDF compared to FTC/TDF, but they demonstrate that once-daily oral TDF or FTC/TDF both provide high protection against HIV-1 acquisition among heterosexual men and women.
doi:10.1016/S1473-3099(14)70937-5
PMCID: PMC4252589  PMID: 25300863
pre-exposure prophylaxis; HIV-1 prevention; randomized clinical trial; Africa
19.  Hepatotoxicity in a 52-week randomized trial of short-term versus long-term treatment with buprenorphine/naloxone in HIV-negative injection opioid users in China and Thailand* 
Drug and alcohol dependence  2014;0:139-145.
Background
Buprenorphine/naloxone (BUP/NX), an effective treatment for opioid dependence, has been implicated in hepatic toxicity. However, as persons taking BUP/NX have multiple hepatic risk factors, comparative data are needed to quantify the risk of hepatoxicity with BUP/NX.
Methods
We compared rates of alanine aminotransferase (ALT) elevation ≥ grade 3 (ALT ≥ 5.1 times the upper limit of normal) and graded bilirubin elevations in HIV-negative opioid injectors randomized to long-term (52 weeks) or short-term (18 days) medication assisted treatment (LT-MAT and ST-MAT, respectively) with BUP/NX in a multisite trial conducted in China and Thailand. ALT and bilirubin were measured at baseline, 12, 26, 40 and 52 weeks, times temporally remote from BUP/NX exposure in the ST-MAT participants.
Results
Among1036 subjects with at least one laboratory follow-up measurement, 76 (7%) participants experienced ALT elevation ≥ grade 3. In an intent-to-treat analysis, the risk of ALT events was similar in participants randomized to LT-MAT compared with ST-MAT (adjusted hazard ratio 1.25, 95% confidence interval 0.79 to 1.98). This finding was supported by an as-treated analysis, in which actual exposure to BUP/NX was considered. Hepatitis C seroconversion during follow-up was strongly associated with ALT events. Bilirubin elevations ≥ grade 2 occurred in 2% of subjects, with no significant difference between arms.
Conclusions
Over 52-week follow-up, the risk of hepatotoxicity was similar in opioid injectors receiving brief and prolonged treatment with BUP/NX. These data suggest that most hepatotoxic events observed during treatment with BUP/NX are due to other factors.
doi:10.1016/j.drugalcdep.2014.06.013
PMCID: PMC4127183  PMID: 24999060
buprenorphine/naloxone; injection drug use; opioid dependence; HIV prevention; safety; hepatotoxicity; alanine aminotransferase; hepatitis C virus
20.  An intervention to support HIV pre-exposure prophylaxis (PrEP) adherence in HIV serodiscordant couples in Uganda 
Background
Daily pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy, but adherence is required for maximum benefit. To date, there are no empirically supported PrEP adherence interventions. This manuscript describes the process of developing a PrEP adherence intervention and presents results on its impact on adherence.
Methods
The Partners PrEP Study was a placebo-controlled efficacy trial of daily oral tenofovir and emtricitabine/tenofovir PrEP among uninfected members of HIV serodiscordant couples. An ancillary adherence study was conducted at three study sites in Uganda. Participants with <80% adherence as measured by unannounced pill count received an additional adherence counseling intervention based on Lifesteps, an evidence-based HIV treatment adherence intervention, based on principles of cognitive-behavioral theory.
Findings
Of the 1,147 HIV seronegative participants were enrolled in the ancillary adherence study, 168 (14.6%) triggered the adherence intervention. Of participants triggering the intervention, 62% were male; median age was 32.5 years. The median number of adherence counseling sessions was 10. Mean adherence during the month before the intervention was 75.7%, and increased significantly to 84.1% in the month after the first intervention session (p<0.001). The most frequently endorsed adherence barriers at session one were travel and forgetting.
Interpretation
A PrEP adherence intervention was feasible in a clinical trial of PrEP in Uganda and PrEP adherence increased after the intervention. Future research should identify PrEP users with low adherence for enhanced adherence counseling and determine optimal implementation strategies for interventions to maximize PrEP effectiveness.
doi:10.1097/QAI.0000000000000212
PMCID: PMC4191829  PMID: 24853311
pre-exposure prophylaxis; adherence; intervention; serodiscordant couples; HIV prevention
21.  Pre-exposure prophylaxis for HIV-1 prevention does not diminish the pregnancy prevention effectiveness of hormonal contraception 
AIDS (London, England)  2014;28(12):1825-1830.
Background
For women at risk of HIV-1, effective contraception and effective HIV-1 prevention are global priorities.
Methodology
In a clinical trial of pre-exposure prophylaxis (PrEP) for HIV-1 prevention in HIV-1 serodiscordant couples, we estimated the effectiveness of hormonal contraceptives (oral contraceptive pills, injectable depot medroxyprogesterone acetate, and hormonal implants) for pregnancy prevention relative to no contraception among 1785 HIV-1 uninfected women followed up to 36 months. We compared the effectiveness of each method among women assigned PrEP versus placebo. Contraception was not required for participation but was offered on-site and was recorded monthly; incident pregnancy was determined by monthly urine testing.
Results
For women using no contraception, overall pregnancy incidence was 15.4% per year. Women reporting oral contraceptive use had comparable pregnancy incidence to women using no contraception, and this lack of contraceptive effectiveness was similar for those assigned PrEP and placebo (17.7% and 10.0% incidence per year respectively; p-value for difference in effect by PrEP use=0.24). Women reporting injectable contraception had reduced pregnancy incidence compared to those reporting no contraception, which did not differ by arm (PrEP 5.1%, placebo 5.3% per year; p-value for difference=0.47). Contraceptive effectiveness was highest among women using implants (pregnancy incidence <1% per year in both arms).
Conclusions
PrEP had no adverse impact on hormonal contraceptive effectiveness for pregnancy prevention. As seen previously in similar populations, women reporting contraceptive pill use had little protection from pregnancy, possibly due to poor adherence. Injectable or implantable hormonal contraception plus PrEP provides effective prevention for pregnancy and HIV-1.
doi:10.1097/QAD.0000000000000290
PMCID: PMC4136509  PMID: 24785951
22.  Choosing a metric for measurement of pre-exposure prophylaxis 
The Lancet. Infectious diseases  2014;14(12):1177-1178.
doi:10.1016/S1473-3099(14)70989-2
PMCID: PMC4507263  PMID: 25455980
23.  Pregnancy Incidence and Outcomes among Women Receiving Pre-Exposure Prophylaxis for HIV Prevention: A Randomized Clinical Trial 
JAMA  2014;312(4):362-371.
Importance
Antiretroviral pre-exposure prophylaxis (PrEP), using tenofovir disoproxil fumarate and combination tenofovir disoproxil fumarate / emtricitabine, is efficacious for prevention of HIV acquisition. PrEP could reduce periconception HIV risk, but the effect on pregnancy outcomes is not well defined.
Objective
To assess pregnancy incidence and outcomes among women using PrEP during the periconception period.
Design
Randomized trial among 1785 HIV serodiscordant heterosexual couples (the Partners PrEP Study) in which the female partner was HIV uninfected that demonstrated that PrEP was efficacious for HIV prevention, conducted between July 2008 and June 2013 at 9 sites in Kenya and Uganda.
Intervention
Daily oral tenofovir disoproxil fumarate (TDF) (n=598), combination tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) (n=566), or placebo (n=621) through July 2011, when PrEP demonstrated efficacy for HIV prevention; thereafter, participants continued receiving active PrEP, without placebo. Pregnancy testing occurred monthly and study medication was discontinued upon pregnancy detection.
Main Outcomes
Pregnancy incidence, birth outcomes (pregnancy loss, preterm birth, congenital anomalies), infant growth.
Results
A total of 431 pregnancies occurred. Pregnancy incidence was 10.0 per 100 person-years among women assigned placebo, 11.9 among those assigned TDF (incidence difference 1.9, 95% confidence interval [CI] −1.1–4.9, p=0.22 versus placebo), and 8.8 among those assigned TDF-FTC (incidence difference −1.3, 95% CI −4.1–1.5, p=0.39 versus placebo). Prior to discontinuation of the placebo treatment group in July 2011, the occurrence of pregnancy loss (96 of 288 pregnancies), was 42.5% for women receiving TDF-FTC compared with 32.3% for those receiving placebo (difference for TDF-FTC versus placebo 10.2%, 95% CI −5.3–25.7, p=0.16) and was 27.7% for those receiving TDF alone (difference versus placebo −4.6%, 95% CI −18.1–8.9, p=0.46). After July 2011, the frequency of pregnancy loss (52 of 143 pregnancies) was 37.5% for TDF-FTC and 36.7% for TDF alone (difference 0.8%, 95% CI −16.8–18.5, p=0.92). Preterm birth and congenital anomalies did not differ significantly for those who received PrEP versus placebo. Infants born to women randomized to PrEP had growth throughout the first year of life not statistically different than placebo and with point estimates that did not suggest growth restriction.
Conclusions and Relevance
Among HIV serodiscordant heterosexual African couples, differences in pregnancy incidence, birth outcomes, and infant growth were not statistically different for women receiving PrEP with TDF alone or combination TDF-FTC compared to placebo at the time of conception. Given that PrEP was discontinued when pregnancy was detected and that confidence intervals for the birth outcomes were wide, definitive statements about safety of PrEP in the periconception period cannot be made. These results should be discussed with HIV uninfected women receiving PrEP who are considering becoming pregnant. (ClinicalTrials.gov number, NCT00557245)
doi:10.1001/jama.2014.8735
PMCID: PMC4362516  PMID: 25038355
pre-exposure prophylaxis; HIV; pregnancy
24.  Frequency of False Positive Rapid HIV Serologic Tests in African Men and Women Receiving PrEP for HIV Prevention: Implications for Programmatic Roll-Out of Biomedical Interventions 
PLoS ONE  2015;10(4):e0123005.
Background
Rapid HIV assays are the mainstay of HIV testing globally. Delivery of effective biomedical HIV prevention strategies such as antiretroviral pre-exposure prophylaxis (PrEP) requires periodic HIV testing. Because rapid tests have high (>95%) but imperfect specificity, they are expected to generate some false positive results.
Methods
We assessed the frequency of true and false positive rapid results in the Partners PrEP Study, a randomized, placebo-controlled trial of PrEP. HIV testing was performed monthly using 2 rapid tests done in parallel with HIV enzyme immunoassay (EIA) confirmation following all positive rapid tests.
Results
A total of 99,009 monthly HIV tests were performed; 98,743 (99.7%) were dual-rapid HIV negative. Of the 266 visits with ≥1 positive rapid result, 99 (37.2%) had confirmatory positive EIA results (true positives), 155 (58.3%) had negative EIA results (false positives), and 12 (4.5%) had discordant EIA results. In the active PrEP arms, over two-thirds of visits with positive rapid test results were false positive results (69.2%, 110 of 159), although false positive results occurred at <1% (110/65,945) of total visits.
Conclusions
When HIV prevalence or incidence is low due to effective HIV prevention interventions, rapid HIV tests result in a high number of false relative to true positive results, although the absolute number of false results will be low. Program roll-out for effective interventions should plan for quality assurance of HIV testing, mechanisms for confirmatory HIV testing, and counseling strategies for persons with positive rapid test results.
doi:10.1371/journal.pone.0123005
PMCID: PMC4401675  PMID: 25885664
25.  HIV-1 subtype C is not associated with higher risk of heterosexual HIV-1 transmission: a multinational study among African HIV-1 serodiscordant couples 
AIDS (London, England)  2014;28(2):235-243.
Background
HIV-1 subtype C has emerged as the most prevalent strain of HIV-1 worldwide, leading to speculation that subtype C may be more transmissible than other subtypes. We compared the risk of HIV-1 transmission for subtype C versus non-C subtypes (A, D, G and recombinant forms) among heterosexual African HIV-1 serodiscordant couples.
Methods
We conducted a nested case-control analysis using data from two prospective cohort studies of heterosexual HIV-1 serodiscordant couples from 6 countries in eastern and southern Africa. Cases (N=121) included incident HIV-1 transmissions that were established as linked within the serodiscordant partnership by viral sequencing; controls (N=501) were non-transmitting HIV-1 infected partners. Subtype was determined for partial env and gag genes. Multiple logistic regression controlled for age and gender of the HIV-1 infected partner and self-reported unprotected sex. Plasma and genital HIV-1 RNA concentrations were compared between subtype C and non-C subtypes using generalized estimating equations.
Results
HIV-1 subtype C was not associated with increased risk of HIV-1 transmission compared to non-C subtypes: env adjusted odds ratio (adjOR) 1.14 (95% confidence interval [CI] 0.74–1.75, p=0.6) and gag adjOR 0.98 (95% CI 0.63–1.52, p=0.9). Plasma and genital HIV-1 RNA levels did not differ significantly for subtype C versus non-C.
Conclusion
In a geographically diverse population of heterosexual African HIV-1 serodiscordant couples, subtype C was not associated with greater risk of HIV-1 transmission compared to non-C subtypes, arguing against the hypothesis that subtype C is more transmissible compared to other common subtypes.
doi:10.1097/QAD.0000000000000024
PMCID: PMC4090091  PMID: 24413311
HIV-1 subtype; transmission; serodiscordant couples; Africa

Results 1-25 (91)