Ariane van der Straten

Tenofovir-Based Preexposure Prophylaxis for HIV Infection among African Women

BACKGROUND Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection. METHODS We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. RESULTS Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. In the modified intention-to-treat analysis, the effectiveness was -49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), -4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P=0.004). We observed no significant differences in the frequencies of other adverse events. CONCLUSIONS None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low. (Funded by the National Institutes of Health; VOICE ClinicalTrials.gov number, NCT00705679.).

Diaphragm and lubricant gel for prevention of HIV acquisition in southern African women: a randomised controlled trial.

BACKGROUND Female-controlled methods of HIV prevention are urgently needed. We assessed the effect of provision of latex diaphragm, lubricant gel, and condoms (intervention), compared with condoms alone (control) on HIV seroincidence in women in South Africa and Zimbabwe. METHODS We did an open-label, randomised controlled trial in HIV-negative, sexually active women recruited from clinics and community-based organisations, who were followed up quarterly for 12-24 months (median 21 months). All participants received an HIV prevention package consisting of pre-test and post-test counselling about HIV and sexually transmitted infections, testing, treatment of curable sexually transmitted infections, and intensive risk-reduction counselling. The primary outcome was incident HIV infection. This study is registered with ClinicalTrials.gov, number NCT00121459. FINDINGS Overall HIV incidence was 4.0% per 100 woman-years: 4.1% in the intervention group (n=2472) and 3.9% in the control group (n=2476), corresponding to a relative hazard of 1.05 (95% CI 0.84-1.32, intention-to-treat analysis). The proportion of women using condoms was significantly lower in the intervention than in the control group (54%vs 85% of visits, p<0.0001). The proportions of participants who reported adverse events (60% [1523] vs 61% [1529]) and serious adverse events (5% [130] vs 4% [101]) were similar between the two groups. INTERPRETATION We observed no added protective benefit against HIV infection when the diaphragm and lubricant gel were provided in addition to condoms and a comprehensive HIV prevention package. Our observation that lower condom use in women provided with diaphragms did not result in increased infection merits further research. Although the intervention seemed safe, our findings do not support addition of the diaphragm to current HIV prevention strategies.

Unraveling the divergent results of pre-exposure prophylaxis trials for HIV prevention.

Although the balance of recent evidence supports the efficacy of antiretroviral (ARV)-based pre-exposure prophylaxis (PrEP) against HIV-1 infection, recent negative trial results are perplexing. Of seven trials with available HIV endpoints, three different products have been tested: tenofovir 1% vaginal gel, oral tenofovir disoproxil fumarate (TDF) tablets, and TDF/emtricitabine tablets. Six of these trials were conducted exclusively in sub-Saharan Africa; all found the products to be well tolerated, and four demonstrated effectiveness. Furthermore, the HIV Prevention Trial Network (HPTN) 052 trial recently confirmed that antiretroviral treatment leads to 96% reduction in transmission to HIV-negative partners in HIV-serodiscordant couples. These results, along with human and animal data, provide substantial evidence for the efficacy of antiretroviral-based HIV prevention. Yet assessment of oral TDF/emtricitabine in the FEM-PrEP study and of oral and vaginal tenofovir in the Microbicide Trial Network (MTN)-003 trial (VOICE) was stopped for futility. How do we make sense of these discrepant results? We believe that adherence is a key factor, although it cannot be the only factor. Expanding upon a recent editorial in the Lancet, we discuss the impact of suboptimal product adherence on PrEP efficacy in the context of variable drug concentration at the exposure site, integrity of the vaginal epithelium, and the role of acute infection.

Couple communication, sexual coercion and HIV risk reduction in Kigali, Rwanda.

ObjectivesTo describe sexual interaction, and HIV-related communication in Rwandan couples, and to examine their relationship to HIV testing, and condom use. Study designCross-sectional survey of a longitudinal cohort. MethodsIn 1988, women recruited for an epidemiological study of HIV, and interested male partners, received confidential HIV testing, and counseling. Two years after enrollment, 876 women reporting one steady partner in the past year completed a questionnaire addressing sexual, and HIV-related communication, sexual motivation, and violence in the partnership. ResultsMen control sexual decision making, and coercive sex, and violence between partners is not uncommon. HIV-positive women were more likely to report coercive sex, and less likely to have discussed their test results with their partner. Women with HIV-positive partners were more likely to report being physically abused. Condom use was more common if the man had been previously tested, and if women reported discussing or negotiating condom use. HIV-negative women with untested or seronegative partners were the least likely to use condoms or to discuss or attempt to negotiate condom use. ConclusionsParticipation of the male partner is crucial for successful HIV risk reduction in couples. HIV testing, and counseling of couples has beneficial long term effects on condom use, and HIV-related communication. Couple communication is associated with condom use, but only when the discussion is specific (sexually transmitted disease risks, and using condoms). Seronegative women with untested partners are at increased risk for HIV as they are the least likely to discuss or attempt to negotiate condom use.

Sexual Coercion, Physical Violence, and HIV Infection Among Women in Steady Relationships in Kigali, Rwanda

The relationship between sexual coercion, physical violence, and HIV serostatus was examined at 24 months of follow-up in a cohort of 921 women with steady partners in Kigali, Rwanda. One third of the women reported sexual coercion, and physical violence perpetrated by their male partner was reported by 21%. Sexual coercion was associated with women being HIV-positive, and physical violence was associated with their partner testing HIV-positive. Independent predictors of sexual coercion included the woman being HIV-positive, refusal to have sex, condom negotiation, financial inequality, and male partners alcohol use. Independent predictors of physical violence were similar to predictors of sexual coercion. Sexual coercion and physical violence are public health issues relevant to HIV prevention, and are associated with financial and sexual gender power differentials. Results suggest the need to expand HIV behavioral interventions to address womens economic and cultural realities.

Hormonal Contraception and the Risk of HIV Acquisition: An Individual Participant Data Meta-analysis:

In a meta-analysis of individual participant data, Charles Morrison and colleagues explore the association between hormonal contraception use and risk of HIV infection in sub-Saharan Africa.

Sexual risk behaviors among heterosexual HIV serodiscordant couples in the era of post-exposure prevention and viral suppressive therapy.

ObjectivesTo describe awareness and use of antiretroviral treatments, viral load monitoring, and post-exposure prevention; to assess changing concerns about HIV transmission; and to examine the effect of these advances on sexual behavior in HIV-serodiscordant heterosexual couples. MethodsCross-sectional analysis of a baseline sample of 104 couples (n = 208 individuals) from the California Partners Study II, an intervention trial for HIV-serodiscordant couples in California. Questions on sexual practices, viral load testing, HIV treatment, post-exposure prevention, and their effect on sexual behaviors, risk taking and transmission concerns were measured at intake. ResultsOver two-thirds of couple members surveyed reported unprotected sex with their partner in the past 6 months. Among seropositive respondents, 37% were taking protease inhibitor therapy, 92% had undergone viral load testing, and of those, 40% said it had ben undetectable at their most recent test. Most respondents, regardless of serostatus, said that viral load testing and awareness of post-exposure prevention had no effect on their condom use. In addition, perceiving that their partner had an undetectable viral load was associated with having protected sex among seronegative subjects (P < 0.05). Seropositive respondent taking protease inhibitors were 2.4 times less likely to report unprotected sex compared with those not taking protease inhibitors (P = 0.05). However, up to 33% of seropositive and 40% of seronegative respondents acknowledged decreased transmission concerns in the light of the new HIV treatments. In comparison with their seropositive partners, seronegative individuals were more likely to acknowledge increased risk taking and decreased HIV transmission concerns (P < 0.05). ConclusionsNew medical advances were not associated with unprotected sex in HIV-serodiscordant couples. However, new treatment options may decrease concerns about HIV transmission, particularly among seronegative partners. Providers should discuss the effect of antiretroviral treatments on sexual transmission risk with their patients. The inclusion of seronegative partners in counseling interventions may decrease risk taking in serodiscordant couples.

Sexual practices of HIV discordant and concordant couples in Rwanda: effects of a testing and counselling programme for men:

As part of a longitudinal investigation, the husbands and cohabiting male partners of 684 Rwandan women were recruited to participate in an HIV testing and counselling programme. All of the women and 256 of the men (37%) had previously received standard testing and generic counselling services. In this project, all of the men participated in an extensive, male-focused counselling programme. This included 428 men who were receiving testing and counselling for the first time. Interview responses indicated that rates of condom use during sexual intercourse increased dramatically at the one-year follow-up assessment for the serodiscordant couples. This effect was especially strong for couples whose male partners were receiving testing and counselling for the first time. Rates of condom use also increased substantially in seroconcordant HIV-positive couples whose partners had both been tested previously. Women in couples with at least one seropositive partner reported lower rates of coercive sex by their male partners after they completed the counselling programme. Male-focused and couple-focused testing and counselling programmes appear to be effective in reducing risky sexual behaviours in heterosexual couples, even if one or both partners have received testing and counselling services previously.

Biomarker Validation of Reports of Recent Sexual Activity: Results of a Randomized Controlled Study in Zimbabwe

Challenges in the accurate measurement of sexual behavior in human immunodeficiency virus (HIV) prevention research are well documented and have prompted discussion about whether valid assessments are possible. Audio computer-assisted self-interviewing (ACASI) may increase the validity of self-reported behavioral data. In 2006-2007, Zimbabwean women participated in a randomized, cross-sectional study that compared self-reports of recent vaginal sex and condom use collected through ACASI or face-to-face interviewing (FTFI) with a validated objective biomarker of recent semen exposure (prostate-specific antigen (PSA) levels). Of 910 study participants, 196 (21.5%) tested positive for PSA, an indication of semen exposure during the previous 2 days. Of these 196 participants, 23 (11.7%) reported no sex in the previous 2 days, with no difference in reported sexual activity between interview modes (12.5% ACASI vs. 10.9% FTFI; Fishers exact test: P = 0.72). In addition, 71 PSA-positive participants (36.2%) reported condom-protected vaginal sex only; their reports also indicated no difference between interview modes (33.7% ACASI vs. 39.1% FTFI; P = 0.26). Only 52% of PSA-positive participants reported unprotected sex during the previous 2 days. Self-report was a poor predictor of recent sexual activity and condom use in this study, regardless of interview mode, providing evidence that such data should be interpreted cautiously.

Intravaginal Practices, Bacterial Vaginosis, and HIV Infection in Women: Individual Participant Data Meta-analysis

Pooling of data from 14,874 women in an individual participant data meta-analysis by Nicola Low and colleagues reveals that some intravaginal practices increase the risk of HIV acquisition.