Women's motivations for participating in the dapivirine vaginal ring open label extension study.

Open-Label Extension (OLE) studies are important in the drug development process and are used to further support the licensing applications and regulatory approvals of products. We aimed to understand why women chose to join the HOPE OLE study - where women were offered the dapivirine vaginal ring after two pivotal trials were completed - through data collected from individual in-depth interviews. Ten women at each of the six HOPE research sites in Lilongwe, Malawi; Durban (2 sites) and Johannesburg, South Africa; Kampala, Uganda; and Chitungwiza, Zimbabwe, were enrolled (n = 60). Access to an effective user-initiated HIV prevention product was one of the main reasons women joined HOPE. Although many participants worried that their male partners might expose them to HIV, they chose to remain in their relationships and avoid conflict or confrontation with their partners by discreetly using the ring to protect themselves. Other reasons for joining were quality healthcare, reimbursement and altruism. Researchers should better understand social and personal motivators behind research participation in order to recognize community sociocultural norms and its influences on product acceptability and adherence challenges.

Acceptability of the dapivirine vaginal ring for HIV-1 prevention among women reporting engagement in transactional sex.

We assessed if acceptability of the dapivirine vaginal ring for HIV prevention differed among the subgroup of women who reported engaging in transactional sex prior to enrollment in MTN-020/ASPIRE (phase III trial in Malawi, South Africa, Uganda, and Zimbabwe, 2012-2015; n = 2629). Transactional sex was defined as receipt of money, goods, gifts, drugs, or shelter in exchange for sex in the past year. Dimensions of acceptability included: ease of use and physical sensation in situ, impacts on sex, partner's opinion, and likelihood of future use. We used Poisson regression models with robust standard errors to compare risk of acceptability challenges by baseline history of transactional sex. At product discontinuation, women exchanging sex found the ring comfortable (90%), easy to insert (92%) and nearly all (96%) were likely to use the ring in the future. Women who had exchanged sex were more likely to report feeling the ring during sex (ARR 1.43, 95% CI: 1.09, 1.89; p = 0.01) and slightly more likely to mind wearing the ring during menses (ARR 1.22, 95% CI: 1.01, 1,46; p = 0.04) and during sex (ARR 1.22, 95% CI: 1.02, 1.45; p = 0.03). Messaging and counseling should include enhanced support for use during sex and menses to support optimal use.

Experience with Contraceptive Dosage Forms and Interest in Novel PrEP Technologies in Women.

New pre-exposure prophylaxis (PrEP) strategies tailored to the needs and expectations of individuals at risk of HIV acquisition are needed. In the CAPRISA 082 prospective cohort study in KwaZulu-Natal, South Africa, sexually active women aged 18 to 30 reported, through interviewer-administered questionnaires, on their prior contraceptive experience and interest in both approved and potential future PrEP dosage forms (oral PrEP, long-acting injectable PrEP, and PrEP implants) between March 2016 and February 2018. Univariable and multivariable Poisson regression models with robust standard errors were used to detect associations between women's prior and current contraceptive use and interest in PrEP options. Of 425 women enrolled, 381 (89.6%) had used at least one modern female contraceptive method previously, with injectable depot medroxyprogesterone acetate (DMPA) being used by 79.8% (n = 339). Women were more likely to show interest in a future PrEP implant if they were currently using (aRR 2.1, CI 1.43-3.07, p = 0.0001) or had ever used (aRR 1.65, CI 1.14-2.40, p = 0.0087) a contraceptive implant, and were more likely to choose an implant as their first choice method than the implant-naïve (current users aRR 3.2, CI 1.79-5.73, p < 0.0001; "ever" users aRR 2.12, CI 1.16-3.86, p = 0.0142). Women were more interested in injectable PrEP if they had used injectable contraceptives (current users aRR 1.24, CI 1.06-1.46, p = 0.0088; "ever" users aRR 1.72, CI 1.20-2.48, p = 0.0033); and were more interested in oral PrEP if they had ever used oral contraceptives (aRR 1.3, CI 1.06-1.59, p = 0.0114). This apparent relationship between women's contraceptive experience and their interest in novel forms of PrEP in an equivalent dosage form may play a future role in strengthening HIV prevention efforts in women at high risk of HIV acquisition.

Correlates of Dapivirine Vaginal Ring Acceptance among Women Participating in an Open Label Extension Trial.

MTN-025/HOPE was an open-label trial of the dapivirine vaginal ring conducted in four African countries between 2016 and 2018. Women were first offered one ring monthly (at baseline, months 1 and 2), thereafter, transitioned to a more applicable real-world dispensation schedule, - 3 rings quarterly (at months 3, 6 and 9). Logistic regression analysis was used to assess correlates of ring acceptance at baseline and through follow-up. A total of 1456 women (median age 31 years) enrolled, 1342 (92.2%) accepted the ring at baseline and 1163 (79.9%) accepted the ring(s) at all visits. Changing ring dispensation from a monthly to a quarterly schedule had no negative effect on acceptance. Having a primary partner and him knowing about the ring being offered in HOPE, use of long-acting contraception (implants, injections, IUDs) or sterilization were associated with ring acceptance, along with prior strong intention to use the ring in the future. Efforts should consider these factors when rolling out the ring for HIV prevention.

Integrating Gender-Based Violence Screening and Support into the Research Clinic Setting: Experiences from an HIV Prevention Open-Label Extension Trial in Sub-Saharan Africa.

HIV and gender-based violence (GBV) are syndemic in sub-Saharan Africa and provision of support for participants who disclose GBV constitutes part of comprehensive care. Consequently, a process was undertaken to develop, implement, and evaluate standard operating procedures (SOPs) in MTN-025/HOPE, a study of the dapivirine vaginal ring for HIV prevention. The SOP was developed using needs assessment surveys in addition to World Health Organization (WHO) guidelines and other literature. Sites tailored and implemented the SOP through HOPE implementation. At study end, staff reported increased training 32/35 (91.43%); improved confidence (18/26; 69.23%); and improved vicarious trauma prevention onsite (17/28; 60.71%). Leadership reported increased staff competence in GBV response. Obstacles included limited referral organizations and time for follow-up, continued training needs, and cultural norms. Development and implementation of an SOP is a feasible strategy to build a GBV response to improve health systems and support sustained effective use of HIV prevention products.

Post-trial access to and use of pre-exposure prophylaxis in Durban, South Africa.

BACKGROUND: HIV endpoint-driven clinical trials increasingly provide oral pre-exposure prophylaxis (PrEP) as standard of prevention during the trial, however, among participants desiring to continue using PrEP at trial exit, little is known about post-trial PrEP access and continued use. METHODS: We conducted one-time, semi-structured, face-to-face, in-depth interviews with 13 women from Durban, South Africa, from November to December 2021. We interviewed women who initiated oral PrEP as part of the HIV prevention package during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial, elected to continue using PrEP at study exit, and were given a 3-month PrEP supply and referred to facilities for PrEP refills at the final trial visit. The interview guide probed for barriers and enablers to post-trial PrEP access, and current and future PrEP use. Interviews were audio-recorded and transcribed. Thematic analysis was facilitated using NVivo. RESULTS: Of the 13 women, six accessed oral PrEP post-trial exit, but five later discontinued. The remaining seven women did not access PrEP. Barriers to post-trial PrEP access and continued use included PrEP facilities having long queues, inconvenient operating hours, and being located far from women's homes. Some women were unable to afford transport costs to collect PrEP. Two women reported visiting their local clinics and requesting PrEP but were informed that PrEP was unavailable at the clinic. Only one woman was still using PrEP at the time of the interview. She reported that the PrEP facility was located close to her home, staff were friendly, and PrEP education and counselling were provided. Most women not on PrEP reported wanting to use it again, particularly if barriers to access could be alleviated and PrEP was easily available at facilities. CONCLUSIONS: We identified several barriers to post-trial PrEP access. Strategies to enhance PrEP access such as a reduction in waiting queues, convenient facility operating hours, and making PrEP more widely available and accessible are needed. It is also worth noting that oral PrEP access has expanded in South Africa from 2018 till now and this could improve access to PrEP for participants exiting trials who desire to continue PrEP.

Key stakeholders' perspectives on providing oral pre-exposure prophylaxis as HIV-prevention standard of care in clinical trials in South Africa.

Introduction: HIV-prevention and endpoint-driven clinical trials enrol individuals at substantial risk of HIV. Recently, these trials have provided oral pre-exposure prophylaxis (PrEP) as HIV-prevention standard of care; however, data on PrEP uptake and use during the trial and post-trial access are lacking.Methods: We conducted once-off, telephonic, in-depth interviews from August 2020 to March 2021, with 15 key stakeholders (including site directors/leaders, principal investigators and clinicians), purposively recruited from research sites across South Africa that are known to conduct HIV-prevention and endpoint-driven clinical trials. The interview guide probed for facilitators and barriers to PrEP uptake and use during the trial, and post-trial PrEP access. Interviews were audio recorded and transcribed. Coding was facilitated using NVivo and emergent themes were identified.Results: Most stakeholders reported incorporating PrEP as part of the HIV-prevention package in HIV-prevention and endpoint-driven clinical trials. Stakeholders identified multiple barriers to PrEP uptake and use, including difficulties with daily pill taking, side effects, stigma, a lack of demand creation and limited knowledge and education about PrEP in communities. Facilitators of PrEP uptake and use included demand-creation campaigns and trial staff providing quality counselling and education. Post-trial PrEP access was frequently challenging as facilities were located a considerable distance from research sites, had long queues and inconvenient operating hours.Conclusions: Strategies to address barriers to PrEP uptake and use during trials and post-trial access, such as PrEP demand creation, education and counselling, addressing stigma, support for daily pill-taking and increased post-trial access, are urgently needed.

Genital Immune Cell Activation and Tenofovir Gel Efficacy: A Case-Control Study.

Genital inflammation (GI) undermines topical human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) efficacy through unknown mechanisms. Here, associations between activated endocervical CD4 + T-cell numbers and higher deoxyadenosine triphosphate (dATP) concentrations suggest that competition for intracellular metabolites within HIV target cells may reduce the efficacy of antiretroviral-based PrEP in women with GI.

Daily Oral Pre-exposure Prophylaxis (PrEP) Continuation Among Women from Durban, South Africa, Who Initiated PrEP as Standard of Care for HIV Prevention in a Clinical Trial.

HIV incidence among women in Eastern and Southern Africa remains unacceptably high, highlighting the need for effective HIV prevention options, including pre-exposure prophylaxis (PrEP). The Evidence for Contraceptive Options and HIV Outcomes trial offered daily oral PrEP to participants during the latter part of the clinical trial as an additional HIV prevention choice. We explored daily oral PrEP continuation at trial exit among women enrolled from Durban, South Africa who initiated oral PrEP at the trial site. Of the 132 women initiating oral PrEP, 87% reported continuation of oral PrEP at month 1, 80% at month 3, and 75% continued using oral PrEP at their final trial visit and were referred to off-site facilities for ongoing oral PrEP access. The median duration of oral PrEP use in trial participants who used oral PrEP was 91 days (IQR 87 to 142 days). Women who disclosed their oral PrEP use to someone had increased odds of continuing oral PrEP at trial exit. Women who reported > 1 sex partner and those who felt they would probably or definitely get infected with HIV had reduced odds of continuing oral PrEP at trial exit. Of those discontinuing oral PrEP (n = 32), > 50% discontinued within the first month, and the most common reason for discontinuation was reporting side effects. The high rates of oral PrEP continuation in our study are encouraging and our findings can be utilized by other clinical trials providing oral PrEP as standard of care for HIV prevention and by oral PrEP implementation programmes.

Ring-ing in the Future: Participant and Male Partner Perspectives Regarding Future Use of the Dapivirine Vaginal Ring for HIV Prevention.

Women account for a disproportionate percentage of new HIV infections in sub-Saharan Africa indicating a need for female-initiated HIV prevention options congruent with their lifestyles. The dapivirine vaginal ring for HIV prevention is one such option. We explored the interest of women, who used this ring during the Microbicide Trials Network's ASPIRE and HOPE studies, in using the ring post-licensure and what they perceived as important considerations for future use. We also explored perspectives of HOPE participants' male partners on their involvement in their partners' future ring use. Women appeared keen to use the ring in the future and expressed desires for easy access, support for both ongoing and new users and intense community engagement. In parallel, male partners indicated high levels of interest in supporting their partners' ring use and being involved in ring use decision making. These data offer important insights for ring rollout planning and engagement activities.

Does the Ring Work? Perceptions and Understanding of the Efficacy of a Dapivirine Vaginal Ring for HIV Prevention Amongst Women in a Placebo-Controlled Trial.

As demonstrated by the Phase III clinical trial, MTN-020/ASPIRE, the monthly dapivirine vaginal ring is well tolerated and reduces the risk of HIV-1 as a woman-initiated prevention option. This analysis uses data from the follow-on MTN-032/Assessment of ASPIRE and HOPE Adherence (AHA) qualitative study to understand how perceptions (or misperceptions) of ring efficacy may have influenced behavior during ASPIRE, and affected intention to use the ring in future ring projects, specifically HOPE, the planned open-label extension study. Single in-depth interviews (n = 98) and 12 focus group discussions (n = 89) were conducted with women at seven sites in Malawi, South Africa, Uganda and Zimbabwe. Eligibility included participation in the ASPIRE active arm, and ring use for ≥ 3 months or at least 1 month if seroconversion occurred. Interviews were audio-recorded, transcribed into English, coded in Dedoose and thematically analyzed. Demographic and behavioral questionnaire data were summarized in Stata. Most AHA participants perceived the ring to be effective, and described simply trusting it or having confidence in it because they, or other participants in risky situations, remained HIV-uninfected. Participants described ring efficacy after receiving ASPIRE results as a binary assessment: the ring worked or not. Many did not remember exact efficacy percentages because of lack of comprehension or memory but recalled key details about age differences. The majority expressed interest in future ring use. There is a need to investigate improved ways of explaining placebo-controlled trials and efficacy to women in Sub-Saharan Africa. Now that ring efficacy, is known, these benefits must be well communicated, and understood by end-users and key stakeholders. Engagement with end-users to construct effective messages and to develop tools to measure understanding of partial efficacy will be essential.

Exploring the Use of Oral Pre-exposure Prophylaxis (PrEP) Among Women from Durban, South Africa as Part of the HIV Prevention Package in a Clinical Trial.

HIV endpoint-driven clinical trials in Africa enroll women who are at heightened risk of acquiring HIV. In 2017, the South African Medical Research Council recommended the provision of oral pre-exposure prophylaxis (PrEP) in HIV prevention trials, at which time the Evidence for Contraceptive Options and HIV Outcomes trial was ongoing and began to provide PrEP on-site at some trial sites. We interviewed 132 women who initiated PrEP on-site at the Durban, South Africa trial site to explore PrEP use, and conducted phone-based interviews 4-6 months post-trial exit to explore post-trial PrEP access. PrEP uptake was high (42.6%). Among women initiating PrEP on-site, 87.9% felt at risk of acquiring HIV. Most women (> 90%) heard of PrEP for the first time from study staff and three-quarters who initiated PrEP on-site continued at trial-exit. PrEP use declined post-trial exit with more than 50% of women discontinuing PrEP, and barriers relating to access emerged.

Men's Sexual Experiences with the Dapivirine Vaginal Ring in Malawi, South Africa, Uganda and Zimbabwe.

The dapivirine vaginal ring has been well-tolerated and shown to prevent HIV in clinical trials. The ring is female initiated, yet endorsement for use is sought from male partners in many relationships. In clinical studies, participants have expressed worries about men detecting rings during vaginal sex, which introduces concerns about product use disclosure, sexual pleasure, penile harm, inter-partner dynamics, and ring removals. This study reports African men's firsthand sexual experiences with the ring. Qualitative data were captured through 11 focus group discussions and one in-depth interview with 54 male partners of ring-users at six research sites in Malawi, South Africa, Uganda and Zimbabwe. Following a semi-structured guide, and using demonstration rings, vulva and penis models, men were asked to discuss the ring's impact on sex and views on male engagement and ring use. Interviews were facilitated by local male social scientists, audio-recorded, translated into English, and analyzed thematically. 22 (41%) of the male partners reported feeling the ring during sex, often attributed to perceived incorrect insertion. Many men described the ring as "scratching" the tip of their penises, and sensations of "prodding" something that "blocked" the vagina and prohibited "full entry". In most cases, feelings dissipated with time or when sexual fluids increased. Less common descriptions included perceiving the vaginal texture, wetness and size as different, which increased pleasure for some, and decreased for others. Over half (59%) never noticed the ring; some attempting and failing to feel it during intercourse. A majority of men reported that the ring did not lead to changes in sexual positions, feelings, frequency or experience of sex, although some were initially afraid that the ring was a "magic snake" or "potion". Male partners expressed strong opinions that ring use was a shared prevention responsibility that men should be engaged in, especially for maintaining trust and open communication in relationships. The ring was noticed by many male partners, particularly during women's initial stages of ring use, although this led to few sexual problems or changes. Nevertheless, results suggest that risk of ring discovery should be discussed with women to mitigate any potential negative reactions or social harm. Strategies to increase male partner engagement will enhance support of this prevention method for women.

Using Emoji Stickers to Understand End-User Opinions of the Dapivirine Vaginal Ring for HIV Prevention.

Globally, HIV affects women disproportionally to men, particularly in sub-Saharan Africa. While the monthly dapivirine vaginal ring (VR) is a promising female-initiated HIV prevention method, it is important to understand how well the ring is liked. With former participants of HOPE, an open-label extension trial of the ring, we used emoji stickers and a worksheet to explore female end-user's acceptability of and opinions about the VR. We aimed to understand these participants' opinions about the VR, and how they had changed over time, particularly in the context of known efficacy of the dapivirine VR. Most participants easily understood the exercise and how to use the emoji stickers, with a few exceptions. For those who had trouble understanding how to use the emoji, interviewer support and encouragement helped them to understand and continue with the exercise. Emoji interpretation varied widely with participants using the same emoji to express divergent opinions. Using the emoji stickers, participants expressed mostly positive opinions of the vaginal ring for HIV prevention, with some lingering concerns about the product's partial effectiveness. This paper contributes to the literature supporting the assertion that the dapivirine VR for HIV prevention is acceptable to women, and that acceptability increases with time and proper education. This analysis also provides evidence that emoji visual tools can enhance understanding of acceptability of an intervention when used in qualitative research.

Correlates of Adherence to the Dapivirine Vaginal Ring for HIV-1 Prevention.

Understanding characteristics associated with adherence to pre-exposure prophylaxis (PrEP) methods for HIV-1 prevention may assist with optimizing implementation efforts. The dapivirine vaginal ring is a novel topical PrEP delivery method. Using data from a randomized, double-blind, placebo-controlled, phase III trial of the dapivirine vaginal ring conducted in four African countries, generalized estimating equation models were used to evaluate correlates of ring adherence. Two levels of quarterly dapivirine blood plasma, and dapivirine released from returned rings defined measures of adherence for recent and cumulative use, respectively. Time on study, calendar time, primary partner knowledge that the participant was taking part in the study, and use of long-acting contraceptive methods were associated with ring adherence whereas younger age, ring worries, condom use, episodes of menstrual bleeding and vaginal washing were associated with non-adherence. These findings may be useful for recruitment into future clinical studies and dapivirine ring implementation efforts.

The Influence of Perceived Dapivirine Vaginal Ring Effectiveness on Social Disclosure and Ring Adherence.

We analyzed data from 1428 users of the dapivirine vaginal ring, who participated in the MTN-020/ASPIRE phase III trial and subsequent open-label extension MTN-025/HOPE trial, to examine relationships between perceived ring protection, social disclosures, and self-reported ring adherence. In HOPE, 77% perceived the ring to be highly effective, and this view was associated with speaking: (a) to a greater number of people about the study, (b) with other participants, (c) to more people who were in favor of the ring, and (d) to more people whose opinions were valued. Reported adherence was not directly associated with perceived protection but was associated with disclosing to someone who was in favor of the ring. These findings suggest the importance of women's internalized ideas about the protective benefits of the DVR in sharing information about the ring and the importance of social support on adherence.

Impact and experience of participant engagement activities in supporting dapivirine ring use among participants enrolled in the phase III MTN-020/ASPIRE study.

BACKGROUND: Low adherence to investigational products can negatively impact study outcomes, limiting the ability to demonstrate efficacy. To continue advancing potential new HIV prevention technologies, efforts are needed to improve adherence among study participants. In MTN-020/ASPIRE, a phase III randomized, double-blind, placebo-controlled study of the dapivirine vaginal ring carried out across 15 sites in sub-Saharan Africa, a multifaceted approach to adherence support was implemented, including a strong focus on participant engagement activities (PEAs). In this manuscript, we describe PEAs and participant attendance, and analyze the potential impact of PEAs on ring use. METHODS: All sites implemented PEAs and submitted activity and attendance reports to the study management team throughout the study. Participant demographics were collected via case report forms. Residual dapivirine remaining in the last ring returned by each participant was used to estimate drug released from the ring, which was then adjusted for time participants had the ring to calculate probable use categorized into three levels (low/intermittent/high). Product use was connected to PEA attendance using participant identification numbers. We used multivariate Poisson regression with robust standard errors to explore differences in ring use between PEA attendance groups and reviewed qualitative reports for illustrative quotes highlighting participant experiences with PEAs. RESULTS: 2312 of 2629 study participants attended at least one of 389 PEAs conducted across sites. Participant country and partner knowledge of study participation were most strongly associated with PEA attendance (p < 0.005) with age, education, and income status also associated with event attendance (p < 0.05). When controlling for these variables, participants who attended at least one event were more likely to return a last ring showing at least some use (RR = 1.40) than those who never attended an event. There was a stronger correlation between a last returned ring showing use and participant attendance at multiple events (RR = 1.52). CONCLUSIONS: Our analysis supports the growing body of work illustrating the importance of meaningfully engaging research participants to achieve study success and aligns with other analyses of adherence support efforts during ASPIRE. While causation between PEA attendance and product use cannot be established, residual drug levels in returned rings strongly correlated with participant attendance at PEAs, and the benefits of incorporating PEAs should be considered when designing future studies of investigational products.

Importance of early identification of PrEP breakthrough infections in a generalized HIV epidemic: a case report from a PrEP demonstration project in South Africa.

BACKGROUND: The World Health Organisation recommends the use of tenofovir-containing pre-exposure prophylaxis (PrEP) as an additional Human Immunodeficiency Virus (HIV) prevention choice for men and women at substantial risk of HIV infection. PrEP could fill an important HIV prevention gap, especially for sexually active young women who are limited in their ability to negotiate mutual monogamy or condom use. As PrEP is scaled up in high HIV incidence settings, it is crucial to consider the importance of early identification of HIV infection during PrEP use, to allow for rapid discontinuation of PrEP to reduce the risk of antiretroviral (ARV) resistance. The purpose of this case study is to provide this critical evidence. CASE PRESENTATION: This report describes a 20-year-old woman in a HIV sero-discordant relationship who initiated oral PrEP (tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC)) through a demonstration project (CAPRISA 084) in October 2017. Despite good adherence throughout her PrEP use, she tested HIV antibody positive at month nine of study participation. Retrospective testing showed increasing HIV viral load over time, and retrospective use of fourth-generation rapid HIV tests showed HIV detection (positive antigen/antibody) at month one. Sequencing confirmed a dominant wild type at month one with dual therapy resistance patterns emerging by month three (M184V and K65R mutations), which is suggestive of protracted PrEP use during an undetected HIV infection. The participant was referred to infectious diseases for further management of her HIV infection and was initiated on a first line, tenofovir-sparing regimen. At the time of this report (January 2020), the participant had been on ARV- therapy (ART) for 13 months and had no signs of either clinical, immunologic or virologic failure. CONCLUSIONS: This case report highlights the importance of appropriate HIV screening during wider oral PrEP scale-up in high HIV incidence settings to circumvent the consequences of prolonged dual therapy in an undiagnosed HIV infection and in turn prevent ARV resistance.

Tenofovir Gel for the Prevention of Herpes Simplex Virus Type 2 Infection.

BACKGROUND: Globally, herpes simplex virus type 2 (HSV-2) infection is the most common cause of genital ulcer disease. Effective prevention strategies for HSV-2 infection are needed to achieve the goals of the World Health Organization global strategy for the prevention and control of sexually transmitted infections. METHODS: We assessed the effectiveness of pericoital tenofovir gel, an antiviral microbicide, in preventing HSV-2 acquisition in a subgroup of 422 HSV-2-negative women enrolled in the Centre for the AIDS Programme of Research in South Africa (CAPRISA) 004 study, a double-blind, randomized, placebo-controlled trial. Incident HSV-2 cases were identified by evidence of seroconversion on an HSV-2 IgG enzyme-linked immunosorbent assay between study enrollment and exit. A confirmatory analysis was performed by Western blot testing. RESULTS: The HSV-2 incidence rate was 10.2 cases per 100 person-years (95% confidence interval [CI], 6.8 to 14.7) among 202 women assigned to tenofovir gel, as compared with 21.0 cases per 100 person-years (95% CI, 16.0 to 27.2) among 222 women assigned to placebo gel (incidence rate ratio, 0.49; 95% CI, 0.30 to 0.77; P=0.003). The HSV-2 incidence rate among the 25 women with vaginal tenofovir concentrations of 10,000 ng per milliliter or more was 5.7 cases per 100 person-years, as compared with 15.5 cases per 100 person-years among the 103 women with no detectable vaginal tenofovir (incidence rate ratio, 0.37; 95% CI, 0.04 to 1.51; P=0.14). As confirmed by Western blot testing, there were 16 HSV-2 seroconversions among women assigned to tenofovir gel as compared with 36 among those assigned to the placebo gel (incidence rate ratio, 0.45; 95% CI, 0.23 to 0.82; P=0.005). CONCLUSIONS: In this study in South Africa, pericoital application of tenofovir gel reduced HSV-2 acquisition in women. (Funded by the U.S. Agency for International Development and others; ClinicalTrials.gov number, NCT00441298.).

Cervicovaginal Inflammation Facilitates Acquisition of Less Infectious HIV Variants.

We evaluated whether genital inflammation affects the selection of the transmitted virus. Among South African women, we found that preinfection genital inflammation facilitates transmission of less infectious human immunodeficiency virus, but highly infectious viruses are able to establish infection regardless of inflammation status. This suggests that viral phenotype can influence transmission risk.