HIV Incidence Among Pregnant and Nonpregnant Women in the FACTS-001 Trial: Implications for HIV Prevention, Especially PrEP Use.

BACKGROUND: During pregnancy and postpartum period, the sexual behaviors of women and their partners change in ways that may either increase or reduce HIV risks. Pregnant women are a priority population for reducing both horizontal and vertical HIV transmission. SETTING: Nine sites in 4 South African provinces. METHODS: Women aged 18-30 years were randomized to receive pericoital tenofovir 1% gel or placebo gel and required to use reliable modern contraception. We compared HIV incidence in women before, during, and after pregnancy and used multivariate Cox Proportional hazards models to compare HIV incidence by pregnancy status. RESULTS: Rates of pregnancy were 7.1 per 100 woman-years (95% confidence interval [CI]: 6.3 to 8.1) and highest in those who reported oral contraceptive use (25.1 per 100 woman-years; adjusted hazard ratio 22.97 higher than other women; 95% CI: 5.0 to 105.4) or had 2 children. Birth outcomes were similar between trial arms, with 59.8% having full-term live births. No difference was detected in incident HIV during pregnancy compared with nonpregnant women (2.1 versus 4.3%; hazard ratio = 0.56, 95% CI: 0.14 to 2.26). Sexual activity was low in pregnancy and the early postpartum period, as was consistent condom use. CONCLUSIONS: Pregnancy incidence was high despite trial participation being contingent on contraceptive use. We found no evidence that rates of HIV acquisition were elevated in pregnancy when compared with those in nonpregnant women. Risks from reductions in condom use may be offset by reduced sexual activity. Nevertheless, high HIV incidence in both pregnant and nonpregnant women supports consideration of introducing antiretroviral-containing pre-exposure prophylaxis for pregnant and nonpregnant women in high HIV prevalence settings.

Tenofovir 1% vaginal gel for prevention of HIV-1 infection in women in South Africa (FACTS-001): a phase 3, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Young women in southern Africa have substantial risk of HIV acquisition. Female-controlled biomedical interventions are needed to mitigate this risk. We aimed to assess the safety and efficacy of a pericoitally applied tenofovir 1% gel. METHODS: We did a phase 3, double-blind, randomised, placebo-controlled trial at nine community-based clinical trial sites in South Africa to evaluate the safety and efficacy of tenofovir 1% gel. Sexually active women who were HIV negative and aged 18-30 years were enrolled. Participants were randomly assigned (1:1) using sequential participant numbers to either tenofovir 1% gel or a placebo gel (one dose within 12 h before sex and one dose within 12 h after sex [BAT-24 regimen]), using dynamic permuted block sizes of 8 and 16 within each site. Women received monthly HIV-1 testing, risk reduction support, physical examinations, and product dispensing for up to 27 months. The primary efficacy outcome was incident HIV infection and the primary safety outcome was occurrence of grade 2-4 adverse events, both analysed in the modified intention-to-treat population. To assess the efficacy of tenofovir gel, the cumulative probability of HIV infection was calculated for each treatment using the Kaplan-Meier method. This trial is registered with ClinicalTrials.gov, number NCT01386294. FINDINGS: From Oct 11, 2011, to Aug 29, 2014, 3844 women were screened, 2059 enrolled, and 2029 included in the primary analysis (1032 in the tenofovir group and 1027 in the placebo group); 39 (4%) in the tenofovir group and 36 (4%) in the placebo group were lost to follow-up. 123 HIV-1 infections occurred over 3036 woman-years of observation; 61 in the tenofovir group (HIV incidence 4·0 per 100 woman-years, 95% CI 3·1-5·2) and 62 in the placebo group (4·0 per 100 woman-years, 3·1-5·2; incidence rate ratio [IRR] 0·98, 95% CI 0·7-1·4). A higher incidence of grade 2 adverse events was observed in the tenofovir group than in the placebo group (IRR 1·09, 95% CI 1·0-1·2; p=0·02). The most common grade 2 or higher product-related adverse events were hypophosphataemia (n=22 for tenofovir vs n=22 for placebo), genital symptoms (n=6 for tenofovir vs n=2 for placebo), or elevated transaminases (n=2 for tenofovir vs n=2 for placebo). No product-related serious adverse events were reported, and no differences in product-related adverse events (p=0·78), grade 3 events (p=0·64), or grade 4 events (p=0·74) were observed between treatment groups. INTERPRETATION: Overall, pericoital tenofovir gel did not prevent HIV-1 acquisition in this population of young women at risk of HIV infection in South Africa. Alternate safe and effective products that are less user dependent than this product or do not require high adherence are needed. FUNDING: The US Agency for International Development (USAID), the Bill & Melinda Gates Foundation, and the South African Department of Science and Technology and Department of Health.

"It Was Not My Aim to Sleep There": The Impact of Timing and Location of Sex on Adherence to Coitally-Dependent HIV Pre-exposure Prophylaxis.

The FACTS 001 trial found that vaginal pre- and post-coital application of 1% tenofovir gel did not prevent HIV-1 infection amongst young South African women. The trial included a multi-faceted approach to adherence support and collected objective and self-reported adherence measures. Using qualitative data collected from a random sub-set of FACTS 001 participants (135 in-depth interviews at product discontinuation and 13 focus group discussions at dissemination of trial results), we explore the importance of 'place' and 'timing' in shaping acts of sexual intimacy and product adherence. Demographically, this qualitative sub-sample is similar to the trial cohort of predominantly young, unemployed women living with parents or other family members. Sexual intimacy was largely unpredictable and happened across multiple locations in which women had limited privacy, autonomy, or control over the timing of sex. This made adherence to the dosing strategy challenging. Findings may inform the development of future event-driven pre-exposure prophylaxis regimens or products.

Gender differences in prevalence and correlates of high sexual self-efficacy among adolescents in Soweto, South Africa: implications for gender-sensitive research and programming.

Sexual self-efficacy (SSE) - one's confidence in their ability to perform given sexual behaviours, has been shown to predict adolescents' HIV-prevention practices (e.g., Condom use). Few studies within sub-Saharan Africa, where HIV incidence and prevalence disproportionately affects young women, have examined gendered differences in SSE. We used multivariable logistic regression to identify correlates of high-SSE separately among adolescent men and women (aged 14-19) in Soweto, South Africa using a previously validated SSE scale (high-SSE [>3/6 items]; study-alpha = 0.75). SSE scale items assessed self-efficacy related to sexual refusal and condom use. Adolescent women were significantly more likely to report high-SSE than adolescent men (72.3% versus 49.5%; p < 0.01). High-SSE among adolescent men was associated with more positive beliefs about sexual relationships and negatively associated with probable depression. High-SSE among adolescent women was associated with increased HIV knowledge, more positive beliefs about condom use and sexual relationships, having an adult in the home, and negatively associated with being an older adolescent (16-17 versus ≤15), and ever experiencing physical violence. Differences in prevalence and correlates of SSE among adolescent men and women in South Africa highlight important areas for gender-sensitive interventions. Targeted efforts to reduce negative sexual beliefs, improve HIV knowledge and mental well-being may improve SSE and thus the uptake of HIV-prevention practices among adolescent men. For adolescent women, findings indicate programming should move beyond individual-levels determinants of behaviour to focus on improving enabling environments (e.g., Reduced violence and improved family relationships) in which sexual agency can be enacted.

Gender, Sexual Self-Efficacy and Consistent Condom Use Among Adolescents Living in the HIV Hyper-Endemic Setting of Soweto, South Africa.

Within HIV-endemic settings, few studies have examined gendered associations between sexual self-efficacy (SSE), one's confidence or perceived control over sexual behavior, and uptake of HIV prevention behaviors. Using cross-sectional survey data from 417 sexually-experienced adolescents (aged 14-19, median age = 18, 60% female) in Soweto, South Africa, we measured SSE using a 6-item scale (range:0-6) with 'high-SSE' = score > 3 (study alpha = 0.75). Gender-stratified logistic regression models assessed associations between high-SSE and lifetime consistent condom use. A higher proportion of women reported high-SSE (68.7%) than men (49.5%, p < 0.001). We observed no difference in reported consistent condom use by gender (45.5% among women, 45.8% among men; p = 0.943). In confounder models, high-SSE was associated with consistent condom use among men (aOR = 3.51, 95%CI = 1.86-6.64), but not women (aOR = 1.43, 95%CI = 0.74-2.77). Findings highlight that individual-level psychosocial factors are insufficient for understanding condom use and must be considered alongside the relational, social, and structural environments within which young women navigate their sexual lives.

Prevalence, type, and correlates of trauma exposure among adolescent men and women in Soweto, South Africa: implications for HIV prevention.

BACKGROUND: Youth trauma exposure is associated with syndemic HIV risk. We measured lifetime prevalence, type, and correlates of trauma experience by gender among adolescents living in the HIV hyper-endemic setting of Soweto, South Africa. METHODS: Using data from the Botsha Bophelo Adolescent Health Survey (BBAHS), prevalence of "ever" experiencing a traumatic event among adolescents (aged 14-19) was assessed using a modified Traumatic Event Screening Inventory-Child (TESI-C) scale (19 items, study alpha = 0.63). We assessed self-reported number of potentially traumatic events (PTEs) experienced overall and by gender. Gender-stratified multivariable logistic regression models assessed independent correlates of 'high PTE score' (≥7 PTEs). RESULTS: Overall, 767/830 (92%) participants were included (58% adolescent women). Nearly all (99.7%) reported experiencing at least one PTE. Median PTE was 7 [Q1,Q3: 5-9], with no gender differences (p = 0.19). Adolescent men reported more violent PTEs (e.g., "seen an act of violence in the community") whereas women reported more non-violent HIV/AIDS-related PTEs (e.g., "family member or someone close died of HIV/AIDS"). High PTE score was independently associated with high food insecurity among adolescent men and women (aOR = 2.63, 95%CI = 1.36-5.09; aOR = 2.57, 95%CI = 1.55-4.26, respectively). For men, high PTE score was also associated with older age (aOR = 1.40/year, 95%CI = 1.21-1.63); and recently moving to Soweto (aOR = 2.78, 95%CI = 1.14-6.76). Among women, high PTE score was associated with depression using the CES-D scale (aOR = 2.00, 95%CI = 1.31-3.03,) and inconsistent condom use vs. no sexual experience (aOR = 2.69, 95%CI = 1.66-4.37). CONCLUSION: Nearly all adolescents in this study experienced trauma, with gendered differences in PTE types and correlates, but not prevalence. Exposure to PTEs were distributed along social and gendered axes. Among adolescent women, associations with depression and inconsistent condom use suggest pathways for HIV risk. HIV prevention interventions targeting adolescents must address the syndemics of trauma and HIV through the scale-up of gender-transformative, youth-centred, trauma-informed integrated HIV and mental health services.

Predictors of parent-adolescent communication in post-apartheid South Africa: a protective factor in adolescent sexual and reproductive health.

In the HIV context, risky sexual behaviours can be reduced through effective parent-adolescent communication. This study used the Parent Adolescent Communication Scale to determine parent-adolescent communication by ethnicity and identify predictors of high parent-adolescent communication amongst South African adolescents post-apartheid. A cross-sectional interviewer-administered survey was administered to 822 adolescents from Johannesburg, South Africa. Backward stepwise multivariate regressions were performed. The sample was predominantly Black African (62%, n = 506) and female (57%, n = 469). Of the participants, 57% (n = 471) reported high parent-adolescent communication. Multivariate regression showed that gender was a significant predictor of high parent-adolescent communication (Black African OR:1.47, CI: 1.0-2.17, Indian OR: 2.67, CI: 1.05-6.77, White OR: 2.96, CI: 1.21-7.18). Female-headed households were predictors of high parent-adolescent communication amongst Black Africans (OR:1.49, CI: 1.01-2.20), but of low parent-adolescent communication amongst Whites (OR:0.36, CI: 0.15-0.89). Overall levels of parent-adolescent communication in South Africa are low. HIV prevention programmes for South African adolescents should include information and skills regarding effective parent-adolescent communication.

Adolescent experiences of HIV and sexual health communication with parents and caregivers in Soweto, South Africa.

Communication about sexual health between parents and adolescents has been shown to have a protective influence on behaviours that reduce the risk of HIV transmission. This study explored experiences of HIV and sexual health (HSH) communication between parents and/or caregivers and adolescents in an urban HIV-endemic community in Southern Africa. Adolescents (aged 14-19 years) were recruited from the Kganya Motsha Adolescent Centre and the Kliptown community between June and August 2009. Qualitative data were collected through focus group discussions (n=10 adolescents) and semi-structured interviews (n=31 adolescents). In total, 41 adolescents (56% female, 44% male, mean age=17.2) participated in the study. Adolescent participants identified emotional, physical and sociocultural barriers to initiating HSH communication with parents and caregivers including fear of verbal warnings, threats and physical assault. Adolescents also expressed a desire for mentorship around HSH communication beyond abstinence and peer-based information. Public health interventions need to support adolescents' access to bi-directional HSH information from adult mentors that address the lived realities of adolescents beyond expectations of abstinence.

Assessment of service availability and health care workers' opinions about young women's sexual and reproductive health in Soweto, South Africa.

Young women in South Africa experience high HIV and unintended pregnancy rates. Health care workers' (HCWs') opinions about sexual and reproductive health (SRH) issues impact young women's ability to access SRH services. We explored HCW opinions through interviews with a purposive sample of 29 HCWs in three primary health clinics in Soweto, South Africa and examined service availability through facility assessments. Most HCWs believed young women should not have sex before marriage and thought that young women ignore information they receive about HIV and pregnancy prevention. HCWs acknowledged outside factors influencing young women's ability to protect themselves. Most thought injectables were the most appropriate contraception for young women; all recognized the importance of condoms for dual protection. Some services were only reported to be provided to those over 18 years. HCWs may benefit from workshops providing technical and policy information and values clarification exercises highlighting the impact of opinions on service provision.

A qualitative study of obstacles to diaphragm and condom use in an HIV prevention trial in sub-Saharan Africa.

Consistent condom use and the substitution of condoms with potential HIV prevention methods of lower or unknown effectiveness are important concerns in the development of new prevention technologies. This qualitative study explored obstacles to consistent condom use with the diaphragm in MIRA, an HIV prevention trial in South Africa and Zimbabwe. We conducted 26 focus group discussions (FGDs) with 206 women and 7 FGDs and 10 in-depth interviews with 41 male partners of intervention-arm women. The belief that the diaphragm/gel prevented HIV, women's difficulties negotiating condom use, and men's unawareness that using the products together was recommended were obstacles to consistent condom use with the diaphragm/gel. Concerns about protection from HIV and pregnancy, recognition that the diaphragm was not yet proven to prevent HIV or sexually transmitted infections, and the trial context were facilitators. Understanding selective study product use in HIV prevention trials may inform improved adherence counseling and male involvement strategies.

Establishing a continuum of care between HIV prevention trials and public healthcare systems: the MIRA Standard of Care program.

BACKGROUND: The ability of researchers to provide sustainable care to individuals who acquire HIV during participation in HIV prevention trials has rapidly expanded along with national treatment options. The METHODS: for Improving Reproductive Health in Africa (MIRA) trial (2003-2006), a phase III multi-site randomized controlled trial, measured the effectiveness of the diaphragm used with Replens lubricant gel in preventing heterosexual acquisition of HIV among women in Zimbabwe and South Africa. The MIRA Standard of Care program, which started towards the end of the trial period and continued for 5 months after trial closeout, enabled women who acquired HIV during the trial to receive additional counseling and clinical care and facilitated links to long-term HIV-related care and treatment from public health facilities. PURPOSE: To describe eligible participants' uptake of these optional services and evaluate the program's strengths and limitations. Methods All women who acquired HIV during their MIRA participation were re-contacted and invited to return to the study clinics for additional care and referrals. Sites reported monthly statistics of uptake of services. RESULTS: From start to end, 185 of 323 (57%) HIV-positive participants accepted additional care; 81 (25%) could not be relocated. 142 (44%) women received referrals to government healthcare facilities and 90 (28%) enrolled in wellness/ treatment programs. Fifty-seven (18%) declined further care, but reasons for doing so were not recorded systematically. LIMITATIONS: The program began after most participants had exited from the MIRA trial and required re-contacting women, resulting in difficulty in locating some participants. CONCLUSIONS: In the future, care for participants who seroconvert should be offered at the trial onset and fully integrated into clinical trials to avoid losing these participants for further care. More research is needed to identify and understand perceived barriers to establishing a continuum of care between clinical trials and public sector health facilities. Clinical Trials 2010; 7: 256-264. http:// ctj.sagepub.com.

Novel strategies implemented to ensure high participant retention rates in a community based HIV prevention effectiveness trial in South Africa and Zimbabwe.

BACKGROUND: The identification of new HIV prevention methods that women can initiate themselves are urgently needed, particularly in high prevalence settings. HIV prevention trials must be designed with large sample sizes and/or substantial follow-up periods to ensure enough statistical power to measure product effectiveness. This paper describes the attendance rates of the Methods for Improving Reproductive Health in Africa (MIRA) trial, reasons for missed visits, and strategies used to retain participants; and examines demographic and behavioural predictors of retaining women. METHODS: HIV negative, sexually active females were enrolled into the MIRA trial in Zimbabwe and South Africa. Once enrolled, women were expected to visit the clinic at 2 weeks and quarterly thereafter for 12 to 24 months. Tabulations of visit-specific retention rates are presented, along with a descriptive summary of retention strategies established prior to and in response to challenges incurred during implementation. Both univariate and multivariate logistic regression models were created in STATA to examine predictors of being retained vs. lost-to-follow-up. RESULTS: At the three sites, the final retention rates were 94%, 93% and 89% for Zimbabwe, Durban and Johannesburg, respectively. This was achievable through intensive outreach efforts toward the latter part of the trial and a commitment from all staff. Each site implemented several retention strategies. CONCLUSION: The high retention rates were achievable in this trial through added staff efforts and resources. Community involvement was also crucial to achieve these rates. Retention of trial participants should be considered during trial design and implemented from the onset.

Injectable progestin contraceptive use and risk of HIV infection in a South African family planning cohort.

OBJECTIVE: To investigate whether the incidence of HIV infection is higher among sexually active women using depot medroxyprogesterone acetate (DMPA) or noresthisterone enanthate (NET-EN) injections for contraception than among women using nonhormonal or no contraception. METHODS: Five hundred and fifty-one initially HIV-negative women were followed up for a total of 491 person-years. Participants were interviewed, counselled, examined, tested for HIV and other STIs, and treated, at three monthly intervals for 1 year. RESULTS: There was no significant association between progestin contraceptive use and HIV infection (rate ratio 1.1, 95% CI 0.5 to 2.8; log-rank test, p=.73). In proportional hazards regression, the only significant hazard ratios for HIV acquisition were prevalent Neisseria gonorrhoea (5.2; 95% CI 1.1 to 23.7, p=.035) and Trichomonas vaginalis (4.8; 95% CI 1.0 to 22.8, p=.049); bacterial vaginosis was marginally significant (2.8; 95% CI 1.0 to 8.3, p=.057). The adjusted hazard ratios for NET-EN and DMPA were 1.76 (95% CI 0.64 to 4.84) and 0.46 (95% CI 0.06 to 3.79), respectively, relative to nonuse. Five hundred and twelve of 551 women had one or more confirmed STIs during the study. CONCLUSIONS: There is no evidence of an association between HIV infection and injectable contraceptives. Due to the limited power of this study and because similar studies have not included young women using NET-EN, we recommend that further research be carried out to focus on the use of NET-EN and HIV acquisition in high risk groups.

The ethics of nurse poaching from the developing world.

Recruiting nurses from other countries is a long-standing practice. In recent years many countries in the developed world have more frequently recruited nurses from the developing world, causing an imbalance in the health services in often already impoverished countries. Despite guidelines and promises by developed countries that the practice should cease, it has largely failed to do so. A consortium of authors from countries that have experienced significant nurse poaching consider the ethical aspects behind this continuing practice.