Explore the vast range of titles available.

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.

Observational data suggest lower HIV risk with norethisterone enanthate (NET-EN) than with depo-medroxyprogesterone acetate intramuscular (DMPA-IM) injectable contraceptives. If confirmed, a switch between these similar injectable methods would be programmatically feasible and could impact the trajectory of the HIV epidemic. We aimed in this paper to investigate the effects of DMPA-IM and NET-EN on estradiol levels, measures of depression and sexual activity and menstrual effects, relevant to HIV risk; and to ascertain whether these measures are associated with estradiol levels. This open-label trial conducted at two sites in South Africa from 5 November 2018 to 30 November 2019, randomized HIV-negative women aged 18-40 to DMPA-IM 150 mg intramuscular 12-weekly (n = 262) or NET-EN 200 mg intramuscular 8-weekly (n = 259). Data were collected on hormonal, behavioral and menstrual effects at baseline and at 25 weeks (25W). At 25W, median 17β estradiol levels were substantially lower than at baseline (p<0.001) for both methods: 76.5 pmol/L (interquartile range (IQR) 54.1 to 104.2) in the DMPA-IM group (n = 222), and 69.8 pmol/L (IQR: 55.1 to 89.3) in the NET-EN group (n = 225), with no statistical difference between the two methods (p = 0.450). Compared with DMPA-IM, NET-EN users reported significantly less amenorrhoea, fewer sexual acts, fewer users reporting at least one act of unprotected sex, more condom use with steady partner, more days with urge for sexual intercourse, more days feeling partner does not love her, and more days feeling sad for no reason. We did not find a clear association between estradiol levels and sexual behavior, depression and menstrual effects. Behavioral outcomes suggest less sexual exposure with NET-EN than DMPA-IM. The strength of this evidence is high due to the randomized study design and the consistency of results across the outcomes measured. Estradiol levels were reduced to postmenopausal levels by both methods. Secondary outcomes suggesting less sexual exposure with NET-EN are consistent with reported observational evidence of less HIV risk with NET-EN. A randomized trial powered for HIV acquisition is feasible and needed to answer this important question. PACTR 202009758229976.

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.

HIV acquisition risk with norethisterone (NET) enanthate (NET-EN) is reportedly less than for depo-medroxyprogesterone acetate intramuscular (DMPA-IM). We investigated the effects of these progestin-only injectable contraceptives on serum testosterone and sex hormone binding globulin (SHBG) levels, since these may play a role in sexual behavior and HIV acquisition. The open-label WHICH clinical trial, conducted at two sites in South Africa from 2018–2019, randomized HIV-negative women aged 18–40 years to 150 mg DMPA-IM 12-weekly (n = 262) or 200 mg NET-EN 8-weekly (n = 259). We measured testosterone by UHPLC-MS/MS and SHBG by immunoassay in matched pairs of serum samples collected at baseline (D0) and at peak serum progestin levels at 25 weeks post initiation (25W) (n = 214–218 pairs). Both contraceptives substantially decreased, from D0 to 25W, the total testosterone [DMPA-IM D0 0.560, 25W 0.423 nmol/L, -24.3% (p < 0.0001); NET-EN D0 0.551, 25W 0.253 nmol/L, -54.1%, (p < 0.0001)], SHBG [DMPA-IM D0 45.0, 25W 32.7 nmol/L, -29.8% (p < 0.0001); NET-EN D0 50.2, 25W 17.6 nmol/L, -65.1% (p < 0.0001)], and calculated free testosterone levels [DMPA-IM D0 6.87, 25W 5.38 pmol/L, -17.2% (p = 0.0371); NET-EN D0 6.00, 25W 3.70, -40.0% (p < 0.0001)]. After adjusting for change from D0, the total testosterone, SHBG and calculated free testosterone levels were significantly higher for DMPA-IM than NET-EN (64.9%, p < 0.0001; 101.2%, p < 0.0001; and 38.0%, p = 0.0120, respectively). The substantial and differential decrease in testosterone and SHBG levels does not explain our previous finding of no detected decrease in risky sexual behavior or sexual function for DMPA-IM or NET-EN users from D0 to 25W. Medroxyprogesterone (MPA) and NET are androgenic and are both present in molar excess over testosterone and SHBG concentrations at 25W. Any within or between contraceptive group androgenic effects on behavior in the brain are likely dominated by the androgenic activities of MPA and NET and not by the decreased endogenous testosterone levels. The clinical trial was registered with the Pan African Clinical Trials Registry (PACTR 202009758229976).

Background Sexually transmitted infection (STI) partner notification is key to fostering STI cure and preventing onward STI transmission; this is critical among people planning for pregnancy given the high STI morbidity and mortality among neonates. This qualitative study explores how women planning for pregnancy and considering HIV pre-exposure prophylaxis approach STI partner notification in Durban, South Africa to inform future interventions. Methods We conducted a cohort study evaluating pre-exposure prophylaxis use as a part of safer conception care among adult women (≥ 18 years) without HIV, partnered with a man living with HIV or unknown HIV-serostatus, and planning for pregnancy. As part of an STI-focused sub-study, 25 women who completed etiologic STI screening also completed qualitative interviews exploring participant STI partner notification practices, preferences, and interaction with pregnancy. We used an inductive and deductive approach to generate a codebook, organized our findings according to the Disclosure Processes Model, and identified preliminary themes using content analysis. Results The median age of sub-study participants was 25 (range 19–33) years, five (20%) were diagnosed with an STI during the study, and 2 (8%) became pregnant during the study. Preliminary themes included 1) Participants’ perceptions of their own and their partner’s additional partnerships affected STI partner notification perceptions and practices; 2) Participants’ asymptomatic presentation and etiologic, laboratory diagnosis supported partner notification; 3) Participants reported male reluctance to engage with healthcare services and a reliance on female participant testing and subsequent partner notification; 4) Participants endorsed provider-assisted STI partner notification; 5) STI diagnoses and partner notification led participants to mistrust their partners and subsequently impacted their condom use during pregnancy planning. Conclusions We found a lack of partner concurrency and asymptomatic infection to influence STI partner notification with partner notification affecting pregnancy planning and condom use. Since women report having high STI testing and care engagement, they bear a high burden of partner notification and potential subsequent blame and often appreciated provider assistance. Interventions are needed to engage men in STI testing and care and to mitigate the potential harms of STI partner notification.

Progestin-only injectable contraceptives, mainly depo-medroxyprogesterone acetate intramuscular (DMPA-IM), are the most widely used contraceptive methods in sub-Saharan Africa. Insufficient robust data on their relative side-effects and serum concentrations limit understanding of reported outcomes in contraception trials. The WHICH clinical trial randomized HIV-negative women to DMPA-IM (n = 262) or norethisterone enanthate (NET-EN) (n = 259) at two South African sites between 2018–2019. We measured serum concentrations of study and non-study progestins at initiation (D0) and peak serum levels, one week after the 24-week injection [25 weeks (25W)], (n = 435) and investigated associations between study progestin levels, and BMI and weight of participants. Peak median serum concentrations were 6.59 (IQR 4.80; 8.70) nM for medroxyprogesterone (MPA) (n = 161) and 13.6 (IQR 9.01; 19.0) nM for norethisterone (NET) (n = 155). MPA was the most commonly quantifiable non-study progestin at D0 in both arms (54%) and at 25W in the NET-EN arm (27%), followed by NET at D0 in both arms (29%) and at 25W in the DMPA-IM arm (19%). Levonorgestrel was quantifiable in both arms [D0 (6.9%); 25W (3.4%)], while other progestins were quantifiable in ≤ 14 participants. Significant negative time-varying associations were detected between MPA and NET concentrations and weight and BMI in both contraceptive arms and a significant increase was detected for peak serum progestin concentrations for normal weight versus obese women. Contraceptive-related reported outcomes are likely confounded by MPA, more so than NET, with reported DMPA-IM effects likely underestimated, at sites where DMPA-IM is widely used, due to misreporting of contraceptive use before and during trials, and ‘tail’ effects of DMPA-IM use more than six months before trial enrolment. Peak serum levels of MPA and NET are negatively associated with BMI and weight, suggesting another source of variability between trial outcomes and a potential increase in side-effects for normal weight versus overweight and obese women. Trail registration: The clinical trial was registered with the Pan African Clinical Trials Registry (PACTR 202009758229976 ).

Contraceptive use has complex effects on sexual behaviour and mood, including those related to reduced concerns about unintended pregnancy, direct hormonal effects and effects on endogenous sex hormones. We set out to obtain robust evidence on the relative effects of three contraceptive methods on sex behaviours, which is important for guiding contraceptive choice and future contraceptive developments. This is a secondary analysis of data from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial in which 7,829 HIV-uninfected women from 12 sites in Eswatini, Kenya, South Africa and Zambia seeking contraception were randomly assigned to intramuscular depot-medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (Cu-IUD) or the levonorgestrel (LNG) implant. Data collected for 12 to 18 months using 3-monthly behavioural questionnaires that relied on recall from the preceding 3 months, were used to estimate relative risk of post-baseline sex behaviours, as well as sexual desire and menstrual bleeding between randomized groups using modified Poisson regression. We observed small but generally consistent effects wherein DMPA-IM users reported lower prevalence of specified high risk sexual behaviours than implant users than Cu-IUD users (the '>' and '<' symbols indicate statistically significant differences): multiple sex partners 3.6% < 4.8% < 6.2% respectively; new sex partner 3.0% < 4.0% <5.3%; coital acts 16.45, 16.65, 17.12 (DMPA-IM < Cu-IUD); unprotected sex 65% < 68%, 70%; unprotected sex past 7 days 33% <36%, 37%; sex during vaginal bleeding 7.1%, 7.1% < 8.9%; no sex acts 4.1%, 3.8%, 3.4% (DMPA-IM > Cu-IUD); partner has sex with others 10% < 11%, 11%. The one exception was having any sex partner 96.5%, 96.9% < 97.4% (DMPA-IM < Cu-IUD). Decrease in sexual desire was reported by 1.6% > 1.1% >0.5%; amenorrhoea by 49% > 41% >12% and regular menstrual pattern by 26% <35% < 87% respectively. These findings suggest that women assigned to DMPA-IM may have a modest decrease in libido and sexual activity relative to the implant, and the implant relative to the Cu-IUD. We found more menstrual disturbance with DMPA-IM than with the implant (and as expected, both more than the Cu-IUD). These findings are important for informing the contraceptive choices of women and policymakers and highlight the need for robust comparison of the effects of other contraceptive methods as well.

IntroductionSouth African women are vulnerable to HIV acquisition during the postpartum period which can result in perinatal transmission via breastfeeding; many male partners do not know their HIV status. Biomedical approaches to preventing HIV for postpartum women include pre-exposure prophylaxis (PrEP) and antiretroviral treatment for male partners with HIV. Gaps in implementation include low uptake of PrEP among postpartum women and infrequent testing of men who may be motivated to test for HIV to protect the health of their infant.Methods and analysisWe will conduct a randomised pilot trial in KwaZulu-Natal (KZN) Province, South Africa among postpartum women and their male partners. The study will pilot a combination intervention consisting of cognitive behavioural strategies (including communication skills training, motivational interviewing and problem-solving) to promote HIV self-testing (HIVST) for Partners and PrEP uptake for HIV-uninfected Postpartum Women, the ‘H4P’ intervention. The study aims to determine the feasibility, acceptability and preliminary effectiveness of the H4P intervention. We will enrol 60 HIV-uninfected women, aged 18 years and older, in their third trimester of pregnancy and reporting a partner whose HIV-serostatus is unknown. Sixty male partners will also be eligible to enrol. Enrolled women will receive three oral HIVST kits to distribute to their male partners and standard of care information on HIVST and PrEP. Women randomised to the intervention arm will receive additional counselling and reproductive health-centred HIVST information for the male partner, including information about why HIV testing is important during their partners’ postpartum period. To evaluate feasibility, we will calculate screening-to-enrolment ratios for women and men, the number of women who distribute HIVST kits to their male partners and the number of men who test. Acceptability will be evaluated using the Client Satisfaction Questionnaire and qualitative interviews. Effectiveness will be assessed at 3 months by measuring the proportion of women initiating PrEP via self-report and urine tenofovir measurements or receipt of injectable PrEP and the proportion of men who test positive who link to HIV care. Qualitative interviews will explore perceptions of the intervention.Ethics and disseminationEthics approval for this study was obtained from the Human Research Ethics Committee at The University of the Witwatersrand, Johannesburg, South Africa (Reference number: 250612) and the Institutional Review Boards at Massachusetts General Brigham (2025P002271, Boston, Massachusetts, USA) and the University of Alabama at Birmingham (300015167, Birmingham, Alabama, USA) in the USA. Site support and approvals were obtained from the health facility and the KwaZulu-Natal Provincial Department of Health. Results will be disseminated through peer-reviewed manuscripts, reports and both local and international presentations.Trial registration numberNCT07194902.

Disclosure of oral pre-exposure prophylaxis (PrEP) use for HIV prevention may improve adherence to PrEP; however, disclosure can be challenging and may result in stigma. Here, we describe disclosure of PrEP use among young women enrolled in a contraceptive study. In this qualitative study, we conducted semi-structured, in-depth, face-to-face interviews with 13 women aged 18-25 years who initiated oral PrEP for HIV prevention during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. Interviews were conducted in 2021 with women from Durban, South Africa. In this analysis, we explore women's experiences of PrEP disclosure including whether they disclosed PrEP use, who they disclosed to and the reaction to disclosure, and the impact of disclosure on PrEP use. Interviews were conducted in English, audio-recorded and transcribed. Data were analysed thematically. All women disclosed oral PrEP use to at least one individual, with some women disclosing to multiple individuals including family, friends, partners and community members. Few women did not disclose oral PrEP use to their partner due to anticipating a negative reaction from the partner, feeling that the partner would assume the woman has HIV and is taking antiretroviral therapy and fear that the partner would associate PrEP use with the woman having other partners. Reactions to oral PrEP disclosure were generally supportive or neutral, however, few women reported negative reactions that included distrust in the efficacy of PrEP to prevent HIV, discouraging the woman from using oral PrEP because of the assumption that PrEP is HIV treatment, and concern about the woman having oral PrEP side effects. Negative reactions to disclosure generally did not impact on oral PrEP use. Supportive disclosures sometimes resulted in reminders for oral PrEP dosing. Our findings indicate that women are willing to disclose their PrEP use to at least one other person when supported. These study findings may contribute to future PrEP counselling guidelines and strategies.

Cisgender women, particularly pregnant and postpartum women in Eastern and Southern Africa, face an unacceptably high risk of HIV acquisition. Oral pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention that can reduce HIV acquisition and vertical transmission. In this qualitative study, we interviewed 21 postpartum women from Cape Town, South Africa who initiated PrEP during pregnancy and who self-reported low PrEP adherence or missed > 1 PrEP follow-up collection. We identified multiple overlapping barriers to PrEP continuation and/or adherence. Individual factors included forgetting to take PrEP daily, being away from home when PrEP should be taken, anticipated stigma and limited disclosure of PrEP use. Women also reported pill-related factors such as side effects and having to take PrEP in addition to other tablets during pregnancy and the postpartum period. Facility-related barriers included logistics around PrEP collection especially when not in antenatal care, as well as transport and financial barriers.