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Current guidelines recommend starting antiretroviral therapy (ART) as soon as possible after HIV diagnosis to reduce morbidity, mortality and onward HIV transmission. We examined factors influencing ART initiation by women who seroconverted during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. ECHO, conducted between 2015 and 2018, enrolled HIV-negative, sexually active women, aged 16-35 years, from four African countries. Follow-up was 12-18 months, with quarterly HIV testing. Women with incident HIV infection received extensive counselling by trial staff and referral to local facilities for HIV care. Of 304 women with ≥90 days follow-up time since HIV diagnosis, 186(61.2%) initiated ART within 90 days, 69(22.7%) initiated after 90 days, and 49(16.1%) had not initiated by the end of the study. There were no statistically significant differences in characteristics among women who initiated ART ≤90 days versus those who did not. Frequent reasons for delayed or non-initiation of ART included not feeling ready to start ART and being newly diagnosed. In a large clinical trial, ART initiation was modest within 90 days of HIV diagnosis and grew to 84% with longer observation. Despite extensive counselling on the importance of early ART initiation, personal barriers delayed some women from starting ART.

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.

Supplemental Digital Content is Available in the Text., Background: HIV-1 risk scoring tools could help target provision of prevention modalities such as pre-exposure prophylaxis. Recent research suggests that risk scores for women aged 18–45 may not predict risk well among young women aged 18–24. We evaluated the predictive performance of age-specific risk scores compared with the existing non–age-specific VOICE risk score, developed for women aged 18–45. Methods: We conducted a secondary analysis of the Evidence for Contraceptive Options and HIV Outcomes Trial to develop and internally validate HIV-1 risk scores for women aged 18–24 and 25–35 in South Africa. Candidate predictors included baseline demographic, clinical, behavioral, and contextual characteristics readily available in clinical settings. The VOICE risk score was applied to women aged 18–35. We evaluated predictive performance of each risk score by area under the receiver operating characteristic curve (AUC). Results: Predictive performance of all risk scores was moderate, with AUC (95% confidence interval) of 0.64 (0.60 to 0.67) among women aged 18–24, 0.68 (0.62 to 0.73) among those aged 25–35, and 0.61 (0.58 to 0.65) for the VOICE risk score applied to women aged 18–35; The AUC was similar in internal validation. Among women aged 18–24, HIV-1 incidence was high even at low risk scores, at 3.9 per 100 person-years (95% confidence interval: 3.2 to 4.7). Conclusions: All risk scores were moderately predictive of HIV-1 acquisition, and age-specific risk scores performed only marginally better than the VOICE non–age-specific risk score. Approaches for targeted pre-exposure prophylaxis provision to women in South Africa may require more extensive data than are currently available to improve prediction.

Background HIV-exposed women in African settings planning to conceive are at heightened risk of acquiring sexually transmitted infections (STIs). STIs can increase HIV acquisition risks and cause maternal and child morbidity. Here, we describe the prevalence of curable STIs among HIV-uninfected women planning pregnancy with a partner who is living with HIV or of unknown serostatus in an HIV-endemic setting (eThekwini, KwaZulu-Natal (KZN)). Methods This is a descriptive longitudinal sub-study nested within the Safer Conception for Women study. HIV-uninfected women, aged 18–35 years with personal or partner plans for pregnancy were enrolled from November 2019 in eThekwini, KZN. A questionnaire was administered, and women were examined for STIs, and tested for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV), and Mycoplasma genitalium (MG) via PCR of a provider-collected swab, and Treponema Pallidum (TP) via TPHA testing. Women with symptomatic and/or laboratory-confirmed STIs are treated and provided with partner notification letters. Repeat sample collection is scheduled after six months, and during pregnancy. Here, we report on prevalent curable STIs at baseline. Results Among the 50 women enrolled, [median age: 24 (range: 19–33), HIV serostatus of partner: 47(94%) unknown], 3 (6%) reported STI symptoms, and 12 (24%) had curable STI organisms detected on laboratory testing. CT was the most frequent pathogen (6, 12%), followed by TV (5, 10%), NG (2, 4%) and MG (1, 2%). Two women had >1 STI pathogen. No TP was detected. Baseline demographic and sexual behavioural characteristics did not differ between women with and without STIs. Conclusion Our findings indicate a high prevalence of curable STIs, mostly asymptomatic, among HIV-uninfected women planning for a pregnancy in the next year. Given the impact of asymptomatic curable STIs on maternal and neonatal health, this population should be prioritized for objective STI testing.

Objectives : The use of intrauterine devices (IUDs) and contraceptive implants in South Africa (SA) is low with limited data on patterns of use and reasons for discontinuation. We describe contraceptive preferences and reasons for discontinuation among women enrolled in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial from one trial site. Study Design : ECHO, conducted between 2015 and 2018, enrolled and randomized sexually active women, aged 16-35, and desiring contraception, to intramuscular depot medroxyprogesterone acetate (DMPA-IM), a copper intrauterine device (C-IUD) or a levonorgestrel (LNG) implant; follow-up was 12-18 months. We interviewed 829 women at the Durban, SA trial site at ECHO Trial exit to ascertain contraceptive preferences at randomization. Reasons for randomized contraceptive discontinuation were collected at ECHO Trial exit and six months later. Data were analysed descriptively. Results : At the final ECHO Trial visit, among women using their randomized contraceptive method (n=757), 21% discontinued DMPA-IM, 20% discontinued LNG implant and 22% discontinued the C-IUD. About a quarter from each group discontinued due to problems with bleeding. Among women continuing their randomized contraceptive at trial exit (n=597), 25% discontinued DMPA-IM within six months of exiting the study, 8% discontinued LNG implant and 4% discontinued C-IUD. A third of women reported wanting to be assigned DMPA-IM at randomization, 20% wanted the LNG implant and 18% the C-IUD. Conclusions : Despite some women having preferences about which contraceptive they might be randomized to, discontinuation rates for all three methods at ECHO Trial exit and 6-month post-trial follow-up were low. Implications : Despite limited prior use of IUDs and implants among women enrolled in this study, and a desire by some women to not receive these methods at randomization, discontinuation rates remained low. The provision of quality contraceptive counselling and support may increase uptake and continued use of implants and IUDs.

Background: There is limited evidence on the impact of the use of progestin-only hormonal contraception (POC) on weight change. We conducted a secondary analysis of prospective weight change among women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial. Methods: The ECHO trial was conducted at 12 sites in eSwatini, Kenya, South Africa and Zambia. HIV negative, women aged 16-35 years, desiring contraception, were randomized (1:1:1) to either 3-monthly intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel (LNG) implant or copper intrauterine device (IUD). Follow-up was up to 18 months. Weight (kgs) was measured at baseline and study exit. Analysis was performed as intention to treat (ITT) and time on continuous contraceptive use. Findings: 7829 women were randomly assigned to DMPA-IM (n=2609), copper IUD (n=2607) or LNG implant (n=2613). The ITT population included 7014 women 2293 DMPA-IM group, 2372 copper IUD group and 2349 LNG group) who were not lost to follow-up, pregnant on study, or missing weight data. The mean weight increased in all groups but was significantly different in magnitude: 3.5kg (SD=6.3), 2.4kg (SD=5.9) and 1.5kg (SD=5.7) in the DMPA-IM, LNG implant and copper IUD groups, respectively. Comparative differences between groups were (2.02 kg 95% CI, 1.68,2.36, p

Background: Globally, women have higher herpes simplex type 2 (HSV-2) prevalence than men; data from observational studies suggest a possible association of HSV-2 acquisition with use of certain contraceptive methods, particularly intramuscular depot medroxyprogesterone acetate (DMPA-IM). Methods: Within a randomized trial of the effect of three contraceptive methods – DMPA-IM, a copper intrauterine device (IUD), and a levonorgestrel (LNG) implant – on HIV acquisition, we assessed HSV-2 acquisition. We followed women who were HSV-2 and HIV seronegative, aged 16-35 years, and seeking effective contraception for 12-18 months at 12 sites in Eswatini, Kenya, South Africa, and Zambia from 2015-2018. HSV-2 serologic testing was done at enrollment and final study visits according to a standardized algorithm. Intention–to-treat analysis using Poisson regression with robust standard errors compared HSV-2 incidence by contraceptive method. Findings: At baseline, 4062 randomized women were HSV-2 seronegative, of whom 3898 (96.0%) had a conclusive HSV-2 result at their final study visit. Of these, 614 (15.8%) acquired HSV-2, at an incidence of 12.4/100 person-years (p-y): 10.9/100 p-y among women assigned DMPA-IM, 13.7/100 p-y the copper IUD, and 12.7/100 p-y the LNG implant. Incidence rate ratios (IRR) for HSV-2 acquisition were 0.80 (95% confidence interval [CI] 0.65-0.97) for DMPA-IM compared with copper IUD, 0.86 (95% CI 0.71-1.05) for DMPA-IM compared with LNG implant, and 1.08 (95% CI 0.89-1.30) for copper IUD compared with LNG implant. HSV-2 acquisition risk was significantly increased among women who also acquired HIV during follow-up (IRR 3.55, 95% CI 2.78-4.48). Interpretation: In a randomized trial, DMPA-IM was not associated with increased risk of HSV-2 acquisition. HSV-2 incidence was >10% per year, emphasizing the need for development of novel HSV-2 prevention strategies for African women. Clinical Trial Registration Details: ClinicalTrials.gov number NCT02550067. Funding Information: The ECHO Trial was made possible by the combined generous support of the Bill & Melinda Gates Foundation, the American people through the United States Agency for International Development and the President’s Emergency Plan for AIDS Relief, the Swedish International Development Cooperation Agency as part of the EDCTP2 programme supported by the European Union, the South African Medical Research Council, and the United Nations Population Fund. Contraceptive supplies were donated by the Government of South Africa and United States Agency for International Development. Additional funding for testing for herpes simplex type 2 infection was provided in part by the US Centers for Disease Control and Prevention (U48 DP 005013 SIP 14-023) and the University of Washington/Fred Hutch Center for AIDS Research (US National Institutes of Health P30 AI057757). Declaration of Interests: None. Ethics Approval Statement: Ethics review committees at each study site approved the study protocol. All participants provided written informed consent, which included counseling about randomization, each study contraceptive method, and their rights as research participants.

Summary Background As oral pre-exposure prophylaxis (PrEP) becomes the standard of prevention globally, its potential effect on HIV incidence in clinical trials of new prevention interventions is unknown, particularly for trials among women. In a trial measuring HIV incidence in African women, oral PrEP was incorporated into the standard of prevention in the trial's last year. We assessed the effect of on-site access to PrEP on HIV incidence in this natural experiment. Methods We did a nested interrupted time-series study using data from the ECHO trial. At 12 sites in four countries (Eswatini, Kenya, South Africa, and Zambia), women (aged 16–35 years) were randomly assigned to receive one of three contraceptives between Dec 14, 2015, and Sept 12, 2017, and followed up quarterly for up to 18 months to determine the effect of contraceptive method on HIV acquisition. Women were eligible if they wanted long-acting contraception, were medically qualified to receive study contraceptives, and had not used any of the study contraceptives in the past 6 months. The present analyses are limited to nine South African sites where on-site access to oral PrEP was implemented between March 13 and June 12, 2018. Using an interrupted time-series design, we compared HIV incidence before versus after PrEP access, limited to quarterly study visits at which on-site PrEP access was available to at least some participants and, in a sensitivity analysis, to the 180 days before and after access. The outcome was incident HIV infection, detected using two rapid HIV tests done in parallel for each participant at every scheduled follow-up visit. This study is registered on ClinicalTrials.gov, NCT02550067. Findings 2124 women were followed up after on-site PrEP access began, of whom 543 (26%) reported PrEP use. A total of 12 HIV seroconversions were observed in 556 person-years (incidence 2·16%) after on-site PrEP access, compared with 133 HIV seroconversions in 2860 person-years (4·65%) before PrEP access (adjusted incidence rate ratio [IRR] 0·45, 95% CI 0·25–0·82, p=0·0085). Similar results were also observed when limiting the analysis to 180 days before versus after PrEP access. A total of 46 HIV seroconversions were observed in 919 person-years within 180 days before PrEP access, compared with 11 seroconversions in 481 person-years in the 180 days following PrEP access (incidence 5·00 vs 2·29 per 100 person-years; IRR 0·43, 95% CI 0·22–0·88, p=0·012). Interpretation On-site access to PrEP as part of standard of prevention in a clinical trial among women in South Africa was associated with halving HIV incidence, when approximately a quarter of women started PrEP. Providing access to on-site PrEP could decrease incidence in HIV prevention trials. These data are also among the first to show in any setting that access to PrEP is associated with decreased HIV acquisition among South African women. Funding Bill & Melinda Gates Foundation, United States Agency for International Development, President's Emergency Plan for AIDS Relief, the Swedish International Development Cooperation Agency, South African Medical Research Council, and United Nations Population Fund.

Pubic hair grooming is common in many countries, but little is known about this practice in Africa. Grooming has been positively associated with self-reported sexually transmitted infections (STIs). This study aimed to investigate the prevalence and safety of pubic hair grooming in two South African settings. In KwaZulu-Natal province, 1218 women participating in the Evidence for Contraceptive Options and HIV Outcomes Trial completed an interviewer-administered questionnaire on pubic hair grooming practices, and were tested for Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG) and herpes simplex virus type 2 (HSV-2). Pubic hair removal was reported by 705 (58.2%) of women. Common areas for grooming were the pubis (n = 616, 99.4%), vagina/perineum (n = 529, 85.3%) and inner thigh (n = 255, 41.1%). Half (n= 361, 51.4%) removed some or all of their pubic hair at least monthly and 59 (8.4%) once a week or more often. Common side effects reported included itching (n = 439, 77.1%) and pimples and blisters (n = 249, 43.9%). A quarter (n = 173, 24.5%) of groomers had a positive result for either or both of CT and NG compared to a fifth (n = 98, 19.4%) of non-groomers (p-value

Limited data exist on the effects of contraceptives on HIV disease progression. We studied the association between intramuscular injectable depot medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (IUD), and the levonorgestrel (LNG) implant on markers of HIV disease progression at the time of HIV detection and 3 months postdetection and time from detection to CD4 count

Introduction Global guidelines emphasize the ethical obligation of investigators to help participants in HIV‐endpoint trials reduce HIV risk by offering an optimal HIV prevention package. Oral pre‐exposure prophylaxis (PrEP) has increasingly become part of state‐of‐the‐art HIV prevention. Here we describe the process of integrating oral PrEP delivery into the HIV prevention package of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. Methods ECHO was an open‐label randomized clinical trial that compared HIV incidence among women randomized to one of three effective contraceptives. In total, 7830 women aged 16 to 35 years from 12 sites in four African countries (Eswatini, Kenya, South Africa and Zambia) were enrolled and followed for 12 to 18 months, from 2015 to 2018. Part‐way through the course of the trial, oral PrEP was provided to study participants either off‐site via referral or on site via trained trial staff. PrEP uptake was compared between different contraceptive users using Chi‐squared tests or t‐tests. HIV seroincidence rates were compared between participants who never versus ever initiated PrEP using exact Poisson regression. Results PrEP access in ECHO began through public availability in Kenya in May 2017 and was available at all sites by June 2018. When PrEP became available, 3626 (46.3%) eligible women were still in follow‐up in the study, and of these, 622 (17.2%) initiated PrEP. Women initiating PrEP were slightly older; more likely to be unmarried, not living with their partner, having multiple partners; and less likely to be earning their own income and receiving financial support from partners (all p

Background. The contraceptive implant, Implanon NXT, was introduced in South Africa (SA) in 2014 and, although it offers multiple advantages, users may request to have it removed early for several reasons. The number of insertions of Implanon NXT has declined in SA and there have been concerns about early removals. Objectives. To gain an understanding of patterns of Implanon NXT use, reasons for requesting removal and duration of use at the time of requesting removal. Methods. This was a cross-sectional study conducted at an urban public-sector reproductive health clinic in the eThekwini District of KwaZulu-Natal, SA. A total of 120 women ≥18 years of age requesting removal of Implanon NXT completed an interviewer-administered questionnaire that probed experiences of use and reasons for removal. Data were collected electronically on Wits REDCap (Research Electronic Data Capture) and analysed using Stata 14 (StataCorp, USA). The study was conducted from 2017 to 2018. Results. A total of 120 women were interviewed. Their mean age was 28 (range 19 - 44) years and most women ( n= 103; 85.8%) had completed secondary school. The majority were black ( n= 115; 95.8%) and unmarried ( n= 102; 85%). Implants had been inserted primarily by nurses ( n= 110; 91.7%) at public-sector clinics ( n= 91; 75.8%). Three-quarters of the women ( n= 91; 75.8%) requested removal of Implanon NXT because it had reached the intended 3-year duration. Reasons for early removal were mainly due to side-effects, e.g. bleeding problems ( n= 19; 15.8%), weight gain ( n= 7; 5.8%), loss of libido ( n= 2; 1.7%), headaches ( n= 5; 4.2%), dizziness ( n= 4; 3.3%) and pain/numbness in the arm ( n= 2; 1.7%). Just more than half (57.1%) of the women who had received the implant for the intended 3-year duration had requested reinsertion of Implanon NXT. Conclusions. The main reason for requesting removal was that Implanon NXT had reached its intended 3-year duration, and more than half of the women requested reinsertion of the device following removal. Implanon NXT is a highly effective, safe, acceptable, long-acting contraceptive and important in the SA contraceptive method mix.