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Background Youth in southern Africa, particularly adolescent girls and young women, are a key population for HIV prevention interventions. Untreated genital tract infections (GTIs) increase both HIV transmission and acquisition risks. South African GTI treatment guidelines employ syndromic management, which relies on individuals to report GTI signs and symptoms. Syndromic management may, however, underestimate cases, particularly among youth. We compared genital tract infection (GTI) prevalence by symptom-based and laboratory assessment among sexually-experienced youth in South Africa, overall and stratified by sex. Methods Interviewer-administered surveys assessed socio-demographics, behaviors, and GTI symptoms among 352 youth (16-24 yrs., HIV-negative or unknown HIV status at enrollment) enrolled in community-based cohorts in Durban and Soweto (2014–2016). Laboratory tests assessed HIV, Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Mycoplasma genitalium (MG), Trichomonas vaginalis (TV) infections and, among females, bacterial vaginosis (BV) and Candida species. Youth with genital ulcers were tested for HSV-2 and syphilis. We assessed sensitivity (and specificity) of symptom-based reporting in identifying laboratory-confirmed GTIs. Results At baseline, 16.2% of females (32/198) and < 1% (1/154) of males reported ≥1 GTI symptom. However, laboratory tests identified ≥1 GTI in 70.2% and 10.4%, respectively. Female CT prevalence was 18.2%, NG 7.1%, MG 9.6%, TV 8.1%, and 5.1% were newly diagnosed with HIV. BV prevalence was 53.0% and candidiasis 9.6%. One female case of herpes was identified (0 syphilis). Male CT prevalence was 7.8%, NG 1.3%, MG 3.3%, TV < 1%, and 2.0% were newly diagnosed with HIV. Overall, 77.8% of females and 100% of males with laboratory-diagnosed GTIs reported no symptoms or were asymptomatic. Sensitivity (and specificity) of symptom-based reporting was 14% (97%) among females and 0% (99%) among males. Conclusion A high prevalence of asymptomatic GTIs and very poor sensitivity of symptom-based reporting undermines the applicability of syndromic GTI management, thus compromising GTI control and HIV prevention efforts among youth. Syndromic GTI management does not meet the sexual health needs of young people. Policy changes incorporating innovations in GTI diagnostic testing are needed to reduce GTIs and HIV-associated risks among youth.

A baseline cross-sectional survey among female sex workers (FSWs) was conducted in four cities within the context of an implementation research project aiming to improve FSWs' access to HIV, and sexual and reproductive health (SRH) services. The survey measured where FSWs seek HIV/SRH care and what motivates their choice. Using respondent-driven sampling (RDS), FWSs were recruited in Durban, South Africa (n = 400), Tete, Mozambique (n = 308), Mombasa, Kenya (n = 400) and Mysore, India (n = 458) and interviewed. RDS-adjusted proportions were estimated by non-parametric bootstrapping, and compared across cities using post-hoc pairwise comparison tests. Across cities, FSWs most commonly sought care for the majority of HIV/SRH services at public health facilities, most especially in Durban (ranging from 65% for condoms to 97% for HIV care). Services specifically targeting FSWs only had a high coverage in Mysore for STI care (89%) and HIV testing (79%). Private-for-profit clinics were important providers in Mombasa (ranging from 17% for STI care and HIV testing to 43% for HIV care), but not in the other cities. The most important reason for the choice of care provider in Durban and Mombasa was proximity, in Tete 'where they always go', and in Mysore cost of care. Where available, clinics specifically targeting FSWs were more often chosen because of shorter waiting times, perceived higher quality of care, more privacy and friendlier personnel. The place where care is sought for HIV/SRH services differs substantially between cities. Targeted services have limited coverage in the African cities compared to Mysore. Convenience appears more important for choosing the place of care than aspects of quality of care. The best model to improve access, linking targeted interventions with general health services, will need to be tailored to the specific context of each city.

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).

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.

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.

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.

Measures used to assess equitable relationship dynamics, including the sexual relationship power scale (SRPS) have previously been associated with lower HIV-risk among young women, and reduced perpetration of intimate partner violence among men. However, few studies describe how the SRPS has been adapted and validated for use within global youth sexual health studies. We examined gender-specific psychometric properties, reliability, and validity of a SRPS used within a South African youth-engaged cohort study. Young men and women (16-24 years) enrolled in community-based cohorts in Durban and Soweto (2014-2016) reporting a primary partner at 6-month follow-up completed a 13-item (strongly agree/agree/disagree/strongly disagree) South African adaptation of Pulerwitz's SRPS (range 13-52, higher scores indicating greater sexual relationship power [SRP] equity). SRPS modifications were made using gender-specific exploratory factor analyses (EFAs), removing items with factor loadings <0.3. Cronbach alphas were conducted for full and modified scales by gender. Using modified scales, unadjusted and adjusted regression models examined associations between 1. relevant socio-demographic and relationship determinants and SRP equity, and 2. SRP equity and sexual relationship related outcomes. All models adjusted for education, age, site, and current employment. 235 sexually-active youth (66% women, median age = 20) were included. Mean scores across all 13 scale items were 2.71 (SD 0.30) for women and 2.70 (SD 0.4) for men. Scale Cronbach's alphas were 0.63 for women and 0.64 for men. EFAs resulted in two gender-specific single-factor SRPS. Modified SRPS Cronbach alphas increased to 0.67 for women (8-items) and 0.70 for men (9-items). After adjusting for age, site and current employment, higher education remained associated with SRP equity across genders. In adjusted models, correlates of SRP equity included primary partnerships that were age-similar (<5 years older) and <2 years in length for women and living in Soweto and younger age for men. Greater SRP equity among women was also independently associated with no recent partner violence. Results highlight important gender differences in SRP equity measures and associations, highlighting the critically need for future research to examine gendered constructions of SRP equity in order to accurately develop, validate and use appropriate measures within quantitative surveys.

Background In the context of an operational research project in Tete, Mozambique, use of, and barriers to, HIV and sexual and reproductive health (HIV/SRH) commodities and services for female sex workers (FSWs) were assessed as part of a baseline situational analysis. Methods In a cross-sectional survey 311 FSWs were recruited using respondent driven sampling and interviewed face-to-face, and three focus group discussions were held with respectively 6 full-time Mozambican, 7 occasional Mozambican and 9 full-time Zimbabwean FSWs, to investigate use of, and barriers to, HIV/SRH care. Results The cross-sectional survey showed that 71 % of FSWs used non-barrier contraception, 78 % sought care for their last sexually transmitted infection episode, 51 % of HIV-negative FSWs was tested for HIV in the last 6 months, 83 % of HIV-positive FSWs were in HIV care, 55 % sought help at a health facility for their last unwanted pregnancy and 48 % after sexual assault, and none was ever screened for cervical cancer. Local public health facilities were by far the most common place where care was sought, followed by an NGO-operated clinic targeting FSWs, and places outside the Tete area. In the focus group discussions, FSWs expressed dissatisfaction with the public health services, as a result of being asked for bribes, being badly attended by some care providers, stigmatisation and breaches of confidentiality. The service most lacking was said to be termination of unwanted pregnancies. Conclusions The use of most HIV and SRH services is insufficient in this FSW population. The public health sector is the main provider, but access is hampered by several barriers. The reach of a FSW-specific NGO clinic is limited. Access to, and use of, HIV and SRH services should be improved by reducing barriers at public health facilities, broadening the range of services and expanding the reach of the targeted NGO clinic.

BackgroundPsychosocial risks during pregnancy impact maternal health in resource-limited settings, and HIV-positive women often bear a heavy burden of these factors. This study sought to use network modeling to characterize co-occurring psychosocial risks to maternal and child health among at-risk pregnant women.MethodsTwo hundred pregnant HIV-positive women attending antenatal care in South Africa were enrolled. Measured risk factors included younger age, low income, low education, unemployment, unintended pregnancy, distress about pregnancy, antenatal depression, internalized HIV stigma, violence exposure, and lack of social support. Network analysis between risk factors was conducted in R using mixed graphical modeling. Centrality statistics were examined for each risk node in the network.ResultsIn the resulting network, unintended pregnancy was strongly tied to distress about pregnancy. Distress about pregnancy was most central in the network and was connected to antenatal depression and HIV stigma. Unintended pregnancy was also associated with lack of social support, which was itself linked to antenatal depression, HIV stigma, and low income. Finally, antenatal depression was connected to violence exposure.ConclusionsOur results characterize a network of psychosocial risks among pregnant HIV-positive women. Distress about pregnancy emerged as central to this network, suggesting that unintended pregnancy is particularly distressing in this population and may contribute to further risks to maternal health, such as depression. Prevention of unintended pregnancies and interventions for coping with unplanned pregnancies may be particularly useful where multiple risks intersect. Efforts addressing single risk factors should consider an integrated, multilevel approach to support women during pregnancy.Trial RegistrationClinicalTrials.gov identifier: NCT03069417

As new female-initiated HIV prevention products enter development, it is crucial to incorporate women’s preferences to ensure products will be desired, accepted, and used. A discrete-choice experiment was designed to assess the relative importance of six attributes to stated choice of a vaginally delivered HIV prevention product. Sexually active women in South Africa and Zimbabwe aged 18–30 were recruited from two samples: product-experienced women from a randomized trial of four vaginal placebo forms and product-naïve community members. In a tablet-administered survey, 395 women chose between two hypothetical products over eight choice sets. Efficacy was the most important, but there were identifiable preferences among other attributes. Women preferred a product that also prevented pregnancy and caused some wetness (p < 0.001). They disliked a daily-use product (p = 0.002) and insertion by finger (p = 0.002). Although efficacy drove preference, wetness, pregnancy prevention, and dosing regimen were influential to stated choice of a product, and women were willing to trade some level of efficacy to have other more desired attributes.