Effects of injectable contraception with depot medroxyprogesterone acetate or norethisterone enanthate on estradiol levels and menstrual, psychological and behavioral measures relevant to HIV risk: The WHICH randomized trial.

BACKGROUND: 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. METHODS: 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). RESULTS: At 25W, median 17ß 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. CONCLUSIONS: 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. TRIAL REGISTRATION: PACTR 202009758229976.

Economic hardship and perpetration of intimate partner violence by young men in South Africa during the COVID-19 pandemic (2021-2022): a cross-sectional study.

BACKGROUND: Economic hardship is a potential trigger for intimate partner violence (IPV) perpetration. While higher IPV rates have been reported in low-income regions, few African studies have focused on IPV being triggered by economic hardship among young men during the COVID-19 pandemic. We therefore estimated economic hardship's effect on IPV perpetration by young men in eThekwini District, South Africa, during the COVID-19 pandemic. METHODS: A cross-sectional survey of COVID-19 pandemic experiences was conducted among youth aged 16-24 years through an anonymous self-administered questionnaire, including questions about economic hardship (increased difficulty accessing food or decreased income) and IPV perpetration. A prespecified statistical analysis plan with a directed acyclic graph of assumed exposure, outcome, and confounder relationships guided our analyses. We measured association of economic hardship and IPV perpetration through odds ratios (ORs) computed from a multivariable logistic regressions adjusted for measured confounders. Secondary outcomes of physical and sexual IPV perpetration were analyzed separately using the same specifications. Propensity score matching weights (PS-MW) were used in sensitivity analyses. Analysis code repository: https://github.com/CAndrewBasham/Economic_Hardship_IPV_perpetration/ RESULTS: Among 592 participants, 12.5% reported perpetrating IPV, 67.6% of whom reported economic hardship, compared with 45.6% of those not reporting IPV perpetration (crude OR = 2.49). Median age was 22 years (interquartile range 20-24). Most (80%) were in a relationship and living together. Three quarters identified as Black, 92.1% were heterosexual, and half had monthly household income < R1600. We estimated an effect of economic hardship on the odds of perpetrating IPV as OR = 1.83 (CI 0.98-3.47) for IPV perpetration overall, OR = 6.99 (CI 1.85-36.59) for sexual IPV perpetration, and OR = 1.34 (CI 0.69-2.63) for physical IPV perpetration. PS-MW-weighted ORs for IPV perpetration by economic hardship were 1.57 (overall), 4.45 (sexual), and 1.26 (physical). CONCLUSION: We estimated 83% higher odds of self-reported IPV perpetration by self-reported economic hardship among young South African men during the COVID-19 pandemic. The odds of sexual IPV perpetration were The seven-times higher by economic hardship, although with limited precision. Among young men in South Africa, economic hardship during COVID-19 was associated with IPV perpetration by men. Our findings warrant culturally relevant and youth-oriented interventions among young men to reduce the likelihood of IPV perpetration should they experience economic hardship. Further research into possible causal mechanisms between economic hardship and IPV perpetration could inform public health measures in future pandemic emergencies.

Misreporting contraceptive use and the association of peak study progestin levels with weight and BMI among women randomized to the progestin-only injectable contraceptives DMPA-IM and NET-EN.

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).

Prevalence and incidence of sexually transmitted infections among South African women initiating injectable and long-acting contraceptives.

BACKGROUND: South Africa is among the countries with the highest prevalence of sexually transmitted infections (STIs), including Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). In 2017, there were an estimated 6 million new CT, 4.5 million NG and 71 000 Treponema pallidum infections among South African men and women of reproductive age. METHODS: We evaluated STI prevalence and incidence and associated risk factors in 162 women aged 18-33 years old, residing in eThekwini and Tshwane, South Africa who were part of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial. Women were randomised to use depot medroxyprogesterone acetate (n = 53), copper intrauterine device (n = 51), or levonorgestrel (n = 58) implant. Lateral vaginal wall swab samples were collected prior to contraceptive initiation and at months one and three following contraceptive initiation for STI testing. RESULTS: There were no significant differences in STI incidence and prevalence across contraceptive groups. At baseline, 40% had active STIs (CT, NG, Trichomonas vaginalis (TV), Mycoplasma genitalium (MG) or herpes simplex virus-2 shedding across all age groups- 18-21 years (46%), 22-25 years (42%) and 26-33 years (29%). The incidence of STIs during follow-up was exceptionally high (107.9/100 women-years [wy]), with younger women (18-21 years) more likely to acquire CT (75.9/100 wy) compared to 26-33 year olds (17.4/100 wy; p = 0.049). TV incidence was higher in the 26-33 year old group (82.7/100 wy) compared to the 18-21 year olds (8.4/100 wy; p = 0.01). CONCLUSIONS: Although the study participants received extensive counselling on the importance of condom use, this study highlights the high prevalence and incidence of STIs in South African women, especially amongst young women, emphasising the need for better STI screening and management strategies.

Examining gender and sexual orientation differences in physical intimate partner violence experienced and perpetrated by youth living in eThekwini district South Africa during the COVID-19 pandemic.

BACKGROUND: Young women and Lesbian, Gay, Bisexual, Trans, Non-binary/no gender, or Questioning (LGBTQ+) youth in South Africa face some of the highest global levels of intimate partner violence (IPV). Given limited evidence in the wake of the COVID-19 pandemic, which has fuelled IPV globally, we aimed to describe and compare experiences and perpetration of IPV of youth aged 16-24 by sexual orientation and gender identity (SOGI). METHODS: During the study period (December 2021-May 2022), youth aged 16-24 from eThekwini district, South Africa completed an online survey to understand multilevel impacts of the pandemic on youth. Participants were asked about experiences and perpetration of physical IPV since the start of the COVID-19 pandemic (March 2020). Descriptive statistics and adjusted logistic regressions compared the likelihood of experiencing and/or perpetrating physical IPV between cisgender and transgender inclusive heterosexual men; heterosexual women; gay, bisexual, or questioning men [GBQM]; lesbian, gay, bisexual, or questioning women [LGBQW]; or gender/sexual non-conforming youth [non-conforming]. RESULTS: Of 1,588 youth (mean age = 21.7 [SD = 2.3]; 71.7% Black) with non-missing SOGI and physical IPV data, 238 (15.0%) were LGBTQ+ (40.3% LGBQW and 36.1% non-conforming). Overall, 14.6% of respondents experienced physical IPV and 9.8% perpetrated physical IPV since the start of the pandemic, which differed by SOGI (12.3% of heterosexual men, 13.9% of heterosexual women, 22.0% of GBQM, 18.2% of LGBQW, and 25.0% of non-conforming youth experienced and 10.3% of heterosexual men; 7.7% of heterosexual women; 10.0% of GBQM; 18.2% of LGBQW; and 16.7% of non-conforming youth perpetrated). In adjusted models, compared to heterosexual women, non-conforming youth had increased odds of experiencing (adjusted odds ratio [aOR] = 2.36; 95%CI, 1.26-4.39) physical IPV and compared to heterosexual men, non-conforming youth had greater odds of perpetrating physical IPV (aOR = 2.19; 95%CI, 1.07-4.48) during the pandemic. CONCLUSION: Over one in six youth in our study experienced and one in ten perpetrated physical IPV since the onset of the COVID-19 pandemic, with gender and sexual non-conforming youth experiencing and perpetrating IPV at significantly greater rates than cisgender/heterosexual peers. Our findings highlight the need for gender transformative efforts that move beyond the gender binary to support healthy relationships and IPV prevention for LGBTQ + youth in South Africa and globally.

Relationship impacts of the COVID-19 pandemic and lockdown restrictions on young women and men in Durban and Soweto, South Africa.

To deepen our understanding of the impact of the COVID-19 pandemic on intimate and/or sexual relationships, we conducted a qualitative study among 26 South African women and men aged 21-30 years in Durban and Soweto between September 2020 and March 2021. Overall, 13 women and 12 men who had been in an intimate and/or sexual relationship since the start of the COVID-19 pandemic were asked about the impact of COVID-19 on their relationships with their current or most recent primary partners. Data were analysed using reflexive thematic analysis. The three most common impacts of the COVID-19 pandemic on relationships were on (i) communication and connection; (ii) strained relationships; and (iii) job and economic loss. Both women and men discussed how COVID-19-related lockdowns provided opportunities to foster better communication, connection and support to one another. However, too little or too much time together strained relationships. Finally, income loss among young men meant that some young women became the primary income earner, changing relationship power dynamics. Findings highlight the importance of young people's relationships and the need for action to support young people in building positive relationships in challenging times.

Female condom color and scent preference in Durban, South Africa.

Objectives: To assess preferences for female condom (FC) colors and scents. Study design: Women aged 18-40 years were randomized to one of three FCs (FC2, Cupid1, Cupid2) two of which offered a choice of color and scent (red/strawberry, purple/vanilla, natural/unscented). Women could choose any variety within condom types while participating in an FC contraceptive efficacy study in South Africa. Results: One hundred and thirty-three women were allocated to each FC type. Strawberry was the most popular variety for both FC2 and Cupid1 (60.9%, 78.3% respectively). Some women chose more than one variety but few chose the natural. Conclusions: Data support a clear preference for colored and scented FCs. Implications: These data can inform FC programme managers to predict demand for different varieties of FC and can adjust supply of FCs accordingly.

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.

Cultural considerations and beliefs surrounding preterm birth in Kenya and South Africa.

BACKGROUND: Preterm birth (PTB) is a global health epidemic, sub-Saharan Africa is severely impacted due to its limited healthcare resources. Pregnancy knowledge, cultural beliefs and practices play a role in the identification of risk and management of PTB. This study explored knowledge, understandings, cultural beliefs and attitudes to pregnancy and PTB, as well as cultural considerations for the introduction of an intravaginal device which could be used to identify PTB risk. METHODS: Qualitative research was conducted in South Africa and Kenya. In-depth interviews were conducted using semi-structured guides with women with a history of PTB (n = 10), healthcare providers (n = 16) and health systems experts (n = 10); and 26 focus group discussions with pregnant women seeking antenatal care (n = 132) and community male partners/fathers (n = 54). Interviews/discussions were transcribed, translated, and analysed thematically. RESULTS: Pregnancy knowledge, especially for first time pregnancies was poor, with many reporting late entry to antenatal care. Knowledge about PTB was understood in terms of gestational age, weight or small size of baby, with concerns about long term health and stigma. Various risk factors for PTB were described, including those related to traditions and beliefs of witchcraft/curses. Cultural practices, such as the use of traditional medicines and pica, and religion and its impact on health seeking behaviour were also viewed as risk factors. Although insertion of intravaginal devices was not widely acceptable in traditional communities, especially during pregnancy, it was felt that the use of one to detect risk of PTB would be accepted if proven effective in reducing PTB risk. CONCLUSIONS: Various culturally-informed beliefs exist which explain understandings of and attitudes toward pregnancy, pregnancy risk, and PTB. An inclusive exploratory process is critical to facilitate an understanding of the beliefs and traditions which could impact the introduction and design of a product to detect the risk of PTB.

Intimate partner violence victimization during pregnancy increases risk of postpartum depression among urban adolescent mothers in South Africa.

BACKGROUND: It is estimated that 38.8% of mothers develop postpartum depression (PPD) in South Africa. While empirical evidence documents an association between intimate partner violence (IPV) victimization in pregnancy and PPD among adult women, the association has been underexamined among adolescent mothers (< 19 years). The study's purpose is to examine whether IPV victimization during pregnancy is associated with PPD among adolescent mothers. METHODS: Adolescent mothers (14-19 years) were recruited at a regional hospital's maternity ward in KwaZulu Natal, South Africa between July 2017-April 2018. Participants completed behavioral assessments at two visits (n = 90): baseline (up to 4 weeks postpartum) and follow-up (6-9 weeks postpartum, when PPD is typically assessed). The WHO modified conflict tactics scale was used to create a binary measure of any physical and/or psychological IPV victimization that occurred during pregnancy. Participants with scores ≥ 13 on the Edinburgh Postpartum Depression Scale (EPDS) were classified as having symptoms of PPD. We used a modified Poisson regression with robust standard errors to assess PPD in association with IPV victimization during pregnancy, controlling for relevant covariates. RESULTS: Nearly one-half (47%) of adolescent mothers reported symptoms of PPD by 6-9 weeks post-delivery. Further, IPV victimization during pregnancy was highly prevalent (40%). Adolescent mothers who reported IPV victimization during pregnancy had marginally higher risk of PPD at follow-up (RR: 1.50, 95 CI: 0.97-2.31; p = 0.07). The association was strengthened and significant in covariate-adjusted analysis (RR: 1.62, 95 CI: 1.06-2.49; p = 0.03). CONCLUSIONS: Poor mental health was common among adolescent mothers, and IPV victimization during pregnancy was associated with PPD risk among adolescent mothers. Implementing IPV and PPD routine screenings during the perinatal period may aid in identifying adolescent mothers for IPV and PPD interventions and treatment. With the high prevalence of IPV and PPD in this vulnerable population and the potential negative impact on maternal and infant outcomes, interventions to reduce IPV and PPD are needed to improve adolescent mothers' well-being and their baby's health.

BACKGROUND: More than one-third of adult mothers experience postpartum depression (PPD) in South Africa and intimate partner violence (IPV) victimization is a strong risk factor of PPD for adult mothers. However, there are no studies on adolescent mothers that look at the link between IPV victimization and PPD. This paper aims to examine whether IPV victimization during pregnancy is associated with PPD among adolescent South African mothers. METHODS: We had 90 adolescent mothers (aged 14­19 years old) complete an initial survey between delivery and 4 weeks postpartum to collect information on IPV during their pregnancy. Participants completed an additional survey between 6 and 9 week postpartum to collect information on the symptoms of PPD. RESULTS: Nearly one-half (47%) of adolescent mothers reported symptoms of PPD by 6­9 weeks post-delivery. Report of IPV victimization during pregnancy was also very high (40%). Adolescent mothers who experienced IPV victimization during pregnancy were more likely to report symptoms of PPD between 6 and 9 weeks postpartum. CONCLUSIONS: PPD and IPV was very common in our sample, and IPV victimization during pregnancy was linked to PPD among adolescent mothers. Having routine screenings during pregnancy and postpartum period can identify adolescent mothers IPV and PPD interventions and treatment. With the high reports of IPV and PPD in this sample and the potential negative impact on maternal and infant outcomes, interventions to reduce IPV and PPD are needed to improve adolescent mothers' well-being and their baby's health.

Perspectives on sexual and reproductive health self-care among women, healthcare providers, and other key informants: a mixed-methods study in South Africa and Zambia.

BACKGROUND: "Self-care" for sexual and reproductive health (SRH) includes contraceptive methods and other supplies that people can use with or without the support of a healthcare provider. Self-administered tests, self-injection of injectable contraception, or self-removal of intrauterine devices (IUDs) can increase people's access to and autonomy over their own SRH. Objectives of this study were to assess women's current interest in and use of SRH self-care and explore key informants' (KI) opinions of self-care, especially during the COVID-19 pandemic. METHODS: Data for this study came from female participants in the longitudinal Contraceptive Use Beyond ECHO (CUBE) study, and KIs, including healthcare providers, in South Africa and Zambia between September 2020 and June 2021. For this analysis, we used data from a participant phone survey (n = 537), and from in-depth interviews (IDIs) completed with a sub-sample of women (n = 39) and KIs (n = 36). Survey data were analyzed with descriptive statistics, and IDI data were analyzed using applied thematic analysis. RESULTS: Female survey participants in South Africa were more interested in learning about emergency contraceptive pills, subcutaneous injectable contraception, and CycleBeads, while Zambian participants wanted more information and access to condoms. However, in IDIs in both countries, women described minimal experience with self-care beyond condom use. In the Zambian KI IDIs, COVID-19 led to increased self-care counseling on subcutaneous injectable contraception and HIV self-testing. KIs who do not counsel on self-care were concerned that women may harm themselves or blame the provider for difficulties. Two KIs thought that women could possibly self-remove IUDs, but most expressed concerns. Reported barriers to self-care included COVID movement restrictions, transport costs, lack of accessible pharmacies, women's low awareness, and possible stigma. CONCLUSIONS: Women surveyed reported interest in learning more about SRH self-care methods and resources, but in IDIs did not report extensive previous use besides condoms. KIs described some concerns about women's ability to use self-care methods. Counseling on and provision of self-care methods and supplies may have increased during the COVID-19 pandemic, but ensuring that self-care is more than just a temporary measure in health systems has the potential to increase access to SRH care and support women's autonomy and healthcare needs.

BACKGROUND: "Self-care" refers to healthcare that does not have to be given by a provider, but that people can use themselves. In sexual and reproductive health (SRH), this includes medicines or supplies like pills and injections that people can use to prevent or test for pregnancy or sexually transmitted infections. This study wanted to better understand women's interest in and use of SRH self-care and explore key informants' opinions of self-care, especially during the COVID-19 pandemic. METHODS: We surveyed 537 women in KwaZulu-Natal province, South Africa and Lusaka, Zambia in 2020­2021. We also conducted interviews with 39 women and 36 key informants, including healthcare providers, government officials, and community advocates. RESULTS: Women surveyed in South Africa were more interested than those in Zambia in learning more about self-care contraception, especially daily pills, emergency pills, and injections they could give themselves. In interviews, some key informants said that they do not tell women about self-care because they worried that women could hurt themselves or blame the provider if they experienced problems. COVID movement restrictions, transport costs, and inaccessible pharmacies were all barriers that key informants mentioned to accessing tests, tools, or contraceptive methods that women could give or use themselves. CONCLUSIONS: Women surveyed were interested in learning more about self-care and those interviewed reported minimal previous use of self-care methods besides condoms. Providers also have some concerns about women's ability to use self-care methods. Counseling on and providing self-care methods and supplies may have increased during COVID-19, but increasing access to self-care could help more women take care of their own sexual and reproductive healthcare.

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.

Contraceptive Continuation and Experiences Obtaining Implant and IUD Removal Among Women Randomized to Use Injectable Contraception, Levonorgestrel Implant, and Copper IUD in South Africa and Zambia.

Few longitudinal studies have measured contraceptive continuation past one year in sub-Saharan Africa. We surveyed 674 women who had been randomized to receive the three-month intramuscular contraceptive injectable (DMPA-IM), levonorgestrel (LNG) implant, or copper intrauterine device (IUD) during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial in South Africa and Zambia and were subsequently followed for two additional years to explore method continuation, reasons for discontinuation, and access to implant and IUD removal services. We also conducted in-depth qualitative interviews with 39 participants. We estimated cumulative discontinuation probabilities using Kaplan-Meier estimates and assessed factors associated with discontinuation using Cox-proportional hazards models. The LNG implant continuation rate over the maximum 44-month study period was 60 percent, while rates for the copper IUD and DMPA-IM were 52 percent and 44 percent, respectively. Reasons for method discontinuation included side effects, particularly menstrual changes, and method stock-outs. Most implant and IUD users who sought removal were able to access services; however, room for improvement exists. In this cohort originally randomized to receive a contraceptive method and attend regular study visits, implants and IUDs continued to be highly acceptable over an additional two years, but facilities should continue to ensure that insertions and removals are available as requested.

Is long-acting reversible contraceptive method use associated with HIV testing frequency in KwaZulu-Natal, South Africa and Lusaka, Zambia? Findings from the CUBE study.

Objectives: To assess differences in HIV testing at 6-months intervals over 24 months among intramuscular depot medroxyprogesterone acetate (DMPA-IM) injectable, levonorgestrel implant, or copper intrauterine devices (IUD) users in KwaZulu-Natal, South Africa, and Lusaka, Zambia. Testing at recommended intervals has not been previously assessed in long-acting reversible contraceptive (LARC) users (implant and IUD users) compared to those using effective but shorter-acting methods (such as DMPA-IM) in sub-Saharan Africa. Study design: As part of the longitudinal contraceptive use beyond ECHO (CUBE) study, we measured HIV testing over 24 months. Participants were considered continuous users of DMPA-IM, levonorgestrel implant, or copper IUD if they used the same method across all months of their study participation, or not continuous users of their baseline CUBE method if they switched or discontinued their method. We used multivariable logistic regression models with generalized estimating equations and robust standard errors, stratified by country, to assess differences in HIV testing. Results: Among the 498 participants, HIV testing rates were higher in Zambia for all methods compared to South Africa. In bivariate analyses, continuous implant or IUD users (the LARC users) were significantly less likely to report having received HIV testing at the 6-months and 24-months surveys, compared to continuous DMPA-IM users. In adjusted longitudinal models, continuous IUD users (adjusted odds ratio: 0.42, 95% CI: 0.24, 0.74), continuous implant users (adjusted odds ratio: 0.23, 95% CI: 0.12, 0.42) in South Africa had significantly lower odds of HIV testing compared to continuous DMPA-IM users. There were no significant differences in Zambia in the adjusted models. Conclusion: LARC use may reduce opportunities for HIV testing and users should be counseled on regular HIV testing and the option of HIV self-testing. Implications: Due to infrequent clinical contacts which may lead to lower rates of HIV testing at recommended intervals, LARC users should be provided opportunities to test for HIV at home or when seeking other health services.

Functional performance of the Wondaleaf condom: A crossover, noninferiority, randomized clinical trial.

BACKGROUND: New female condom (FC) products wishing to apply for United Nations Population Fund/World Health Organisation (UNFPA/WHO) prequalification are required to conduct a randomized, controlled clinical investigation comparing the new FC to the marketed FC, in order to comply with UNFPA/WHO and International Organization for Standardization (ISO) specifications. We aimed to assess the functional performance, acceptability and safety of the Wondaleaf female condom compared to the control FC2 female condom. METHODS: This randomized clinical trial enrolled 220 women in one South African site. The primary outcome of the study was the rate of female condom (FC) failure. Participants were asked to use five of each FC type and to collect information on use in a condom diary at home, and were interviewed after use of each FC type. RESULTS: Noninferiority was demonstrated for the Wondaleaf with respect to the reference FC2 for all condom functions. The Wondaleaf was found to be superior to the FC2 reference condom for invagination (p > .000), misdirection (p > .000) and clinical failure (p > .000). Acceptability ratings for a range of features were similar between the two FCs. Few safety events were reported for either device. CONCLUSION: The Wondaleaf performs as well as the FC2, and is equally acceptable. Results from this study will inform further refinement of this FC design. Trial registrations: ClinicalTrials.gov Identifier: NCT04076774 https://clinicaltrials.gov/. South African National Clinical Trials Database (SANCTR) number DOH-27-0319-6020.

"It's a 50/50 Thing You Know": Exploring the Multileveled Intersections of Gender and Power Within the Relationships of Young South African Men and Women.

Efforts to advance sexual health globally require greater understandings of youth intimate relationship dynamics. Among 38 South African youth (21 women/17 men aged 21-30 from Durban and Soweto) we conducted qualitative cognitive interviews to explore how gender and power intersect to shape intimate relationship dynamics (October 2019-March 2021). Participants discussed perceptions and relevance of each of 13 items comprising the Sexual Relationship Power (SRP) scale, a widely used measure of gender equity, and the influence of SRP on youth sexual health. Data analysis was guided by constructivist grounded theory. The findings were organized using the socio-ecological model, revealing how gender and power intersected at multiple levels to influence youth intimate relationships. Key influencing factors included individual-level gender attitudes, male partner expectations, and women's resistance to dominance; intimate relationship-level power dynamics, consent, and intimacy; family-level household configurations and parental monitoring of daughters; and societal-level traditional gender norms. At all levels, women discussed resisting power inequities through communication and rejection of inequitable relationships. While men also displayed resistance to inequitable power structures, most upheld traditional gender norms through institutional affiliation (e.g. church) and deep-rooted socialized beliefs and attitudes. Efforts to improve youth sexual health require multileveled approaches that address inequitable power dynamics.

High Levels of Pretreatment HIV-1 Drug Resistance Mutations Among South African Women Who Acquired HIV During a Prospective Study.

BACKGROUND: Pretreatment HIV drug resistance (PDR) undermines individual treatment success and threatens the achievement of UNAIDS 95-95-95 targets. In many African countries, limited data are available on PDR as detection of recent HIV infection is uncommon and access to resistance testing is limited. We describe the prevalence of PDR among South African women with recent HIV infection from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. METHODS: HIV-uninfected, sexually active women, aged 18-35 years, and seeking contraception were enrolled in the ECHO Trial at sites in South Africa, from 2015 to 2018. HIV testing was done at trial entry and repeated quarterly. We tested stored plasma samples collected at HIV diagnosis from women who seroconverted during follow-up and had a viral load >1000 copies/mL for antiretroviral resistant mutations using a validated laboratory-developed population genotyping assay, which sequences the full protease and reverse transcriptase regions. Mutation profiles were determined using the Stanford Drug Resistance Database. RESULTS: We sequenced 275 samples. The median age was 23 years, and majority (98.9%, n = 272) were infected with HIV-1 subtype C. The prevalence of surveillance drug resistance mutations (SDRMs) was 13.5% (n = 37). Nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations were found in 12.4% of women (n = 34). Few women had NRTI (1.8%, n = 5) and protease inhibitor (1.1%, n = 3) mutations. Five women had multiple NRTI and NNRTI SDRMs. CONCLUSIONS: The high levels of PDR, particularly to NNRTIs, strongly support the recent change to the South African national HIV treatment guidelines to transition to a first-line drug regimen that excludes NNRTIs.

Brief Report: Quantifiable Plasma Tenofovir Among South African Women Using Daily Oral Pre-exposure Prophylaxis During the ECHO Trial.

BACKGROUND: HIV endpoint-driven clinical trials provide oral pre-exposure prophylaxis (PrEP) as HIV prevention standard of care. We evaluated quantifiable plasma tenofovir among South African women who used oral PrEP during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. METHODS: ECHO, a randomized trial conducted in 4 African countries between 2015 and 2018, assessed HIV incidence among HIV-uninfected women, aged 16-35 years, randomized to 1 of 3 contraceptives. Oral PrEP was offered onsite as part of the HIV prevention package at the South African trial sites. We measured tenofovir in plasma samples collected at the final trial visit among women reporting ongoing PrEP use. We used bivariate and multivariate logistical regression to assess demographic and sexual risk factors associated with plasma tenofovir quantification. RESULTS: Of 260 women included, 52% were ≤24 years and 22% had Chlamydia trachomatis at enrollment. At PrEP initiation, 68% reported inconsistent/nonuse of condoms. The median duration of PrEP use was 90 days (IQR: 83-104). Tenofovir was quantified in 36% (n = 94) of samples. Women >24 years had twice the odds of having tenofovir quantified vs younger women (OR = 2.12; 95% confidence interval = 1.27 to 3.56). Women who reported inconsistent/nonuse of condoms had lower odds of tenofovir quantification (age-adjusted OR = 0.47; 95% confidence interval = 0.26 to 0.83). CONCLUSIONS: Over a third of women initiating PrEP and reporting ongoing use at the final trial visit had evidence of recent drug exposure. Clinical trials may serve as an entry point for PrEP initiation among women at substantial risk for HIV infection with referral to local facilities for ongoing access at trial end. CLINICAL TRIAL NUMBER: NCT02550067.

Toward an intravaginal device to detect risk of preterm labor: a user-centered design approach in Sub-Saharan Africa.

BACKGROUND: Prematurity and its complications are the leading cause of death and disability in children under five in Africa and North America, affecting as many as one in ten pregnancies. Screening tests to predict preterm birth (PTB) are insensitive, costly, and often unavailable in low resource settings. In parallel with early-stage U.S.-based testing of a novel self-placed intravaginal device to predict PTB risk, we elicited key stakeholder input from two sub-Saharan African countries to ensure local contextual factors inform future development of the device and its acceptability. METHODS: A qualitative study was conducted in Kiambu County, Kenya and KwaZulu-Natal Province, South Africa. We conducted 26 focus group discussions with pregnant women (n = 132) and males from the community (n = 54); in-depth interviews with women who had a history of PTB (n = 10), healthcare providers (n = 16), and health system experts (n = 10). Interviews were transcribed and thematic analysis was performed using an iterative coding technique. In addition, we facilitated user-centered design sessions to generate prototype preferences. RESULTS: Women with a personal history of PTB were almost unanimous in support of the proposed device, whereas those with no experience of PTB expressed the greatest degree of reservation. Healthcare providers anticipated that women with a history of PTB would accept the device. However, various potential challenges were identified, including potential discomfort with device insertion, hygiene, and sexual activity, as well as need for provider training, and attention to country-specific regulatory processes. Both community participants and providers expressed a preference for a provider inserted device. Design recommendations included preference for a small, soft, pliable device, with a shape that could facilitate easy removal. CONCLUSIONS: Use of an intravaginal device to detect risk of PTB was generally acceptable, however stakeholders expressed a notable preference for insertion by providers. This reflects the significance of end-user consultation in device design and use. Recommended device modifications as well as educational messaging and provider technical assistance may facilitate utilization.

Prematurity and its complications are the leading cause of death and disability in children under 5 years of age. Up to ten percent of pregnancies in North America and Africa are affected. Screening tests to predict preterm birth (PTB) are insensitive, costly, and often unavailable in low resource settings. A U.S.-based study has developed an intravaginal device to detect preterm labor. In order to assess acceptability and guide development for a low-resource setting, a qualitative study was conducted in Kenya and South Africa. We conducted focus group discussions and interviews with pregnant women, male community members, health care providers and health systems experts. Participants with a personal history of PTB were almost unanimous in support of the proposed device; women with no experience of PTB expressed the greatest degree of reservation. Various potential challenges were identified: discomfort, hygiene, and sexual activity, the need for provider training and attention to country-specific regulatory processes. Design recommendations included preference for a small, soft, pliable device, with a shape that could facilitate easy removal. Stakeholders expressed a strong preference for insertion by providers. These findings reflect the significance of end-user consultation in device design and use.

"I feel like it is asking if he is a stalker but I also feel like it is asking if he cares": exploring young South African women and men's perceptions of the Sexual Relationship Power Scale.

BACKGROUND: Gender inequity and the subsequent health impacts disproportionately affect communities in the Global South. However, most gender equity measures, such as Pulerwitz' (2000) Sexual Relationship Power Scale (SRPS), are developed and validated in the Global North and then applied in Global South settings without investigation of context applicability or validity. This study examines the SRPS' validity evidence, comprehensiveness, and contemporary relevance for young South African women and men. METHODS: Between 2019 and 2021, 38 cognitive interviews (CIs) were conducted among previous participants of a South African youth cohort study 'AYAZAZI' (2015-2017) to explore youth's perceptions of the SRPS. The SRPS measures women's perceptions of their partner's controlling behaviours, and men's perceptions of their own controlling behaviours. Using CIs, participants responded to a 13-item adaptation of the SRPS for use among South African youth (strongly agree-strongly disagree), and then were asked to think-aloud their reasoning for responses, their understanding and perceived relevance of each item, and made overall suggestions for scale adaptations. An item appraisal coding process was applied, whereby Cognitive Coding assessed the types of cognitive problems youth had with understanding the items, and Question Feature Coding assessed which item features caused problems for participant understandings. Finally, youth recommendations for scale adaptations were summarized. RESULTS: Overall, 21 women and 17 men aged 21-30 participated in CIs in Durban and Soweto, South Africa. Cognitive Coding revealed 1. Comprehension issues, and 2. Judgements related to items' applicability to lived experiences and identities (e.g., being unmarried). Question Feature Coding revealed items' 1. Lack of clarity or vagueness in wording and 2. Logical problems in assumptions leading to multiple interpretations (e.g., item 'my partner always need to know where I am' interpreted as both controlling and caring behaviour). Multiple, overlapping issues revealed how many items failed to "fit" within the present-day living realities of South African youth. Youth recommended several item adaptations and additions, including strength-based items, to existing measures of gender equity and relationship power. CONCLUSION: Given identified issues, several adaptations including revising items to be more inclusive, contemporary, context specific, relational, and strength-based are needed to validly measure gender equity and power dynamics within the relationships of South African youth.