Sexual behaviour among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Data from the ECHO randomized trial.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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.

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).

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.

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.

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.

Optimizing PMTCT Adherence by Treating Depression in Perinatal Women with HIV in South Africa: A Pilot Randomized Controlled Trial.

BACKGROUND: South Africa (SA) has the greatest HIV prevalence in the world, with rates as high as 40% among pregnant women. Depression is a robust predictor of nonadherence to antiretroviral therapy (ART) and engagement in HIV care; perinatal depression may affect upwards of 47% of women in SA. Evidence-based, scalable approaches for depression treatment and ART adherence in this setting are lacking. METHOD: Twenty-three pregnant women with HIV (WWH), ages 18-45 and receiving ART, were randomized to a psychosocial depression and adherence intervention or treatment as usual (TAU) to evaluate intervention feasibility, acceptability, and preliminary effect on depressive symptoms and ART adherence. Assessments were conducted pre-, immediately post-, and 3 months post-treatment, and included a qualitative exit interview. RESULTS: Most (67.6%) eligible individuals enrolled; 71% completed at least 75% of sessions. Compared to TAU, intervention participants had significantly greater improvements in depressive symptoms at post-treatment, ß = - 11.1, t(24) = - 3.1, p < 0.005, 95% CI [- 18.41, - 3.83], and 3 months, ß = - 13.8, t(24) = - 3.3, p < 0.005, 95% CI [- 22.50, - 5.17]. No significant differences in ART adherence, social support, or stigma were found. Qualitatively, perceived improvements in social support, self-esteem, and problem-solving adherence barriers emerged as key benefits of the intervention; additional sessions were desired. CONCLUSION: A combined depression and ART adherence intervention appears feasible and acceptable, and demonstrated preliminary evidence of efficacy in a high-need population. Additional research is needed to confirm efficacy and identify dissemination strategies to optimize the health of WWH and their children. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03069417. Protocol available at https://clinicaltrials.gov/ct2/show/NCT03069417.

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.

High HIV incidence among young women in South Africa: Data from a large prospective study.

INTRODUCTION: South Africa has the highest national burden of HIV globally. Understanding drivers of HIV acquisition in recently completed, prospective studies in which HIV was an endpoint may help inform the strategy and investments in national HIV prevention efforts and guide the design of future HIV prevention trials. We assessed HIV incidence and correlates of incidence among women enrolled in ECHO (Evidence for Contraceptive Options and HIV Outcomes), a large, open-label randomized clinical trial that compared three highly effective. reversible methods of contraception and rates of HIV acquisition. METHODS: During December 2015 to October 2018, ECHO followed sexually active, HIV-seronegative women, aged 16-35 years, seeking contraceptive services and willing to be randomized to one of three contraceptive methods (intramuscular depot medroxyprogesterone acetate, copper intrauterine device, or levonorgestrel implant) for 12-18 months at nine sites in South Africa. HIV incidence based on prospectively observed HIV seroconversion events. Cox proportional hazards regression models were used to define baseline cofactors related to incident HIV infection. RESULTS: 5768 women were enrolled and contributed 7647 woman-years of follow-up. The median age was 23 years and 62.5% were ≤24 years. A total of 345 incident HIV infections occurred, an incidence of 4.51 per 100 woman-years (95%CI 4.05-5.01). Incidence was >3 per 100 woman-years at all sites. Age ≤24 years, baseline infection with sexually transmitted infections, BMI≤30, and having new or multiple partners in the three months prior to enrollment were associated with incident HIV. CONCLUSIONS: HIV incidence was high among South African women seeking contraceptive services. Integration of diagnostic management of sexually transmitted infections alongside delivery of HIV prevention options in health facilities providing contraception services are needed to mitigate ongoing risks of HIV acquisition for this vulnerable population. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT02550067 was the main Clinical Trial from which this secondary, non-randomized / observational analysis was derived with data limited to just South African sites.

Color, Scent and Size: Exploring Women's Preferences Around Design Characteristics of Drug-Releasing Vaginal Rings.

Steroid-releasing vaginal rings are available for contraception and estrogen replacement therapy, and a new antiretroviral-releasing ring was recently approved for HIV prevention. Marketed rings are white or transparent in appearance, non-scented, and supplied as one-size-fits-all devices with diameters ranging from 54 to 56 mm. In this study, drug-free silicone elastomer rings were manufactured in different sizes, colors and scents, and the opinions/preferences of 16 women (eThekwini District, South Africa; 20-34 years) assessed through focus group discussions and thematic analysis. Opinions varied on ring color and scent, with some women preferring specific colors or scent intensities, while for others these attributes were unimportant. Concerns about color and scent were linked to perceptions around vaginal health and safety related to chemical composition. There was greater agreement on preferred ring size; flexibility and width were considered important factors for insertion and comfort. Greater choice with ring products could facilitate acceptability and overall uptake.

Daily Oral Pre-exposure Prophylaxis (PrEP) Continuation Among Women from Durban, South Africa, Who Initiated PrEP as Standard of Care for HIV Prevention in a Clinical Trial.

HIV incidence among women in Eastern and Southern Africa remains unacceptably high, highlighting the need for effective HIV prevention options, including pre-exposure prophylaxis (PrEP). The Evidence for Contraceptive Options and HIV Outcomes trial offered daily oral PrEP to participants during the latter part of the clinical trial as an additional HIV prevention choice. We explored daily oral PrEP continuation at trial exit among women enrolled from Durban, South Africa who initiated oral PrEP at the trial site. Of the 132 women initiating oral PrEP, 87% reported continuation of oral PrEP at month 1, 80% at month 3, and 75% continued using oral PrEP at their final trial visit and were referred to off-site facilities for ongoing oral PrEP access. The median duration of oral PrEP use in trial participants who used oral PrEP was 91 days (IQR 87 to 142 days). Women who disclosed their oral PrEP use to someone had increased odds of continuing oral PrEP at trial exit. Women who reported > 1 sex partner and those who felt they would probably or definitely get infected with HIV had reduced odds of continuing oral PrEP at trial exit. Of those discontinuing oral PrEP (n = 32), > 50% discontinued within the first month, and the most common reason for discontinuation was reporting side effects. The high rates of oral PrEP continuation in our study are encouraging and our findings can be utilized by other clinical trials providing oral PrEP as standard of care for HIV prevention and by oral PrEP implementation programmes.

Gender, Power, and Health: Measuring and Assessing Sexual Relationship Power Equity Among Young Sub-Saharan African Women and Men, a Systematic Review.

Gender inequity, including low sexual relationship power (SRP), is an important determinant of intimate partner violence (IPV) and negative sexual, reproductive, and mental health. Different versions of the Sexual Relationship Power Scale (SRPS) are commonly used within youth studies to examine how gender inequities, including controlling behaviors, in heterosexual relationships impact the lives of young people in sub-Saharan Africa. This review aims to (1) describe definitions and measures of SRP within sub-Saharan African youth studies and (2) review and summarize associations between SRP equity, IPV, and sexual, reproductive, and mental health. After searching Pubmed, Ovid Med, Psych info, Web of Science, Google Scholar, and relevant research forums, 304 papers were identified, of which 29 papers based on 15 distinct studies (published 2004-2019) met our criteria for being youth-specific, conducted in sub-Saharan Africa, and including a quantitative measure of SRP. Details of each SRPS are described, including any adaptations and psychometric properties, as well as associations with IPV, sexual, reproductive, and mental health behaviors and outcomes. Results indicate that there are variations to the SRPS, and a paucity of evidence has detailed the psychometric properties of such measures within sub-Saharan African youth studies. Measures of SRP equity are associated with experiences (among women) and perpetration of (among men) IPV as numerous pathways to HIV risk; however, the evidence remains mixed. In order to address overlapping epidemics of violence against women and HIV, efforts are needed to ensure that measures, including the SRPS, are valid and reliable among highly affected populations.

High cellphone use associated with greater risk of depression among young women aged 15-24 years in Soweto and Durban, South Africa.

BACKGROUND: The ubiquity of cellular phone (cellphone) use in young people's daily lives has emerged as a priority area of concern for youth mental health. OBJECTIVE: This study measured the prevalence of depression and its association with high cellphone use among youth in Soweto and Durban, South Africa. METHODS: We analysed cross-sectional, baseline survey data among youth aged 16-24 who participated in a dual-site cohort study, 'AYAZAZI', conducted from 2014 to 2017. The primary outcome was depression using the 10-item Center for Epidemiologic Studies Depression Scale, with a score of ≥ 10 indicating probable depression. Cellphone use was measured via self-reported average number of hours of active use, with 'high cellphone use' defined as daily usage of ≥ 8. Multivariable logistic regression models assessed the independent relationship between high cellphone use and probable depression, adjusting for potential confounders. RESULTS: Of 425 participants with a median age of 19 years (IQR = 18-21), 59.5% were young women. Overall, 43.3% had probable depression, with a higher prevalence among women (49.0% vs. 34.9%, P = .004). Nearly all (94.6%) owned a cellphone. About one-third (29.5%) reported spending ≥ 8 hours per day using their cellphone (39.3% of women vs. 14.9% of men, P < .001). In the overall adjusted model, youth reporting high daily cellphone use had higher odds of probable depression (aOR: 1.83, 95% CI: 1.16-2.90). In gender-stratified models, high daily cellphone use was associated with probable depression among women (aOR: 2.51, 95% CI: 1.47-4.31), but not among men (aOR: 0.87, 95% CI: 0.35-2.16). CONCLUSIONS: Among a cohort of South African youth, we found a high prevalence of probable depression and high cellphone use (30%). The findings indicate a need for intersectoral initiatives focused on meaningful mental health support for South African youth to support positive growth and development.

Weight change among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Findings from a randomised, multicentre, open-label trial.

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 between December 2015 and October 2018. HIV negative, women aged 16-35 years, desiring contraception, were randomised (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 (kg) was measured at baseline and study exit. Analysis was performed as intention to treat (ITT) and time on continuous contraceptive use. The primary outcome of this secondary analysis is weight change from study enrolment to the final visit at study month 12-18. The ECHO trial is registered with ClinicalTrials.gov, NCT02550067. 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: 3.5 kg (SD = 6.3), 2.4 kg (SD = 5.9) and 1.5 kg (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 < 0.001) for DMPA-IM versus copper IUD, 0.87 kg (0.53,1.20 p < 0.001) for LNG implant compared to copper IUD and 1.16 kg (0.82, 1.50, p < 0.001) for DMPA-IM compared with LNG implant. Results for continuous contraceptive use were similar. INTERPRETATION: We found differences in weight gain between POC users compared to the non-hormonal copper IUD group over 12-18 months of use. Women using POCs should be counselled about this potential side effect when choosing a contraceptive method.

Food insecurity and depression: a cross-sectional study of a multi-site urban youth cohort in Durban and Soweto, South Africa.

OBJECTIVE: To assess the prevalence of food insecurity and the independent association between depression and food insecurity among youth living in two urban settings in South Africa. METHODS: Baseline cross-sectional survey data was analysed from a prospective cohort study conducted between 2014 and 2016 among youth (aged 16-24 years) in Soweto and Durban. Interviewer-administered questionnaires collecting socio-demographic, sexual and reproductive health and mental health data were conducted. Household food insecurity was measured using the 3-item Household Hunger Scale, with food insecure participants defined as having 'moderate' or 'severe hunger' compared to 'no hunger'. Depression was assessed using the 10-item Center for Epidemiological Studies Depression (CES-D 10) Scale (range 0-30, probable depression ≥ 10). Multivariable logistic regression models were used to estimate the association between depression and food insecurity. RESULTS: There were 422 participants. Median age was 19 years (interquartile range [IQR] 18-21) and 60% were women. Overall, 18% were food insecure and 42% had probable depression. After adjustment for socio-demographic variables (age, gender, female-headed household, household size and school enrolment), participants with probable depression had higher odds of being food insecure than non-depressed participants (2.79, 95%CI 1.57-4.94). CONCLUSION: Nearly one-fifth of youth in this study were food insecure. Those with probable depression had increased odds of food insecurity. Interventions are needed to address food insecurity among urban youth in South Africa, combining nutritional support and better access to quality food with mental health support.

Intimate Partner Violence, Depression, and Anxiety Are Associated With Higher Perceived Stress Among Both Young Men and Women in Soweto and Durban, South Africa.

Objectives: Psychological stress is an important determinant of health, including for mental well-being and sexual health. However, little is known about the prevalence and psychosocial and sexual health correlates of perceived stress among young people in South Africa, where elevated life-stressors are an important driver of health inequities. This study examines the association between intimate partner violence (IPV), psychosocial and sexual health, and perceived stress, by gender, among South African adolescents and young adults. Methods: Using baseline survey data from AYAZAZI, a cohort study enrolling youth (16-24 years) from Durban and Soweto, we used the 10-item Perceived Stress Scale (PSS-10) to measure the degree to which an individual perceives their life situations as unpredictable, uncontrollable, and overloaded. Possible scores range between 0 and 40; higher scores indicating higher perceived stress. Crude and adjusted gender-stratified linear regression models examined associations between sexual health factors, experiences (young women) and perpetration (young men) of IPV, anxiety (APA 3-item Scale, ≥2 = probable anxiety), and depression (10-item CES-D Scale, ≥10 = probable depression) and perceived stress. Multivariable models adjusted for age, income, sexual orientation, and financial dependents. Results: Of the 425 AYAZAZI participants, 60% were young women. At baseline, 71.5% were students//learners and 77.2% earned ≤ ZAR1600 per month (~$100 USD). The PSS-10 had moderate reliability (α = 0.70 for young women, 0.64 for young men). Young women reported significantly higher mean PSS scores than young men [18.3 (6.3) vs. 16.4 (6.0)]. In adjusted linear regression models, among young women experiences of IPV (ß = 4.33; 95% CI: 1.9, 6.8), probable depression (ß = 6.63; 95% CI: 5.2, 8.1), and probable anxiety (ß = 5.2; 95% CI: 3.6, 6.8) were significantly associated with higher PSS scores. Among young men, ever perpetrating IPV (ß = 2.95; 95% CI: 0.3, 5.6), probable depression (ß = 6; 95% CI: 4.3, 7.6), and probable anxiety (ß = 3.9; 95% CI: 2.1, 5.8) were significantly associated with higher perceived stress. Conclusion: We found that probable depression, anxiety, perpetration of IPV among young men, and experiences of IPV among young women, were associated with higher perceived stress. Critical efforts are needed to address the gendered stressors of young men and women and implement services to address mental health within violence prevention efforts.

Gender and Power Dynamics of Social Relationships Shape Willingness to Participate in Biomedical HIV Prevention Research Among South African Adolescents and Young Adults.

Background: Understanding young women and men's perceived barriers and facilitators to participation in biomedical HIV prevention research is important for designing youth friendly services (YFS) and acceptable technologies, which are necessary for preventing high sustained HIV incidence in South Africa. This study explores the multileveled barriers and facilitators to young men and women's willingness to participate in hypothetical biomedical HIV prevention research. Methods: Eight age- (16-18 and 19-24 years) and gender-stratified focus group discussions (FGDs) were conducted using semi-structured interview guides to explore young South African women and men's willingness, perceived barriers, and facilitators to participating in biomedical HIV prevention research. FGD transcripts were uploaded to NVivo and coded collaboratively with youth study team members. Thematic analysis using Bronfenbrenner's ecological model (individual, inter-personal, community, and societal) was used to guide a deductive coding procedure, which was documented and compared by gender. Results: Thirty-one participants from Durban and 34 from Soweto participated in FGDs. Individual facilitators for participation were discussed more by young men and included financial incentives and altruism. Concerns about side-effects of biomedical products were a common barrier. Interpersonal relationships with peers, intimate partners and caregivers influenced young people's willingness to participate in HIV prevention research, more so among young women. For young women, gendered power dynamics and distrust of intimate partners and parents influenced both communication regarding participation and willingness to participate in research that is often stigmatized, due to societal norms around women's sexuality. On a societal level, participants expressed distrust in medical and research institutions, however a sense of community that was developed with the study staff of this project, was a motivator to participate in future studies. Discussion: At each level of the ecological model, we found participants expressed gendered barriers and facilitators for participation. Gender norms as well as distrust of partners, parents, and health care professionals were key barriers that cut across all levels. At each level participants discussed facilitators that were youth-engaged, underscoring the need to implement YFS, establish trust and address gender inequities within future biomedical HIV prevention studies wishing to engage and retain South African youth.

Preferences and Acceptability of Vaginal Delivery Forms for HIV Prevention Among Women, Male Partners and Key Informants in South Africa and Zimbabwe: Qualitative Findings.

The attributes of an HIV microbicide may affect its acceptability, uptake and use. Quatro, a clinical study with a qualitative component, was conducted to elicit input from end-users and key informants (KIs) on four different placebo vaginal microbicide delivery forms; fast dissolving insert, ring, film and gel. In-depth interviews and focus group discussions were conducted with young women, their male partners and KIs, to explore acceptability and preferences of the four placebo products, with the intention of improving product attributes, adherence, and consequently, long term effectiveness. None of the four microbicide delivery forms stood well above others as the most preferred. Product attributes; long-action, ease of use, invisibility, female initiated and non-interference during sex were favourable in both countries. Despite preference for the long-action, on-demand products were the most liked by women. Qualitative data from the Quatro study provided rich feedback on specific attributes important to the acceptability of four HIV prevention product platforms currently in development, enabling more informed and guided product development efforts moving forward.

Exploring the Use of Oral Pre-exposure Prophylaxis (PrEP) Among Women from Durban, South Africa as Part of the HIV Prevention Package in a Clinical Trial.

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.