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.

Effects of depot medroxyprogesterone acetate, the copper IUD and the levonorgestrel implant on testosterone, sex hormone binding globulin and free testosterone levels: ancillary study of the ECHO randomized clinical trial.

BACKGROUND: Robust information on relative effects of hormonal contraceptives on endogenous androgens is important for understanding beneficial and adverse effects, method choice and development of new methods. METHODS: In this ancillary study at the East London, South Africa site of the ECHO multicentre randomized trial, we compared effects of three contraceptive methods on serum androgen levels among contraceptive users aged 18 to 35 years. Participants were allocated by centrally-managed randomization to open label depot medroxyprogesterone acetate (DMPA-IM), copper intrauterine device (IUD) or levonorgestrel implant. The primary outcome was free testosterone at 6 months. RESULTS: We analysed stored baseline and 6-month serum samples in 398/615 participants (DMPA-IM 131/205, IUD 135/205 and implant 132/205). Median testosterone levels at baseline were DMPA-IM 0.82, IUD 0.9 and implant 0.87 nmol/L; at 6 months, DMPA 0.68 (lower than IUD, mean percentage difference 28.35, (p <  0.001), IUD 0.86 (unchanged) and implant 0.66, lower than IUD, mean percentage difference - 22.98, p <  0.001). Median SHBG levels at baseline were DMPA 52.4, IUD 50.5 and implant 55.75 nmol/L; at 6 months, DMPA 40.65, lower than IUD (mean percentage difference 21.19, p = 0.005), IUD 49.1 (unchanged), and implant 23.35 nmol/L, lower than IUD (mean percentage difference - 50.04, p <  0.001 and than DMPA (mean percentage difference - 39.45, p <  0.001). Free testosterone levels at baseline were DMPA 10, IUD 12 and implant 11 pmol/L; at 6 months, DMPA 11, less than IUD (mean percentage difference 13.53, p = 0.047), IUD 12 and implant 14, higher than IUD (mean percentage difference 14.15, p = 0.038) and than DMPA, (mean percentage difference 29.60, p < 0.001). CONCLUSIONS: This is the first randomized trial to show lower SHBG and higher free testosterone with the levonorgestrel implant than with DMPA, and contrasts with reports of increased SHBG with combined oral ethinyl estradiol/levonorgestrel use, and reduced androgens (and impaired sexual function) reported with the etonorgestrel implant. The higher free testosterone with the LNG implant might improve sexual function, mood and bone health as well as increasing side-effects such as acne and hirsutism, and is consistent with the greater sexual activity (with respect to multiple sex partners, new sex partner and unprotected sex) with the implant compared with DMPA documented in the ECHO study. ECHO TRIAL REGISTRATION: ClinicalTrials.gov , number NCT02550067 15/09/2015. Contraception, or family planning, is central to the role of women in societies. It is most important to have accurate information on the relative side-effects of various contraceptive options in order to empower women to make informed choices regarding their preferred method. Hormonal contraceptives contain various forms of the female sex hormones, estrogens and/or progestogens. These hormones have direct effects on the users, as well as modifying the levels of the users' own circulating sex hormones, both the 'female' and the 'male' sex hormones (androgens). In this study, consenting participants requesting contraception, were allocated randomly to receive either depot medroxyprogesterone acetate (DMPA-IM) a 3-monthly progestogen injection, the copper intrauterine device (IUD), a non-hormonal contraceptive inserted within the womb, or the levonorgestrel implant, a device placed under the skin which releases a progestogen for 5 years. We measured the participants' androgen levels after 6 months, and found for the first time that the active form of testosterone (free testosterone) was 29% higher with the implant than with DMPA-IM. The level with the IUD was intermediate, and significantly different from the other two methods. This finding is relevant to the effects experienced by users of these methods, because free testosterone has effects on sexual function, bone health and mood, as well as on conditions such as acne and hair distribution patterns.

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).

Effects of Depot Medroxyprogesterone Acetate Intramuscular Injection, Copper Intrauterine Device and Levonorgestrel Implant Contraception on Estradiol Levels: An Ancillary Study of the ECHO Randomized Trial.

Introduction: Hormonal contraception affects endogenous sex steroid levels. Robust evidence from randomized trials of the relative effects of different contraceptive methods is scarce. We compared the effects of three contraceptive methods on serum estradiol levels using data from women (18-35 years) requesting contraception in the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial. Methods: Women were randomly allocated to the depot medroxyprogesterone acetate intramuscular (DMPA-IM) injection, copper intrauterine device (IUD) or levonorgestrel (LNG) implant. In this sub-study, stored baseline and 6-month serum samples were analyzed in 401 participants from East London, South Africa (DMPA-IM: 131, IUD: 135 and LNG: 135). Results: Baseline median (interquartile range, IQR) estradiol levels were similar between the three groups [DMPA-IM 229 (152-455), IUD 235 (168-426) and LNG 216 (153-419 pmol/L)]. At 6-months, median estradiol in the IUD group was unchanged (298 (163-467) pmol/L), whilst levels in the DMPA-IM and implant groups were significantly reduced from baseline. The median estradiol level in the DMPA-IM group [139 (97-193) pmol/L] was significantly lower than in both IUD (p < 0.0001) and implant (p = 0.005) groups; and level in the implant group [156 (112-250) pmol/L] was significantly lower than in the IUD group (p = 0.004). Conclusions: At 6-months (DMPA-IM nadir), median estradiol with DMPA-IM was 53% lower and with the LNG implant, 48% lower than with the IUD. The greater reduction in estradiol levels with the DMPA-IM injection compared to the LNG implant and IUD has implications for the relative psychological, sexual as well as physiological side-effects of these contraceptive methods. ECHO Study Registration: ClinicalTrials.gov, identifier: 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.

Cumulative incidence of SARS-CoV-2 and associated risk factors among healthcare workers: a cross-sectional study in the Eastern Cape, South Africa.

OBJECTIVES: This study assesses the cumulative incidence of SARS-CoV-2 infection among healthcare workers (HCWs) during South Africa's first wave and examines the associated demographic, health-related and occupational risk factors for infection. METHODS: Multistage cluster sampling was used in a cross-sectional study to recruit 1309 HCWs from two academic hospitals in the Eastern Cape, South Africa over 6 weeks in November and December 2020. Prior test results for SARS-CoV-2 PCR and participants' characteristics were recorded while a blood sample was drawn for detection of IgG antibodies against SARS-CoV-2 nucleocapsid protein. The primary outcome measure was the SARS-CoV-2 cumulative incidence rate, defined as the combined total of positive results for either PCR or IgG antibodies, divided by the total sample. The secondary outcome was significant risk factors associated with infection. RESULTS: Of the total participants included in the analysis (n=1295), the majority were women (81.5%), of black race (78.7%) and nurses (44.8%). A total of 390 (30.1%) HCWs had a positive SARS-CoV-2 PCR result and SARS-CoV-2 antibodies were detected in 488 (37.7%), yielding a cumulative incidence of 47.2% (n=611). In the adjusted logistic regression model, being overweight (adjusted OR (aOR)=2.15, 95% CI 1.44 to 3.20), obese (aOR=1.37, 95% CI 1.02 to 1.85) and living with HIV (aOR=1.78, 95% CI 1.38 to 2.08) were independently associated with SARS-CoV-2 infection. There was no significant difference in infection rates between high, medium and low COVID-19 exposure working environments. CONCLUSIONS: The high SARS-CoV-2 cumulative incidence in the cohort was surprising this early in the epidemic and probably related to exposure both in and outside the hospitals. To mitigate the impact of SARS-CoV-2 among HCWs, infection prevention and control strategies should target community transmission in addition to screening for HIV and metabolic conditions.

"Suction Tube Uterine Tamponade" for treatment of refractory postpartum hemorrhage: Internal feasibility and acceptability pilot of a randomized clinical trial.

OBJECTIVE: To assess feasibility and acceptability of a novel, low-cost "Suction Tube Uterine Tamponade" (STUT) treatment for refractory postpartum hemorrhage (PPH). METHODS: We allocated patients with refractory PPH by randomly ordered envelopes to STUT or routine uterine balloon tamponade (UBT, Ellavi free-flow system) in 10 hospitals in South Africa. In the STUT group, a 24FG Levin stomach tube was inserted into the uterine cavity and vacuum created with a vacuum pump or manual vacuum aspiration syringe. RESULTS: For this internal pilot study, 12 participants were allocated to STUT and 12 to UBT. Insertion failed in one of each group and was recorded as difficult in 3/10 STUT and 4/9 UBT insertions respectively (five missing data). There were two laparotomies and one intensive care unit admission in the UBT group. Pain during STUT insertion was graded as none/mild in 9/10 and severe in 1/10. The experience of the STUT procedure was graded as fine in 4/11 and "uncomfortable but acceptable" in 7/11. CONCLUSION: STUT is feasible and acceptable, justifying continuation of our trial. These data will also inform a large World Health Organization trial to test effectiveness of uterine tamponade methods. The numbers are too small to support any clinical recommendation.

ART initiation among women newly diagnosed with HIV in a contraceptive trial in sub-Saharan Africa.

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

Acceptance of COVID-19 Vaccine among the Healthcare Workers in the Eastern Cape, South Africa: A Cross Sectional Study.

BACKGROUND: This study assesses the perceptions and acceptance of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) vaccination. It also examines its influencing factors among the healthcare workers (HCWs) in the Eastern Cape, South Africa. METHODS: In this cross-sectional study performed in November and December 2020, a total of 1308 HCWs from two large academic hospitals participated in the Eastern Cape Healthcare Workers Acquisition of SARS-CoV-2 (ECHAS) study. Validated measures of vaccine hesitancy were explored using a questionnaire. Logistic regression was used to identify the determinants of vaccine hesitancy. RESULTS: The majority were nurses (45.2%), and at risk for unfavourable Covid-19 outcome, due to obesity (62.9%) and having direct contact with individuals confirmed to have Covid-19 (77.1%). The overall acceptance of SARS-CoV-2 vaccine was 90.1%, which differed significantly by level of education. Individuals with lower educational attainment (primary and secondary education) and those with prior vaccine refusal were less likely to accept the SARS-CoV-2 vaccine. However, positive perceptions about the SARS-CoV-2 vaccine were independently associated with vaccine acceptance. CONCLUSIONS: The high level of acceptance of SARS-CoV-2 vaccine is reassuring; however, HCWs with a lower level of education and those with prior vaccine refusal should be targeted for further engagements to address their concerns and fears.

Incorporating oral PrEP into standard prevention services for South African women: a nested interrupted time-series study.

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

Growth, clinical and neurodevelopmental outcomes at school age are similar for children who received 1-year lamivudine or lopinavir/ritonavir HIV prophylaxis in early life.

In the ANRS 12174 trial, HIV-exposed uninfected African neonates who received lopinavir-ritonavir (LPV/r) prophylaxis for 1 year exhibited slower growth from birth to week 50 compared with those receiving lamivudine (3TC). We assessed whether this difference in growth persisted over time, and was accompanied by differences in neuropsychological and clinical outcomes. Between February 2017 and February 2018, we conducted a cross-sectional clinical evaluation among former trial participants who completed the 50-week follow-up and who were not HIV-infected. In addition to clinical examination, neuropsychological outcomes were assessed using the tests Kaufman-ABCII, Test of Variables of Attention, Movement Assessment Battery for Children and the Strengths and Difficulties questionnaire, parent version. Of 1101 eligible children, aged 5-7 years, 553 could be traced and analysed (274 in the LPV/r and 279 in the 3TC groups). Growth, clinical and neuropsychological outcomes did not differ between treatment groups. At school age, children exposed to LPV/r and 3TC at birth for 1 year had comparable growth and neuropsychological outcomes without evidence of long-term side-effects of LPV/r. It provides reassuring data on clinical outcomes for all HIV-infected children treated with this antiretroviral drug in early life.

Eastern Cape Healthcare Workers Acquisition of SARS-CoV-2 (ECHAS): Cross-Sectional (Nested Cohort) Study Protocol.

Healthcare workers (HCWs) are at increased risk of infection by the virulent severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Though data exist on the positivity rate of the SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) test as well as COVID-19-related deaths amongst HCWs in South Africa, the overall infection rate remains underestimated by these indicators. It is also unclear whether the humoral immune response after SARS-CoV-2 infection offers durable protection against reinfection. This study will assess the SARS-CoV-2 seroprevalence amongst HCWs in the Eastern Cape (EC) and examine the longitudinal changes (rate of decay) in the antibody levels after infection in this cohort. Using a multi-stage cluster sampling of healthcare workers in selected health facilities in the EC, a cross-sectional study of 2250 participants will be recruited. In order to assess the community infection rate, 750 antenatal women in the same settings will be recruited. Relevant demographic and clinical characteristics will be obtained by a self-administered questionnaire. A chemiluminescent microparticle immunoassay (CMIA) will be used for the qualitative detection of IgG antibodies against SARS-CoV-2 nucleocapsid protein. A nested cohort study will be conducted by performing eight-weekly antibody assays (X2) from 201 participants who tested positive for both SARS-CoV-2 RT-PCR and serology. Logistic regression models will be fitted to identify the independent risk factors for SARS-CoV-2 infection. The cumulative SARS-CoV-2 infection rate and infection fatality rate among the frontline HCWs will be estimated. In addition, the study will highlight the overall effectiveness of infection prevention and control measures (IPC) per exposure sites/wards at the selected health facilities. Findings will inform the South African Department of Health's policies on how to protect HCWs better as the country prepares for the second wave of the SARS-CoV pandemic.

Sexually transmitted infections among women randomised to depot medroxyprogesterone acetate, a copper intrauterine device or a levonorgestrel implant.

OBJECTIVES: Reproductive aged women are at risk of pregnancy and sexually transmitted infections (STI). Understanding drivers of STI acquisition, including any association with widely used contraceptives, could help us to reduce STI prevalence and comorbidities. We compared the risk of STI among women randomised to three contraceptive methods. METHODS: We conducted a secondary analysis to assess the risk of chlamydia and gonorrhoea in a clinical trial evaluating HIV risk among 7829 women aged 16-35 randomised to intramuscular depot medroxyprogesterone acetate (DMPA-IM), a copper intrauterine device (IUD) or a levonorgestrel (LNG) implant. We estimated chlamydia and gonorrhoea prevalences by contraceptive group and prevalence ratios (PR) using log-binomial regression. RESULTS: At baseline, chlamydia and gonorrhoea prevalences were 18% and 5%, respectively. Final visit chlamydia prevalence did not differ significantly between DMPA-IM and copper IUD groups or between copper IUD and LNG implant groups. The DMPA-IM group had significantly lower risk of chlamydia compared with the LNG implant group (PR 0.83, 95% CI 0.72 to 0.95). Final visit gonorrhoea prevalence differed significantly only between the DMPA-IM and the copper IUD groups (PR 0.67, 95% CI 0.52 to 0.87). CONCLUSIONS: The findings suggest that chlamydia and gonorrhoea risk may vary with contraceptive method use. Further investigation is warranted to better understand the mechanisms of chlamydia and gonorrhoea susceptibility in the context of contraceptive use.

Integrating oral PrEP delivery among African women in a large HIV endpoint-driven clinical trial.

INTRODUCTION: Global guidelines emphasize the ethical obligation of investigators to help participants in HIV-endpoint trials reduce HIV risk by offering an optimal HIV prevention package. Oral pre-exposure prophylaxis (PrEP) has increasingly become part of state-of-the-art HIV prevention. Here we describe the process of integrating oral PrEP delivery into the HIV prevention package of the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. METHODS: ECHO was an open-label randomized clinical trial that compared HIV incidence among women randomized to one of three effective contraceptives. In total, 7830 women aged 16 to 35 years from 12 sites in four African countries (Eswatini, Kenya, South Africa and Zambia) were enrolled and followed for 12 to 18 months, from 2015 to 2018. Part-way through the course of the trial, oral PrEP was provided to study participants either off-site via referral or on site via trained trial staff. PrEP uptake was compared between different contraceptive users using Chi-squared tests or t-tests. HIV seroincidence rates were compared between participants who never versus ever initiated PrEP using exact Poisson regression. RESULTS: PrEP access in ECHO began through public availability in Kenya in May 2017 and was available at all sites by June 2018. When PrEP became available, 3626 (46.3%) eligible women were still in follow-up in the study, and of these, 622 (17.2%) initiated PrEP. Women initiating PrEP were slightly older; more likely to be unmarried, not living with their partner, having multiple partners; and less likely to be earning their own income and receiving financial support from partners (all p < 0.05). PrEP initiation did not differ across study randomized groups (p = 0.7). Two-thirds of PrEP users were continuing PrEP at study exit. CONCLUSIONS: There is a need for improved HIV prevention services in clinical trials with HIV endpoints, especially trials among African women. PrEP as a component of a comprehensive HIV prevention package provided to women in a large clinical trial is practical and feasible. Provision of PrEP within clinical trials with HIV outcomes should be standard of prevention.