Point-of-care testing for sexually transmitted infections and HIV pre-exposure prophylaxis among pregnant women in South Africa, 2021-2022: randomised controlled trial.

OBJECTIVE: Pregnant and postpartum women (PPW) in Southern Africa are at increased risk of acquiring HIV and curable sexually transmitted infections (STIs). Oral pre-exposure prophylaxis (PrEP) is safe and effective to use during pregnancy to reduce HIV acquisition and vertical transmission. Point-of-care (POC) STI testing can identify PPW at risk of HIV and facilitate risk-differentiated and person-centred counselling to improve PrEP initiation, persistence and adherence. We evaluated the impact of POC STI testing compared with STI syndromic management on PrEP outcomes among PPW in Cape Town, South Africa. METHODS: The STI and PrEP in Pregnancy Study enrolled PPW without HIV and ≤34 weeks pregnant at their regular antenatal care visit with follow-up after 1 month. PPW were randomised to receive POC STI testing or STI syndromic management. PPW randomised to POC STI testing self-collected vaginal swabs for Chlamydia trachomatis, Neisseria gonorhoeae and Trichomonas vaginalis (Cepheid GeneXpert) testing and were offered same-day treatment if diagnosed. We compared PrEP initiation at baseline, PrEP prescription refill at 1 month (persistence) and adherence through tenofovir-diphosphate detection in dried blood spots by randomisation arm. In a secondary analysis, we evaluated the association between an STI diagnosis (positive STI test or reporting STI symptoms) with PrEP outcomes. RESULTS: We enrolled and randomised 268 pregnant women. Twenty-eight per cent of women were diagnosed with ≥1 STI. Overall, 65% of women initiated and 79% persisted on PrEP with no significant differences by randomisation arm. Secondary analysis demonstrated that an STI diagnosis (positive STI test or reporting STI symptoms) was associated with higher PrEP initiation (adjusted relative risk=1.28; 95% CI 1.08 to 1.52), controlling for arm, maternal and gestational age. CONCLUSIONS: POC STI testing was not associated with PrEP initiation or persistence relative to syndromic management. However, improving STI diagnosis by supplementing syndromic management with POC STI testing could improve PrEP initiation among PPW. TRIAL REGISTRATION NUMBER: NCT03902418; Clinical Trials.gov; 1 April 2019.

Sexual Risk among Pregnant Women at Risk of HIV Infection in Cape Town, South Africa: What Does Alcohol Have to Do with It?

This study examines baseline associations between alcohol use and HIV sexual risk among a cohort of HIV-uninfected pregnant women (n = 1201) residing in a high HIV burdened community in Cape Town, South Africa. Alcohol use was measured using a modified version of the Alcohol Use Disorder Identification Test (AUDIT). HIV sexual risk was measured through a composite variable of four risk factors: diagnosis with a STI, self-report of > 1 recent sex partners, partner HIV serostatus (unknown or HIV+) and condomless sex at last sex. Any past year alcohol use prior to pregnancy was reported by half of participants (50%); 6.0% reported alcohol use during pregnancy. Alcohol use prior to pregnancy was associated with increased odds of being at high risk of HIV (aOR = 1.33, 95% CI 1.05-1.68, for 2 risks and aOR = 1.47, 95% CI 0.95-2.27 for 3 risks). In addition to reducing alcohol use, several other strategies to address HIV sexual risk were identified. Evidence-based interventions to address alcohol use and other HIV sexual risk behaviors during pregnancy in South Africa are desperately needed. Qualitative work exploring individual and community level drivers of alcohol use among pregnant and breastfeeding women in this setting could support development of a culturally tailored intervention to address these issues in this population.

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.

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.

Barriers to Oral HIV Pre-exposure Prophylaxis (PrEP) Adherence Among Pregnant and Post-partum Women from Cape Town, South Africa.

Cisgender women, particularly pregnant and postpartum women in Eastern and Southern Africa, face an unacceptably high risk of HIV acquisition. Oral pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention that can reduce HIV acquisition and vertical transmission. In this qualitative study, we interviewed 21 postpartum women from Cape Town, South Africa who initiated PrEP during pregnancy and who self-reported low PrEP adherence or missed > 1 PrEP follow-up collection. We identified multiple overlapping barriers to PrEP continuation and/or adherence. Individual factors included forgetting to take PrEP daily, being away from home when PrEP should be taken, anticipated stigma and limited disclosure of PrEP use. Women also reported pill-related factors such as side effects and having to take PrEP in addition to other tablets during pregnancy and the postpartum period. Facility-related barriers included logistics around PrEP collection especially when not in antenatal care, as well as transport and financial barriers.

Maternal PrEP Use in HIV-Uninfected Pregnant Women in South Africa: Role of Stigma in PrEP Initiation, Retention and Adherence.

Pregnant women in sub-Saharan Africa are at high risk of HIV acquisition and require effective methods to prevent HIV. In a cohort of pregnant women offered Pre-exposure prophylaxis (PrEP), we evaluate the relationship between internalized and anticipated stigma and PrEP initiation at first antenatal visit, 3-month continuation and adherence using multivariable logistic regression. High internalized and anticipated PrEP stigma are associated with lower PrEP care initiation at first antenatal visit (aOR internalized stigma = 0.06; 95% CI = 0.03-0.11 and aOR anticipated stigma = 0.55; 95% CI = 0.31-1.00) compared to women with low reported stigma, after controlling for covariates. Women whose partners have not been tested for HIV or whose serostatus remains unknown have 1.6-times odds of PrEP retention at 3-months compared to women whose partners have been tested (aOR = 1.60; 95% CI = 1.02-2.52) after adjusting for covariates. PrEP counseling and maternal PrEP interventions must consider individual- and relational-level interventions to overcome anticipated PrEP stigma and other barriers to PrEP initiation and adherence.

Alcohol use and intimate partner violence in HIV-uninfected pregnant women in Cape Town, South Africa.

In settings with a high burden of HIV, pregnant women often experience a cluster of risk factors, including alcohol use and intimate partner violence (IPV). These interrelated risks are poorly understood among pregnant women at risk of HIV in sub-Saharan Africa. We aim to determine cross-sectional associations between pregnant women's alcohol use and victimization due to IPV in the HIV-Unexposed-Uninfected Mother-Infant Cohort Study in Cape Town, South Africa. Women who tested HIV-negative at first antenatal care (ANC) visit were followed to delivery. Trained interviewers collected demographic and psychosocial information, including recent alcohol use and experiences of IPV victimization. We assess the prevalence of alcohol use and associations with IPV using multivariable logistic regression. In 406 HIV-uninfected pregnant women (mean age = 28 years; mean gestational age = 21 weeks), 41 (10%) reported alcohol consumption in the past 12 months; 30/41 (73%) of these at hazardous levels. Any and hazardous alcohol use were associated with greater odds of reporting past year IPV (adjusted odds ratio [aOR] for hazardous use: 3.24, 95% CI = 1.11, 7.56; aOR for any alcohol use: 2.97, 95% CI = 1.19, 7.45). These data suggest the occurrence of overlapping HIV risk factors among pregnant women and may help design improved health interventions in this population.

Low prevalence of hepatitis B virus infection in HIV-uninfected pregnant women in Cape Town, South Africa: implications for oral pre-exposure prophylaxis roll out.

BACKGROUND: Oral daily preexposure prophylaxis (PrEP) using emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) is recommended as standard of care for prevention in individuals at high risk for HIV infection, including pregnant and postpartum cisgender women. FTC/TDF is also active against hepatitis B virus (HBV); however, concern has been raised that providing PrEP to individuals infected with HBV could lead to hepatitis flares and liver injury, especially in the setting of suboptimal PrEP use. METHODS: We conducted a cross-sectional analysis of baseline data from the PrEP in pregnant and postpartum women (PrEP-PP) cohort study from February 2020-March 2022 in one antenatal care clinic in Cape Town, South Africa (SA) to evaluate: (1) the field performance of a point of care test (POCT) (Determine II, Abbott Inc., Japan) for diagnosis of hepatitis B surface antigen (HBsAg) in a maternity setting, (2) the prevalence of HBV in a cohort of pregnant women not living with HIV. RESULTS: We enrolled 1194 HIV sero-negative pregnant women at their first antenatal visit. Median age was 26 years (IQR = 22-31 years); 52% were born before 1995 (before universal HBV vaccination had started in South Africa). Median gestational age was 22 weeks (IQR = 16-30 weeks). There were 8 POCT and laboratory confirmed HBV cases among 1194 women. The overall prevalence of 0.67% (95% CI = 0.34-1.32%). In women born before 1995, 8 of 622 women were diagnosed with HBsAg; the prevalence was 1.29% (95% CI = 0.65-2.52%), and in women born in 1995 or after (n = 572); the prevalence was 0% (95% CI = 0.0-0.67%). We confirmed the test results in 99.8% of the rapid HBsAg (Determine II). Sensitivity was 100% (95% CI = 68-100%). Specificity was 100% (95% CI = 99.67-100%). CONCLUSION: The prevalence of HBV was very low in pregnant women not living with HIV and was only in women born before the HBV vaccine was included in the Expanded Program of Immunization. The Determine II POCT HBsAg showed excellent performance against the laboratory assay. HBV screening should not be a barrier to starting PrEP in the context of high HIV risk communities.

Impact of aetiological screening of sexually transmitted infections during pregnancy on pregnancy outcomes in South Africa.

BACKGROUND: Sexually transmitted infections (STIs) during pregnancy may increase the risk of adverse pregnancy outcomes. STI syndromic management is standard of care in South Africa but has its limitations. We evaluated the impact of diagnosing and treating curable STIs during pregnancy on adverse pregnancy and birth outcomes. METHODS: We combined data from two prospective studies of pregnant women attending public sector antenatal care (ANC) clinics in Tshwane District and Cape Town, South Africa. Pregnant women were enrolled, tested and treated for STIs. We evaluated the association between any STI at the first ANC visit and a composite adverse pregnancy outcome (miscarriage, stillbirth, preterm birth, early neonatal death, or low birthweight) using modified Poisson regression models, stratifying by HIV infection and adjusting for maternal characteristics. RESULTS: Among 619 women, 61% (n = 380) were from Tshwane District and 39% (n = 239) from Cape Town; 79% (n = 486) were women living with HIV. The prevalence of any STI was 37% (n = 228); C. trachomatis, 26% (n = 158), T. vaginalis, 18% (n = 120) and N. gonorrhoeae, 6% (n = 40). There were 93% (n = 574) singleton live births, 5% (n = 29) miscarriages and 2% (n = 16) stillbirths. Among the live births, there were 1% (n = 3) neonatal deaths, 7% (n = 35) low birthweight in full-term babies and 10% (n = 62) preterm delivery. There were 24% (n = 146) for the composite adverse pregnancy outcome. Overall, any STI diagnosis and treatment at first ANC visit was not associated with adverse outcomes in women living with HIV (adjusted relative risk (aRR); 1.43, 95% CI: 0.95-2.16) or women without HIV (aRR; 2.11, 95% CI: 0.89-5.01). However, C. trachomatis (aRR; 1.57, 95% CI: 1.04-2.39) and N. gonorrhoeae (aRR; 1.69, 95% CI: 1.09-3.08), were each independently associated with the composite adverse outcome in women living with HIV. CONCLUSION: Treated STIs at the first ANC visit were not associated with adverse pregnancy outcome overall. In women living with HIV, C. trachomatis or N. gonorrhoeae at first ANC were each independently associated with adverse pregnancy outcome. Our results highlights complex interactions between the timing of STI detection and treatment, HIV infection and pregnancy outcomes, which warrants further investigation.