Evaluating the use of oral pre-exposure prophylaxis among pregnant and postpartum adolescent girls and young women in Cape Town, South Africa.

Background: Adolescent girls and young women (AGYW) in South Africa are at a higher risk of acquiring HIV. Despite the increasing availability of daily oral pre-exposure prophylaxis (PrEP) for HIV prevention, knowledge on PrEP use during pregnancy and postpartum periods at antenatal care (ANC) facilities remains inadequate. Methods: Data from HIV-uninfected pregnant women in Cape Town, South Africa, were used in this study. These women aged 16-24 years were enrolled in the PrEP in pregnancy and postpartum (PrEP-PP) cohort study during their first ANC visit. Using the PrEP cascade framework, the outcomes of the study were PrEP initiation (prescribed tenofovir disoproxil fumarate and emtricitabine at baseline), continuation (returned for prescription), and persistence [quantifiable tenofovir diphosphate (TFV-DP) in dried blood samples]. The two primary exposures of this study were risk perception for HIV and baseline HIV risk score (0-5), which comprised condomless sex, more than one sexual partner, partner living with HIV or with unknown serostatus, laboratory-confirmed sexually transmitted infections (STIs), and hazardous alcohol use before pregnancy (Alcohol Use Disorders Identification Test for Consumption score ≥ 3). Logistic regression was used to examine the association between HIV risk and PrEP, adjusting for a priori confounders. Results: A total of 486 pregnant women were included in the study, of which 16% were "adolescents" (aged 16-18 years) and 84% were "young women" (aged 19-24 years). The adolescents initiated ANC later than the young women [median = 28 weeks (20-34) vs. 23 weeks (16-34), p = 0.04]. Approximately 41% of the AGYW were diagnosed with sexually transmitted infection at baseline. Overall, 83% of the AGYW initiated PrEP use during their first ANC. The percentage of PrEP continuation was 63% at 1 month, 54% at 3 months, and 39% at 6 months. Approximately 27% consistently continued PrEP use through 6 months, while 6% stopped and restarted on PrEP use at 6 months. With a higher risk score of HIV (≥2 vs. ≤1), the AGYW showed higher odds of PrEP continuation [adjusted odds ratio: 1.85 (95% CI: 1.12-3.03)] through 6 months, adjusting for potential confounders. Undergoing the postpartum period (vs. pregnant) and having lower sexual risk factors were found to be the barriers to PrEP continuation. TFV-DP concentration levels were detected among 49% of the AGYW, and 6% of these women had daily adherence to PrEP at 3 months. Conclusions: AGYW were found to have high oral PrEP initiation, but just over one-third of these women continued PrEP use through 6 months. Pregnant AGYW who had a higher risk of acquiring HIV (due to condomless sex, frequent sex, and STIs) were more likely to continue on PrEP use through the postpartum period. Pregnant and postpartum AGYW require counseling and other types of support, such as community delivery and peer support to improve their effective PrEP use through the postpartum period. Clinical Trial Number: ClinicalTrials.gov, NCT03826199.

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.

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.

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.

HIV testing and linkage to ART following secondary distribution of HIV self-test kits to male partners of women living with HIV: a pilot randomized control trial in Mpumalanga, South Africa.

INTRODUCTION: South African men are underrepresented in HIV testing and treatment services. Secondary distribution of oral HIV self-test (HIVST) kits by women living with HIV (WLHIV) to their male partners (i.e. index partner HIVST) may increase men's testing and treatment but has been understudied. METHODS: Between March and July 2021, we evaluated the effectiveness of index partner HIVST versus the standard of care (SOC) (invitations for men's facility-based testing) on men's testing in a 1:1 randomized control trial. Eligibility criteria included: WLHIV; ≥18 years of age; attending one of four high-density rural clinics; have a working cell phone; and self-reported having a primary male partner of unknown serostatus. The primary outcome was the proportion of WLHIV reporting that her partner tested for HIV within 3 months after enrolment. RESULTS: We enrolled 180 WLHIV and 176 completed an endline survey (mean age = 35 years, 15% pregnant, 47% unmarried or non-cohabiting). In the HIVST arm, 78% of male partners were reported to have tested for HIV versus 55% in SOC (RR = 1.41; 95% CI = 1.14-1.76). In the HIVST arm, nine men were reactive with HIVST (14% positivity), six were confirmed HIV positive with standard testing (67%) and all of those started antiretroviral therapy (ART), and four HIV-negative men started pre-exposure prophylaxis (PrEP) (5%). In SOC, six men were diagnosed with HIV (12% positivity), 100% started ART and seven HIV-negative men started PrEP (16%). One case of verbal intimate partner violence was reported in the HIVST arm. CONCLUSIONS: Secondary distribution of HIVST to partners of WLHIV was acceptable and effective for improving HIV testing among men in rural South Africa in our pilot study. Interventions are needed to link reactive HIVST users to confirmatory testing and ART.

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.

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.

Where are the pregnant and breastfeeding women in new pre-exposure prophylaxis trials? The imperative to overcome the evidence gap.

Pregnant and breastfeeding populations are at substantial risk of acquiring HIV in some settings, yet are underrepresented in clinical trials of new pre-exposure prophylaxis (PrEP) agents. Several PrEP formulations are in development (eg, vaginal rings, long-acting injectables, and other modalities). Pregnant and breastfeeding populations are typically excluded from initial clinical trials. We identified 14 PrEP trials of novel agents in non-pregnant or non-breastfeeding populations, and six phase 1-3 trials and open label extensions among pregnant and breastfeeding populations, that are currently ongoing or complete. A framework shift is needed to consider the ethical costs of excluding pregnant and breastfeeding populations at risk for HIV in PrEP clinical trials and promote inclusion to maximise the benefits from PrEP tools in the pipeline. Research on new PrEP agents should include pregnant and breastfeeding populations to avoid delays in reaching those who could benefit from PrEP after efficacy is established.

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.

Participatory Prototyping of a Tailored Undetectable Equals Untransmittable Message to Increase HIV Testing Among Men in Western Cape, South Africa.

Daily antiretroviral therapy (ART) suppresses viral replication, rendering HIV undetectable through viral load (VL) testing. People living with HIV (PLWH) who have an undetectable VL cannot transmit HIV to sexual partners or through giving birth, a message commonly referred to as U = U (undetectable equals untransmittable). To increase knowledge and understanding of U = U among men, who have poorer HIV testing and treatment outcomes than women, we engaged men from high HIV burden communities in Cape Town in two interactive human-centered design cocreation workshops to develop local U = U messaging for men. Two trained workshop facilitators, explained the U = U message to 39 adult men (in two separate workshops), and asked them how to effectively communicate U = U to other men in the local language (isiXhosa). Participant-designed messages sought to inform men about U = U to help assuage fears of testing HIV positive (by removing the stigma of living with HIV and being a vector of disease), and to explain that ART enables PLWH to live normal healthy lives, making HIV "untransmittable" to sex partners. Participants' messages emphasized that when virally suppressed, "I cannot spread HIV to the other person" and "(the pill) keeps on killing the virus so I can live a normal life for the rest of my life." Men cocreated simple local U = U messages to address fears of testing HIV positive and emphasizing ART's positive effects. Cocreated tailored messaging may reduce stigma associated with living with HIV and improve the uptake of HIV testing and treatment among South African men. This study was registered at clinicaltrials.gov under NCT04364165.

"I had Made the Decision, and No One was Going to Stop Me" -Facilitators of PrEP Adherence During Pregnancy and Postpartum in Cape Town, South Africa.

PrEP is safe and effective but requires adherence during potential HIV exposure, yet the facilitators of long-term maternal adherence are not well understood. We conducted semi-structured interviews with 25 postpartum women who reported high adherence (PrEP use ≥ 25 days in last 30-days and never missed a PrEP prescription in pregnancy/postpartum period) within a PrEP service for pregnant and postpartum women. A thematic approach guided an iterative process of coding and analysis. Themes identified as drivers of optimal PrEP use were HIV risk perception, mainly because of partner's behaviors and unknown serostatus, and a strong desire to have a baby free of HIV. Reported disclosure of PrEP use facilitated PrEP adherence. Women discussed having partner and family support, which included reminders to take PrEP daily. Primary barriers were anticipated or experienced stigma, overcome through education of partners and family about PrEP. Pregnant women experienced transient side-effects, but found ways to continue, including taking PrEP at night. PrEP programs for pregnant and postpartum women should integrate strategies to assist women with realistic appraisals of risk and teach skills for disclosure and securing support from significant others.

RESUMEN: La profilaxis Pre-exposición (PrEP, siglas en inglés) es segura y eficaz, pero requiere adherencia durante una posible exposición al VIH; sin embargo, no se conocen bien los factores que facilitan la adherencia materna a largo plazo. Realizamos entrevistas semiestructuradas con 25 mujeres en posparto que informaron un alto cumplimiento (uso de PrEP> 25 días en los últimos 30 días y nunca omitieron una receta de PrEP en el embarazo y período posparto) dentro de un servicio de PrEP para mujeres embarazadas y posparto. Un enfoque temático guio un proceso iterativo de codificación y análisis. Los temas identificados como impulsores del uso óptimo de la PrEP fueron la percepción del riesgo de VIH, principalmente debido a los comportamientos de la pareja y el estado serológico desconocido, y un fuerte deseo de tener un bebé libre de VIH. La divulgación informada del uso de PrEP facilitó la adherencia a la PrEP. Las mujeres hablaron sobre el apoyo de su pareja y familia, incluidos recordatorios para tomar la PrEP cada dia. Las barreras primarias fueron el estigma anticipado o experimentado, superado a través de la educación de los socios y familiares sobre la PrEP. Las mujeres embarazadas experimentaron efectos secundarios transitorios, pero encontraron formas de continuar, incluida la toma de PrEP por la noche. Los programas de PrEP para mujeres embarazadas y posparto deben integrar estrategias para ayudar a las mujeres con evaluaciones realistas del riesgo y enseñar habilidades para la divulgación y obtener el apoyo de otras personas importantes.

Healthcare provider knowledge and attitudes about pre-exposure prophylaxis (PrEP) in pregnancy in Cape Town, South Africa.

Pre-exposure prophylaxis (PrEP) in pregnancy can reduce HIV incidence and vertical transmission. Healthcare providers (HCPs) play a critical role in delivering PrEP in antenatal care but little is known about HCP knowledge and attitudes about PrEP in pregnancy. We conducted a qualitative study in two healthcare facilities to assess HCPs' PrEP knowledge and perspectives relating to HIV prevention in pregnant women. Between January-March'19, we administered in-depth interviews among antenatal HCPs. We utilized a constant comparison approach to identify major qualitative findings. We enrolled 35 female HCPs (median age=43yrs. Fewer than half of HCPs had heard of PrEP before. Of those who had heard of PrEP, most felt that it was safe to take during pregnancy. Most HCPs described inaccurate PrEP knowledge regarding effectiveness, and most who knew about PrEP lacked clinical detail. HCPs highlighted important potential barriers to maternal PrEP use including: fear that PrEP may be unsafe, or belief that women must talk to partners/parents before initiating PrEP. Facilitators include good knowledge about serodiscordancy and vulnerability to seroconversion in pregnancy and desire to help women gain control overHIV prevention. We recommend integrating PrEP training into HIV testing and PMTCT nurse training to improve counseling and maternal PrEP delivery.

Emerging evidence from a systematic review of safety of pre-exposure prophylaxis for pregnant and postpartum women: where are we now and where are we heading?

INTRODUCTION: HIV incidence is high during pregnancy and breastfeeding with HIV acquisition risk more than doubling during pregnancy and the postpartum period compared to when women are not pregnant. The World Health Organization recommends offering pre-exposure prophylaxis (PrEP) to pregnant and postpartum women at substantial risk of HIV infection. However, maternal PrEP national guidelines differ and most countries with high maternal HIV incidence are not offering PrEP. We conducted a systematic review of recent research on PrEP safety in pregnancy to inform national policy and rollout. METHODS: We used a standard Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) approach to conduct a systematic review by searching for completed, ongoing, or planned PrEP in pregnancy projects or studies from clinicaltrials.gov, PubMed and NIH RePORTER from 2014 to March 2019. We performed a systematic review of studies that assess tenofovir disoproxil fumarate (TDF)-based oral PrEP safety in pregnant and breastfeeding HIV-uninfected women. RESULTS AND DISCUSSION: We identified 14 completed (n = 5) and ongoing/planned (n = 9) studies that evaluate maternal and/or infant outcomes following PrEP exposure during pregnancy or breastfeeding. None of the completed studies found differences in pregnancy or perinatal outcomes associated with PrEP exposure. Nine ongoing studies, to be completed by 2022, will provide data on >6200 additional PrEP-exposed pregnancies and assess perinatal, infant growth and bone health outcomes, expanding by sixfold the data on PrEP safety in pregnancy. Research gaps include limited data on (1) accurately measured PrEP exposure within maternal and infant populations including drug levels needed for maternal protection; (2) uncommon perinatal outcomes (e.g. congenital anomalies); (3) infant outcomes such as bone growth beyond one year following PrEP exposure; (4) outcomes in HIV-uninfected women who use PrEP during pregnancy and/or lactation. CONCLUSIONS: Expanding delivery of PrEP is an essential strategy to reduce HIV incidence in pregnancy and breastfeeding women. Early safety studies of PrEP among pregnant women without HIV infection are reassuring and ongoing/planned studies will contribute extensive new data to bolster the safety profile of PrEP use in pregnancy. However, addressing research gaps is essential to expanding PrEP delivery for women in the context of pregnancy.

Prevalence and correlates of sexually transmitted infections in pregnancy in HIV-infected and- uninfected women in Cape Town, South Africa.

OBJECTIVES: Sexually transmitted infections (STIs) are associated with adverse outcomes in pregnancy, including mother-to-child HIV transmission. Yet there are limited data on the prevalence and correlates of STI in pregnant women by HIV status in low- and middle-income countries, where syndromic STI management is routine. METHODS: Between November 2017 and July 2018, we conducted a cross-sectional study of consecutive pregnant women making their first visit to a public sector antenatal clinic (ANC) in Cape Town. We interviewed women ≥18 years and tested them for Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG) and Trichomonas vaginalis (TV) using Xpert assays (Cepheid, USA); results of syphilis serology came from routine testing records. We used multivariable logistic regression to identify correlates of STI in pregnancy. RESULTS: In 242 women (median age 29 years [IQR = 24-34], median gestation 19 weeks [IQR = 14-24]) 44% were HIV-infected. Almost all reported vaginal sex during pregnancy (93%). Prevalence of any STI was 32%: 39% in HIV-infected women vs. 28% in HIV-uninfected women (p = 0.036). The most common infection was CT (20%) followed by TV (15%), then NG (5.8%). Of the 78 women diagnosed with a STI, 7 (9%) were identified and treated syndromically in ANC. Adjusting for age and gestational age, HIV-infection (aOR = 1.89; 95% CI = 1.02-3.67), being unmarried or not cohabiting with the fetus' father (aOR = 2.19; 95% CI = 1.16-4.12), and having STI symptoms in the past three days (aOR = 6.60; 95% CI = 2.08-20.95) were associated with STI diagnosis. CONCLUSION: We found a high prevalence of treatable STIs in pregnancy among pregnant women, especially in HIV-infected women. Few women were identified and treated in pregnancy.

Modelling the potential impact of providing preexposure prophylaxis in pregnant and breastfeeding women in South Africa.

OBJECTIVE: HIV-uninfected pregnant and breastfeeding women are at high risk of HIV acquisition, contributing to vertical transmission of HIV. Preexposure prophylaxis (PrEP) is safe in pregnancy, but PrEP in pregnancy is not policy in many countries including South Africa. We evaluated the potential impact of providing PrEP for pregnant/breastfeeding women using a HIV model for South Africa. METHODS: Our model considers two scenarios: a conservative scenario that matches the experience reported in the Kenyan PrEP programme for pregnant women (probability of uptake = 32% and 11% in high-risk and low-risk women, respectively); and an optimistic scenario with PrEP initiated by 80% of all pregnant women. We compared this with PrEP for female sex workers, MSM and adolescent girls/young women. Women are assumed to remain on PrEP throughout pregnancy and breastfeeding, and an equivalent average PrEP duration (2 years) is assumed in other scenarios. RESULTS: Between 2020 and 2030, if PrEP is provided to pregnant/breastfeeding mothers, we project a 2.5% reduction in total HIV transmission [95% credibility interval (CI): 2.4-2.6%] in the conservative scenario and 7.2% (95% CI: 6.8-7.5%) in the optimistic scenario, which is similar to that in the female sex worker and MSM PrEP scenarios (1.9% and 3.0%, respectively). Without PrEP, 76 000 (95% CI: 64 000-90 000) new cases of vertical transmission are expected; PrEP provision may reduce these infections by 13% (95% CI: 13-14%) in the conservative scenario and 41% (95% CI: 39-44%) in the optimistic scenario. CONCLUSION: High levels of uptake of and adherence to PrEP among pregnant/breastfeeding women could substantially reduce maternal and infant HIV acquisition in South Africa.