“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 efective 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 identifed 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-efects, 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 signifcant others

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

BackgroundAdolescent 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.MethodsData 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.ResultsA 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.ConclusionsAGYW 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 NumberClinicalTrials.gov, NCT03826199

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.Eunice Kennedy Shriver Institute of Child Health and Human Development, National Institute of Allergy and Infectious Diseases & National Institutes of Health.http://www.biomedcentral.com/bmcpregnancychildbirthMedical Microbiolog

Stepped care to optimize pre-exposure prophylaxis (PrEP) effectiveness in pregnant and postpartum women (SCOPE-PP) in South Africa: a randomized control trial

Background HIV incidence among pregnant and postpartum women remains high in South Africa. Pre-exposure prophylaxis (PrEP) use remains suboptimal in this population, particularly during the postpartum period when women’s engagement with routine clinic visits outside PrEP decreases. Key barriers to sustained PrEP use include the need for ongoing contact with the health facility and suboptimal counseling around effective PrEP use. Methods Stepped Care to Optimize PrEP Effectiveness in Pregnant and Postpartum women (SCOPE-PP), is a two-stepped unblinded, individually randomized controlled trial (RCT) that aims to optimize peripartum and postpartum PrEP use by providing a stepped package of evidence-based interventions. We will enroll 650 pregnant women (> 25 weeks pregnant) who access PrEP at a busy antenatal clinic in Cape Town at the time of recruitment and follow them for 15 months. We will enroll and individually randomize pregnant women > 16 years who are not living with HIV who are either on PrEP or interested in starting PrEP during pregnancy. In step 1, we will evaluate the impact of enhanced adherence counselling and biofeedback (using urine tenofovir tests for biofeedback) and rapid PrEP collection (to reduce time required) on PrEP use in early peripartum compared to standard of care (SOC) (n = 325 per arm). The primary outcome is PrEP persistence per urine tenofovir levels and dried blood spots of tenofovir diphosphate (TFV-DP) after 6-months. The second step will enroll and individually randomize participants from Step 1 who discontinue taking PrEP or have poor persistence in Step 1 but want to continue PrEP. Step 2 will test the impact of enhanced counseling and biofeedback plus rapid PrEP collection compared to community PrEP delivery with HIV self-testing on PrEP use (n = up to 325 postpartum women). The primary outcome is PrEP continuation and persistence 6-months following second randomization (~ 9-months postpartum). Finally, we will estimate the cost effectiveness of SCOPE-PP vs. SOC per primary outcomes and disability-adjusted life-years (DALYs) averted in both Step 1 and 2 using micro-costing with trial- and model-based economic evaluation. Discussion This study will provide novel insights into optimal strategies for delivering PrEP to peripartum and postpartum women in this high-incidence setting. Trial registration NCT05322629 : Date of registration: April 12, 2022

The importance of assessing and addressing mental health barriers to PrEP use during pregnancy and postpartum in sub-Saharan Africa: state of the science and research priorities

INTRODUCTION: Pregnant and postpartum women (PPW) in sub-Saharan Africa are at disproportionately high risk of HIV infection compared to non-pregnant women. When used consistently, pre-exposure prophylaxis (PrEP) can prevent HIV acquisition and transmission to the foetus or infant during these critical periods. Recent studies have demonstrated associations between mental health challenges (e.g. depression and traumatic stress associated with intimate partner violence) and decreased PrEP adherence and persistence, particularly among adolescents, younger women and women in the postpartum period. However, mental health is not currently a major focus of PrEP implementation research and programme planning for PPW. DISCUSSION: PrEP implementation programmes for PPW need to assess and address mental health barriers to consistent PrEP use to ensure effectiveness and sustainability in routine care. We highlight three key research priorities that will support PrEP adherence and persistence: (1) include mental health screening tools in PrEP implementation research with PPW, both to assess the feasibility of integrating these tools into routine antenatal and postpartum care and to ensure that limited resources are directed towards women whose symptoms may interfere most with PrEP use; (2) identify cross-cutting, transdiagnostic psychological mechanisms that affect consistent PrEP use during these periods and can realistically be targeted with intervention in resource-limited settings; and (3) develop/adapt and test interventions that target those underlying mechanisms, leveraging strategies from existing interventions that have successfully mitigated mental health barriers to antiretroviral therapy use among people with HIV. CONCLUSIONS: For PPW, implementation of PrEP should be guided by a robust understanding of the unique psychological difficulties that may act as barriers to uptake, adherence and persistence (i.e. sustained adherence over time). We strongly encourage PrEP implementation research in PPW to incorporate validated mental health screening tools and ultimately treatment in routine antenatal and postnatal care, and we stress the potential public health benefits of identifying women who face mental health barriers to PrEP use.K23MH131438 - National Institute on Mental Health AwardPublished versio

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

Quantifiable plasma tenofovir among South African women using daily oral pre-exposure prophylaxis during the ECHO trial

Access to data from the ECHO study may be requested through submission of a research concept to ude.wu@crci. The concept must include the research question, data requested, analytic methods, and steps taken to ensure ethical use of the data. Access will be granted if the concept is evaluated to have scientific merit and if sufficient data protections are in place. As of the time of publication, data access applications are in process with the governing institutional review boards of the ECHO study to make deidentified data publicly available.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.The Bill & Melinda Gates Foundation, the American people through the United States Agency for International Development, the Swedish International Development Cooperation Agency, the South Africa Medical Research Council, and the United Nations Population Fund. Contraceptive supplies were donated by the Government of South Africa and US Agency for International Development.http://journals.lww.com/jaidshj2023Family MedicineMedical Microbiolog

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.https://www.thelancet.com/journals/lanhiv/homehj2023Paediatrics and Child Healt

High levels of pretreatment HIV-1 drug resistance mutations among South African women who acquired HIV during a prospective study

Access to data from the ECHO Study may be requested through submission of a research concept to [email protected]. The concept must include the research question, data requested, analytic methods, and steps taken to ensure ethical use of the data. Access will be granted if the concept is evaluated to have scientific merit and if sufficient data protections are in place. As of the time of publication, data access applications are in process with the governing institutional review boards of the ECHO Study to make de-identified data publicly available.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.The Bill & Melinda Gates Foundation, the American people through the United States Agency for International Development, the Swedish International Development Cooperation Agency, the South Africa Medical Research Council, and the United Nations Population Fund.http://journals.lww.com/jaidshj2023Family MedicineMedical Microbiolog