Frequency of Viremic Episodes in HIV-Infected Women Initiating Antiretroviral Therapy During Pregnancy: A Cohort Study.

Background: The numbers of human immunodeficiency virus (HIV)-infected women initiating antiretroviral therapy (ART) in pregnancy are increasing rapidly with global policy changes. There are widespread concerns about ART adherence during pregnancy and postpartum but few data on viral suppression (VS) over time in these populations. Methods: We followed a cohort of 523 women in Cape Town, South Africa, initiating ART in pregnancy (once-daily tenofovir 300 mg, emtricitabine 200 mg, and efavirenz 600 mg) and achieving VS (<50 copies/mL). Participants provided specimens through 12 months postpartum for batched viral load (VL) testing separate from routine care. Analyses described the incidence of major (>1000 copies/mL) and minor (50-1000 copies/mL) viremic episodes (VEs) and factors associated with major VEs. Results: In the cohort (median age, 28 years; median pre-ART VL, 3.99 copies/mL; 3% previously defaulted ART; 24% with previous exposure to short-course antiretrovirals), the median time of follow-up from VS was 322 days. Overall, 70% maintained VS throughout follow-up, 8% experienced minor VEs only, and at least 1 major VE was documented in 22% of women. In women with VEs, peak viremia (median, 3.79 log10 copies/mL) was linearly related to pre-ART VL. The incidence of major VEs after initial VS was independently associated with younger age, ART initiation during the third trimester, previous defaulting on ART, and postpartum follow-up. Conclusions: Viremia appears to occur frequently, particularly postpartum, among HIV-infected women after initial VS in this setting. More intensive VL monitoring is warranted in this population; the immediate causes and long-term implications of VE require investigation.

Depression, alcohol use, and stigma in younger versus older HIV-infected pregnant women initiating antiretroviral therapy in Cape Town, South Africa.

HIV-infected pregnant women in sub-Saharan Africa are at risk for depression and alcohol abuse. Young women may be more vulnerable, but little is known about the psychosocial functioning of this population. We compared younger (18-24 years old) and older (≥25 years old) HIV-infected pregnant women initiating antiretroviral therapy (ART) in Cape Town, South Africa. Women were assessed on a range of psychosocial measures, including the Alcohol Use Disorders Identification Test and the Edinburgh Postnatal Depression Scale (EPDS). Among 625 women initiating ART, 16 % reported risky alcohol use and 21 % alcohol-related harm; these percentages were similar across age groups. When younger women were stratified by age, 37 % of 18-21 years old versus 20 % of 22-24 years old reported alcohol-related harm (p = 0.02). Overall, 11 % of women had EPDS scores suggesting probable depression, and 6 % reported self-harming thoughts. Younger women reported more depressive symptoms. Report of self-harming thoughts was 11 % in younger and 4 % in older women (p = 0.002). In multivariable analysis, age remained significantly associated with depressive symptoms and report of self-harming thoughts. Level of HIV-related stigma and report of intimate partner violence modified the association between age and depressive symptoms. Young HIV-infected pregnant women in South Africa were more likely to report depressive symptoms and self-harming thoughts compared to older women, and the youngest women reported the highest levels of alcohol-related harm. HIV-related stigma and intimate partner violence may be moderating factors. These findings have implications for maternal and infant health, underscoring the urgent need for effective targeted interventions in this vulnerable population.

The dimensionality of disclosure of HIV status amongst post-partum women in Cape Town, South Africa.

Disclosure of HIV status to sexual partners and others has been presented as positive health behaviour and is widely encouraged by antiretroviral treatment (ART) programmes, providers and policies. However, disclosure is also highly contextual and its positive effects are not universal. We explore the dimensions of disclosure amongst post-partum women who initiated ART during pregnancy in Cape Town, South Africa. Forty-seven semi-structured interviews with post-partum women were conducted as part of the Maternal Child Health-Antiretroviral Therapy (MCH-ART) study. Primary elements of disclosure were coded and interpreted according to dominant themes and subthemes. Disclosure was commonplace in the sample, ranging from widely disclosing status (rare); to disclosing to some family, friends and partners; to tacit disclosure, where participants took medication in front of others without explicitly discussing their status. Women described reasons for non-disclosure in terms of not being ready, fear of negative reactions (including violence and loss of financial support), and fear of their status being widely known. Self-reported adherence was uniformly high throughout the range of disclosure. Even those who made special efforts to avoid disclosure, such as attending clinics distant from their homes, reported good adherence. Those who disclosed experienced a range of responses to their disclosure, from support to shunning. Despite access to ART, stigma remained a persistent feature in descriptions of disclosure, particularly in relation to partner disclosure. Our findings suggest that disclosure is not always positive and adherence can be maintained within a wide range of disclosure behaviours. It is important that clinic settings allow women to retain control over their disclosure process.

In Utero Tenofovir Exposure Is not Associated With Fetal Long Bone Growth.

BACKGROUND: Despite widespread use of tenofovir disoproxil fumarate (TDF) in pregnant and breastfeeding women, few data exist on fetal bone development after in utero TDF exposure. We evaluated fetal long bone growth in human immunodeficiency virus (HIV)-infected pregnant woman/fetus dyads in Cape Town, South Africa. METHODS: Women were recruited from primary care antenatal services and underwent ultrasonography to determine femur (FLZ) and humerus (HLZ) length z scores. The duration of in utero TDF exposure was calculated in weeks. Linear regression models were applied to assess the associations between the duration of in utero TDF exposure and change in FLZ and HLZ. RESULTS: A total of 646 woman/fetus dyads contributed 1376 ultrasonographic scans to this analysis: 132 dyads with ≥25 weeks, 326 with 10-24 weeks, and 188 with <10 weeks of TDF exposure. Women receiving TDF for ≥25 weeks were older than those receiving TDF for 10-24 or <10 weeks (median age, 31 vs 28 and 28 years, respectively; P < .01), and had lower HIV RNA levels (median log10 HIV RNA level, 1.59 vs 4.08 and 3.83, respectively; P < .01). Throughout gestation, overall median FLZ and HLZ were 0.30 (interquartile range, -0.03 to 0.63) and 0.22 (-0.26 to 0.59) respectively. In multivariate analysis, there was no association between duration of in utero TDF exposure per 1-week increment and change in FLZ (ß = .00; P = .51) or change in HLZ (ß = .00; P = .40). Results were similar using mixed-effects models. CONCLUSIONS: Although longer follow-up is needed, these in utero data are reassuring and support the continued use of TDF in pregnancy.

The association between timing of initiation of antenatal care and stillbirths: a retrospective cohort study of pregnant women in Cape Town, South Africa.

BACKGROUND: There is renewed interest in stillbirth prevention for lower-middle income countries. Early initiation of and properly timed antenatal care (ANC) is thought to reduce the risk of many adverse birth outcomes. To this end we examined if timing of the first ANC visit influences the risk of stillbirth. METHODS: We conducted an analysis of a retrospective cohort of women (n = 34,671) with singleton births in a public perinatal service in Cape Town, South Africa. The main exposure was the gestational age at the first ANC visit. Bivariable analyses examining maternal characteristics by stillbirth status and gestational age at the first ANC visit, were conducted. Logistic regression, adjusting for maternal characteristics, was conducted to determine the risk of stillbirth. RESULTS: Of the 34,671 women who initiated ANC, 27,713 women (80%) were retained until delivery. The population stillbirth rate was 4.3 per 1000 births. The adjusted models indicated there was no effect of gestational age at first ANC visit on stillbirth outcomes when analyzed as a continuous variable (aOR 1.01; 95% CI: 0.99-1.04) or in trimesters (2nd Trimester aOR 0.78, 95% CI: 0.39-1.59; 3rd Trimester OR 1.03, 95% CI: 0.50-2.13, both with 1st Trimester as reference category). The findings were unchanged in sensitivity analyses of unobserved outcomes in non-retained women. CONCLUSION: The timing of a woman's first ANC visit may not be an important determinant of stillbirths in isolation. Further research is required to examine how quality of care, incorporating established, effective biomedical interventions, influences outcomes in this setting.

Cohort profile: the Western Cape Pregnancy Exposure Registry (WCPER).

PURPOSE: The Western Cape Pregnancy Exposure Registry (PER) was established at two public sector healthcare sentinel sites in the Western Cape province, South Africa, to provide ongoing surveillance of drug exposures in pregnancy and associations with pregnancy outcomes. PARTICIPANTS: Established in 2016, all women attending their first antenatal visit at primary care obstetric facilities were enrolled and followed to pregnancy outcome regardless of the site (ie, primary, secondary, tertiary facility). Routine operational obstetric and medical data are digitised from the clinical stationery at the healthcare facilities. Data collection has been integrated into existing services and information platforms and supports routine operations. The PER is situated within the Provincial Health Data Centre, an information exchange that harmonises and consolidates all health-related electronic data in the province. Data are contributed via linkage across a unique identifier. This relationship limits the missing data in the PER, allows validation and avoids misclassification in the population-level data set. FINDINGS TO DATE: Approximately 5000 and 3500 pregnant women enter the data set annually at the urban and rural sites, respectively. As of August 2021, >30 000 pregnancies have been recorded and outcomes have been determined for 93%. Analysis of key obstetric and neonatal health indicators derived from the PER are consistent with the aggregate data in the District Health Information System. FUTURE PLANS: This represents significant infrastructure, able to address clinical and epidemiological concerns in a low/middle-income setting.

Prevalence and determinants of unplanned pregnancy in HIV-positive and HIV-negative pregnant women in Cape Town, South Africa: a cross-sectional study.

OBJECTIVES: Prevention of unplanned pregnancy is a crucial aspect of preventing mother-to-child HIV transmission. There are few data investigating how HIV status and use of antiretroviral therapy (ART) may influence pregnancy planning in high HIV burden settings. Our objective was to examine the prevalence and determinants of unplanned pregnancy among HIV-positive and HIV-negative women in Cape Town, South Africa. DESIGN: Cross-sectional analysis. SETTINGS: Single primary-level antenatal care clinic in Cape Town, South Africa. PARTICIPANTS: HIV-positive and HIV-negative pregnant women, booking for antenatal care from March 2013 to August 2015, were included. MAIN OUTCOME MEASURES: Unplanned pregnancy was measured at the first antenatal care visit using the London Measure of Unplanned Pregnancy (LMUP). Analyses examined LMUP scores across four groups of participants defined by their HIV status, awareness of their HIV status prior to the current pregnancy and/or whether they were using antiretroviral therapy (ART) prior to the current pregnancy. RESULTS: Among 2105 pregnant women (1512 HIV positive; 593 HIV negative), median age was 28 years, 43% were married/cohabiting and 20% were nulliparous. Levels of unplanned pregnancy were significantly higher in HIV-positive versus HIV-negative women (50% vs 33%, p<0.001); and highest in women who were known HIV positive but not on ART (53%). After adjusting for age, parity and marital status, unplanned pregnancy was most common among women newly diagnosed and women who were known HIV positive but not on ART (compared with HIV-negative women, adjusted OR (aOR): 1.43; 95% CI 1.05 to 1.94 and aOR: 1.57; 95% CI 1.13 to 2.15, respectively). Increased parity and younger age (<24 years) were also associated with unplanned pregnancy (aOR: 1.42; 95% CI 1.25 to 1.60 and aOR: 1.83; 95% CI 1.23 to 2.74, respectively). CONCLUSIONS: We observed high levels of unplanned pregnancy among HIV-positive women, particularly among those not on ART, suggesting ongoing missed opportunities for improved family planning and counselling services for HIV-positive women.

Antiretroviral therapy use during pregnancy and adverse birth outcomes in South African women.

Background: Studies of antiretroviral therapy (ART) use during pregnancy in HIV-infected women have suggested that ART exposure may be associated with adverse birth outcomes. However, there are few data from sub-Saharan Africa where HIV is most common, and few studies involving the World Health Organization's (WHO's) recommended first-line regimens. Methods: We enrolled consecutive HIV-infected pregnant women and a comparator cohort of uninfected women at a primary-level antenatal care facility in Cape Town, South Africa. Gestational assessment combined clinical history, examination and ultrasonography; outcomes included preterm (PTD), low birthweight (LBW) and small for gestational age (SGA) deliveries. In analysis we compared birth outcomes between HIV-infected and -uninfected women, and HIV-infected women who initiated ART before vs during pregnancy. Results: In 1554 women (mean age 29 years) with live singleton births at time of analysis, 82% were HIV-infected, 92% of whom received a first-line regimen of tenofovir, emtricitabine and efavirenz. Overall, higher levels of PTD [22% vs 13%; odds ratio (OR) 1.94, 95% confidence interval (CI): 1.34, 2.82] and LBW (14% vs 9%; OR 1.62, 95% CI: 1.05, 2.29) were observed in HIV-infected vs uninfected women, although SGA deliveries were similar (9% vs 11%; OR 1.06, 95% CI: 0.71, 1.61). Adjusting for demographic characteristics and HIV disease measures, HIV-infected (vs HIV-uninfected) women had persistently increased odds of PTD [adjusted odds ratio (AOR) 2.03; CI 1.33, 3.10]; associations with LBW were attenuated (AOR 1.47; CI 0.90, 2.40). Among all HIV-infected women, there appeared to be no association between the timing of ART initiation (before or during pregnancy) and adverse birth outcomes. Conclusions: These findings suggest that current WHO-recommended ART regimens appear relatively safe in pregnancy, although more data are required to understand the aetiology of preterm delivery in HIV-infected women using ART.

Self-Reported Side Effects and Adherence to Antiretroviral Therapy in HIV-Infected Pregnant Women under Option B+: A Prospective Study.

BACKGROUND: Antiretroviral therapy (ART) regimens containing efavirenz (EFV) are recommended as part of universal ART for pregnant and breastfeeding women. EFV may have appreciable side effects (SE), and ART adherence in pregnancy is a major concern, but little is known about ART SE and associations with adherence in pregnancy. METHODS: We investigated the distribution of patient-reported SE (based on Division of AIDS categories) and the association of SE with missed ART doses in a cohort of 517 women starting EFV+3TC/FTC+TDF during pregnancy. In analysis, SE were considered in terms of their overall frequency, by systems category, and by latent classes. RESULTS: Overall 97% of women reported experiencing at least one SE after ART initiation, with 48% experiencing more than five SE. Gastrointestinal, central nervous system, systemic and skin SE were reported by 81%, 85%, 79% and 31% of women, respectively, with considerable overlap across groups. At least one missed dose was reported by 32% of women. In multivariable models, ART non-adherence was associated with systemic SE compared to other systems categories, and measures of the overall burden of SE experienced were most strongly associated with missed ART doses. CONCLUSION: These data demonstrate very high levels of SE in pregnant women initiating EFV-based ART and a strong association between SE burden and ART adherence. ART regimens with reduced SE profiles may enhance adherence, and as countries expand universal ART for all adult patients, counseling must include preparation for ART SE.

Intimate partner violence experienced by HIV-infected pregnant women in South Africa: a cross-sectional study.

OBJECTIVES: Intimate partner violence (IPV) during pregnancy may be common in settings where HIV is prevalent but there are few data on IPV in populations of HIV-infected pregnant women in Southern Africa. We examined the prevalence and correlates of IPV among HIV-infected pregnant women. SETTING: A primary care antenatal clinic in Cape Town, South Africa. PARTICIPANTS: 623 consecutive HIV-infected pregnant women initiating lifelong antiretroviral therapy. MEASURES: IPV, depression, substance use and psychological distress were assessed using the 13-item WHO Violence Against Women questionnaire, the Edinburgh Postnatal Depression Scale (EPDS), Alcohol and Drug Use Disorders Identification Tests (AUDIT/DUDIT) and the Kessler 10 (K-10) scale, respectively. RESULTS: The median age in the sample was 28 years, 97% of women reported being in a relationship, and 70% of women reported not discussing and/or agreeing on pregnancy intentions before conception. 21% of women (n=132) reported experiencing ≥1 act of IPV in the past 12 months, including emotional (15%), physical (15%) and sexual violence (2%). Of those reporting any IPV (n=132), 48% reported experiencing 2 or more types. Emotional and physical violence was most prevalent among women aged 18-24 years, while sexual violence was most commonly reported among women aged 25-29 years. Reported IPV was less likely among married women, and women who experienced IPV were more likely to score above threshold for substance use, depression and psychological distress. In addition, women who reported not discussing and/or not agreeing on pregnancy intentions with their partner prior to conception were significantly more likely to experience violence. CONCLUSIONS: HIV-infected pregnant women in the study reported experiencing multiple forms of IPV. While the impact of IPV on maternal and child health outcomes in the context of HIV infection requires further research attention, IPV screening and support services should be considered within the package of routine care for HIV-infected pregnant women. TRIAL REGISTRATION NUMBER: NCT01933477.

Optimizing Antiretroviral Therapy (ART) for Maternal and Child Health (MCH): Rationale and Design of the MCH-ART Study.

BACKGROUND: Prevention of mother-to-child transmission of HIV implementation faces significant challenges globally, particularly in the context of universal lifelong antiretroviral therapy (ART) for all HIV-infected pregnant women. METHODS: We describe the rationale and methods of the Maternal and Child Health-Antiretroviral Therapy (MCH-ART) study, an implementation science project examining strategies for providing HIV care and treatment to HIV-infected women who initiate ART during pregnancy and their HIV-exposed infants. RESULTS: MCH-ART is composed of 3 interrelated study designs across the antenatal and postnatal periods. Phase 1 is a cross-sectional evaluation of consecutive HIV-infected pregnant women seeking antenatal care; phase 2 is an observational cohort of all women from phase 1 who are eligible for initiation of ART following local guidelines; and phase 3 is a randomized trial of strategies for delivering ART to breastfeeding women from phase 2 during the postpartum period. During each phase, a set of study measurement visits is carried out separately from antenatal care and ART services; a maximum of 9 visits takes place from the beginning of antenatal care through 12 months postpartum. In parallel, in-depth interviews are used to examine issues of ART adherence and retention qualitatively, and costs and cost-effectiveness of models of care are examined. Separate substudies examine health outcomes in HIV-uninfected women and their HIV-unexposed infants, and the role of the adherence club model for long-term adherence and retention. DISCUSSION: Combining observational and experimental components, the MCH-ART study presents a novel approach to understand and optimize ART delivery for MCH.