Changes in the Vaginal Microbiome During Pregnancy and the Postpartum Period in South African Women: a Longitudinal Study.

Pregnant women in sub-Saharan Africa have high rates of maternal morbidity. There is interest in the impact of the vaginal microbiome on maternal health, including HIV and sexually transmitted infection (STI) acquisition. We characterized the vaginal microbiota of South African women ≥ 18 years with and without HIV in a longitudinal cohort over two visits during pregnancy and one visit postpartum. At each visit, we obtained HIV testing and self-collected vaginal swabs for point-of-care testing for STIs and microbiota sequencing. We categorized microbial communities and evaluated changes over pregnancy and associations with HIV status and STI diagnosis. Across 242 women (mean age 29, 44% living with HIV, 33% diagnosed with STIs), we identified four main community state types (CSTs): two lactobacillus-dominant CSTs (dominated by Lactobacillus crispatus and Lactobacillus iners respectively) and two diverse, non-lactobacillus-dominant CSTs (one dominated by Gardnerella vaginalis and one by diverse facultative anaerobes). From the first antenatal visit to the third trimester (24-36 weeks gestation), 60% of women in the Gardnerella-dominant CST shifted to lactobacillus-dominant CSTs. From the third trimester to postpartum (mean 17 days post-delivery), 80% of women in lactobacillus-dominant CSTs shifted to non-lactobacillus-dominant CSTs with a large proportion in the facultative anaerobe-dominant CST. Microbial composition differed by STI diagnosis (PERMANOVA R2 = 0.002, p = 0.004), and women diagnosed with an STI were more likely to be categorized as L. iners-dominant or Gardnerella-dominant CSTs. Overall, we found a shift toward lactobacillus dominance during pregnancy and the emergence of a distinct, highly diverse anaerobe-dominant microbiota profile in the postpartum period.

Pregnancy outcomes following self-reported and objective-measured exposure to oral preexposure prophylaxis in South Africa.

OBJECTIVE: To compare pregnancy outcomes using self-reported and objective levels of intracellular tenofovir diphosphate (TFV-DP) in pregnant women using preexposure prophylaxis (PrEP). DESIGN: We enrolled pregnant women >15 years without HIV at first antenatal care visit in an observational cohort study to compare pregnancy outcomes by PrEP use. METHODS: Exposure defined as: any PrEP use [tenofovir disoproxil and emtricitabine (TDF/FTC]) prescription + reported taking PrEP], or objectively-measured TFV-DP in dried blood spots in PrEP-using pregnant women. The primary outcome was a composite of pregnancy loss, preterm birth (<37weeks), low birthweight (<2500 g), small for gestational age ([SGA] ≤ tenth percentile), or neonatal death. Multivariable logistic regression models evaluated individual and composite adverse outcomes by self-reported or objectively measured PrEP use adjusting for age, gestational age, gravidity and socio-economic status. RESULTS: Between August 19 and February 23, we followed 1195 pregnant women and ascertained 1145 pregnancy outcomes (96%); 72% ( n  = 826) reported taking PrEP while pregnant, 16% did not take PrEP ( n  = 178), 12% were unconfirmed ( n  = 141). Overall, 94.5% ( n  = 1082) had singleton live births with a median birthweight of 3.2 kg [interquartile range (IQR) = 2.9-3.5], with no difference in pregnancy loss between self-reported PrEP exposed vs. unexposed [4.0 vs. 5.6%; adjusted odds ratio (aOR) = 0.65, 95% confidence interval (CI) = 0.32-1.47]. Composite adverse outcomes did not differ by reported PrEP use (20% for both groups; aOR = 1.07, 95% CI = 0.71-1.63). Comparing objective PrEP use (any TFV-DP vs. no TFV-DP or not on PrEP), adverse outcomes did not differ (aOR = 0.64, 95% CI = 0.39-1.04), nor did other outcomes including preterm birth nor SGA. CONCLUSIONS: Pregnancy outcomes did not differ by PrEP exposure (self-reported or objective), suggesting real-world efficacy that TDF/FTC as PrEP is safe in pregnancy.

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.

Maternal weight trajectories and associations with infant growth in South African women.

BACKGROUND: Despite the close relationship between pre-pregnancy body mass index (BMI), gestational weight gain (GWG) and postpartum weight (PPW), these factors are often studied separately. There are no data characterising longitudinal weight trajectories among pregnant and postpartum women in urban African populations. We examined maternal weight trajectories from pregnancy through to 12 months postpartum, factors associated with higher weight trajectory class membership and associations of weight trajectories with infant growth at 12 months. METHODS: Data from 989 women were examined for weight trajectories from first antenatal care visit in pregnancy to 12 months postpartum using latent-class growth models. Baseline factors associated with class membership were assessed using multinomial logistic regression. Of the enrolled women, 613 of their infants were assessed for growth at 12 months. Anthropometry measurements for mothers and infants were conducted by a trained study nurse. Associations between maternal weight trajectory class and infant weight-for-age (WAZ), length-for-age (LAZ), weight-for-length (WLZ) at 12 months of age were analysed using linear regression. RESULTS: Four distinct classes of maternal weight trajectories were identified. The classes included consistent low (29%), consistent medium (37%), medium-high (24%) and consistent high (10%) trajectories. Similar to trends observed with medium-high trajectory, baseline factors positively associated with consistent high class membership included age (OR 1.05, 95% CI 1.01-1.09), pre-pregnancy BMI (OR 2.24, 95% CI 1.97-2.56), stage 1 hypertension (OR 3.28, 95% CI 1.68-6.41), haemoglobin levels (OR 1.39, 95% CI 1.11-1.74) and parity (OR 1.39, 95% CI 1.15-1.67); living with HIV (OR 0.47, 95% CI 0.30-0.74) was inversely associated. In adjusted analyses, compared to consistent medium weight trajectory, consistent low weight trajectory (mean difference -0.41, 95% CI -0.71;-0.12) was associated with decreased, and consistent high weight trajectory (mean difference 1.21, 95% CI 0.59-1.83) with increased infant WAZ at 12 months of age. CONCLUSION: Identification of unique longitudinal weight trajectory groupings might inform comprehensive efforts targeted at improving healthy maternal weight and infant outcomes.

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.

Changes in the vaginal microbiome during pregnancy and the postpartum period in South African women: a longitudinal study.

African women have more diverse vaginal microbiota than women of European descent, and there is interest in the impact of this diversity on maternal health, including HIV and STI acquisition. We characterized the vaginal microbiota in a cohort of women ≥ 18 years with and without HIV in a longitudinal cohort over two visits during pregnancy and one visit postpartum. At each visit we obtained HIV testing and self-collected vaginal swabs for point of care testing for STIs and microbiome sequencing. We categorized microbial communities and evaluated changes over pregnancy and associations with HIV status and STI diagnosis. Across 242 women (mean age 29, 44% living with HIV, 33% diagnosed with STIs), we identified four main community state types (CSTs): two lactobacillus-dominant CSTs (dominated by Lactobacillus crispatus and Lactobacillus iners respectively) and two diverse, non-lactobacillus-dominant CSTs (one dominated by Gardnerella vaginalis and one by other facultative anaerobes). From first antenatal visit to third trimester (24-36 weeks gestation), 60% of women in the Gardnerella -dominant CST shifted to L actobacillus -dominant CSTs. From third trimester to postpartum (mean 17 days post-delivery), 80% of women in Lactobacillus -dominant CSTs shifted to non-lactobacillus-dominant CSTs with a large proportion in the facultative anaerobe-dominant CST. Microbial composition differed by STI diagnosis (PERMANOVA R 2 = 0.002, p = 0.004), and women diagnosed with an STI were more likely to be categorized with L. iners -dominant or Gardnerella -dominant CSTs. Overall we found a shift toward lactobacillus dominance during pregnancy, and the emergence of a distinct, highly diverse anaerobe-dominant microbiome population in the postpartum period.

Point-of-Care Sexually Transmitted Infection Testing Improves HIV Preexposure Prophylaxis Initiation in Pregnant Women in Antenatal Care in Cape Town, South Africa, 2019 to 2021.

Preexposure prophylaxis (PrEP) programs present a platform for diagnostic sexually transmitted infection (STI) testing in low- and middle-income countries, and availability of targeted STI testing has been hypothesized to influence PrEP use. We evaluated the association of STI testing modality and PrEP uptake among pregnant women in antenatal care. We enrolled pregnant, HIV-uninfected women (16 years or older) at their first antenatal visit with follow-up through 12 months postpartum. Women were offered oral PrEP and tested for Chlamydia trachomatis and Neisseria gonorrhoeae using a point-of-care (POC; Cepheid, August 2019­November 2020) or laboratory-based (Thermofisher, December 2020­October 2021) test. We compared the proportion of women initiating and continuing PrEP by STI test adjusting for confounders. We evaluated 1194 women (median age, 26 years [interquartile range, 22­31 years]) with an STI result (46% POC and 54% laboratory-based). The prevalence of any STI was the same in POC-tested (28%) and laboratory-tested (28%) women­25% versus 23% for C. trachomatis ( P = 0.35) and 7% versus 9% for N. gonorrhoeae ( P = 0.11). Mean time from testing to result was 0 day for POC and 26 days for laboratory testing, and mean time from testing to treatment was 3 days for POC and 38 days for laboratory testing. Receiving a POC STI test was associated with higher PrEP initiation compared with women receiving a laboratory-based test (90% vs. 78%; adjusted odds ratio, 2.1; 95% confidence interval, 1.5­2.9), controlling for age, gravidity, STI diagnosis, intimate partner violence, gestational age, employment, HIV risk perception, and cohabiting status. Point-of-care STI testing, offering same-day results and treatment initiation, may increase PrEP initiation among pregnant women in antenatal care.

Adherence challenges with daily oral pre-exposure prophylaxis during pregnancy and the postpartum period in South African women: a cohort study.

INTRODUCTION: Daily oral pre-exposure prophylaxis (PrEP) can reduce HIV acquisition. However, prevention effectiveness requires daily adherence prior to and during periods of sexual activity. Little is known about pharmacologic measures of PrEP adherence during pregnancy and postpartum and the factors related to optimal adherence during periods of sexual activity in this population. METHODS: Between August 2019 and October 2021, we enrolled pregnant women without HIV at their first antenatal care visit followed-up through 12 months postpartum. Eligible women ≥16 years old received HIV prevention counselling and were offered oral PrEP (TDF-FTC). We quantified tenofovir-diphosphate (TFV-DP) in dried blood spots in women who reported taking PrEP in the past 30 days (at quarterly follow-up visits). We used regression models with generalized estimating equations to evaluate correlates of TFV-DP (any vs. none, and ≥2 vs. <2 doses/week), adjusting for maternal age and pregnancy status. RESULTS AND DISCUSSION: In 382 women who started PrEP in pregnancy, returned for follow-up and reported PrEP use in the past 30 days, the median age was 27 years (interquartile range [IQR] = 23-32), and the median time on PrEP was 168 days (IQR = 84-252 days). Half of the samples had quantifiable TFV-DP at any time point (52%), declining from 67% of pregnant women 3 months post-initiation to 31% of postpartum women by 12 months. Overall, 72% had concentrations corresponding to <2 doses/week; 25% ≥2 doses/week; 3% 7 doses/week. Concentrations were lower in postpartum versus pregnancy (age-adjusted odds ratio [aOR] = 0.44; 95% confidence interval [CI] = 0.35-0.54). The correlation of self-reported adherence and TFV-DP ranged from -0.07 in pregnancy to 0.25 in postpartum women. Variables associated with having quantifiable TFV-DP included partner living with HIV/unknown serostatus (aOR = 1.50; 95% CI = 1.01-2.22), and reported frequency of sexual activity in the past month (aOR sex >5/month vs. no sex or <5 times/month = 2.11; 95% CI = 1.58-2.82) adjusting for age and pregnancy versus postpartum status. TFV-DP concentrations declined over follow-up time (aOR for 6 vs. 3 months = 0.49; 95% CI = 0.36-0.67). CONCLUSIONS: Objectively measured adherence to PrEP was low overall and did not correlate with self-reported use. There is an urgent need for objective adherence measures to support clinical decision-making as well as adherence support interventions as part of PrEP services for pregnant and postpartum women at risk of HIV.

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.

Determining antenatal medicine exposures in South African women: a comparison of three methods of ascertainment.

BACKGROUND: In the absence of clinical trials, data on the safety of medicine exposures in pregnancy are dependent on observational studies conducted after the agent has been licensed for use. This requires an accurate history of antenatal medicine use to determine potential risks. Medication use is commonly determined by self-report, clinician records, and electronic pharmacy data; different data sources may be more informative for different types of medication and resources may differ by setting. We compared three methods to determine antenatal medicine use (self-report, clinician records and electronic pharmacy dispensing records [EDR]) in women attending antenatal care at a primary care facility in Cape Town, South Africa in a setting with high HIV prevalence. METHODS: Structured, interview-administered questionnaires recorded self-reported medicine use. Data were collected from clinician records and EDR on the same participants. We determined agreement between these data sources using Cohen's kappa and, lacking a gold standard, used Latent Class Analysis to estimate sensitivity, specificity and positive predictive value (PPV) for each data source. RESULTS: Between 55% and 89% of 967 women had any medicine use documented depending on the data source (median number of medicines/participant = 5 [IQR 3-6]). Agreement between the datasets was poor regardless of class except for antiretroviral therapy (ART; kappa 0.6-0.71). Overall, agreement was better between the EDR and self-report than with either dataset and the clinician records. Sensitivity and PPV were higher for self-report and the EDR and were similar for the two. Self-report was the best source for over-the-counter, traditional and complementary medicines; clinician records for vaccines and supplements; and EDR for chronic medicines. CONCLUSIONS: Medicine use in pregnancy was common and no single data source included all the medicines used. ART was the most consistently reported across all three datasets but otherwise agreement between them was poor and dependent on class. Using a single data collection method will under-estimate medicine use in pregnancy and the choice of data source should be guided by the class of the agents being investigated.

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.

Pre-exposure Prophylaxis Recent Adherence With Real-Time Adherence Feedback and Partner Human Immunodeficiency Virus Self-Testing: A Pilot Trial Among Postpartum Women.

BACKGROUND: Pre-exposure prophylaxis (PrEP) is safe and effective in postpartum women. Human immunodeficiency virus self-testing (HIVST) for male partners combined with biofeedback counseling through real-time adherence measures may improve PrEP use among postpartum women. METHODS: Between August 2020 and April 2021, we randomized postpartum women who initiated PrEP in pregnancy 1:1 to the intervention group (HIVST + biofeedback counseling after urine tenofovir test) or to standard of care ([SOC] facility-based human immunodeficiency virus [HIV] tests and routine counseling without biofeedback). The outcomes of interest were PrEP adherence in the past 48-72 hours via urine tenofovir tests and partner HIV testing, measured 1-month after randomization. Secondary outcomes included the proportion of partners who tested for HIV and the discrepancy between self-reported PrEP adherence and urine tenofovir result. RESULTS: We enrolled 106 women (median age = 26 years). At enrollment, 72% of women reported missing <2 doses in the past 7 days; 36% of women had tenofovir present in her urine. One month after enrollment, 62% (n = 33) of women in the intervention arm had tenofovir present in their urine compared to 34% (n = 18) in SOC (risk ratio [RR] = 1.83; 95% confidence interval [CI] = 1.19-2.82; P = .001). Two thirds of women in the intervention arm reported that her partner tested for HIV (66%; n = 35), compared to 17% (n = 9) in SOC (RR = 3.89; 95% CI = 2.08-7.27; P < .001). Self-reported PrEP adherence (took PrEP >5 of last week) with no tenofovir in urine test was lower in the intervention group (17% vs 46%; RR = 0.33; 95% CI = 0.17-0.67; P = .03). No social or clinical adverse events were reported in the intervention arm. CONCLUSIONS: The HIVST for partners and biofeedback counseling increased levels of recent PrEP adherence, pointing to the importance of these interventions to support PrEP use in this population.

Growth patterns of infants with in- utero HIV and ARV exposure in Cape Town, South Africa and Lusaka, Zambia.

BACKGROUND: Infants born HIV-exposed yet remain uninfected (HEU) are at increased risk of poorer growth and health compared to infants born HIV-unexposed (HU). Whether maternal antiretroviral treatment (ART) in pregnancy ameliorates this risk of poorer growth is not well understood. Furthermore, whether risks are similar across high burden HIV settings has not been extensively explored. METHODS: We harmonized data from two prospective observational studies conducted in Cape Town, South Africa, and Lusaka, Zambia, to compare weight-for-age (WAZ), length-for-age (LAZ) and weight-for-length (WLZ) Z-scores between infants who were HEU and HU, converting infant anthropometric measures using World Health Organisation Growth Standards adjusted for age and sex. Linear mixed effects models were fit to identify risk factors for differences in anthropometrics at 6-10 weeks and 6 months by infant HIV exposures status and by timing of exposure to maternal ART, either from conception or later in gestation. RESULTS: Overall 773 mother-infant pairs were included across two countries: women living with HIV (WLHIV), 51% (n = 395) with 65% on ART at conception and 35% initiating treatment in pregnancy. In linear mixed effects models, WAZ and WLZ at 6-10 weeks were lower among infants who were HEU vs HU [ß = - 0.29 (95% CI: - 0.46, - 0.12) and [ß = - 0.42 (95% CI: - 0.68, - 0.16)] respectively after adjusting for maternal characteristics and infant feeding with a random intercept for country. At 6 months, LAZ was lower [ß = - 0.28 CI: - 0.50, - 0.06)] among infants who were HEU, adjusting for the same variables, with no differences in WAZ and WLZ. Within cohort evaluations identified different results with higher LAZ among infants who were HEU from Zambia at 6-10 weeks, [ß = + 0.34 CI: + 0.01, + 0.68)] and lower LAZ among infants who were HEU from South Africa [ß = - 0.30 CI: - 0.59, - 0.01)] at 6 months, without other anthropometric differences at either site. CONCLUSION: Infant growth trajectories differed by country, highlighting the importance of studying contextual influences on outcomes of infants who were HEU.

Prevalence of curable STIs and bacterial vaginosis during pregnancy in sub-Saharan Africa: a systematic review and meta-analysis.

OBJECTIVE: STIs remain a global public health problem with a high burden among pregnant women. STIs in pregnant women may lead to various adverse pregnancy outcomes. In most sub-Saharan African countries, syndromic management is used for screening and treatment of STIs. We aimed to update and summarise pooled prevalence of curable STIs and bacterial vaginosis (BV) among pregnant women in sub-Saharan Africa. METHODS: Electronic databases and reference lists of relevant published and unpublished studies were searched from March 2015 to October 2020. Studies were included if they estimated prevalence of Chlamydia trachomatis (CT), Trichomonas vaginalis (TV), Neisseria gonorrhoeae (NG), Treponema pallidum (syphilis), Mycoplasma genitalium (MG) and BV among pregnant women in sub-Saharan Africa. Meta-analyses were performed with observed prevalences corrected for diagnostic errors to estimate the pooled prevalence of diagnosed infections by region. RESULTS: A total of 48 studies met the inclusion criteria, providing 85-point prevalence estimates for curable STIs and BV. Pooled prevalence estimates (with 95% CI and number of women tested) were as follows: MG: 13.5% (4.0-27.2, n=1076); CT: 10.8% (6.9-15.5, n=6700); TV: 13.8% (10.0-18.0, n=9264); NG: 3.3% (2.1-4.7, n=6019); syphilis: 2.9% (2.0-4.0, n=95 308) and BV: 36.6% (27.1-46.6, n=5042). By region, BV was the most prevalent and ranged from 28.5% (24.5-32.8, n=1030) in Eastern Africa to 52.4% (33.5-70.9, n=2305) in Southern Africa; NG had the lowest prevalence, ranging from 1.4% (95% CI 0.1 to 3.1, n=367) in Central Africa to 4.4% (95% CI 2.6 to 6.4, n=4042) in Southern Africa. CONCLUSION: The prevalence of curable STIs and BV in sub-Saharan Africa is substantial in pregnant women but most prevalent in Southern Africa where HIV prevalence is highest. It is crucial to integrate screening of curable STIs into antenatal care programmes that have previously focused on diagnosis and treatment of syphilis and HIV.

Association between food intake and obesity in pregnant women living with and without HIV in Cape Town, South Africa: a prospective cohort study.

BACKGROUND: Although global nutrition/dietary transition resulting from industrialisation and urbanisation has been identified as a major contributor to widespread trends of obesity, there is limited data in pregnant women, including those living with HIV in South Africa. We examined food-based dietary intake in pregnant women with and without HIV at first antenatal care (ANC) visit, and associations with maternal overweight/obesity and gestational weight gain (GWG). METHODS: In an urban South African community, consecutive women living with (n = 479) and without (n = 510) HIV were enrolled and prospectively followed to delivery. Interviewer-administered non-quantitative food frequency questionnaire was used to assess dietary intake (starch, protein, dairy, fruits, vegetables, legumes, oils/fats) at enrolment. Associations with maternal body mass index (BMI) and GWG were examined using logistic regression models. RESULTS: Among women (median age 29 years, IQR 25-34), the prevalence of obesity (BMI ≥ 30 kg/m2) at first ANC was 43% and that of excessive GWG (per IOM guidelines) was 37% overall; HIV prevalence was 48%. In women without HIV, consumption of potato (any preparation) (aOR 1.98, 95% CI 1.02-3.84) and pumpkin/butternut (aOR 2.13, 95% CI 1.29-3.49) for 1-3 days a week increased the odds of overweight/obesity compared to not consuming any; milk in tea/coffee (aOR 6.04, 95% CI 1.37-26.50) increased the odds of excessive GWG. Consumption of eggs (any) (aOR 0.52, 95% CI 0.32-0.86) for 1-3 days a week reduced the odds of overweight/obesity while peanut and nuts consumption for 4-7 days a week reduced the odds (aOR 0.34, 95% CI 0.14-0.80) of excessive GWG. In women with HIV, consumption of milk/yoghurt/maas to drink/on cereals (aOR 0.35, 95% CI 0.18-0.68), tomato (raw/cooked) (aOR 0.50, 95% CI 0.30-0.84), green beans (aOR 0.41, 95% CI 0.20-0.86), mixed vegetables (aOR 0.49, 95% CI 0.29-0.84) and legumes e.g. baked beans, lentils (aOR 0.50, 95% CI 0.28-0.86) for 4-7 days a week reduced the odds of overweight/obesity; tomato (raw/cooked) (aOR 0.48, 95% CI 0.24-0.96) and mixed vegetables (aOR 0.38, 95% CI 0.18-0.78) also reduced the odds of excessive GWG. CONCLUSIONS: Diet modification may promote healthy weight in pregnant women living with and without HIV.

Increased infectious-cause hospitalization among infants who are HIV-exposed uninfected compared with HIV-unexposed.

OBJECTIVES: Increased risk of morbidity and hospitalization has been observed in children who are HIV-exposed uninfected (HEU) compared with HIV-unexposed uninfected (HUU). Studies in the era of universal maternal antiretroviral treatment (ART) are limited. DESIGN: Prospective cohort. METHODS: We investigated hospitalization between 29 days and 12 months of life in a South African cohort of infants born between February 2017 and January 2019 (HEU = 455; HUU = 458). All mothers known with HIV during pregnancy received ART. We reviewed hospital records and classified and graded infectious diagnoses using a standardized tool. We examined factors associated with infectious-cause hospitalization using mixed-effects Poisson regression. RESULTS: Infants HEU vs. HUU had higher all-cause and infectious-cause hospitalization (13 vs. 7%, P = 0.004 and 10 vs. 6%, P = 0.014, respectively). Infectious causes accounted for most hospitalizations (77%). More infants HEU were hospitalized with severe or very severe infections than those HUU (9 vs. 6%; P = 0.031). Mortality (<1%) did not differ between groups. HIV exposure was a significant risk factor for infectious-cause hospitalization [adjusted incidence rate ratios (aIRRs) = 2.8; 95% confidence interval (CI) 1.5-5.4]. Although increased incidence of preterm birth (14 vs. 10%; P < 0.05) and shorter duration of breastfeeding (44 vs. 68% breastfed for ≥3 months, P < 0.001) among infants HEU vs. HUU contributed to increased hospitalization, they did not account for all the increased risk. CONCLUSION: Infectious-cause hospitalization incidence was higher among infants HEU vs. HUU, likely partly because of higher incidence of preterm birth and lower breastfeeding rates among infants HEU. The increased infectious disease burden in HEU infants has important implications for health services in sub-Saharan Africa.

Lower birth weight-for-age and length-for-age z-scores in infants with in-utero HIV and ART exposure: a prospective study in Cape Town, South Africa.

BACKGROUND: Successful scale-up of antiretroviral therapy (ART) during pregnancy has minimized infant HIV acquisition, and over 1 million infants are born HIV-exposed but uninfected (HEU), with an increasing proportion also exposed in utero to maternal ART. While benefits of ART in pregnancy outweigh risks, some studies have reported associations between in utero ART exposure and impaired fetal growth, highlighting the need to identify the safest ART regimens for use in pregnancy. METHODS: We compared birth anthropometrics of infants who were HEU with those HIV-unexposed (HU) in Cape Town, South Africa. Pregnant women had gestational age assessed by ultrasound at enrolment. Women living with HIV were on ART (predominately tenofovir-emtricitabine-efavirenz) either prior to conception or initiated during pregnancy. Birth weights and lengths were converted to weight-for-age (WAZ) and length-for-age (LAZ) z-scores using Intergrowth-21st software. Linear regression was used to compare mean z-scores adjusting for maternal and pregnancy characteristics. RESULTS: Among 888 infants, 49% (n = 431) were HEU and 51% (n = 457) HU. Of 431 HEU infants, 62% (n = 268) were exposed to HIV and antiretrovirals (ARVs) from conception and 38% (n = 163) were exposed to ARVs during gestation but after conception (median fetal ARV exposure of 21 weeks [IQR; 17-26]). In univariable analysis, infants who were HEU had lower mean WAZ compared with HU [ß = - 0.15 (95% Confidence Interval (CI): - 0.28, - 0.020)]. After adjustment for maternal age, gravidity, alcohol use, marital and employment status the effect remained [adjusted ß - 0.14 (95%CI: - 0.28, - 0.01]. Similar differences were noted for mean LAZ in univariable [ß - 0.20 (95%CI: - 0.42, - 0.01] but not multivariable analyses [adjusted ß - 0.18 (95%CI: - 0.41, + 0.04] after adjusting for the same variables. Mean WAZ and LAZ did not vary by in utero ARV exposure duration among infants who were HEU. CONCLUSION: In a cohort with high prevalence of ART exposure in pregnancy, infants who were HEU had lower birth WAZ compared with those HU. Studies designed to identify the mechanisms and clinical significance of these disparities, and to establish the safest ART for use in pregnancy are urgently needed.

Preterm birth and severe morbidity in hospitalized neonates who are HIV exposed and uninfected compared with HIV unexposed.

OBJECTIVES: Infants who are HIV exposed but uninfected (HEU) compared with HIV unexposed uninfected (HUU) have an increased risk of adverse birth outcomes, morbidity and hospitalization. In the era of universal maternal antiretroviral treatment, there are few insights into patterns of neonatal morbidity specifically. DESIGN: A prospective cohort study. METHODS: We compared neonatal hospitalizations among infants who were HEU (n = 463) vs. HUU (n = 466) born between 2017 and 2019 to a cohort of pregnant women from a large antenatal clinic in South Africa. We examined maternal and infant factors associated with hospitalization using logistic regression. RESULTS: Hospitalization rates were similar between neonates who were HEU and HUU (13 vs. 16%; P = 0.25). Overall, most hospitalizations occurred directly after birth (87%); infection-related causes were identified in 34%. The most common reason for hospitalization unrelated to infection was respiratory distress (25%). Very preterm birth (<32 weeks) (29 vs. 11%; P = 0.01) as well as very low birthweight (<1500 g) (34 vs. 16%; P = 0.02) occurred more frequently among hospitalized neonates who were HEU. Of those hospitalized, risk of intensive care unit (ICU) admission was higher in neonates who were HEU (53%) than HUU (27%) [risk ratio = 2.1; 95% confidence interval (95% CI) 1.3-3.3]. Adjusted for very preterm birth, the risk of ICU admission remained higher among neonates who were HEU (aRR = 1.8; 95% CI 1.1-2.9). CONCLUSION: Neonates who were HEU (vs. HUU) did not have increased all-cause or infection-related hospitalization. However, very preterm birth, very low birthweight and ICU admission were more likely in hospitalized neonates who were HEU, indicating increased severity of neonatal morbidity.

Prevalence, incidence and associated risk factors of STIs during pregnancy in South Africa.

OBJECTIVE: STIs during pregnancy increase adverse pregnancy and birth outcomes and may increase HIV risk. STI syndromic management is standard of care in South Africa. Our study evaluated the prevalence and incidence of STIs in pregnant women and the associated risk factors. METHODS: We combined data from two prospective observational studies of pregnant women enrolled while attending their first antenatal clinic (ANC) visit in Tshwane District and Cape Town. Women ≥18 years were tested at first ANC visit and at their first postpartum visit for Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis using Xpert assays (Cepheid, USA). We evaluated the prevalence and incidence of STI and the associated risk factors using multivariable regression models. RESULTS: We enrolled 669 pregnant women, 64% (n=427) from Tshwane District and 36% (n=242) from Cape Town; 80% (n=534) were women living with HIV (WLHIV) and 20% (n=135) without HIV. At enrolment, 37% (n=250) were diagnosed with at least one STI, of which 76% (n=190) were asymptomatic. STI prevalence was 40% (n=213) in WLHIV and 27% (n=37) in women without HIV (p=0.01). Baseline STI infection was associated with younger age (OR=0.95 per year, 95% CI 0.92 to 0.98), higher gestational age (adjusted OR (aOR)=1.03 per week, 95% CI 1.00 to 1.05), single relationship status (aOR=1.53, 95% CI 1.09 to 2.15) and HIV status (aOR=1.86, 95% CI 1.17 to 2.95). Of 419 participants with no STI at baseline, 21 had an incident STI during follow-up, with a mean follow-up time of 140 days. The incidence rate of STI during pregnancy and early post partum was 15 infections per 100 women-years (95% CI 9 to 23). Younger age was associated with STI incidence. CONCLUSION: Our study shows high prevalence and incidence of STIs in pregnancy, especially in WLHIV, demonstrating the need for STI screening in ANC to prevent adverse pregnancy and birth outcomes. Most STI cases were asymptomatic and would have gone untreated with syndromic management. Aetiological STI screening is urgently needed to reduce the burden of STIs in pregnancy.

Partner notification and treatment for sexually transmitted infections among pregnant women in Cape Town, South Africa.

Curable sexually transmitted infections (STIs) including Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV) are associated with adverse pregnancy outcomes. Partner notification is an important component of STI control as it has been shown to prevent re-infection and reduce infectious burden. Between October 2017 and February 2019, we conducted a cohort study of women attending antenatal care in Cape Town, South Africa. Self-collected vulvovaginal swabs were tested for CT, NG, and TV using Xpert® assays at first antenatal visit, during the third trimester, and postpartum. At the visit following a positive diagnosis, women were asked if they notified their partner and if their partner was treated. Among 242 participants, 97% reported being willing to notify partners if they tested positive and 78% thought their partner would be willing to treat the STI. Of the 73 women who were diagnosed with one or more STIs and reported having a sex partner, 93% reported notifying their partner and 63% reported their partner was treated. Younger maternal age was associated with partner notification and treatment (OR = 3.82; 95%CI = 1.34-10.90). Acceptability of partner notification was high in pregnant women, but partner treatment was low. Future interventions to improve partner notification and treatment are needed.