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IntroductionOptimal adherence to antiretroviral therapy (ART) is crucial to promoting maternal-infant health.SettingFourteen sites in 7 countries within sub-Saharan Africa and India.MethodsThe multicomponent, open-label strategy PROMISE trial enrolled breastfeeding mother-infant pairs not meeting in-country criteria for maternal ART (mART) initiation in the postpartum component within 5 days of delivery. Randomization was to mART versus infant NVP (iNVP) prophylaxis. Infants in the mART arm also received 6 weeks of iNVP. Self-reported adherence was assessed in a secondary analysis. Time-to-event analyses were performed to explore the association between adherence and maternal viral load (mVL) in the mART arm.ResultsTwo thousand four hundred thirty-one mother-infant pairs were enrolled between 2011 and 2014; the baseline maternal median CD4 was 686 (IQR 553-869), and the median mVL was 322 copies/mL (IQR 40-1422). Self-reported adherence was lower in the mART arm compared with the iNVP arm (no missed doses within 4 weeks of all study visits: 66% vs 83%; within 2 weeks: 71% vs 85%; P < 0.0001). The iNVP adherence at week 6 was high in both arms: 97% in mART arm; 95% in iNVP arm. Time-to-event analyses showed that adherence to mART was associated with time to first mVL ≥400 copies/mL ( P < 0.0001). Missing 1 full day of doses over 3 days was associated with a 66% risk of mVL ≥1000 copies/mL (HR: 1.66; 95% CI: 1.37, 1.99).ConclusionsPostpartum women were less adherent to their own ART than mothers providing their infant's nevirapine prophylaxis. The self-reported missed mART doses were associated with high mVL. Strategies to optimize postpartum mART adherence are urgently needed.Clinical trial numberClinicalTrials.gov: NCT01061151; closed to follow-up.

There is a paucity of data on COVID-19 vaccines in people living with HIV-1, who could be at increased risk of severe illness and death from COVID-19. We evaluated the safety and immunogenicity of a Matrix-M adjuvanted recombinant spike protein nanoparticle COVID-19 vaccine (NVX-CoV2373; Novavax) in HIV-negative people and people living with HIV-1.In this randomised, observer-blinded, multicentre, placebo-controlled phase 2A/B trial in South Africa, participants aged 18-84 years, with and without underlying HIV-1, were enrolled from 16 sites and randomly assigned (1:1) to receive two intramuscular injections of NVX-CoV2373 or placebo, 21 days apart. People living with HIV-1 were on stable antiretroviral therapy and had an HIV-1 viral load of less than 1000 copies per mL. Vaccine dosage was 5 μg SARS-CoV-2 recombinant spike protein with 50 μg Matrix-M adjuvant, whereas 0·9% saline was used as placebo injection (volume 0·5 mL each). All study staff and participants remained masked to study group assignment. We previously reported an interim analysis on the efficacy and safety of the NVX-CoV2373 vaccine (coprimary endpoints). In this Article, we present an expanded safety analysis for the full cohort of participants and report on the secondary objective of vaccine immunogenicity in the full cohort of people living with HIV-1 and in HIV-negative individuals overall and stratified by baseline SARS-CoV-2 serostatus. This trial is registered with ClinicalTrials.gov, NCT04533399, and the Pan-African Clinical Trials Registry, PACTR202009726132275.Participants were enrolled between Aug 17 and Nov 25, 2020. The safety analysis set included 4164 HIV-negative participants (2089 in the intervention group and 2075 in the placebo group) and 244 people living with HIV-1 (122 in the intervention group and 122 in the placebo group). 1422 (34·1%) of 4164 HIV-negative people and 83 (34·0%) of 244 people living with HIV-1 were categorised as baseline SARS-CoV-2-positive (ie, anti-spike IgG reactive at enrolment or had a reactive SARS-CoV-2 nucleic acid amplification test by 14 days after the second study vaccination). In the NVX-CoV2373 group, solicited local and systemic adverse events were more common in HIV-negative participants (427 [30·6%] local and 401 [28·7%] systemic) than in people living with HIV-1 (20 [25·3%] local and 20 [25·3%] systemic) among those who were baseline SARS-CoV-2-seronegative (naive). Of the serious adverse events that occurred among HIV-negative people (of whom, two [0·1%] were baseline SARS-CoV-2-negative and four [0·6%] were baseline SARS-CoV-2-positive) and people living with HIV-1 (for whom there were no serious adverse events) in the NVX-CoV2373 group, none were assessed as related to the vaccine. Among participants who were baseline SARS-CoV-2-negative in the NVX-CoV2373 group, the anti-spike IgG geometric mean titres (GMTs) and seroconversion rates (SCRs) were lower in people living with HIV-1 (n=62) than in HIV-negative people (n=1234) following the first vaccination (GMT: 508·6 vs 1195·3 ELISA units [EU]/mL; SCR: 51·6% vs 81·3%); and similarly so 14 days after the second vaccination for GMTs (14 420·5 vs 31 631·8 EU/mL), whereas the SCR was similar at this point (100·0% vs 99·3%). In the NVX-CoV2373 group, anti-spike IgG GMTs 14 days after the second vaccination were substantially higher in those who were baseline SARS-CoV-2-positive than in those who were baseline SARS-CoV-2-seronegative for HIV-negative participants (100 666·1 vs 31 631·8 EU/mL) and for people living with HIV-1 (98 399·5 vs 14 420·5 EU/mL). This was also the case for angiotensin-converting enzyme 2 receptor-binding antibody and neutralising antibody titres.The safety of the NVX-CoV2373 vaccine in people living with HIV-1 was similar to that in HIV-negative participants. However, people living with HIV-1 not previously exposed to SARS-CoV-2 had attenuated humoral immune responses to NVX-CoV2373 compared with their HIV-negative vaccine counterparts, but not so if they were baseline SARS-CoV-2-positive.Novavax and the BillMelinda Gates Foundation; investigational vaccine manufacturing support was provided by the Coalition for Epidemic Preparedness Innovations.

BackgroundAdherence to antiretroviral treatment (ART) among postpartum women with HIV is essential for optimal health and prevention of perinatal transmission. However, suboptimal adherence with subsequent viremia is common, and adherence challenges are often underreported. We aimed to predict viremia to facilitate targeted adherence support in sub-Saharan Africa during this critical period.MethodsData are from PROMISE 1077BF/FF, which enrolled perinatal women between 2011 and 2014. This analysis includes postpartum women receiving ART per study randomization or country-specific criteria to continue from pregnancy. We aimed to predict viremia (single and confirmed events) after 3 months on ART at >50, >400, and >1000 copies/mL within 6-month intervals through 24 months. We built models with routine clinical and demographic data using the least absolute shrinkage and selection operator and SuperLearner (which incorporates multiple algorithms).ResultsAmong 1321 women included, the median age was 26 years and 96% were in WHO stage 1. Between 0 and 24 months postpartum, 42%, 31%, and 28% of women experienced viremia >50, >400, and >1000 copies/mL, respectively, at least once. Across models, the cross-validated area under the receiver operating curve ranged from 0.74 [95% confidence interval (CI): 0.72 to 0.76] to 0.78 (95% CI: 0.76 to 0.80). To achieve 90% sensitivity predicting confirmed viremia >50 copies/mL, 64% of women would be classified as high risk.ConclusionsUsing routinely collected data to predict viremia in >1300 postpartum women with HIV, we achieved moderate model discrimination, but insufficient to inform targeted adherence support. Psychosocial characteristics or objective adherence metrics may be required for improved prediction of viremia in this population.

Research in rapidly evolving policy contexts can lead to the following ethical challenges for sponsors and researchers: the study’s standard of care can become different than what patients outside the study receive, there may be political or other pressure to move ahead with unproven interventions, and new findings or revised policies may decrease the relevance of ongoing studies. These ethical challenges are considerable, but not unprecedented. In this article, we review the case of a multinational, randomized, controlled perinatal HIV prevention trial, the “PROMISE” (Promoting Maternal Infant Survival Everywhere) study. PROMISE compared the relative efficacy and safety of interventions to prevent mother to child transmission of HIV. The sponsor engaged an independent international ethics panel to address controversy about the study’s standard of care and relevance as national and international guidelines changed. This ethics panel concluded that continuing the PROMISE trial as designed was ethically permissible because: (1) participants in all arms received interventions that were effective, and there was insufficient evidence about whether one intervention was more effective or safer than the other, and (2) data from PROMISE could be useful for a diverse range of stakeholders. In general, trials designed to inform rapidly evolving policy issues should develop mechanisms to revisit social value while recognizing that the value of research varies for diverse stakeholders with legitimate reasons to weigh evidence differently. We conclude by providing four reasons that trials may depart from the standard of care after a change in policy, while remaining ethically justifiable, and by suggesting how to improve existing trial oversight mechanisms to address evolving social value.

Up to two-thirds of South African adolescent mothers drop out of school, which increases their HIV risk and other poor health outcomes. Despite variability in adolescent mothers’ schooling trajecto...

BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the coronavirus disease 2019 (Covid-19) pandemic. In a phase 1-2 trial involving healthy adults, the NVX-CoV2373 nanoparticle vaccine had an acceptable safety profile and was associated with strong neutralizing-antibody and antigen-specific polyfunctional CD4+ T-cell responses. Evaluation of vaccine efficacy was needed in a setting of ongoing SARS-CoV-2 transmission. METHODS: In this phase 2a-b trial in South Africa, we randomly assigned human immunodeficiency virus (HIV)-negative adults between the ages of 18 and 84 years or medically stable HIV-positive participants between the ages of 18 and 64 years in a 1:1 ratio to receive two doses of either the NVX-CoV2373 vaccine (5 μg of recombinant spike protein with 50 μg of Matrix-M1 adjuvant) or placebo. The primary end points were safety and vaccine efficacy against laboratory-confirmed symptomatic Covid-19 at 7 days or more after the second dose among participants without previous SARS-CoV-2 infection. RESULTS: Of 6324 participants who underwent screening, 4387 received at least one injection of vaccine or placebo. Approximately 30% of the participants were seropositive for SARS-CoV-2 at baseline. Among 2684 baseline seronegative participants (94% HIV-negative and 6% HIV-positive), predominantly mild-to-moderate Covid-19 developed in 15 participants in the vaccine group and in 29 in the placebo group (vaccine efficacy, 49.4%; 95% confidence interval [CI], 6.1 to 72.8). Vaccine efficacy among HIV-negative participants was 60.1% (95% CI, 19.9 to 80.1). Of 41 sequenced isolates, 38 (92.7%) were the B.1.351 variant. Post hoc vaccine efficacy against B.1.351 was 51.0% (95% CI, -0.6 to 76.2) among the HIV-negative participants. Preliminary local and systemic reactogenicity events were more common in the vaccine group; serious adverse events were rare in both groups. CONCLUSIONS: The NVX-CoV2373 vaccine was efficacious in preventing Covid-19, with higher vaccine efficacy observed among HIV-negative participants. Most infections were caused by the B.1.351 variant. (Funded by Novavax and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT04533399.).

IMPAACT PROMISE 1077BF/FF was a sequentially randomized study of pregnant and postpartum women living with HIV to investigate the efficacy and safety of antiretroviral therapy (ART). This Maternal Health Component investigated efficacy for the risk of developing AIDS or death; and safety among women randomized to continue ART (CTART: N = 289) or discontinue ART (N = 268) after cessation of breastfeeding or after confirmation of infant infection. No AIDS-defining illnesses were reported during follow-up in either arm. Adverse events of grade 3 or higher were more frequent in the CTART arm [hazard ratio = 1.78, 95% confidence interval: (1.05 to 3.02), P-value = 0.03]. The difference in adverse events in the 2 groups was mostly driven by moderate weight loss for women on the CTART arm.

Background Exclusive breastfeeding for 6 months and breastfeeding with complementary feeds until 12 months for HIV exposed and uninfected (HEU) infants or 24 months for HIV unexposed (HU) infants is the current World Health Organisation (WHO) recommendation for low and middle income countries (LMICs) to improve clinical outcomes and growth trajectories in infants. In a post-hoc evaluation of HEU and HU cohorts, we examine growth patterns and clinical outcomes in the first 9 months of infancy in association with breastfeeding duration. Methods Two cohorts of infants, HEU and HU from a low-socioeconomic township in South Africa, were evaluated from birth until 9 months of age. Clinical, anthropometric and infant feeding data were analysed. Standard descriptive statistics and regression analysis were performed to determine the effect of HIV exposure and breastfeeding duration on growth and clinical outcomes. Results Included in this secondary analysis were 123 HEU and 157 HU infants breastfed for a median of 26 and 14 weeks respectively. Median WLZ score was significantly (p p p p p Conclusion Our study has generated additional evidence that HEU infants are at substantial risk of infectious morbidity and decreased growth trajectories however we have further demonstrated that these adverse outcomes were independent of breastfeeding duration.

BACKGROUND: There is limited information on perinatal outcomes in HIV-hepatitis B virus (HBV) coinfection. METHODS: HIV Prevention Trials Network (HPTN) 046 was a randomized double-blind placebo-controlled trial of perinatal transmission that evaluated 6 months of infant nevirapine versus placebo among breast-fed infants. Women living with HIV and their infants enrolled in sub-Saharan Africa from 2007 to 2010; 78% received antiretroviral therapy (ART). Maternal samples were tested for hepatitis B surface antigen (HBsAg). High and low HBV viral load (VL) was defined as ≥10 IU/mL and

HIV incidence rates in South Africa are extremely high, particularly postpartum. However, there is limited knowledge of women’s HIV risk behavior postpartum. Women in age-disparate relationships may be less able to negotiate safe sex postpartum than women whose partners are similar ages because they have less relationship power. The study’s purpose is to test whether being in an age-disparate relationship predicts postpartum unsafe sex and to explore relationship control and intimate partner violence (IPV) as explanatory mechanisms. Data are obtained from 516 HIV-negative participants who completed a survey during pregnancy and at 14 weeks postpartum as part of a longitudinal study in Durban. Age variables, relationship control, and IPV during pregnancy were included in a multivariate model predicting unsafe sex postpartum. We also assessed whether the hypothesized mediators explained the association between being in an age-disparate relationship and unsafe sex postpartum by using indirect effect analysis with bootstrapping. Women’s mean age was 24.34 years (range = 18.03–45.36); the mean difference in ages in relationships was 3.19 years (range = −6.1 to 30.1). More than a quarter reported unsafe sex postpartum (27%). Age-disparate relationship, lower relationship control, and higher IPV were each longitudinally associated with unsafe sex. Relationship control, but not IPV, mediated the association between age-disparate relationship and unsafe sex (indirect effect [ B] = 0.01, 95% confidence interval [CI] = [0.0002, 0.0283]). Age disparity, relationship control, and IPV all contributed to unsafe sex postpartum. Interventions that reduce the formation of age-disparate relationships and increase women’s relationship power in pregnancy are needed to reduce women’s HIV risk in the postpartum period.

Background Globally, the number of infected women of childbearing age living with human immunodeficiency virus (HIV) and conceiving on antiretroviral therapy (ART) is increasing. Evidence of ART safety at conception and during pregnancy and adverse pregnancy outcomes remains conflicting. The Promoting Maternal and Infant Survival Everywhere (PROMISE) 1077 breastfeeding (BF) and formula feeding (FF) international multisite trials provide an opportunity to examine the impact of ART at conception on pregnancy outcomes with subsequent pregnancies. Methods The PROMISE 1077BF/1077FF trials were designed to address key questions in the management of HIV-infected women who did not meet clinical guidelines for ART treatment during the time of the trials. After the period of risk of mother-to-child transmission was over, women were randomized to either continue or discontinue ART. We compared subsequent pregnancy outcomes of nonbreastfeeding women randomized to continue ART following delivery, or breastfeeding women randomized to continue ART following breastfeeding cessation who conceived while on ART to women randomized to discontinue ART, who restarted ART after pregnancy was diagnosed. Results Pregnancy outcomes of 939 subsequent pregnancies of 826 mothers were recorded. The intention-to-treat analyses showed increased incidence of low birth weight (, Globally more women living with HIV conceive on antiretroviral therapy (ART). This study reports an increased risk of low birth weight, spontaneous abortion, stillbirth, and neonatal death for women conceiving on ART compared to those not on ART at conception.

In this study we aimed to identify factors that condition (i.e., buffer or exacerbate) the impact of exposure to intimate partner violence (IPV) on postpartum emotional distress among South African women. Hypothesized buffering factors included: socioeconomic status, family social support, and religiosity. Hypothesized exacerbating factors included: baseline distress, HIV status, and childhood abuse. Longitudinal analyses examined interactions between putative buffering and exacerbating factors and exposure to physical or sexual IPV, assessed during pregnancy (T1), as predictors of emotional distress, measured at 14 weeks (T2) and 9 months postpartum (T3). Consistent with hypotheses, at both T2 and T3 the impact of IPV exposure on emotional distress was significantly stronger among women who reported greater baseline distress and weaker among women of greater socioeconomic status. At T3, an interaction emerged with HIV status; the impact of IPV exposure on emotional distress was stronger for women who were diagnosed as HIV-positive during pregnancy. Findings support the need for targeted mental health promotion interventions for IPV-exposed women who are newly diagnosed with HIV and/or report high levels of emotional distress during pregnancy. Although more research is needed, findings also suggest that strengthening socioeconomic supports for IPV-exposed women may buffer impacts on postpartum mental health.

IntroductionSexually transmitted infection (STI) prevalence and incidence estimates for pregnant adolescents are under-reported. We estimated prevalence and incidence of STIs in pregnant adolescents (15–19 years) in comparison with pregnant women 20–24 and >25 years.MethodsPregnant women registering at primary care clinics in Umlazi, a periurban subdistrict in KwaZulu-Natal, South Africa, were enrolled in an HIV incidence cohort study during February 2017–March 2018. Women were examined for abnormal vaginal discharge, received empirical treatment, tested for HIV-1 and had vaginal swabs taken at their first and a subsequent visit in the third trimester. Vaginal swabs were stored for STI testing at completion of study and tested forTrichomonas vaginalis, Chlamydia trachomatis, Neisseria gonorrhoeaeandMycoplasma genitaliumusing PCR.ResultsA total of 752 HIV-negative pregnant women were enrolled at a median gestational age of 17 weeks: 180 (23.9%), 291 (38.7%) and 281 (37.4%) in the 15–19, 20–24 and >25 years age groups. Pregnant adolescents had an STI prevalence of 26.7% at baseline, not significantly lower than the 20–24 (34.7%, OR 1.4; 95% CI 1.0 to 2.1, p=0.09) and >25 years (33.8%, OR 1.4; 95% CI 0.9 to 2.1, p=0.12) age groups.T. vaginalis(11.1%),C. trachomatis(7.8%) andN. gonorrhoeae(4.4%) were most prevalent in adolescents, a trend similar to the other age groups. Overall, 43.4% were symptomatic and treated at baseline. Overall, 40.7% (118 of 290) of women who tested negative for an STI at baseline tested positive at the repeat visit (incidence 19.5/100 person years). STI incidence in pregnant adolescents was 23.9/100 person years and comparable with older age groups (20.5/100 person years and 16.2/100 person years). At the repeat visit, 19.0% of all women with an STI were symptomatic and treated. Performance of syndromic management was poor at baseline (negative predictive value (NPV) 68.6%, positive predictive value (PPV) 34.0%) and at repeat visit (NPV 58.4%, PPV 34.3%).ConclusionsPrevalence of asymptomatic curable STIs in pregnant adolescents is high and comparable with women >20 years old. Adolescents remain at substantial risk of asymptomatic incident STIs during pregnancy.

Tenofovir disoproxil fumarate (TDF) in combination with other antiretroviral (ARV) drugs has been in clinical use for HIV treatment since its approval in 2001. Although the effectiveness of TDF in preventing perinatal HIV infection is well established, information about renal safety during pregnancy is still limited.The IMPAACT PROMISE study was an open-label, strategy trial that randomized pregnant women to one of three arms: TDF based antiretroviral therapy (ART), zidovudine (ZDV) based ART, and ZDV alone (standard of care at start of enrollment). The P1084s substudy was a nested, comparative study of renal outcomes in women and their infants.PROMISE participants (n = 3543) were assessed for renal dysfunction using calculated creatinine clearance (CrCl) at study entry ( 14 weeks gestation), delivery, and postpartum weeks 6, 26, and 74. Of these women, 479 were enrolled in the P1084s substudy that also assessed maternal calcium and phosphate as well as infant calculated CrCl, calcium, and phosphate at birth.Among the 1338 women who could be randomized to TDF, less than 1% had a baseline calculated CrCl below 80 mL/min. The mean (standard deviation) maternal calculated CrCl at delivery in the TDF-ART arm [147.0 mL/min (51.4)] was lower than the ZDV-ART [155.0 mL/min (43.3); primary comparison] and the ZDV Alone [158.5 mL/min (45.0)] arms; the mean differences (95% confidence interval) were - 8.0 mL/min (- 14.5, - 1.5) and - 11.5 mL/min (- 18.0, - 4.9), respectively. The TDF-ART arm had lower mean maternal phosphate at delivery compared with the ZDV-ART [- 0.14 mg/dL (- 0.28, - 0.01)] and the ZDV Alone [- 0.17 mg/dL (- 0.31, - 0.02)] arms, and a greater percentage of maternal hypophosphatemia at delivery (4.23%) compared with the ZDV-ART (1.38%) and the ZDV Alone (1.46%) arms. Maternal calcium was similar between arms. In infants, mean calculated CrCl, calcium, and phosphate at birth were similar between arms (all CIs included 0).Although mean maternal calculated CrCl at Delivery was lower in the TDF-ART arm, the difference between arms is unlikely to be clinically significant. During pregnancy, the TDF-ART regimen had no observed safety concerns for maternal or infant renal function.NCT01061151 on 10/02/2010 for PROMISE (1077BF). NCT01066858 on 10/02/2010 for P1084s.

BackgroundThere are limited data on the impact of antenatal antiretroviral regimens (ARV) on pregnancy and infant outcomes in HIV/HBV coinfection. We compared outcomes among 3 antenatal antiretroviral regimens for pregnant women with HIV/HBV.MethodsThe PROMISE study enrolled ARV-naive pregnant women with HIV. Women with HBV were randomized to (no anti-HBV)-zidovudine (ZDV) + intrapartum nevirapine and 1 week of tenofovir disoproxil fumarate and emtricitabine (TDF-FTC); (3TC)-3TC + ZDV + LPV/r; or (FTC-TDF)-FTC + TDF + LPV/r. Pairwise group comparisons were performed with Fisher exact, t , or log rank tests. Adverse pregnancy outcome (APO) was a composite of low birth weight, preterm delivery, spontaneous abortion, stillbirth, or congenital anomaly.ResultsOf 138 women with HIV/HBV, 42, 48, and 48 were analyzed in the no anti-HBV, 3TC, and FTC-TDF arms. Median age was 27 years. APOs trended lower in the no anti-HBV (26%) vs 3TC (38%), and FTC-TDF arms (35%), P ≥ 0.25). More infant deaths occurred among the FTC-TDF [6 (13%)] vs no anti-HBV [2 (5%)] and 3TC [3 (7%)] arms. There were no differences in time-to-death, HIV-free survival, birth or one-year WHO Z-score length-for-age, and head circumference. Hepatitis B e antigen (HBeAg) was associated with an increased risk of APO, 48% vs 27% (odds ratio 2.79, 95% confidence interval: 1.19 to 6.67, post hoc ).ConclusionWith HBV/HIV coinfection, the risk of an APO was increased with maternal ARV compared with ZDV alone, although the differences were not statistically significant. Maternal HBeAg was associated with a significantly increased risk of APO. Infant mortality was highest with FTC + TDF + LPV/r. Early assessment of HBeAg could assist in identifying high-risk pregnancies for close monitoring.

Objective To evaluate the association between HIV antiretroviral therapy (ART) and preterm birth (PTB), when defined by gold standard antenatal ultrasound versus newborn exam. Design A secondary analysis of the PROMISE 1077BF/1077FF randomized controlled trial, which compared antiretroviral strategies to reduce perinatal HIV transmission and improve maternal health. The trial used newborn exam (i.e. New Ballard Score, NBS) to assess gestational age. This analysis included liveborn singleton pregnancies with both newborn exam and ultrasound data. The primary exposure was the trial's antiretroviral strategies: zidovudine with intrapartum nevirapine ('ZDV alone'); zidovudine/lamivudine/lopinavir-ritonavir ('ZDV-based ART'); or tenofovir/emtricitabine/lopinavir-ritonavir ('TDF-based ART'). The primary outcome was PTB less than 37 and less than 34 weeks based on the gold standard of ultrasound dating. We evaluated the association between antiretroviral strategy and PTB. We fit multivariable logistic regression models, adjusting for maternal characteristics, obstetric history, and HIV disease severity. Results Among 720 assessed pregnant women, PTB less than 37 weeks was 15.4% by NBS and 18.3% by ultrasound. The NBS was specific but not sensitive for PTB less than 37 weeks (92.0% and 48.5%). Women receiving ZDV-based and TDF-based ART had significantly higher odds of PTB less than 37 by ultrasound compared with ZDV alone (adjusted odds ratios: 1.68; 95% confidence interval 1.10-2.57, and 2.71; 95% confidence interval 1.39-5.29), as well as for PTB less than 34 weeks. These results held for ultrasounds performed less than 24 weeks, and were generally consistent with prior analyses from the PROMISE trial using the NBS. Conclusion Women starting HIV ART in pregnancy remained at higher risk of PTB when determined by ultrasound, consistent with prior data using newborn exam. However, newborn exam misclassified cases of PTB compared with gold standard ultrasound.

In the multicountry PROMISE 1077BF/1077FF trial, the risk of low birth weight (LBW;2500 g) and preterm delivery (PTD;37 weeks) was significantly higher among women initiating a protease inhibitor-based antiretroviral treatment (ART) regimen than those receiving ZDV alone. Among those assigned to a protease inhibitor regimen, tenofovir/emtricitabine was associated with the more severe outcomes of very LBW (1500 g) and very PTD (34 weeks) compared with zidovudine/lamivudine.We used multivariate logistic regression to further explore these treatment findings, taking into account demographic baseline clinical and postentry obstetrical factors. We evaluated individual adverse outcomes and composites that included stillbirth and early loss/spontaneous abortion.Among 3333 women delivering at least 1 live infant, median maternal age at enrollment was 26 years; 661 (20%) were primiparous, and 110 (3.3%) reported at least 1 previous PTD. Seventeen percent of newborns were LBW, 1% were very LBW, 17% had PTD, and 3% had very PTD. Treatment allocation remained strongly associated with multiple adverse outcomes after controlling for other risk factors with both ART regimens exhibiting increased risk relative to ZDV alone. Other risk factors remaining significant in at least one of the multivariate models included the following: country, gestational age at entry, maternal age, maternal body mass index, previous PTD, history of alcohol use, baseline HIV viral titer, multiple gestation, and several obstetric risk factors.ART effects on adverse pregnancy outcomes reported in the randomized PROMISE trial remained strongly significant even after controlling for demographic, baseline clinical, and obstetrical risk factors, which were also associated with these outcomes.

The rate of mother-to-child transmission (MTCT) of HIV from breastfeeding is increasing relative to other causes of MTCT. Early effective preconception and antenatal antiretroviral therapy (ART) reduces intrauterine and intrapartum MTCT, whereas maternal post-partum HIV acquisition, untreated maternal HIV, and suboptimal postnatal maternal ART adherence increase the risk of MTCT through breastfeeding. Although the absolute number of cases of MTCT acquired through breastfeeding is decreasing, the rate of decrease is less than the decrease in intrauterine and intrapartum MTCT. Unless current strategies are universally applied, they might not be sufficient to eliminate MTCT due to breastfeeding. Urgent action is needed to evaluate and implement additional preventive biomedical strategies in high HIV prevalence and incidence settings to eliminate MTCT from breastfeeding. Preventive strategies include: pre-exposure prophylaxis in breastfeeding women who have an increased risk of acquiring HIV; postnatal reinforcement strategies, such as maternal retesting for HIV, maternal care reinforcement, and prophylaxis in infants exposed to HIV via breastmilk; and active (vaccine) or passive immunoprophylaxis with long-acting broadly neutralising antibodies. acceptedVersion

BackgroundThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants threatens progress toward control of the Covid-19 pandemic. Evaluation of Covid-19 vaccine efficacy against SARS-CoV-2 variants is urgently needed to inform vaccine development and use.MethodsIn this phase 2a/b, multicenter, randomized, observer-blinded, placebo-controlled trial in South Africa, healthy human immunodeficiency virus (HIV)-negative adults (18 to 84 years) or medically stable people living with HIV (PLWH) (18 to 84 years) were randomized in a 1:1 ratio to receive two doses, administered 21 days apart, of either NVX-CoV2373 nanoparticle vaccine (5 µg recombinant spike protein with 50 µg Matrix-M1 adjuvant) or placebo. The primary endpoints were safety and vaccine efficacy ≥7 days following the second dose against laboratory-confirmed symptomatic Covid-19 in previously SARS-CoV-2 uninfected participants.ResultsA total of 4387 participants were randomized and dosed at least once, 2199 with NVX-CoV2373 and 2188 with placebo. Approximately 30% of participants were seropositive at baseline. Among 2684 baseline seronegative participants (94% HIV-negative; 6% PLWH), there were 15 and 29 predominantly mild to moderate Covid-19 cases in NVX-CoV2373 and placebo recipients, respectively; vaccine efficacy was 49.4% (95% confidence interval [CI]: 6.1 to 72.8). Efficacy in HIV-negative participants was 60.1% (95% CI: 19.9 to 80.1), and did not differ by baseline serostatus. Of the primary endpoint cases with available whole genome sequencing, 38 (92.7%) of 41 were the B.1.351 variant. Post-hoc vaccine efficacy against B.1.351 was 51.0% (95% CI: - 0.6 to 76.2) in HIV-negative participants. Among placebo recipients, the incidence of symptomatic Covid-19 was similar in baseline seronegative vs baseline seropositive participants during the first 2 months of follow-up (5.3% vs 5.2%). Preliminary local and systemic reactogenicity were primarily mild to moderate and transient, and higher with NVX-CoV2373; serious adverse events were rare in both groups.ConclusionsThe NVX-CoV2373 vaccine was efficacious in preventing Covid-19, which was predominantly mild to moderate and due to the B.1.351 variant, while evidence of prior infection with the presumptive original SARS-CoV-2 did not confer protection against probable B.1.351 disease. (Funded by Novavax, The Bill and Melinda Gates Foundation, and the Coalition for Epidemic Preparedness Innovations; ClinicalTrials.gov number, NCT04533399)

International audience; Ameena Goga and colleagues argue that frequent testing of maternal viral load is needed to eliminate HIV transmission through breast milk in low and middle income settings

BACKGROUND Breastfeeding mothers with HIV infection not qualifying for antiretroviral therapy (ART) based on country-specific guidelines at the time of the Promoting Maternal-Infant Survival Everywhere trial and their uninfected neonates were randomized to maternal ART (mART) or infant nevirapine prophylaxis (iNVP) postpartum. HIV transmission proportions were similar (

BackgroundExclusive breastfeeding for six months and breastfeeding with complementary feeds until 12 months for infants exposed to HIV (IEH) or 24 months for infants unexposed to HIV (IUH) is the current World Health Organisation (WHO) recommendation for LMICs to improve clinical outcomes and growth trajectories in infants. In a post hoc evaluation of IEH and IUH cohorts, we examine growth patterns and clinical outcomes in the first six months of infancy in association with breastfeeding duration. MethodsTwo non–contemporaneous cohorts of infants born to women living with HIV and women without HIV, from a low-socioeconomic township in South Africa, were evaluated from birth until nine months of age. Clinical, anthropometric and infant feeding data were analysed. Standard descriptive statistics and regression analysis were performed to determine the effect of HIV exposure and breastfeeding duration on growth and clinical outcomes. ResultsIncluded in this secondary analysis were 123 IEH and 157 IUH infants breastfed for a median of 26 weeks and 14 weeks respectively. Median WLZ score was consistently and significantly lower in IEH than IUH at 3, 6 and 9 months (-0.19 vs 2.09; -0.81 vs 0.28; 0.05 vs 0.97 respectively). In contrast, the median LAZ score was significantly lower among IUH at 3 and 6 (-1.63 vs 0.91; -0.37 vs 0.51). A significantly higher proportion of IUH was classified as stunted (LAZ

BackgroundSubSaharan Africa has a disproportionate burden of HIV and preterm births (PTB). We hypothesized that PTB in HIV-1 infected women are more likely a result of prelabour rupture of membranes (PROM) and could lead to worse birth outcomes than HIV-uninfected women. We also hypothesized that PPROM increased the risk of mother-to-child transmission (MTCT) of HIV-1. Current clinical management protocols for PPROM do not include a differential treatment plan for HIV-infected women.MethodsThe maternity register at a regional hospital in a high HIV-burden district in South Africa was reviewed to identify all preterm births over a 3 month-period in 2018. We determined the incidence of PPROM using predefined criteria. Maternal age, parity, previous pregnancy complications, antenatal care, body mass index, history of smoking or alcohol, HIV infection and syphilis were computed on chi-square contingency tables to determine risk of PPROM. Overall pregnancy outcomes that included mode of delivery, fetal survival, birth weight, gestational age and newborn apgar scores were compared between HIV-infected and HIV-uninfected women whose pregnancies were complicated by PPROM. HIV-exposed newborns are routinely tested at birth for HIV by PCR.ResultsA total of 1758 deliveries were recorded for Jan-Mar, 2018, and 295 (16.8%) were preterm. Maternity charts were retrieved for 236 (80.0%) PTB; 47 of PTB (19.9%; 95%CI 15.0–25.6) were further complicated by PROM which translates to 2.7% (95%CI 1.9–3.4) of all deliveries. None of the risk variables including HIV-positive status (48.9% vs 47.6%) were different between PPROM and non-PPROM groups and the majority of women were receiving cART (94.7 and 92.0%). There were no differences in the proportion of low birth weight (RR 1.2 95%CI 0.6–2.1) or severe preterm birth (RR 1.6; 95%CI 0.9–2.9) between HIV-infected and HIV-uninfected women whose pregnancies were complicated by PPROM. None of the 22 HIV-exposed newborns in the PPROM group were HIV-infected at birth.ConclusionThe PPROM incidence is not higher among HIV-infected women and our findings suggest that HIV-infected women who are virally suppressed on cART and presenting with PPROM are less likely to transmit HIV to their infants and do not have worse birth outcomes than HIV-uninfected women.

Women, and specifically, adolescents, are at high risk of HIV and STIs during the postpartum period. Biological and behavioral factors contribute to adolescents' susceptibility. However, the influence of behavioral factors, like intimate partner violence (IPV), on postpartum STI acquisition has been understudied. The study's purpose is to determine whether IPV victimization during pregnancy predicts incident STIs in the first 6 months postpartum. Adolescent mothers (14-19 years) were recruited at a township hospital's maternity ward near Durban. Adolescent mothers who were HIV-negative and had no laboratory-diagnosed STIs at baseline (6 weeks postpartum) were included in the analysis (

HIV-positive women who engage in postpartum unsafe sex are at risk for sexually transmitted infection (STI), unintended pregnancy, and secondary transmission of HIV to uninfected partners. One factor that may increase risk for postpartum unsafe sex among HIV-positive women is intimate partner violence (IPV) victimization; few studies, however, have examined this association. This longitudinal study examined whether patterns of psychological, physical, and sexual IPV, assessed during pregnancy, predicted unsafe sex at 14 weeks postpartum among South African women diagnosed as HIV-positive during pregnancy (n = 561). In a latent class analysis, we identified three distinct patterns of IPV victimization: non-victims (74%), moderate IPV (20%), and multiform severe controlling IPV (5%). Compared to non-victims, victims of multiform severe controlling IPV were significantly more likely to engage in postpartum unsafe sex (p = .01), even after adjusting for potential confounding factors. Moderate IPV was ...

Objective To investigate the impact of cervical cell abnormalities detected in the puerperium in association with HIV-1 infection on pregnancy outcomes. Methods The present study was a secondary data analysis of pregnancy outcomes, Pap smear results, HIV results, and participant demography from a behavioral intervention randomized controlled trial of 1480 pregnant women aged 18 years or more conducted at a periurban primary health clinic in South Africa during 2008–2010. The Pap smear was performed 14 weeks after delivery. Results In total, 564 (38.1%) women were HIV-1-positive and 78 (8.0%) of 973 women with a categorized Pap smear result tested positive for cervical cell abnormalities; 42 (4.2%) women had low-grade squamous intraepithelial lesions (LGSILs) and 7 (0.7%) had high-grade lesions (HGSILs). In an adjusted analysis, HIV infection was significantly more common among women with LGSILs (28/42 [66.7%]) or HGSILs (6/7 [85.7%]) when compared with the other Pap smear categories (P

Purpose The aim of the study was to characterize sexual relationships in pregnancy and HIV risk behavior in the first 14 weeks postpartum among adolescent (aged 24 years). Methods We use bivariate and multivariate statistical tests to describe differences across adolescent (n = 29), young adult (n = 263), and adult women (n = 207). Results In pregnancy, adolescents were in significantly less stable relationships and had higher risk partners than young adult or adult women. At 14 weeks postpartum, adolescents were significantly more likely to think their partners were having concurrent relationships since delivery and were likely to have lower relationship power than adult women. Furthermore, young adults were significantly more likely to return to sex and report physical intimate partner violence in the first 14 weeks postpartum than adult women. Conclusions Adolescent mothers may benefit from interventions that promote empowerment and the development of healthy relationship skills. Young adult women may benefit from interventions to delay early postpartum engagement in unprotected sex and prevent intimate partner violence exposure. All women, regardless of age group, may benefit from interventions that increase access to pre-exposure prophylaxis and partner's access to HIV testing during the perinatal period.