OBJECTIVE:To compare viral suppression between two models of care [adherence club and integrated maternal and child healthcare (MCH)] for improving engagement of postpartum women with HIV (WWH) to antiretroviral therapy (ART). DESIGN:Individual participant data network meta-analysis (IPD-NMA) of two randomized controlled trials in Cape Town, South Africa [Postpartum Adherence Clubs for Antiretroviral Therapy (PACART) comparing adherence clubs to standard of care (primary healthcare ART clinics, SOC), and MCH-ART comparing integrated MCH for the duration of breastfeeding to SOC]. METHODS:One-step IPD-NMA using generalized linear mixed effects models was performed to indirectly compare viral suppression (viral load<50 copies/ml) between adherence clubs and integrated MCH at 6 and 12 months postpartum, linked by SOC as a comparator. RESULTS:Overall, 882 women were included: 471 enrolled in MCH-ART and 411 in PACART. In MCH-ART, 87 and 79% of women in intervention arm had viral suppression at 6 and 12 months postpartum, compared to 70 and 54% in SOC. In PACART, 87 and 74% of women had viral suppression at 6 and 12 months in intervention arm, compared to 79 and 67% in SOC. Adjusting for age, parity, socioeconomic status, tuberculosis (TB) history, HIV diagnosis time, ART duration, and viral load less than 400 copies/ml at enrolment, relative odds of viral suppression in integrated MCH versus adherence clubs were 2 [95% confidence interval (CI): 0.88-4.53] at 6 months and 2.89 (CI: 1.42-5.90) at 12 months. CONCLUSION:In this setting, an integrated MCH model for delivering ART postpartum achieved higher levels and more sustained effect on viral suppression compared to adherence clubs, a popular differentiated service delivery (DSD) model for ART.

Abstract Background Children in low- and middle-income countries (LMICs) face an elevated risk of developmental delay, yet scalable neuroimaging tools to study early brain development in these contexts remain limited. Children who are HIV-exposed but uninfected (CHEU) represent a growing population with evidence of language and motor delays and altered brain development compared with children who are HIV-unexposed (CHU). Ultra-low-field (ULF) MRI offers a more affordable alternative to conventional high-field (HF) MRI, but its application in early childhood remains underexplored. Methods We compared brain volumes derived from ULF (64mT) and HF (3T) MRI in South African CHEU and CHU as part of the DolPHIN-2 PLUS study. Volumetric segmentation was performed using FreeSurfer v7.4.1 and SynthSeg on the Flywheel platform. Agreement between modalities was assessed using Pearson’s and Lin’s concordance correlation coefficients across global and subcortical regions. Associations between ULF-derived brain volumes and developmental outcomes, measured by the Bayley Scales of Infant Development, Third Edition, were evaluated using partial correlations adjusted for sex and age. Results Forty-five children (9 CHEU, 36 CHU; mean age 45.6 months) had paired ULF and HF scans of usable quality. Strong correlations were observed between ULF and HF volumes for global white and grey matter regions (r > 0.92) and larger subcortical grey matter structures such as the thalamus, caudate, and putamen (r = 0.86–0.89). Moderate-to-weak correlations were evident in smaller structures (hippocampus, pallidum, amygdala). ULF underestimated most grey matter volumes, and overestimated total white matter volume relative to HF. ULF-derived global and subcortical volumes were associated with receptive and expressive communication (r = 0.34–0.59, all p < 0.05). Conclusions ULF MRI produces brain volume estimates comparable to HF MRI and captures meaningful associations with early language development. These findings support ULF MRI as a feasible and scalable tool for studying neurodevelopment in vulnerable paediatric populations in LMICs.

BACKGROUND:The impact of in utero exposure to specific antiretroviral therapy (ART), particularly integrase strand transfer inhibitors, on early brain development, remains poorly understood. We used magnetic resonance imaging (MRI) to compare brain structure in children who are HIV-exposed and uninfected (CHEU) with prenatal dolutegravir (DTG) vs efavirenz (EFV) exposure. METHODS:DolPHIN-2 was a randomized trial of pregnant women initiating DTG- vs EFV-based ART in the third trimester. At 3-4 years of age, a subgroup of their children from the South African cohort, along with HIV-unexposed (CHU) children, underwent T1-weighted MRI (DolPHIN-2 PLUS). Measurements of brain structure, including volume, cortical thickness, and surface area, were extracted using Freesurfer. Associations between ART /HIV exposure and child brain structure were examined using multiple linear regression. RESULTS:This analysis included 58 children (25 CHEU [13 DTG, 12 EFV] and 33 CHU, mean age 46.35 months, 51.7% male). Demographic characteristics were similar across groups. Significant differences in global or regional brain volumes, cortical thickness, or surface area were not detected between DTG- and EFV-exposed children or between CHEU and CHU. CONCLUSION:Among this small sample of children at 3-4 years, statistically significant differences in global or regional brain structure were not detected between those exposed in the third trimester of pregnancy to DTG or EFV and CHU. Given the modest sample size, the study had limited power to detect small-to-moderate differences. Further longitudinal studies with larger sample sizes are needed to assess the effects of specific ART in the context of new regimens and better maternal HIV disease control on CHEU brain structure.

Pregnancy requires tightly regulated immune adaptation, which may be altered by maternal adiposity and HIV infection. In high HIV prevalence settings with rising obesity rates, overlapping metabolic and infectious inflammation may shape gestational immune trajectories. We examined patterns of C-reactive (CRP), serum amyloid A (SAA), and interferon-gamma inducible protein-10 (IP-10) among 527 pregnant women living with HIV in Cape Town, South Africa. Immune markers were measured at up to four antenatal visits. Maternal body mass index (BMI) was categorised as normal, overweight or obese. Antiretroviral therapy (ART) exposure was classified as initiation before conception or during pregnancy. Mixed-effects models assessed associations, adjusting for baseline CD4 cell count and viral load. CRP concentrations remained elevated across pregnancy and were significantly higher among obese women independent of ART timing. In contrast, IP-10 concentrations were strongly associated with ART timing, with higher levels observed prior to ART initiation and declining thereafter; no independent association with BMI was observed. SAA concentrations were modestly lower among obese women and among those on preconception ART. These divergent patterns persisted after adjustment for HIV disease severity. These findings suggest that metabolic and HIV-related inflammatory pathways operate in parallel during pregnancy, with adiposity predominantly influencing acute-phase responses and HIV-related immune activation shaping interferon-associated chemokines trajectories.

Objective To examine the relationship between maternal body mass index (BMI), timing of antiretroviral therapy (ART) initiation, and levels of three proinflammatory immune markers (C reactive protein [CRP], serum amyloid A [SAA], and interferon-gamma inducible protein 10 [IP10]) among pregnant women living with HIV (WLWH) in South Africa. Design Planned analysis of a prospective cohort study. Setting Gugulethu Midwife Obstetric Unit, Cape Town, South Africa. Population or Sample 526 pregnant WLWH enrolled at less than 24 weeks gestation between April 2015 and October 2016. Methods Longitudinal plasma samples were collected at 3 or 4 study visits during pregnancy. CRP, SAA, and IP10 were measured using ELISA. BMI was classified as normal (<25), overweight (25 to 29.9), or obese (≥30). ART status was defined as initiation before conception or during pregnancy. Generalised linear mixed-effects models assessed longitudinal associations between BMI, ART timing, and immune marker concentrations. Main Outcome Measures Plasma concentrations of CRP, SAA, and IP10. Results Median CRP levels exceeded 10000 ng/mL across visits and were significantly higher in obese WLWH compared with normal BMI at baseline and late pregnancy. Obese women initiating ART preconception had the highest baseline CRP levels, which declined across gestation. IP10 levels were significantly higher in women initiating ART during pregnancy before treatment (median 227 pg/mL) compared with those on preconception ART (median 121 pg/mL; p<0.001). SAA levels were lower among obese compared with normal BMI women across visits and showed differing longitudinal patterns by ART status. Conclusions Maternal obesity and ART timing influence inflammatory biomarker trajectories during pregnancy among WLWH. Elevated CRP in obese women and persistently higher IP10 in ART initiators highlight combined metabolic and immune stressors that may underlie adverse pregnancy outcomes. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (Award Number R01HD080385). The funder had no role in study conduct or manuscript preparation. The views expressed are those of the authors and not necessarily those of the NIH. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethical approval for this study was obtained from the University of Cape Town Faculty of Health Sciences Human Research Ethics Committee and the University of Southampton Institutional Review Board. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors.

BACKGROUND:In 2019, the World Health Organization (WHO) changed its recommendations for pregnant women living with HIV from efavirenz-based to dolutegravir-based therapy due to its superior efficacy, tolerability and resistance profile. Perinatal exposure to antiretrovirals may influence infant growth, but limited data exist on the effects of specific regimens over time. AIM:This study aimed to compare growth trajectories over the first 72 weeks of life among infants exposed to dolutegravir-based versus efavirenz-based therapy during late pregnancy. METHODS:The DolPHIN-2 trial was a randomized, open-label trial conducted in South Africa and Uganda, researching the efficacy of dolutegravir-based versus efavirenz-based therapy in pregnant women living with HIV, initiating treatment in the third trimester. In this secondary analysis, we compared growth trajectories until 72 weeks postpartum between HIV-exposed uninfected infants perinatally exposed to dolutegravir-based versus efavirenz-based therapy. Measures of infant weight, length and head circumference were converted to WHO-defined weight-for-age, weight-for-length, length-for-age and head circumference-for-age Z-scores. Subsequently, Z-scores were compared across treatment arms, using linear mixed-effect models. RESULTS:After exclusions, 232 infants remained (dolutegravir: n = 116; efavirenz: n = 116). In both crude models and models adjusted for study site and maternal height, length-for-age Z-scores were 0.277 units higher in the dolutegravir arm. No statistically significant impact of treatment was observed for other outcomes. In both study arms, a decline in mean length-for-age Z-scores occurred over the first 72 weeks, while mean weight-for-age Z-scores declined between weeks 48 and 72. CONCLUSION:Our data support the WHO in recommending dolutegravir-based therapy over efavirenz-based therapy in pregnant women living with HIV.

BACKGROUND:We investigated the impact of Drug-Drug Interactions (DDIs) on virologic control among HIV-positive pregnant women initiating antiretroviral therapy while identifying drivers for Traditional Medicine (TM) use and exploring the nature and extent of TM-related DDIs. METHODS:Employing a three-pronged approach, we examined DDIs arising from comedication, including TM, in ART. The DolPHIN-2 trial (NCT03249181) randomized 268 HIV-positive pregnant women in Uganda and South Africa to dolutegravir (DTG)-based (135) or efavirenz-based (133) regimens while systematically recording comedications and screening for DDIs. We used Cox regression models to compare time-to-virologic control between participants with and without DDIs. We conducted in-depth interviews and focus group discussions among 37 and 67 women with and without HIV, respectively, to explore reasons for TM use during pregnancy. Additionally, in-vitro and in-vivo studies evaluated the composition and impact of clay-based TM, mumbwa, on DTG plasma exposure. RESULTS:The baseline prevalence of DDIs was 67.2%, with TM use prevalent in 34% of participants, with mumbwa being the most frequent (76%, 69/91). There was no difference in virologic response between participants with and without DDIs. Fetal health and cultural norms were among the reasons cited for TM use. Analysis of mumbwa rods confirmed significant amounts of aluminium (8.4%-13.9%) and iron (4%-6%). In Balb-C mice, coadministration of mumbwa led to a reduction in DTG exposure observed in the AUC0-24 (-21%; P = 0.0271) and C24 (-53%; P = 0.0028). CONCLUSIONS:The widespread use of clay-based TM may compromise HIV treatment, necessitating medication screening and counselling to manage DDIs in pregnant women.

BACKGROUND:Both dolutegravir and efavirenz are known to be effective in pregnancy and postpartum to prevent vertical transmission of HIV and to maintain maternal health. Both drugs have also been associated with neuropsychiatric symptoms. To what extent, these symptoms occur in pregnant and postpartum women, however, is not yet known. METHODS:This was a secondary analysis of the DolPHIN2 study, a multicentre randomized trial among women presenting late in pregnancy with untreated HIV - who received either a dolutegravir-containing or efavirenz-containing regimen. Longitudinal measures of depression, anxiety and sleep quality were analysed during pregnancy and up to 48 weeks postpartum. RESULTS:Among 268 women, median (IQR) Edinburgh Post Natal Depression Score (EPDS) scores were 8 (3-11) and highest at enrolment. In the dolutegravir and efavirenz arm, respectively, 23.7 and 25.6% had an EPDS score above 9, indicating possible or probable depression. Abnormal Hospital Anxiety Depression scores (HADS) (above 11) were seen at least once during follow-up in 42 of patients (15.7%), although no differences were seen between treatment arms. No association was found between EPDS, suicidality and HADS scores and the assigned regimen ( P  = 0.93, 0.97 and 0.18 respectively). Median (IQR) Pittsburgh Sleep Quality index (PSQI) scores for dolutegravir and efavirenz were 6 (5-7) and 5 (5-6.5), respectively, P  = 0.70. CONCLUSION:No statistically significant differences were observed between efavirenz-containing or dolutegravir-containing regimens. Rates of depression were high, but decreased over the course of time and confirm the need for psychological support after initial HIV diagnosis in pregnancy.

We previously showed a link between maternal vascular malperfusion and pre-term birth (PTB) in pregnant people living with HIV (PPLH) initiating antiretroviral treatment (ART) before pregnancy, indicating poor placental vascularisation. After measuring antenatal plasma angiogenic factors to seek mechanistic insights, low levels of plasma Factor XIIIA1 (FXIIIA1) and vascular-endothelial-growth-factor (VEGF) was significantly associated with PTB at the time closest to delivery (median 34 weeks) in PPLH initiating ART before pregnancy. Knowing that FXIIIA1 is crucial for haemostasis, angiogenesis, implantation and pregnancy maintenance and that expression is found on placental macrophages (Hofbauer cells), we examined placentae at delivery from matching participants who either initiating ART before pregnancy or during gestation. Highest FXIIIA1 expression was on Hofbauer cells but was significantly lower in PTB regardless of HIV infection, but was significantly lower in PPLH in PTB from women who initiated ART before pregnancy. To test the hypothesis that antiretroviral drugs may disrupt vascularisation in the placenta, we used a human umbilical vein endothelial cell (HUVEC) matrigel angiogenesis assay. We identified that addition of pre-treated FXIIIA1-expressing MCSF- and IL-10-induced placenta-like macrophages with physiological concentrations of tenofovir, 3TC, and efavirenz resulted in significantly inhibited angiogenesis; akin to the inhibition observed with titratable concentrations of ZED1301, an inhibitor of FXIIIA1. Overall, an efavirenz-containing ART combination inhibits vasculogenesis without causing toxicity and likely does so through inhibition of a FXIIIA1-mediated-placental macrophage pathway.

Background HIV partner disclosure rates remain low among pregnant women living with HIV in many African countries despite potential benefits for women and their families. Partner disclosure can trigger negative responses like blame, violence, and separation. Women diagnosed with HIV late in pregnancy have limited time to prepare for partner disclosure. We sought to understand challenges around partner disclosure and non-disclosure faced by women diagnosed with HIV late in pregnancy in South Africa and Uganda and to explore pathways to safe partner disclosure. Methods We conducted in-depth interviews and focus group discussions with pregnant women and lactating mothers living with HIV ( n = 109), disaggregated by antenatal care (ANC) initiation before and after 20 weeks of gestation, male partners ( n = 87), and health workers ( n = 53). All participants were recruited from DolPHIN2 trial sites in Kampala (Uganda) and Gugulethu (South Africa). Topic guides explored barriers to partner disclosure, effects of non-disclosure, strategies for safe disclosure. Using the framework analysis approach, we coded and summarised data based on a socio-ecological model, topic guides, and emerging issues from the data. Data was analysed in NVivo software. Results Our findings illustrate pregnant women who initiate ANC late experience many difficulties which are compounded by the late HIV diagnosis. Various individual, interpersonal, community, and health system factors complicate partner disclosure among these women. They postpone or decide against partner disclosure mainly for own and baby’s safety. Women experience stress and poor mental health because of non-disclosure while demonstrating agency and resilience. We found many similarities and some differences around preferred approaches to safe partner disclosure among female and male participants across countries. Women and male partners preferred healthcare workers to assist with disclosure by identifying the ‘right’ time to disclose, mentoring women to enhance their confidence and communication skills, and providing professional mediation for partner disclosure and couple testing. Increasing the number of counsellors and training them on safe partner disclosure was deemed necessary for strengthening local health services to improve safe partner disclosure. Conclusion HIV diagnosis late in pregnancy amplifies existing difficulties among pregnant women. Late ANC initiation is an indicator for the likelihood that a pregnant woman is highly vulnerable and needs safeguarding. Respective health programmes should be prepared to offer women initiating ANC late in pregnancy additional support and referral to complementary programmes to achieve safe partner disclosure and good health.

Background: Postpartum weight (PPW) contributes to long-term obesity, a growing concern in persons with HIV (PWH). We investigated whether inflammatory markers in pregnancy may be involved in postpartum (PP) obesity in PWH. Setting: A total of 57 pregnant PWH enrolled at ≤14 weeks gestation (T1) in Gugulethu antenatal care clinic in Cape Town and followed through 48 weeks PP were included. Methods: Plasma soluble (s) CD14, sCD163, leptin, tumour necrosis factor receptor 1 (TNFR-1), resistin, adiponectin, and interleukin-6 (IL-6) were assayed in duplicate using the Luminex platform. We considered each inflammatory marker at T1 (n=57) and T3 (29-36 weeks gestation, n=31) as a separate exposure of interest. Linear mixed effects models were fit to examine whether each exposure was associated with average PPW and PPW trajectories; linear regression was used for associations with PPW change between T1 and 48 weeks. Results: Median age was 32 years (IQR, 29-35), 98% were multigravida, and 49% had a BMI≥30 kg/m2. Higher T1 sCD14 levels were associated with higher average weight through 48 weeks PP (ß = 0.002, p=0.04), and T3 sCD14 with higher PPW gain (ß = 0.007, p=0.04). Leptin (ß = 0.414, p<0.01), TNFR-1 (ß = 11.048, p<0.01) and resistin (ß = 0.714, p=0.01) at T3 were associated with higher average PPW, and IL-6 (ß = 2.266, p=0.02) with PPW gain. Conclusion: These findings suggest that low-grade inflammation in pregnancy may play a role in postpartum obesity, pointing to potential mechanisms with implications for long-term cardiometabolic health in PWH.

Objectives Dolutegravir (DTG) has proved to be more efficacious, tolerable, and safer than efavirenz (EFV) among mothers living with HIV and their infants in Uganda. This study assessed the cost-effectiveness of the DTG-based antiretroviral therapy (ART) compared with the standard of care for preventing perinatal transmissions among pregnant women initiating ART in late pregnancy in Uganda. Methods We used data from a randomized open-label trial (DolPHIN-2) and a 2-part cost-effectiveness model composed of a short-term decision tree to estimate the perinatal transmission rate and costs and an individual-based 3-state Markov model (HIV, advanced HIV, dead) to estimate the long-term costs and health outcomes from the Ugandan payer perspective using a lifetime horizon and a 1-year Markov cycle. The main outcomes were the mean annual costs in US dollars ($), disability-adjusted life-years (DALYs), and incremental cost-effectiveness ratio. Both the deterministic and probabilistic sensitivity analyses were conducted to assess the effect of parameter uncertainties on the ultimate results and the model’s robustness. Results Compared with the EFV-based ART, the DTG-based ART was associated with fewer mean annual costs ($43.58 vs $68.44) and DALYs (0.33 vs 0.56), leading to cost savings of $110 per DALY averted. In the incremental analysis, the DTG-based ART dominated the EFV-based ART; that is, it was less costly and more effective. These results were robust to deterministic and probabilistic sensitivity analyses. Conclusion The DTG-based ART is a highly cost-effective strategy compared with the EFV-based ART among women initiating treatment in the third trimester of pregnancy in a low-income setting.

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.

Abstract Background We investigated the association between travel and viraemia in post-partum women with human immunodeficiency virus on antiretroviral therapy (ART). Methods Data are from a trial of post-partum ART delivery strategies. Women who initiated ART during pregnancy, were clinically stable with a viral load (VL) <400 copies/ml and were <10 weeks post-partum were enrolled at a primary care antenatal clinic in Cape Town, South Africa. Study visits at 3, 6, 12, 18 and 24 months post-partum included questions about travel, defined as ≥1 night spent outside of the city, and VL testing. Generalised mixed effects models assessed the association between travel and subsequent VL ≥400 copies/ml. Results Among 402 women (mean age 29 y, 35% born in the Western Cape), 69% reported one or more travel events over 24 months. Being born beyond the Western Cape (adjusted odds ratio [aOR] 2.03 [95% confidence interval {CI} 1.49 to 2.77]), duration post-partum in months (aOR 1.03 [95% CI 1.02 to 1.05]) and living with the child (aOR 0.60 [95% CI 0.38 to 0.93]) were associated with travel. In multivariable analyses, a travel event was associated with a 92% increase in the odds of a VL ≥400 copies/ml (aOR 1.92 [95% CI 1.19 to 3.10]). Conclusions Interventions to support women on ART who travel are urgently required.

The introduction of antiretroviral therapy (ART) during pregnancy represents one of the most important achievements of the public health response to the HIV epidemic. However, the absence of safety and efficacy data for many ART regimens in pregnant and post-partum women remains a concern. Indeed, in interim WHO HIV treatment guidelines from 2018, which recommended a transition from efavirenz to dolutegravir in first-line regimens, the absence of definitive pregnancy-related safety and efficacy evidence was highlighted. 1 WHOUpdated recommendations on first-line and second-line antiretroviral regimens and post-exposure prophylaxis and recommendations on early infant diagnosis of HIV: interim guidelines: supplement to the 2016 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. https://apps.who.int/iris/handle/10665/277395Date: 2018 Date accessed: April 13, 2023 Google Scholar Thereafter, much needed data from randomised trials in women initiating ART in pregnancy, comparing efavirenz-containing and dolutegravir-containing regimens, came from the DolPHIN-2 and IMPAACT 2010/VESTED trials, 2 Kintu K Malaba TR Nakibuka J et al. Dolutegravir versus efavirenz in women starting HIV therapy in late pregnancy (DolPHIN-2): an open-label, randomised controlled trial. Lancet HIV. 2020; 7: e332-e339 Summary Full Text Full Text PDF PubMed Scopus (58) Google Scholar , 3 Lockman S Brummel SS Ziemba L et al. Efficacy and safety of dolutegravir with emtricitabine and tenofovir alafenamide fumarate or tenofovir disoproxil fumarate, and efavirenz, emtricitabine, and tenofovir disoproxil fumarate HIV antiretroviral therapy regimens started in pregnancy (IMPAACT 2010/VESTED): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet. 2021; 397: 1276-1292 Summary Full Text Full Text PDF PubMed Scopus (67) Google Scholar supporting updated 2019 treatment guidelines. 4 WHOUpdate of recommendations on first- and second-line antiretroviral regimens. https://www.who.int/publications/i/item/WHO-CDS-HIV-19.15Date: July 17, 2019 Date accessed: April 13, 2023 Google Scholar Efficacy and safety of three antiretroviral therapy regimens started in pregnancy up to 50 weeks post partum: a multicentre, open-label, randomised, controlled, phase 3 trialSafety and efficacy data during pregnancy and up to 50 weeks post partum support the current recommendation of dolutegravir-based ART (particularly in combination with emtricitabine and tenofovir alafenamide) rather than efavirenz, emtricitabine, and tenofovir disoproxil fumarate, when started in pregnancy. Full-Text PDF

BACKGROUND:Antiretroviral therapy (ART) use during pregnancy may be associated with adverse outcomes, but findings have been inconsistent, at least in part due to unreliably estimated gestational age.OBJECTIVE:To quantify the association between HIV status, ART initiation timing and adverse birth outcomes, with reliably assessed gestational age at booking, in a public sector primary care facility in Cape Town, South Africa.METHODS:Pregnant women, HIV-negative or living with HIV (WLHIV), were enrolled at first antenatal care visit and followed through delivery. Ultrasound-assessed gestational age was deemed the gold standard. Based on quantitative bias analysis for outcome misclassification, gestational age by non-ultrasound assessment was corrected using multiple overimputation, which deals with missing data and measurement error simultaneously. Using bias-corrected gestational age, birth outcomes were compared between WLHIV and HIV-negative women, and among WLHIV who initiated ART before versus during pregnancy, further divided into trimesters.RESULTS:Of 3952 women enrolled, 37% were WLHIV (mostly using tenofovir + emtricitabine + efavirenz). Last menstrual period (LMP)-based gestational age was identified to be biased, and LMP measures were thus corrected using multiple overimputation. Comparing WLHIV and HIV-negative women, adjusted risk ratio (aRR) of overall pregnancy loss was 1.26 (95% confidence interval [CI] 0.98, 1.61); aRR of preterm delivery was 1.02 (95% CI 0.88, 1.20); aRR of small for gestational age infants was 1.43 (95% CI 1.14, 1.80). Among WLHIV, outcomes were similar by ART initiation timing.CONCLUSIONS:In this routine care cohort, risk of SGA, and possibly of pregnancy loss, was increased in WLHIV compared with HIV-negative women, with no evidence of increased risk of preterm delivery. Further research is needed to improve mechanistic understanding of the contribution of ART to adverse birth outcomes to optimize treatment for pregnant WLHIV and ensure optimal maternal and infant outcomes.