Abacavir 300mg / Lamivudine 150mg / Zidovudine 300mg tablets

BackgroundMother-to-child transmission is the primary cause of HIV cases among children. Antiretroviral therapy (ART) plays a critical role in preventing mother-to-child transmission and reducing HIV progression, morbidity, and mortality among mothers. However, after more than two decades of ART during pregnancy, the comparative effectiveness and safety of ART medications during pregnancy are unclear, and existing evidence is contradictory. This study aimed to assess the effectiveness and safety of different ART regimens among pregnant women living with HIV at preconception or during pregnancy.MethodsWe searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science. We included randomized trials that enrolled pregnant women living with HIV and randomized them to receive ART for at least four weeks. Pairs of reviewers independently completed screening for eligible studies, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool. Our outcomes of interest included low birth weight, stillbirth, preterm birth, mother-to-child transmission of HIV, neonatal death, and congenital anomalies. Network meta-analysis was performed using a random-effects frequentist model, and the certainty of evidence was evaluated using the GRADE approach.ResultsWe found 14 eligible randomized trials enrolling 9,561 pregnant women. The median duration of ART uptake ranged from 6.0 to 17.4 weeks. No treatment was statistically better than a placebo in reducing the rate of neonatal mortality, stillbirth, congenital defects, preterm birth, or low birth weight deliveries. Compared to placebo, zidovudine (ZDV)/lamivudine (3TC) and ZDV monotherapy likely reduce mother-to-child transmission (odds ratio (OR): 0.13; 95% CI: 0.05 to 0.31, high-certainty; and OR: 0.50; 95% CI: 0.33 to 0.74, moderate-certainty). Moderate-certainty evidence suggested that ZDV/3TC was associated with decreased odds of stillbirth (OR: 0.47; 95% CI: 0.09 to 2.60).ConclusionsOur analysis provides high- to moderate-certainty evidence that ZDV/3TC and ZDV are more effective in reducing the odds of mother-to-child transmission, with ZDV/3TC also demonstrating decreased odds of stillbirth. Notably, our findings suggest an elevated odds of stillbirth and preterm birth associated with all other ART regimens.

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BackgroundThe World Health Organization recommends antiretroviral therapy (ART) for pregnant women living with HIV (WLHIV), the vast majority of whom reside in sub-Saharan Africa. In recent years, many systematic reviews, meta-analyses, and randomised controlled trials (RCTs) have been performed to assess the risks of adverse perinatal outcomes associated with ART among WLHIV. The aim of this umbrella review is to assess the available evidence regarding the risks of adverse perinatal outcomes for WLHIV receiving ART.MethodsWe conducted a systematic literature review by searching Medline, Global Health, and EMBASE and two clinical trial databases (ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform) for meta-analyses and RCTs published between 1 January 1980 and 12 February 2026. We included meta-analyses and RCTs reporting on the association of pregnant WLHIV receiving ART with perinatal outcomes, compared to WLHIV receiving different ART regimens, WLHIV naïve to ART, and women without HIV. We also included studies that assessed the timing of ART initiation (preconception or antenatal). Twelve predefined perinatal outcomes were assessed: preterm birth (PTB), very PTB (VPTB), spontaneous PTB (sPTB), low birthweight (LBW), very LBW (VLBW), term and preterm LBW, small for gestational age (SGA), very SGA (VSGA), stillbirth, neonatal death, and vertical HIV transmission. Heterogeneity measures (I 2 ) and Peter's test results for publication bias were extracted and assessed. The quality of meta-analyses was assessed using the AMSTAR 2 tool, risk of bias of RCTs was assessed using the Cochrane Risk of Bias tool, and overall certainty of evidence for each exposure comparison and perinatal outcome was assessed according to GRADE. The protocol is registered with PROSPERO, number CRD42021248987.FindingsOf 14,279 studies identified, we included nine meta-analyses of cohort studies, one network meta-analysis of seven RCTs, and three additional RCTs. The meta-analyses were composed of a total of 154 cohort studies and were of low or critically low quality, and RCTs had a high risk of bias. Meta-analyses of cohort studies found that WLHIV receiving ART are at increased risks of PTB (risk ratio (RR) 1.55, 95% confidence interval (CI) 1.38-1.74, I 2 87.4%), sPTB (RR 2.10, 95% CI 1.48-2.96, I 2 12.5%), LBW (RR 1.79, 95% CI 1.51-2.13, I 2 90.6%), term LBW (RR 1.88, 95% CI 1.23-2.85, I 2 0.0%), SGA (RR 1.80, 95% CI 1.34-2.40, I 2 97.6%), and VSGA (RR 1.22, 95% CI 1.10-1.34, I 2 0.0%), compared to HIV-negative women. RCTs comparing ART regimens among WLHIV found few differences in perinatal outcomes assessed. Meta-analyses of cohort studies comparing different ART regimens found that protease inhibitors are associated with an increased risk of SGA (RR 1.28, 95% CI 1.09-1.51, I 2 62.2%) and VSGA (RR 1.41, 95% CI 1.08-1.83, I 2 0.0%), compared to non-nucleoside reverse transcriptase inhibitors. Tenofovir disoproxil fumarate is associated with a lower risk of adverse perinatal outcomes and zidovudine is associated with an increased risk of perinatal outcomes. Compared to HIV-negative women, WLHIV receiving ART remain at increased risk of adverse perinatal outcomes, irrespective of the ART regimen and timing of ART initiation. Publication bias, as determined using the Peter's test, was found for two analyses. Most findings were of low or very low certainty as assessed using GRADE.InterpretationWLHIV receiving ART are associated with increased risks of adverse perinatal outcomes compared to HIV-negative women, irrespective of the ART regimen and timing of ART initiation. To strengthen the evidence base for ART guidelines for pregnant WLHIV, more and larger RCTs and high quality observational studies are needed to optimise ART regimens in pregnancy. Further efforts should be made to improve perinatal outcomes among WLHIV.FundingThis study received no funding.

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BackgroundD²EFT (Dolutegravir and Darunavir Evaluation in Adults Failing Therapy) was a phase 3b/4 randomized clinical trial designed to assess second-line treatment options systematically. This substudy evaluated the distribution of drug resistance mutations (DRMs) before treatment randomization in individuals failing first-line therapy.MethodsFrom a total of 826 participants across 14 countries, 727 sequences that covered the PR-RT-INT (700), PR-RT (24), and RT (3) regions were analyzed for drug resistance. Sequences were submitted to the Stanford HIV drug resistance database to detect DRMs and assign subtypes. By adjusting for country and antiretroviral therapy regimen, we assessed the association between DRMs and country and reported DRMs.ResultsSubtype C of human immunodeficiency virus type 1 (HIV-1) accounted for most (59.3%) infections. There were extraordinarily high rates of high-level resistance to lamivudine and emtricitabine (both at 88.3%) and for efavirenz and nevirapine (92.8% and 96.8%, respectively). On average, nucleoside reverse transcriptase inhibitor mutations had the highest occurrence across countries with M184V/I detected in 86.2% of the samples, while the highest proportion of nonnucleoside reverse transcriptase inhibitor mutations was K103N at 57.8%. K103N had an increased likelihood of occurrence in African and South American countries (P ConclusionsThe regional specificity of mutations underscores the dynamic nature of HIV-1 drug resistance patterns and the importance of monitoring and understanding local mutation profiles.

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