Abstract
OBJECTIVE: Increasingly, pregnant women with HIV (WHIV) initiate antiretroviral therapy (ART) before conception. We assessed the risk of adverse perinatal outcomes among pregnant WHIV initiating ART preconception or antenatally, compared with women without HIV or ART-naive WHIV. DESIGN: Systematic review and meta-analysis. METHODS: We searched PubMed, EMBASE, CINAHL, and Global Health for studies published between 1 January 1980 and 14 July 2023. We assessed the association of preconception/antenatal ART initiation with preterm birth (PTB), very PTB (VPTB), spontaneous PTB (sPTB), low birthweight (LBW), very LBW (VLBW), small for gestational age (SGA), very SGA (VSGA), stillbirth and neonatal death (NND). Data were analysed using random effects meta-analyses. Quality assessments, subgroup and sensitivity analyses were conducted. PROSPERO registration: CRD42021248987. RESULTS: Thirty-one cohort studies were eligible, including 199 156 women in 19 countries. WHIV with preconception ART were associated with increased risk of PTB [risk ratio (RR) 1.55; 95% confidence interval (CI) 1.27-1.90], VPTB (RR 2.14, 95% CI 1.02-4.47), LBW (RR 2.19, 95% CI 1.32-3.63), VLBW (RR 3.34, 95% CI 1.08-10.35), SGA (RR 1.92, 95% CI 1.01-3.66), and VSGA (RR 2.79, 95% CI 1.04-7.47), compared with women without HIV. WHIV with antenatal ART were associated with increased risk of PTB (RR 1.35, 95% CI 1.15-1.58), LBW (RR 2.16, 95% CI 1.39-3.34), VLBW (RR 1.97, 95% CI 1.01-3.84), SGA (RR 1.77, 95% CI 1.10-2.84), and VSGA (RR 1.21, 95% CI 1.09-1.33), compared with women without HIV. Compared to ART-naive WHIV, WHIV with preconception or antenatal ART were associated with increased risk of SGA (preconception: RR 1.40, 95% CI 1.12-1.73; antenatal: RR 1.39, 95% CI 1.11-1.74) and VSGA (preconception: RR 2.44, 95% CI 1.63-3.66; antenatal: RR 2.24, 95% CI 1.48-3.40). CONCLUSION: Among WHIV, both preconception and antenatal initiation of ART are associated with increased risks of adverse perinatal outcomes, compared to women without HIV and ART-naive WHIV.