Association of nucleoside reverse transcriptase inhibitors with adverse perinatal outcomes in pregnant women living with HIV: systematic review and meta-analysis.
Cowdell I., Beck K., Hey M., Portwood C., Sexton H., Kumarendran M., Brandon Z., Kirtley S., Hemelaar J.
BACKGROUND: The World Health Organization (WHO) recommends antiretroviral therapy (ART) containing two nucleoside reverse transcriptase inhibitors (NRTIs) as backbone. WHO recommends tenofovir disoproxil fumarate combined with lamivudine or emtricitabine as first line in pregnancy, and zidovudine, abacavir or tenofovir alafenamide, combined with lamivudine or emtricitabine, as alternatives. OBJECTIVES: Evaluate risk of adverse perinatal outcomes in pregnant women living with HIV (WLHIV) receiving different NRTIs. DATA SOURCES: Medline, CINAHL, Global Health, EMBASE. STUDY ELIGIBILITY CRITERIA: Cohort studies. PARTICIPANTS: Pregnant WLHIV. INTERVENTIONS: ART regimes containing different NRTI drugs. ASSESSMENT OF RISK OF BIAS: Newcastle-Ottawa Scale and GRADE. METHODS OF DATA SYNTHESIS: Random-effects meta-analysis. RESULTS: 22 cohort studies including 124,478 WLHIV met the eligibility criteria. ART containing tenofovir disoproxil fumarate was associated with lower risk of preterm birth (Risk Ratio 0.89; 95% confidence interval 0.81-0.97), very preterm birth (0.58; 0.40-0.86), small for gestational age (0.76; 0.59-0.98), very small for gestational age (0.60; 0.48-0.73), stillbirth (0.49; 0.31-0.78), and neonatal death (0.61; 0.40-0.93), compared to ART not containing tenofovir disoproxil fumarate. ART containing zidovudine was associated with increased risk of very preterm birth (1.59; 1.01-2.49), small for gestational age (1.33; 1.03-1.70), very small for gestational age (1.63; 1.25-2.13), stillbirth (2.23; 1.10-4.55), and neonatal death (1.65; 1.08-2.52), compared to ART not containing zidovudine. For ART regimens also containing either lamivudine or emtricitabine, zidovudine was associated with increased risk of very preterm birth (1.62; 1.04-2.52), small for gestational age (1.52; 1.28-1.82), very small for gestational age (1.68; 1.36-2.06), stillbirth (2.19; 1.03-4.67), and neonatal death (1.65; 1.08-2.52), compared to ART containing tenofovir disoproxil fumarate. Abacavir was not associated with adverse perinatal outcomes. Tenofovir alafenamide was not associated with low birth weight compared to tenofovir disoproxil fumarate. CONCLUSION: Tenofovir disoproxil fumarate is associated with a lower risk of adverse perinatal outcomes, whereas zidovudine is associated with an increased risk of perinatal outcomes. Abacavir is not associated with adverse perinatal outcomes. Our findings support current WHO guidelines.