Adverse perinatal outcomes associated with HAART and monotherapy: systematic review and meta-analysis

Objectives: Assess adverse perinatal outcomes in women living with HIV (WLHIV) receiving HAART or zidovudine (ZDV) monotherapy, compared with antiretroviral therapy (ART)-naive WLHIV and HIV-negative women. Design: Systematic review and meta-analysis. Methods: We conducted a systematic literature review by searching PubMed, CINAHL, Global Health, and EMBASE for studies published during 1 January 1980 to 20 April 2020. We included studies reporting on the association of pregnant WLHIV receiving HAART or ZDV monotherapy with 11 perinatal outcomes: preterm birth (PTB), very PTB, spontaneous PTB (sPTB), low birth weight (LBW), very LBW, term LBW, preterm LBW, small for gestational age (SGA), very SGA (VSGA), stillbirth, and neonatal death. Random-effects meta-analyses were conducted. Results: Sixty-one cohort studies assessing 409 781 women were included. WLHIV receiving ZDV monotherapy were associated with a decreased risk of PTB [relative risk 0.70, 95% confidence interval (CI) 0.62–0.79] and LBW (0.77, 0.67–0.88), and comparable risk of SGA, compared with ART-naive WLHIV. WLHIV receiving ZDV monotherapy had a comparable risk of PTB and LBW, and an increased risk of SGA (1.16, 1.04–1.30) compared with HIV-negative women. In contrast, WLHIV receiving HAART were associated with a comparable risk of PTB and LBW, and increased risk of SGA (1.38, 1.09–1.75), compared with ART-naive WLHIV. WLHIV receiving HAART were associated with an increased risk of PTB (1.55, 1.38–1.74), sPTB (2.09, 1.48–2.96), LBW (1.79, 1.51–2.13), term LBW (1.88, 1.23–2.85), SGA (1.80,1.34–2.40), and VSGA (1.22, 1.10–1.34) compared with HIV-negative women. Conclusion: Pregnant WLHIV receiving HAART have an increased risk of a wide range of perinatal outcomes compared with HIV-negative women