Adverse perinatal outcomes associated with antiretroviral therapy regimens: systematic review and network meta-analysis

Abstract

Assess adverse perinatal outcomes associated with antenatal antiretroviral therapy (ART) regimens. Systematic review and network meta-analysis of randomized controlled trials (RCTS). We conducted a systematic literature review by searching PubMed, CINAHL, Global Health, EMBASE, and the Cochrane Central Register of Controlled Trials and four clinical trial databases from 1 January 1980 to 28 April 2018. We included RCTs of antenatal ART regimens in HIV-positive pregnant women, which assessed preterm birth (PTB), spontaneous preterm birth (sPTB), very preterm birth (VPTB), low birthweight (LBW), very low birthweight (VLBW), small-for-gestational-age (SGA), neonatal death (NND), and mother-to-child-transmission. We used random-effects network meta-analysis models to calculate relative risks for treatment comparisons and the hierarchy of treatments. Of 83 260 citations identified, 10 manuscripts were included, assessing 6285 women. Compared with zidovudine (ZDV) monotherapy, we found a higher risk of LBW after exposure to zidovudine/lamivudine/efavirenz (ZDV/3TC/EFV; relative risk 1.61; 95% CI 1.03-2.51), tenofovir disoproxil fumarate/emtricitabine/ritonavir-boosted lopinavir (TDF/FTC/LPV/r; 1.64; 1.18-2.29), or zidovudine/lamivudine/ritonavir-boosted lopinavir (ZDV/3TC/LPV/r; 1.87; 1.58-2.20). TDF/FTC/LPV/r carried an increased risk of VLBW, compared with ZDV monotherapy (5.40; 1.08-27.08). ZDV/3TC/LPV/r posed a higher risk of PTB than ZDV monotherapy (1.43; 1.08-1.91) and a higher risk of sPTB than zidovudine/lamivudine/abacavir (ZDV/3TC/ABC) (1.81; 1.21-2.71). LPV/r-containing regimens also carried the highest risks of VPTB, SGA and NND, although the limited data showed no significant differences. Of the ART regimens assessed in RCTs in pregnancy, LPV/r-containing regimens were associated with the highest risks of adverse perinatal outcomes.