Safety and effectiveness of antiretroviral therapies for HIV-infected women and their infants and children: protocol for a systematic review and network meta-analysis

BACKGROUND: Antiretroviral therapy reduces mother-to-child transmission of human immunodeficiency virus (HIV) during pregnancy, delivery, and breastfeeding. However, these agents have been associated with preterm birth, anemia and low birth weight. We aim to evaluate the comparative safety and effectiveness of the use of antiretroviral drugs among HIV-infected women and the effects on their infants and children through a systematic review and network meta-analysis. METHODS/DESIGN: Studies examining the effects of six antiretroviral drug classes (nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, fusion inhibitors, co-receptor inhibitors) administered to HIV-infected pregnant women will be included. We will include randomized clinical trials (RCTs), quasi-RCTs, non-RCTs, controlled before-after, interrupted time series, cohort, registry, and case–control studies. No limitations will be imposed on publication status (that is, unpublished studies are eligible for inclusion), duration of follow-up, study conduct period, and language of dissemination. Comprehensive literature searches will be conducted in major electronic databases, including MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. Gray literature will be identified through searching dissertation databases, trial protocol registries, and conference abstracts. Two team members will independently screen all citations, full-text articles, and abstract data; conflicts will be resolved through discussion. The risk of bias and methodological quality will be appraised using appropriate tools (for example, Cochrane Collaboration’s tool for assessing risk of bias, Newcastle-Ottawa Scale, and McMaster Quality Assessment Scale of Harms). If feasible and appropriate, we will conduct random effects meta-analysis. Network meta-analysis will be considered for outcomes with the greatest number of treatment comparisons available that fulfill network meta-analysis assumptions (for example, consistency of evidence between direct and indirect data, and low statistical heterogeneity between included studies). The primary effectiveness outcome is mother-to-child transmission of HIV, and the primary safety outcome is major congenital malformation (overall and specific types) among newborns of HIV-infected women. Secondary safety outcomes include stillbirths, infant/child death, preterm delivery, overall and specific minor congenital malformations, and small for gestational age infants. DISCUSSION: Our systematic review will be of utility to healthcare providers, policy-makers, and HIV-positive women regarding the use of antiretroviral drugs. TRIAL REGISTRATION: PROSPERO registry number: CRD42014009071.