Effect of in utero exposure to HIV and antiretroviral drugs on growth in HIV-exposed uninfected children: a systematic review and meta-analysis protocol

Introduction HIV-exposed uninfected (HEU) children have higher morbidity and mortality compared with HIV unexposed uninfected children. Despite the fact that malnutrition contributes to about half of all infant deaths below 5 years of age in low-income and middle-income countries and that growth impairment has been reported in the HEU population, the spectrum of growth disorders associated with HIV and antiretroviral therapy (ART) exposure during the in utero and perinatal periods is yet to comprehensively summarised among the global HEU population. This protocol for a systematic review and meta-analysis aims to critically synthesise data concerning the prevalence of underweight, stunting and wasting at different ages in the global HEU population. Methods and analysis Medline, EMBASE, Cochrane Library, TOXLINE, WHO Global Index Medicus and the Web of Science will be searched for relevant articles published between 1 January 1989 and 1 December 2017 without language restriction. In addition, conference abstracts and reference lists of eligible papers and relevant review articles will be screened. Authors will screen and select studies, extract data, assess the risk of bias as well as studies individually for heterogeneity. Study-specific estimates will be pooled through a random-effects meta-analysis model for studies that are clinically homogeneous while funnel plots and Egger’s test will be used to detect publication bias. Results will be presented by ART availability period, country income levels and mode of breastfeeding. Ethics and dissemination Ethical approval will not be required for this study because it will be based on published data. The final report of this study will be published in a peer-reviewed journal and presented at scientific conferences. This review will summarise the evidence and quantify the problem of growth impairment in HEU infants and so shed more light on our understanding of the higher morbidity and mortality in this growing population. PROSPERO registration number CRD42018091762.