Secondary Logo

Journal Logo

Institutional members access full text with Ovid®

A Meta-analysis Assessing Diarrhea and Pneumonia in HIV-Exposed Uninfected Compared With HIV-Unexposed Uninfected Infants and Children

Brennan, Alana T. PhD, MPHa,b,c; Bonawitz, Rachael MD,MSca,d; Gill, Christopher J. MD, MSa; Thea, Donald M. MD, MSca; Kleinman, Mary MPHa,e; Long, Lawrence PhD, BBusSci, MComa,b; McCallum, Caitryn MPHa; Fox, Matthew P. MPH, DSca,b,c

JAIDS Journal of Acquired Immune Deficiency Syndromes: September 1, 2019 - Volume 82 - Issue 1 - p 1–8
doi: 10.1097/QAI.0000000000002097
Critical Review

Objective: Previous studies have demonstrated that HIV-exposed uninfected (HEU) infants and children experience morbidity and mortality at rates exceeding those of their HIV-unexposed uninfected (HUU) counterparts. We sought to summarize the association between HEU vs. HUU infants and children for the outcomes of diarrhea and pneumonia.

Design: Meta-analysis.

Methods: We reviewed studies comparing infants and children in the 2 groups for these infectious disease outcomes, in any setting, from 1993 to 2018 from 6 databases.

Results: We included 12 studies, and 17,955 subjects total [n = 5074 (28.3%) HEU and n = 12,881 (71.7%) HUU]. Random-effects models showed HEU infants and children had a 20% increase in the relative risk of acute diarrhea and a 30% increase in the relative risk of pneumonia when compared with their HUU counterparts. When stratifying by time since birth, we showed that HEU vs. HUU children had a 50% and 70% increased risk of diarrhea and pneumonia, respectively, in the first 6 months of life.

Conclusions: We show an increased risk of diarrhea and pneumonia for HEU vs. HUU infants and children. Although we acknowledge, and commend, the immense public health success of prevention of mother-to-child transmission, we now have an enlarging population of children that seem to be vulnerable to not only death, but increased morbidity. We need to turn our attention to understanding the underlying mechanism and designing effective public health solutions. Further longitudinal research is needed to elucidate possible underlying immunological and/or sociological mechanisms that explain these differences in morbidity.

aDepartment of Global Health, Boston University School of Public Health, Boston, MA;

bDepartment of Internal Medicine, School of Clinical Medicine, Health Economics and Epidemiology Research Office, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa;

cDepartment of Epidemiology, Boston University School of Public Health, Boston, MA;

dSection of Hospital Medicine, Saint Christopher's Hospital for Children, Philadelphia, PA; and

eDepartment of Psychology, University of Maryland, College Park, MD.

Correspondence to: Christopher J. Gill, MD, Department of Global Health, Boston University, Crosstown Center, 3rd Floor, 801 Massachusetts Avenue, Boston, MA 02118 (e-mail:

Supported by the American People and the President's Emergency Plan for AIDS Relief (PEPFAR) through USAID under the terms of Cooperative Agreements AID-674-A-12-00029 and 72067419CA00004 to HE2RO. The contents are the responsibility of the authors and do not necessarily reflect the views of PEPFAR, USAID, or the United States Government.

The authors have no conflicts of interest to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received November 10, 2018

Accepted April 26, 2019

Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.