Safety and Immunogenicity of Measles Vaccination in HIV-Infected and HIV-Exposed Uninfected Children: A Systematic Review and Meta-Analysis

Eleonora A.M.L Mutsaerts,Marta C Nunes,Martijn N Van Rijswijk,Kerstin Klipstein-Grobusch,Diederick E Grobbee,Shabir A Madhi

doi:10.1016/j.eclinm.2018.06.002

Abstract

BackgroundHIV-infected and HIV-exposed uninfected (HEU) children have an increased risk of measles that may be due to altered immune responses or suboptimal timing of measles vaccination. We aimed to evaluate the safety and immunogenicity of measles vaccination in HIV-infected and HEU children. MethodsFor this systematic review and meta-analysis, we searched PubMed, Embase, Cochrane Library, CINAHL, Global Health Library and IndMED on May 9, 2018. Studies were included if they reported on safety or seroresponse (either seroprotection/seropositivity/seroconversion) after measles vaccination in HIV-infected or HEU children. We calculated pooled estimates to compare immunogenicity outcomes between HIV-infected, HEU and HIV-unexposed children, using risk ratios [RRs] (with 95%CIs). PROSPERO registration number: CRD42017057411. FindingsSeventy-one studies met the inclusion criteria (15,363 children). Twenty-eight studies reported on safety; vaccine-associated adverse events and deaths were uncommon. Sixty-two studies reported on immunogenicity, 27 were included in the meta-analysis. HIV-infected children had lower seroresponse rates after primary vaccination compared with HIV-unexposed (RR 0.74; 95%CI: 0.61–0.90, I2 = 85.9%) and HEU children (0.78; 0.69–0.88, I2 = 77.1%), which was mitigated by antiretroviral therapy and time interval between vaccination and serology. HEU and HIV-unexposed children had similar seroresponses. Vaccination at 6-months resulted in similar proportions of HIV-infected children having seroresponse compared with HIV-unexposed (0.96; 0.77–1.19) and HEU children (1.00; 0.73–1.37, I2 = 63.7%). InterpretationPrimary measles vaccination at 6-months of age may provide protection against measles during early infancy in settings with high prevalence of maternal HIV-infection, however, further studies are needed to evaluate this strategy in HEU children and HIV-infected children receiving antiretroviral therapy. FundingSouth African Research Chairs Initiative of the Department of Science and Technology and National Research Foundation in Vaccine Preventable Diseases; Medical Research Council: Respiratory and Meningeal Pathogens Research Unit.

Highlights

In 2015, an estimated 1.4 million births occurred in HIV-infected women, of which more than 95% lived in low- and middle-income⁎ Corresponding author at: Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg 2013, South Africa.countries (LMICs) [1]
Recent studies showed that HIV-exposed uninfected (HEU) children are at increased risk of morbidity and mortality compared with their HIV-unexposed peers [5,6,7,8,9,10,11], in particular from infectious diseases in the first 6-months of life [9, 12,13,14,15,16]
Twenty-eight studies reported on safety [24, 25, 29, 33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61] and 62 reported on immunogenicity [23,24,25, 29, 30, 33,34,35,36,37, 39,40,41, 43,44,45, 47, 48, 50, 51, 53, 55,56,57, 59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105], of which 27 were included in the primary metaanalyses (Table 1)

Summary

Introduction

In 2015, an estimated 1.4 million births occurred in HIV-infected women, of which more than 95% lived in low- and middle-income⁎ Corresponding author at: Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg 2013, South Africa.countries (LMICs) [1]. Recent studies showed that HEU children are at increased risk of morbidity and mortality compared with their HIV-unexposed peers [5,6,7,8,9,10,11], in particular from infectious diseases in the first 6-months of life [9, 12,13,14,15,16]. This increased susceptibility could be due to immune aberrations in HIV-exposed infants resulting from in utero exposure to HIV-virion particles or maternal antiretroviral treatment [17].

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