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

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          Abstract

          Background HIV-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. Methods For 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. Findings Seventy-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, I 2  = 85.9%) and HEU children (0.78; 0.69–0.88, I 2  = 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, I 2  = 63.7%). Interpretation Primary 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. Funding South 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.

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          Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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            HIV-exposed uninfected infants are at increased risk for severe infections in the first year of life.

            HIV-exposed uninfected (HEU) infants have higher infectious morbidity than HIV-unexposed uninfected (HUU) infants. We present the clinical outcomes from a pilot cohort study of 27 HEU and 28 HUU infants. In the absence of infant malnutrition or advanced maternal HIV, HEU infants experienced a 2.74 (0.85-8.78) times greater risk of hospitalization in the first year.
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              Timing of HAART defines the integrity of memory B cells and the longevity of humoral responses in HIV-1 vertically-infected children.

              HIV-1 infection induces a progressive disruption of the B cell compartment impairing long-term immune responses to routine immunizations. Depletion of specific memory B cell pools occurs during the 1st stages of the infection and cannot be reestablished by antiretroviral treatment. We reasoned that an early control of viral replication through treatment could preserve the normal development of the memory B cell compartment and responses to routine childhood vaccines. Accordingly, we evaluated the effects of different highly-active antiretroviral therapy (HAART) schedules in 70 HIV-1 vertically-infected pediatric subjects by B cell phenotypic analyses, antigen-specific B cell enzyme-linked immunosorbent spot (ELISpot) and ELISA for common vaccination and HIV-1 antigens. Initiation of HAART within the 1st year of life permits the normal development and maintenance of the memory B cell compartment. On the contrary, memory B cells from patients treated later in time are remarkably reduced and their function is compromised regardless of viral control. A cause for concern is that both late-treated HIV-1 controllers and noncontrollers loose protective antibody titers against common vaccination antigens. Timing of HAART initiation is the major factor predicting the longevity of B cell responses in vaccinated HIV-1-infected children.
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                Author and article information

                Journal
                EClinicalMedicine
                EClinicalMedicine
                Elsevier BV
                25895370
                July 2018
                July 2018
                : 1
                : 28-42
                Article
                10.1016/j.eclinm.2018.06.002
                ce4ffb18-6f72-409b-a60f-23d734b7b8c6
                © 2018

                https://www.elsevier.com/tdm/userlicense/1.0/

                http://creativecommons.org/licenses/by/4.0/

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