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Effect of in-utero HIV exposure and antiretroviral treatment strategies on measles susceptibility and immunogenicity of measles vaccine

Simani, Omphile E.a; Adrian, Peter V.a,b; Violari, Avyc; Kuwanda, Locadiaha,b; Otwombe, Kennedyc; Nunes, Marta C.a,b; Cotton, Mark F.d; Madhi, Shabir A.a,b,e

doi: 10.1097/QAD.0b013e32835fae26
Clinical Science

Introduction: The high burden of maternal HIV-infection in sub-Saharan Africa may affect measles control. We evaluated the effect of in-utero HIV-exposure and antiretroviral treatment (ART) strategies on measles antibody kinetics prior and following measles vaccination.

Methods: Infants aged 6–12 weeks were enrolled. This included HIV-uninfected infants born to HIV-uninfected (HUU) and HIV-infected mothers (HEU). Additionally, we enrolled perinatal HIV-infected infants with CD4% equal or greater than 25% randomized to deferred-ART until clinically or immunologically indicated (Group-3) or immediate-ART initiation (Group-4). Group-4 was further randomized to interrupt ART at 1 year (Group-4a) or 2 years of age (Group-4b). Additionally, a convenience sample of HIV-infected infants with CD4+ less than 25% initiated on immediate-ART was enrolled (Group-5). Measles immunoglobulin-G antibodies were quantified by an indirect enzyme immunoassay with titers 330 mIU/ml or more considered ‘sero-protective’. The referent group was HUU-children.

Results: The proportion with sero-protective titers at 7.3 weeks of age was higher in HUU (65.2%) compared with any HIV-infected group (range: 16.7–41.8%), but dropped to less than 17% in all groups at age 19.6 weeks. Twenty-eight weeks following the first measles vaccine, Group-4a was less likely to have sero-protective titers (79.3%) as compared to HUU (91.1%; P < 0.0001), Group-3 (95.7%; P = 0.003) or Group-4b (92.1%; P = 0.018). Although the proportion with sero-protective levels were similar between groups immediately postbooster dose, this was lower in HEU (79.6%; P = 0.002) and Group-4a (80.3%; P = 0.010) compared with HUU (94.3%) 41-weeks later.

Conclusion: Greater waning of immunity among HIV-infected children in whom ART was interrupted and in HEU following a booster-dose, indicate the possible need for further measles-booster doses after 2 years of age in these children.

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aDepartment of Science and Technology/National Research Foundation, Vaccine Preventable Diseases

bMedical Research Council, Respiratory and Meningeal Pathogens Research Unit

cPerinatal HIV Research Unit, University of the Witwatersrand, Faculty of Health Sciences

dStellenbosch University, Children's Infectious Diseases Clinical Research Unit, Tygerberg

eNational Institute for Communicable Diseases: a division of National Health Laboratory Service, Centre for Vaccines and Immunology, Sandringham, South Africa.

Correspondence to Shabir A. Madhi, National Institute for Communicable Diseases, 1 Modderfontein Road, Sandringham, Gauteng, 2131, South Africa. Tel: +27 86 682 7159; fax: +27 11 386 6137; e-mail:

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© 2013 Lippincott Williams & Wilkins, Inc.