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

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 330mIU/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.