Measles Immunity at 4.5 Years of Age Following Vaccination at 9 and 15-18 Months of Age Among Human Immunodeficiency Virus (HIV)-infected, HIV-exposed-uninfected, and HIV-unexposed Children

Abstract

Background: HIV-infected and HIV-exposed-uninfected (HEU) children may be at increased risk of measles infection due to waning of immunity following vaccination. We evaluated persistence of antibodies to measles vaccination at 4.5 years of age in HIV-unexposed, HEU, and HIV-infected children with CD4+≥25% previously randomised to immediate antiretroviral therapy interrupted at 12 months (HIV/Immed-ART-12), 24 months (HIV/Immed-ART-24), or when clinically/immunologically indicated (HIV/Def-ART). The HIV/Def-ART group had ART initiated by median 5.8 (interquartile range 4.4-10.3) months of age. Methods: This cohort study followed participants from 6-12 weeks through 4.5 years of age. HIV-unexposed (n=95), HEU (n=84), HIV/Immed-ART-12 (n=70), HIV/Immed-ART-24 (n=70), and HIV/Def-ART (n=62) children were scheduled to receive measles vaccination at 9 and 15-18 months of age. Anti-measles serum IgG titres were quantified using enzyme-linked immunosorbent assay at 4.5 years. Results: Compared with HIV-unexposed children (2860 mIU/ml; 95% confidence interval [CI] 2373-3446), measles antibody geometric mean titres (GMTs) were significantly lower in both HIV/Immed-ART-12 (571; 95%CI 409-796; p<0.001) and HIV/Immed-ART-24 (1136; 95%CI 791-1633; p<0.001), but similar in the HIV/Def-ART (2777; 95%CI 2008-3841); p=0.675) and HEU (3242; 95%CI 2617-4014; p=0.525) groups. Furthermore, compared with HIV-unexposed, antibody titres ≥330 mIU/mL (i.e. presumed sero-correlate for protection; 99%) were also significantly lower in HIV/Immed-ART-12 (70%; p<0.001) and HIV/Immed-ART-24 (83%; p<0.001); but similar in the HIV/Def-ART (90%) and HEU (98%) groups. Conclusions: HIV-infected children in whom ART was interrupted at either 12 or 24 months of age had lower GMTs and lower proportions with seroprotective titres than HIV-unexposed children; indicating a potential downside of ART treatment interruption.