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: Human immunodeficiency virus (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 randomized to immediate antiretroviral therapy (ART) 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 initiated ART by median 5.8 (interquartile range, 4.4-10.3) months of age.

Methods: In this study, 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 age 9 and 15-18 months. Antimeasles serum immunoglobulin G titers were quantified using enzyme-linked immunosorbent assay at 4.5 years.

Results: Compared with HIV-unexposed children (2860 mIU/mL), measles antibody geometric mean titers (GMTs) were significantly lower in both HIV/Immed-ART-12 (571; P < .001) and HIV/Immed-ART-24 (1136; P < .001) but similar in the HIV/Def-ART (2777) and HEU (3242) groups. Furthermore, compared with HIV-unexposed, antibody titers ≥330 mIU/mL (ie, presumed serocorrelate for protection; 99%) were also significantly lower in HIV/Immed-ART-12 (70%; P < .001) and HIV/Immed-ART-24 (83%; P < .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 had lower GMTs and lower proportions with seroprotective titers than HIV-unexposed children, indicating a potential downside of ART treatment interruption.

Clinical trials registration: NCT00099658 and NCT00102960.

Keywords: HIV; HIV exposure; antibody response; measles vaccine; persistence.

© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Study profile showing the study population from enrollment through the current analysis. Abbreviations: ART, antiretroviral therapy; HIV, human immunodeficiency virus; HIV/Immed-ART-12, HIV-infected children receiving immediate ART until 12 months of age; HIV/Immed-ART-24, HIV-infected children receiving immediate ART until 24 months of age; HV/Def-ART, HIV‐infected children on deferred ART until clinically or immunologically indicated; HIV/CD4+

Figure 2.

Measles antibody geometric mean titers and proportion of children with seropositive and seroprotective antibody levels at 4.5 years of age. P value deemed significant at ≤.007 after Bonferroni correction. P values were either calculated by linear or logistic regression and adjusted for age at the immunogenicity visit, sex, race, study center, and CD4+ cell percentage at the primary measles dose in HIV-infected children or by Fisher exact test. Abbreviations: ART, antiretroviral therapy; GMT, geometric mean titer; HEU, HIV-exposed uninfected; HIV, human immunodeficiency virus; HIV/Def-ART, HIV‐infected children on deferred ART until clinically or immunologically indicated; HIV/Immed-ART-12, HIV-infected children receiving immediate ART until 12 months of age; HIV/Immed-ART-24, HIV-infected children receiving immediate ART until 24 months of age.