Timing of antiretroviral treatment initiation and seropositivity to measles virus among children living with HIV in rural Zambia

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Abstract
Background: Combination antiretroviral therapy (cART) reduces morbidity among children living with HIV (CHIV) but does not restore vaccine-induced measles immunity. Many CHIV now initiate cART before measles vaccination but the impact on measles seroprevalence is not understood. This study compared measles seropositivty between CHIV initiating cART before and after 9 months in Zambia. Methods: This retrospective study was nested within a cohort study of CHIV and community-based studies in Macha, Zambia conducted from 2007-2020. Samples were tested for measles IgG antibodies by enzyme immunoassay from CHIV initiating cART at ages 0-8, 9-23, and 24-59 months and age-matched community-based controls. A cross-sectional analysis compared measles seroprevalence between CHIV groups after 6-12 months of cART and controls. A longitudinal analysis evaluated antibody concentrations from age 9 months through 48 months of cART and during the 2010-11 measles outbreak. Results: In the cross-sectional analysis, measles seropositivity did not statistically differ after 6-12 months of cART by age at initiation (0-8: 30.8% [n=12/39]; 9-23: 37.0% [n=51/138]; 24-59 months: 26.6% [n=33/124]). Within CHIV groups, seropositivity was significantly lower than age-matched controls (63.5%, 75.7%, and 80.3%). Among 242 CHIV followed longitudinally, 46-56% had an antibody response, with estimated seroreversion in only 1.8-3.2 years. Among CHIV in 2010-11, 50% seroconverted or boosted with estimated seroreversion in 2.1 years. Conclusions: Measles seroprevalence was low among CHIV, even when starting cART before 9 months of age, and the time to seroreversion was short. These findings support recommendations that CHIV, including infants, would benefit from periodic revaccination after immune reconstitution.