Persistent Humoral Immune Defect in Highly Active Antiretroviral Therapy–Treated Children With HIV-1 Infection: Loss of Specific Antibodies Against Attenuated Vaccine Strains and Natural Viral Infection

Abstract

In the pre-highly active antiretroviral therapy era, a loss of specific antibodies was seen. Our objective with this study was to describe the loss of specific antibodies during treatment with highly active antiretroviral therapy. In a prospective, single-center, cohort study of 59 children with HIV-1 infection, we investigated the long-term effect of highly active antiretroviral therapy on the titers and course of specific antibodies against measles, mumps, and rubella vaccine strains compared with wild-type varicella zoster virus, cytomegalovirus, and Epstein-Barr virus. During highly active antiretroviral therapy, age-adjusted CD4+ T cells and B cells increased, whereas total immunoglobulin levels declined. Although these children were preimmunized before the start of highly active antiretroviral therapy, only 24 (43%) had antibodies against all 3 measles, mumps, and rubella. Antibodies against measles, mumps, and rubella were lost in 14 (40%), 11 (38%), and 5 (11%) children who were seropositive at baseline. We also observed loss of varicella zoster virus immunoglobulin G in 7 (21%) of 34, cytomegalovirus immunoglobulin G in 3 (7%) of 45, but none of 53 Epstein-Barr virus-seropositive children. During highly active antiretroviral therapy, primary vaccination in 3 patients and 15 revaccinations in those with negative serology demonstrated incomplete seroconversion. Humoral reactivity in children with HIV-1 infection remains abnormal during highly active antiretroviral therapy. Despite immune reconstitution, antibodies against live-attenuated vaccine and wild-type natural virus strains disappear over time in up to 40% of children with HIV-1 infection.