Antiretroviral therapy interruptions result in loss of protective humoral immunity to neoantigens in HIV-infected individuals.

Abstract

Sustained antiretroviral therapy (ART)-mediated viral suppression restores responses to vaccination in HIV-1-infected individuals. As ART interruption occur frequently in resource-constrained settings, we studied their effects on the ability to mount humoral immune responses against a neoantigen. Treatment-naive HIV-1-infected individuals were treated with stavudine, lamuvidine and lopinavir/ritonovir. Individuals who maintained viral load less than 50 copies/ml and CD4 T-cell counts more than 450 cells/μl for 6 months received three doses of rabies vaccine, and were randomized to 72 weeks of continuous ART (arm 1) or sequential 2, 4 and 8-week ART interruptions (arm 2). An additional vaccine dose was administered at study end. Neutralizing antibody titers to rabies virus were assessed in plasma with a rapid fluorescent focus-inhibiting test. The proportion of participants achieving protective (>0.5 IU/ml) antibody titer after vaccination was similar (arm 1=92%; arm 2=91%), but over time the cumulative proportion of observations with protective titer was greater in arm 1 than arm 2 (P=0.0177). From week 26 after vaccination, antibody titers were lower in arm 2 than arm 1, and volunteers in arm 2 lost protective antibody titers at a greater rate (P=0.0029). After boosting, 100% of arm 1 and 95% arm 2 volunteers achieved protective antibody titer. Our data indicate that individuals undergoing recurring ART interruption retain lower neutralizing antibody titers to a neoantigen, but maintain the ability to mount secondary responses upon boosting, suggesting that they might benefit from vaccine schedule intensification.