AIDS (London, England) · 2012
Antiretroviral therapy interruptions result in loss of protective humoral immunity to neoantigens in HIV-infected individuals.
СтатьяРандомизированное исследованиеПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Azzoni Livio, Foulkes Andrea S, Firnhaber Cynthia, Yin Xiangfan, Xiang Zhi Q, Li Yan, Stevens Wendy, Gross Robert, Ertl Hildegund C J, Sanne Ian, Montaner Luis J
Аннотация
OBJECTIVE: 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.
DESIGN: 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.
METHODS: Neutralizing antibody titers to rabies virus were assessed in plasma with a rapid fluorescent focus-inhibiting test.
RESULTS: 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.
CONCLUSION: 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.
DESIGN: 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.
METHODS: Neutralizing antibody titers to rabies virus were assessed in plasma with a rapid fluorescent focus-inhibiting test.
RESULTS: 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.
CONCLUSION: 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.