Augmented HIV-specific interferon-gamma responses, but impaired lymphoproliferation during interruption of antiretroviral treatment initiated in primary HIV infection

Background: Antiretroviral therapy (ART) introduced during primary HIV infection followed by treatment interruption (TI) is postulated to enhance virologic control through induction of HIV-specific CD4 ⁺ T cells, which foster virus-specific CD8+ T cells that suppress virus replication. This hypothesis was evaluated in 21 subjects enrolled in AIDS Clinical Trials Group 709, a substudy of AIDS Clinical Trials Group 371, which prospectively evaluated subjects who received ≥1 year of ART initiated in acute or recent HIV infection followed by TI. Methods: Lymphoproliferation was assessed by [methyl- ³H] thymidine incorporation and HIV-specific CD8+ T-cell interferongamma responses by enzyme-linked immunospot-forming assays. Virologic success was defined as sustained viral load >5000 copies per milliliter for 24 weeks after TI. Results: HIV-specific lymphoproliferative responses were detected at least once in 5 (24%) of 21 subjects, were generally transient, and were unrelated to HIV-specific interferon-gamma responses (P> 0.4). HIV-specific CD8+ interferon-gamma responses increased after 48 weeks of ART (P = 0.03), but failed to predict virologic success (P = 0.18). Compared with seronegative subjects, lymphoproliferation to Candida, cytomegalovirus, and alloantigens was similar in HIV-infected subjects during ART, but lower during TI (P ≤ 0.04). Conclusions: HIV-specific CD8+ T-cell interferon-gamma responses expand during ART following primary HIV infection, but are not related to HIV-specific lymphoproliferative responses nor virologic success. Impaired non-HIV antigen-specific lymphoproliferation associated with TI suggests this strategy could be deleterious.