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-H] thymidine incorporation and HIV-specific CD8+ T-cell interferon-gamma 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.