HIV dynamics and T-cell immunity after three structured treatment interruptions in chronic HIV-1 infection

Objective: To evaluate whether controlled re-exposures to autologous HIV-1 could boost HIV-specific immunity and limit virus replication in patients w ith chronic HIV-1 infection. Patients and design: Subjects with at least 2 years virus suppression durin g antiretroviral therapy and a CD4:CD8 ratio > 1 were randomly assigned to interrupt highly active antiretroviral treatment (HAART) three times (n =12 ) or to continue their previous HAART (n = 14). Results: In 10/12 interrupter patients a rebound of HIV-1 RNA was detected in all three structured treatment interruptions (STI). Plasma virus doublin g time was shorter during the first STI than in the second and third STI, c orresponding to an average 13% reduction in viral basic reproductive rate. However, the mean time before plasma viral load rose to > 50 copies/ml was significantly shorter in the second and third STI. The average frequency of HIV-specific CD8 T cells in the interrupter patients at the end of the thi rd STI cycle was significantly higher compared with the baseline and the en d of the first STI. A substantial increase in HIV-specific CD8 T cell frequ encies was found in four interrupter patients, whereas there were no change s in all 14 non-interrupter individuals. A weak p24-specific T helper respo nse developed in 5/12 interrupter patients compared with no response in non -interrupters, but these responses were transient and disappeared rapidly. Conclusion: The increase in the control of viral replication, and positive effects of STI on immune responses in this population should encourage the further development of HIV-specific immune-based therapeutic strategies. (C ) 2001 Lippincott Williams & Wilkins.