Prognostic value of proliferative responses to HIV-1 antigen in chronically HIV-infected patients under antiretroviral therapy

Background: In the chronic stage of HIV infection T cell proliferative responses to HIV antigens are rare, mostly of low level, and the influence of responses on antiretroviral therapy is not known. Objectives: To determine a potential correlation between HIV-specific proliferative responses and the subsequent course of infection under antiretroviral therapy. Study design: Proliferation assays were performed with freshly isolated blood mononuclear cells from 45 chronically HIV-infected HAART treated individuals using HIV-p24, other recall antigens, and mitogens as stimulants. Virus load was monitored at the time of stimulation and during 33 months follow-up. Results: A proliferative response to HIV antigen stimulation was detectable in 7 of 45 patients (15.5% responders). This group showed elevated reactions against tetanus toxoid and tuberculin, whereas reactions against standard mitogens were equal in the HIV responder and nonresponder groups. None of the seven HIV-specific responders had a blood virus load rebound of more than 1000 genome copies/ml during follow-up, whereas in 50% of the non-responders higher virus rebounds occurred. CD4 cell levels were slightly higher in the responder group, but mostly independent of virus rebound within the nonsponders. Only four patients with high and continuous virus rebound experienced a significant CD4 cell decline. Conclusions: In patients under HAART, HIV-specific proliferative response is frequently related to anamnestic antigen responses and an enduring control of virus replication.