Kinetics of immune functions and virus replication during HIV-1 infection

Introduction: Kinetics of human immunodeficiency virus type 1 (HIV-1) cytotoxic T lymphocyte (CTL) responses and viral load were evaluated in HIV-I infected homosexual men who progressed to A:IDS within 3-6 years after seroconversion and in long-term survivors who remained AIDS-free for > 9) years with normal CD4(+) T cell counts. Methods: CTL against four major HIV-1 gene products (i.e. Gag, reverse transcriptase (:RT), Nef and Env) were expanded in vitro under limiting dilution conditions using antigen specific stimulation. CTL activity was :measured in standard split-well Cr-51-release assay. Viral load was measured both as serum HIV-1 RNA levels and frequency of circulating CD4(+) T cells productively infected with HIV-1. Polyclonal T cell function in vitro was determined in whole blood lymphocyte cultures, measuring lymphoproliferative responses to CD3 monoclonal antibody. Results: Long-term survival was associated with either persistently high or stable low HIV-I specific CTL responses, accompanied by preserved in vitro polyclonal T cell reactivity and low viral load. In progressors, HIV-1 specific CTL responses were initially generated with similar kinetics as compared to long-term survivors. However, with progression to AIDS antiviral CTL activity and T cell function deteriorated simultaneously, while viral load increased. Conclusions: Our results are consistent with the hypothesis that HIV-I specific CTL are beneficial through control of viremia to the virologic set-point and contribute to maintenance of the asymptomatic phase. However, loss of HIV-1 specific immune control as part of a more general loss of T cell function is the precipitating event in AIDS pathogenesis. (C) 1997 Elsevier Science B.V.