CD8+ cell anti-HIV activity rapidly increases upon discontinuation of early antiretroviral therapy

Abstract

Introduction: CD8+ lymphocytes can suppress HIV replication without killing the infected cells. This CD8+ cell noncytotoxic anti-HIV response (CNAR) is associated with a beneficial clinical course. Materials and Methods: In this longitudinal study of 16 participants in the Options Project at UCSF, we measured the ability of CD8+ lymphocytes to suppress HIV replication in CD4+ cells during primary HIV infection, early antiretroviral therapy, and after treatment. Results and Discussion: CD8+ lymphocytes from subjects with untreated primary HIV-1 infection strongly suppressed HIV replication. Initiation of antiretroviral therapy during primary HIV-1 infection caused a marked decline in this CNAR. CD8+ cells from these subjects regained anti-HIV activity when early therapy was discontinued. The timing of the appearance of CD8+ cell anti-HIV activity directly correlated with the emergence of detectable virus levels. Maximal CNAR activity coincided with a decay in the kinetics of HIV replication. In addition, peak viral loads during treatment interruption were lower than pre-treatment virus levels (median reduction∈=∈0.8 logs, p∈=∈0.005) and CD4+ T cell counts were maintained for a 24-week period of follow-up. Conclusion: These results suggest that CNAR plays an important role in suppressing HIV replication in the setting of antiretroviral treatment interruption in HIV-infected individuals.