Prolonged CD4+Cell/Virus Load Discordance during Treatment with Protease Inhibitor–Based Highly Active Antiretroviral Therapy: Immune Response and Viral Control

Abstract

Mechanisms that underly discordant CD4⁺ cell/virus load (VL) responses in patients who receive highly active antiretroviral therapy (HAART) were studied in 30 human immunodeficiency virus (HIV)–positive patients, in 3 groups. Discordant responders maintained CD4⁺ cell levels >200/mm³ with stable or increasing trend, despite sustained VLs of 500–5000 copies/mL, for >2 years. Treatment-success patients had CD4⁺ cell counts >200/mm³ with stable or increasing trend and VLs 2 years. Treatment-failure patients initially responded to HAART, followed by decreasing CD4⁺ cell counts and increasing VLs. Interferon-γ production to gag and noncytolytic CD8⁺ cell suppressive activity were greater in discordant responders. Cellular activation was greatest in patients with treatment failure. All discordant responders had non–syncytium-inducing (CCR5-tropic) viruses. Viruses from discordant responders and from patients with treatment failure had extensive resistance mutations; discordant responders had significantly lower viral replication capacities. These findings suggest that discordant responses may be related to enhanced HIV-directed immune responses, diminished cellular activation, decreased viral replication capacity, and preservation of non–syncytium-inducing virus strains