Prolonged Suppression of Human Immunodeficiency Virus Type 1 (HIV-1) Viremia in Persons with Advanced Disease Results in Enhancement of CD4 T Cell Reactivity to Microbial Antigens but Not to HIV-1 Antigens

CD4 T cell responses were studied for > 2 years in 27 zidovudine-experienced patients with advanced human immunodeficiency virus type 1 (HIV-1) infection who received triple combination drug therapy with indinavir, zidovudine and lamivudine or zidovudine plus lamivudine or zidovudine alone for 24–42 weeks before switching to the three-drug therapy. Subjects initially given the three drugs had viremia suppressed to undetectable levels and increases in T cell proliferative and cytokine responses to microbial antigens through 2 years of follow-up. Patients receiving the triple-drug therapy after either indinavir or zidovudine-lamivudine treatment had similar increases in T cell responses only if they also had suppression of virus load. CD4 T cell reactivity to HIV-1 antigens was not restored. Prolonged indinavir-zido-vudine-lamivudine treatment has significant but incomplete enhancing effects on CD4 T cell reactivity, which could be important in host control of microbial and persistent HIV-1 infections.