Immunologic reconstitution after 1 year of highly active antiretroviral therapy, with or without protease inhibitors

Objectives: To assess the effectiveness of two triple antiretroviral combinations (2 nucleoside reverse transcriptase inhibitors [NRTIs] + 1 protease inhibitors [PI] vs. 2 NRTIs + I nonnucleoside reverse transcriptase inhibitor [NNRTI]) to correct T-cell,subsets abnormalities and to restore immune functions in asymptomatic antiretroviral-naive HIV-1-infected patients with a baseline CD4 T-cell counts >500/mm(3) and plasma viral load >5000 copies/mL. Design and Methods: Twenty randomized patients from 2 cohort Studies receiving either stavudine (d4T) + lamivudine (3TC) + indinavir (n = 9), or d4T + didanosine (ddI) + nevirapine (NVP) In = I I I were studied. Viral load, T-cell subsets and T-cell functions were analyzed at baseline and after I year of treatment. Results: After 1 year of follow-up, the PI regimen was significantly more effective in reducing plasma and lymphoid tissue VL to undetectable levels. A significant increase in CD4(+) T cells was observed in patients treated with PI (p=.0007) compared with those treated with NVP. Percentages of CD8(+) T-cells and of activated CD8(+) T-cells (CD38(+) and DR+ as well as memory CD45RO(+)) decreased in all patients. An increase of the CD28(+) subset of CD8(+) T-cells also occurred in both groups of treatment. Naive T cells were maintained in the CD4(+) subset and augmented in the CD8(+),subset in all patients. In both PI and NVP groups, memory CD4(+) T-cells increased significantly (p=.03). Peripheral blood mononuclear cell responsiveness to polyclonal stimuli and to tetanus toxoid and cytomegalovirus (CMV) antigen was similar in both groups of treatment. HIV-infected patients treated for I year with both triple combinations lacked significant T-cell responsiveness to HIV-1 proteins. Conclusions: These data suggest that immune reconstitution achieved after I year of therapy with PI-containing or PI-sparing regimens is similar. despite the higher effectiveness of PI-containing, regimens in reducing viral load. Additional therapeutic approaches should be designed to restore HIV-1-specific responses.