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Immunologic Reconstitution After 1 Year of Highly Active Antiretroviral Therapy, With or Without Protease Inhibitors

Plana, Montserrat; Martínez, Catalina; Garcia, Felipe; Maleno, Maria J.; Barceló, Juan J.; Garcia, Ana; Lejeune, Marylène; Vidal, Carmen; Cruceta, Anna; Miró, José M.; Pumarola, Tomás; Gallart, Teresa; Gatell, José M.
JAIDS Journal of Acquired Immune Deficiency Syndromes: April 15th, 2002
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Objectives:To assess the effectiveness of two triple antiretroviral combinations (2 nucleoside reverse transcriptase inhibitors [NRTIs] + 1 protease inhibitors [PI] vs. 2 NRTIs + 1 nonnucleoside reverse transcriptase inhibitor [NNRTI]) to correct T-cell subsets abnormalities and to restore immune functions in asymptomatic antiretroviralnaive HIV-1-infected patients with a baseline CD4 T-cell counts >500/mm3 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) (n = 11) were studied. Viral load, T-cell subsets and T-cell functions were analyzed at baseline and after 1 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 1 year with both triple combinations lacked significant T-cell responsiveness to HIV-1 proteins.

Conclusions:These data suggest that immune reconstitution achieved after 1 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.

Address correspondence and reprint requests to Dr. Montserrat Plana, Servei d'Immunologia. Hospital Clinic. Villarroel. 170, 08036- Barcelona. Spain: e-mail: mplana@medicina.ub.es

Manuscript received August 3, 2001; accepted January 31, 2002.

© 2002 by Lippincott Williams & Wilkins