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

Autor: Plana, M., Martinez, C., Garcia, F., Maleno, M. J., Barcelo, J. J., Garcia, A., Marylène Lejeune, Vidal, C., Cruceta, A., Miro, J. M., Pumarola, T., Gallart, T., Gatell, J. M.
Rok vydání: 2002
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Zdroj: ResearcherID
Scopus-Elsevier
ISSN: 1525-4135
Popis: 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 antiretroviral-naive HIV-1-infected patients with a baseline CD4 T-cell counts500/mm3 and plasma viral load5000 copies/mL.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.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.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.
Databáze: OpenAIRE
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