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 antiretroviral-naive 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 eitherstavudine (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.
RCT Entities:
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 antiretroviral-naive HIV-1-infectedpatients 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-infectedpatients 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.
Authors: Maristela Miyamoto; Silvana D Pessoa; Erika Ono; Daisy M Machado; Reinaldo Salomão; Regina C de M Succi; Savita Pahwa; Maria Isabel de Moraes-Pinto Journal: J Trop Pediatr Date: 2010-04-13 Impact factor: 1.165
Authors: Morgane Rolland; Jonathan M Carlson; Siriphan Manocheewa; J Victor Swain; Erinn Lanxon-Cookson; Wenjie Deng; Christine M Rousseau; Dana N Raugi; Gerald H Learn; Brandon S Maust; Hoosen Coovadia; Thumbi Ndung'u; Philip J R Goulder; Bruce D Walker; Christian Brander; David E Heckerman; James I Mullins Journal: PLoS One Date: 2010-09-01 Impact factor: 3.240