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


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.
Plana
Montserrat
M
Institut Clínic de Infeccions i Immunologia (ICII), Hospital Clínic, University of Barcelona, Villaroel 170, 08036-Barcelona, Spain. mplana@medicina.ub.es
Martínez
Catalina
C
García
Felipe
F
Maleno
María J
MJ
Barceló
Juan J
JJ
García
Ana
A
Lejeune
Marylène
M
Vidal
Carmen
C
Cruceta
Anna
A
Miró
José M
JM
Pumarola
Tomás
T
Gallart
Teresa
T
Gatell
José M
JM
D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000302:isolation & purification* / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D012367:RNA, Viral / Q000097:blood; D016176:T-Lymphocyte Subsets / Q000276:immunology; D019562:Viral Load
D016207:Cytokines; D017320:HIV Protease Inhibitors; D012367:RNA, Viral