Three-year immune reconstitution in PI-sparing and PI-containing antiretroviral regimens in advanced HIV-1 disease.
BACKGROUND
The long-term immunological benefit of protease inhibitor (PI)-sparing antiretroviral therapy (ART) using non-nucleoside reverse transcriptase inhibitors (NNRTIs) remains poorly investigated.


METHODS
A total of 120 ART-naive, HIV-1-infected participants were included in the immunology substudy of INITIO, an international randomized trial comparing two NRTIs (didanosine + stavudine) combined with either: one NNRTI (efavirenz; EFV), one non-boosted PI (nelfinavir; NFV), or one NNRTI + one PI (EFV/NFV). CD4+ T-cell counts, HIV-1 plasma RNA load (VL), T-cell phenotype, T-cell proliferation and IFN-gamma production against opportunistic/recall and HIV-1 antigens/peptides were compared at baseline and at week (W) 96 and W156.


RESULTS
Participants (37 EFV, 44 NFV, 39 EFV/NFV) had similar baseline VL; median CD4+ T-cell counts/mm3 were: 144 (64-303) EFV, 212 (42-313) NFV and 257 (86-331) EFV/NFV. At W156, the proportion of patients with VL < or =50 copies/ml was not different between the arms (P=0.3). From baseline to W156 there was a significant increase in CD4+ T-cell counts (P<0.001) and in naive CD4+ T cells (P<0.001), with no difference between arms and percentages of total and activated CD8+ T cells decreased significantly (P<0.001) in all arms. The decrease in activated memory CD4+ T-cells was significantly greater in the EFV arm at W96 (P=0.03) and W156 (P=0.01), but did not persist after adjusting for baseline CD4+ T-cell counts. During follow-up, responses to opportunistic pathogens increased in all patients while specific T-cell responses to HIV-1-p24 and gp160 recombinant proteins or to Gag and Nef peptides were not restored.


CONCLUSIONS
Regimens using/sparing PIs provide similar levels of long-term immune reconstitution even in patients with low CD4+ T-cell counts.
Laboratoire d'Immunologie Cellulaire, AP-HP, Hôpital Pitié-Salpêtrière, Paris, France.
Assia
A
Samri
Ruth
R
Goodall
Catherine
C
Burton
Nesrina
N
Imami
Giuseppe
G
Pantaleo
Anthony
A
Kelleher
Guido
G
Poli
Frances
F
Gotch
Brigitte
B
Autran
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D004359:Drug Therapy, Combination; D005260:Female; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D015488:HIV Antigens; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D007371:Interferon-gamma