Protease
Inhibitor and PI-sparing Regimens Provide Similar Levels of Long-term Immune Reconstitution
in Patients with Low CD4 Cell Counts
Data
are lacking on the long-term immunological benefit of protease inhibitor (PI)-sparing
antiretroviral therapy using non-nucleoside reverse transcriptase inhibitors (NNRTIs).
Study results that address this issue appear in the current (August 2007) issue
of Antiviral Therapy.
French
researchers enrolled 120 antiretroviral-naive HIV patients in the immunology substudy of INITIO. In this international randomized trial,
investigators compared regimens containing
2 nucleoside reverse transcriptase inhibitors (NRTIs)
-- ddI (didanosine, Videx)
+ d4T (stavudine,
Zerit) -- combined
with either:
1 NNRTI + 1 PI (efavirenz + nelfinavir) (39 patients).
CD4
T-cell counts, HIV-1 plasma viral load, T-cell phenotype, T-cell proliferation,
and interferon-gamma production against opportunistic/recall and HIV-1 antigens/peptides
were compared at baseline and at weeks
96 and 156.
Results
·Participants
in the 3 arms had similar baseline viral loads.
·Median CD4
counts in the efavirenz, nelfinavir,
and efavirenz/nelfinavir arms were 144, 212, and 257 cells/mm3, respectively.
·At week
156, the proportions of patients with viral load ≤ 50 copies/mL were not different among the 3 arms (P = 0.3).
·From baseline
to week 156, there was a significant increase in CD4 cell counts (P < 0.001)
and naive CD4 cells (P < 0.001).
·There was
no difference between the 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 efavirenz arm at week 96 (P = 0.03) and at week 156 (P = 0.01),
but did not persist after adjusting for baseline CD4 cell counts.
·During follow-up,
immune responses to opportunistic pathogens increased in all patients.
·However,
specific T-cell responses to HIV-1-p24 and gp160 recombinant
proteins or to Gag and Nef peptides were
not restored.
Conclusion
Based
on these findings, the authors concluded, “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.
08/17/07
Reference A Samri, R Goodall,
C Burton, and others.Three-year immune reconstitution in
PI-sparing and PI-containing antiretroviral regimens in advanced HIV-1 disease.Antiviral Therapy 12(4): 553-558. August 2007.
