Immunological reconstitution in severely immunosuppressed antiretroviral-naïve patients (<100 CD4+ T cells/mm3) using a non-nucleoside reverse transcriptase inhibitor-based or boosted protease inhibitor-based ART regimen: 3-year results
Abstract number: 1733_1411
Lonca M., De Lazzari E., Plana M., Group the ADVANZ Study, Arrizabalaga J., Miro J.M., Pich J., Domingo P., Podzamczer D., Arribas J.R., Ribera E.
Background: There are few randomised clinical trials involving severely immunosuppressed patients. The aim of this study was to analyse whether there are differences in the timing of immune reconstitution in patients with <100 CD4+ cells/mm3 on non-nucleoside reverse transcriptase inhibitor (NNRTI)- vs. boosted protease inhibitor (PI)-based antiretroviral therapies.
Methods: Multicentre, randomised, prospective, open-label clinical trial in naïve HIV-1-infected patients with <100 CD4 cells/mm3. Enrollment period: Nov. 2001 Jan. 2003. Treatment regimens were two NRTIs plus an NNRTI (efavirenz [EFV] 600 mg QD, with nevirapine [NVP] as the second option for EFV-intolerant patients) or a boosted PI (indinavir/ritonavir [IDV/r] 800/200 mg BID, which, once approved in Spain, could be changed lopinavir/ritonavir [LPV/r] or atazanavir/ritonavir [ATZ/r] as the second option for IND/r-intolerant patients). Analysis was by intention-to-treat (ITT) and per protocol (OT), allowing changes of NNRTI or boosted PI within the same class of antiretrovirals.
Results: Sixty-six patients were randomised: 34 received an NNRTI-based regimen and 32 received a boosted PI-based regimen. 50% had had C events. Median (range) CD4+ and PVL at baseline were 40 (199) cells/mm3 and 5.5 (4.0>6) log10/mL, respectively. All patients completed 3 years of follow-up. Five patients died (NNRTI, 4; PI, 1) and 12 developed a C event (NNRTI, 6; boosted PI, 6), most of them within the first six months. Seventeen patients changed EFV (NVP, 3; LPV/r 1) or IDV/r (LPV/r 9, ATZ/r 3, EFV 3, NVP 1) because of adverse events and eight patients stopped HAART or were lost for follow-up (NNRTI, 1; PI, 7). There were 12 virological failures (NNRTI, 5; PI, 7). PVL < 200 copies/mL for NNRTI/PI arms at 1, 2 and 3 years was 71%/65%, 68%/49% and 65%/29% (p = 0.05 at the last time point) by ITT (M=F) and 73%/77%, 73%/69% and 73%/49% (p=NS at all time points) by OT analysis, respectively. Median CD4+ cell increase after 1, 2 and 3 years by OT analysis was +186/+136, +226/+162 and +303/+220 cells/mm3 (p=NS for all time points) for NNRTI/PI groups, respectively. At 1 and 2 years, immune activation (CD8+CD38+) was significantly lower in the NNRTI group (p = 0.004). There were no differences in T-cell subsets, proliferative responses to mitogens and recall antigens between both study arms.
Conclusions: At 3 years, the virological response and the magnitude of the immune reconstitution induced by an NNRTI-based regimen was at least as potent as that induced by a boosted PI-based regimen.
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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