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Lopinavir/ritonavir (LPV/r) tablets administered once- (QD) or twice-daily (BID) with NRTIs in antiretroviral-experienced HIV-1 infected subjects: results of a 48-week randomized trial (Study M06-802)
Presented by Sharlaa Badal-Faesen (South Africa).
R. Zajdenverg1, S. Badal-Faesen2, J. Andrade-Villanueva3, J. Gathe4, H. Mingrone5, A. Hermes6, I. Gaultier6, L. Fredrick6, W. Woodward6, A. Lawal6, T. Podsadecki6, B. Bernstein6, on behalf of the M06-802 Study Team
1Projeto Praça Onze, UFRJ, Rio de Janeiro, Brazil, 2University of Witwatersrand, Clinical HIV Research Unit, Houghton, Johannesburg, South Africa, 3Hospital Civil de Guadalajara, Guadalajara, Mexico, 4Therapeutic Concepts, Houston, TX, United States, 5Muñiz Hospital, HIV Outpatient Care Unit, Buenos Aires City, Argentina, 6Abbott Laboratories, Abbott Park, IL, United States
Background: In 2 prior studies of antiretroviral-naïve subjects, LPV/r dosed QD was non-inferior to BID when co-administered with NRTIs. Study M06-802 is the first large randomized trial comparing QD and BID dosing of LPV/r in HIV-1-infected antiretroviral-experienced subjects.
Methods: 599 subjects with plasma HIV-1 RNA >1000 copies/mL on current regimen received open-label LPV/r tablet 800/200 mg QD or 400/100 mg BID (randomized 1:1), with >2 NRTIs chosen by investigators based on screening genotype and treatment history. The primary efficacy endpoint was the proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48, based on the FDA time to loss of virologic response (ITT-TLOVR) algorithm, with a non-inferiority margin of -12%.
Results: Demographics were similar across treatment groups, including race (51% white, 35% black), ethnicity (34% Hispanic) and gender (34% female). Mean baseline HIV-1 RNA was 4.3 log10 copies/mL, mean baseline CD4 count was 254 cells/mm3, and a mean of 1.2 PI mutations (range 0-7) were present at baseline. 78% (QD) and 77% (BID) completed the study, with 4% (QD) and 7% (BID) discontinuing due to adverse events (p=NS). The QD regimen was non-inferior to the BID regimen: 55% (QD) and 52% (BID) had HIV-1 RNA < 50 copies/mL at Week 48 (ITT-TLVOR; 95% CI for the difference: -4.5 to 11.5%). By on-treatment analysis, 76% (QD) and 72% (BID) had HIV-1 RNA < 50 copies/mL at Week 48 (p=NS). The mean CD4 increases through 48 weeks were similar (+133 QD, +119 BID, p=NS). Diarrhea (14% QD, 11% BID, p=NS) and nausea (3% QD, 7% BID, p=0.009) were the most common moderate/severe LPV/r-related adverse events.
Conclusions: LPV/r QD was non-inferior to BID when co-administered with NRTIs in antiretroviral-experienced subjects. Immunologic response and overall tolerability were similar with QD and BID.
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