ABSTRACT
This 96-week, open-label, randomized study assessed changes in body composition in treatment-naive patients infected with human immunodeficiency virus type 1 who were treated with either atazanavir or ritonavir-boosted atazanavir, in combination with stavudine and lamivudine. Both treatment groups had similar increases in trunk fat, but patients treated with ritonavir-boosted atazanavir had a significantly lower incidence of lipoatrophy.
Subject(s)
Anti-HIV Agents/adverse effects , Antiretroviral Therapy, Highly Active/adverse effects , Body Composition/drug effects , HIV Infections/drug therapy , Lamivudine/adverse effects , Oligopeptides/adverse effects , Pyridines/adverse effects , Stavudine/adverse effects , Adult , Anti-HIV Agents/therapeutic use , Atazanavir Sulfate , Female , HIV Infections/virology , HIV-1/isolation & purification , Humans , Lamivudine/therapeutic use , Male , Oligopeptides/therapeutic use , Pyridines/therapeutic use , Ritonavir/therapeutic use , Stavudine/therapeutic useABSTRACT
BACKGROUND: In BMS Study 045, once-daily (QD) atazanavir/ritonavir (ATV/RTV) demonstrated comparable efficacy and safety to twice-daily (BID) lopinavir/ritonavir (LPV/RTV) over 48 weeks in treatment-experienced patients. Results of extended follow-up to 96 weeks are presented. METHODS: BMS Study 045 was an open-label, randomized, multi-national trial of HIV-infected patients with virologic failure on two or more prior HAART regimens designed to evaluate the efficacy and safety of ATV/RTV (300/100 mg) QD and LPV/RTV (400/100 mg) BID, each with tenofovir (300 mg) QD and one nucleoside reverse transcriptase inhibitor. The primary efficacy measure was the time-averaged difference (TAD) in reduction in HIV RNA from baseline. Secondary objectives included evaluation of safety and plasma lipid levels through week 96. RESULTS: Over 96 weeks, the ATV/RTV regimen demonstrated similar virologic efficacy to the LPV/RTV regimen. Mean reductions from baseline in HIV RNA were -2.29 and -2.08 log10 copies/ml, respectively [TAD (97.5% confidence interval): 0.14 log10 copies/ml (-0.13, 0.41)]. The LPV/RTV regimen resulted in significant increases in total cholesterol (+9%) and fasting triglycerides (+30%) in comparison with the ATV/RTV regimen, which demonstrated decreases in these parameters [-7 and -2%, respectively, (P < 0.0001)]. Grade 2-4 diarrhoea occurred less frequently in ATV/RTV patients (3%) in comparison with LPV/RTV patients (13%) (P < 0.01). Grade 3-4 elevations in bilirubin were more common in ATV/RTV patients (53%) than LPV/RTV patients (< 1%) (P < 0.0001), with no resulting discontinuations. CONCLUSIONS: Regimens containing once-daily ATV/RTV demonstrated comparable efficacy and safety, with significant reductions in total cholesterol and fasting triglycerides and improved gastrointestinal-tolerability in comparison with twice-daily regimens containing LPV/RTV over 96 weeks in treatment-experienced patients.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV-1 , Adenine/analogs & derivatives , Adenine/therapeutic use , Adult , Antiretroviral Therapy, Highly Active , Atazanavir Sulfate , Didanosine/therapeutic use , Drug Administration Schedule , Drug Therapy, Combination , Female , HIV Infections/virology , HIV-1/genetics , Humans , Lipids/blood , Lopinavir , Male , Oligopeptides/therapeutic use , Organophosphonates/therapeutic use , Pyridines/therapeutic use , Pyrimidinones/therapeutic use , RNA, Viral/blood , Ritonavir/therapeutic use , Saquinavir/therapeutic use , Tenofovir , Time Factors , Treatment OutcomeABSTRACT
OBJECTIVE: To evaluate atazanavir/ritonavir (ATV/RTV) (300/100 mg) once daily, atazanavir/saquinavir (ATV/SQV) (400/1200 mg) once daily, and lopinavir/ritonavir (LPV/RTV) (400/100 mg) twice daily, each with tenofovir (300 mg) once daily and a nucleoside reverse transcriptase inhibitor in treatment-experienced HIV-infected patients. METHODS: Randomized, open-label, 48-week multicenter trial of 358 randomized adult patients who had failed two or more prior HAART regimens with baseline HIV RNA > or = 1000 copies/ml and CD4 cell count > or = 50 x 10(6) cells/l. RESULTS: The primary efficacy endpoint [plasma HIV RNA reduction assessed by time-averaged difference (TAD)] was similar for ATV/RTV and LPV/RTV [TAD 0.13; 97.5% confidence interval, -0.12 to 0.39] at 48 weeks. Mean reductions from baseline for ATV/RTV and LPV/RTV were comparable at 1.93 and 1.87 log10 copies/ml, respectively. Mean CD4 cell count increases were 110 and 121 x 10(6) cells/l for ATV/RTV, and LPV/RTV, respectively. The efficacy of ATV/SQV was lower than LPV/RTV by both these parameters. Declines in total cholesterol and fasting triglycerides were greater with ATV/RTV and ATV/SQV than with LPV/RTV (P < or = 0.005). Lipids in the LPV/RTV arm at week 48 generally increased from baseline. Lipid-lowering agents were used more frequently in the LPV/RTV arm than in the ATV arms (P < 0.05 versus ATV/RTV), as were antidiarrheal agents (P < or = 0.04 versus both ATV treatments). No new or unique safety findings emerged. CONCLUSIONS: ATV boosted with RTV is as effective and well tolerated as LPV/RTV in treatment-experienced patients, with a more favorable impact on serum lipids. Pharmacokinetically enhanced ATV provides a suitable choice for therapy of treatment-experienced HIV-infected patients.