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 ≥ 1000 copies/ml and CD4 cell count ≥ 50 × 106 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 × 106 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 ≤ 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 ≤ 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.
From the aRoyal Free Hospital, London, UK
bInstituto de Pesquisa Clínica Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil
cHospital Argerich, Buenos Aires, Argentina
dPendleton Memorial Methodist Hospital, New Orleans, Louisiana, USA
eIDC Research Initiative, Altamonte Springs, Florida, USA
fS. Raffaele Hospital, Milan, Italy
gUniversity of Colorado Health Sciences, Denver, Colorado, USA
hBristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut, USA
iBristol-Myers Squibb Pharmaceutical Research Institute, Hopewell, New Jersey, USA.
Received 4 August, 2004
Revised 8 October, 2004
Accepted 14 October, 2004
Correspondence to Dr M. Johnson, Royal Free Hospital, Pons St, London NW32QG, UK. E-mail: email@example.com.