Atazanavir plus ritonavir or saquinavir, and lopinavir/ritonavir in patients experiencing multiple virological failures.
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.
Johnson
Margaret
M
Royal Free Hospital, London, UK. margaret.johnson@royalfree.nhs.uk
Grinsztejn
Beatriz
B
Rodriguez
Claudia
C
Coco
Jeffrey
J
DeJesus
Edwin
E
Lazzarin
Adriano
A
Lichtenstein
Kenneth
K
Rightmire
Anna
A
Sankoh
Serap
S
Wilber
Richard
R
D000225:Adenine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D018791:CD4 Lymphocyte Count; D002784:Cholesterol / Q000097:blood; D004334:Drug Administration Schedule; D024921:Drug Resistance, Multiple, Viral; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000097:blood; D061466:Lopinavir; D009842:Oligopeptides / Q000008:administration & dosage*; D063065:Organophosphonates / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage*; D011744:Pyrimidinones / Q000008:administration & dosage; D012367:RNA, Viral / Q000032:analysis; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage; D019438:Ritonavir / Q000008:administration & dosage*; D019258:Saquinavir / Q000008:administration & dosage*; D000068698:Tenofovir; D019562:Viral Load
D019380:Anti-HIV Agents; D008055:Lipids; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D011744:Pyrimidinones; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D002784:Cholesterol; D000068698:Tenofovir; D000225:Adenine; D019258:Saquinavir; D019438:Ritonavir