96-week comparison of once-daily atazanavir/ritonavir and twice-daily lopinavir/ritonavir in patients with multiple virologic failures.
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.
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
Wirtz
Victoria
V
Rightmire
Anna
A
Odeshoo
Linda
L
McLaren
Colin
C
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D000069446:Atazanavir Sulfate; D016049:Didanosine / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000097:blood; D061466:Lopinavir; D008297:Male; D009842:Oligopeptides / Q000627:therapeutic use; D063065:Organophosphonates / Q000627:therapeutic use; D011725:Pyridines / Q000627:therapeutic use; D011744:Pyrimidinones / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000627:therapeutic use; D019258:Saquinavir / Q000627:therapeutic use; D000068698:Tenofovir; D013997:Time Factors; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D008055:Lipids; D009842:Oligopeptides; D063065:Organophosphonates; D011725:Pyridines; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D000069446:Atazanavir Sulfate; D000068698:Tenofovir; D000225:Adenine; D016049:Didanosine; D019258:Saquinavir; D019438:Ritonavir