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  International AIDS Conference
July 13-16, 2003, Paris
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Reyataz+ritonavir vs Kaletra in treatment-experienced
Reported by Jules Levin
  At the Intl AIDS Conference R Badaro and colleagues reported results after 24-weeks of study comparing a once daily regimen of atazanavir (ATV) boosted by a small dose of ritonavir (RTV) to Kaletra in patients with multiple virologic failures.
The primary objective of this study is to compare the magnitude of plasma HIV-RNA reduction from baseline for once daily ATV 300 mg plus RTV 100 mg, once daily ATV 400 mg plus saquinavir 1200 mg, and Kaletra (lopinavir 400mg+RTV 100mg) in treatment experienced patients with PI resistance. The study examines viral response rates, CD4 count response, metabolic changes, and safety and tolerability.
At week 24, ATV 300 mg boosted with 100 mg RTV showed similar efficacy to Kaletra in terms of viral load response, a favorable lipid profile, and elevated bilirubin. Fewer patients were treated with lipid lowering agents in the ATV/RTV group. Bilirubin elevations were not associated with ALT elevations.
The study includes 358 patients who failed two or more HAART regimens, and at least 1 drug from each class of HIV drugs (PI, NRTI, NNRTI). Patients were randomized 1:1:1 for 48 weeks of study. Patients also received tenofovir plus 1 NRTI.
PATIENT DEMOGRAPHICS. Average age 40; 22% female; 60% White; 23% Hispanic/Lation; 15% Black. 28% of patients had AIDS. Median HIV-RNA was 4.44 log, and CD4 count was about 300 cells. These characteristics were comparable across all 3 study groups.
Prior ARV use was comparable acroos the 3 treatment groups: PI, 2.4 to 2.6 years; NRTI, 4.8 to 5.2 years; NNRTI, 1.3 to 1.6 years.
BASELINE SUCEPTIBILITY. 73-77% of patients across the 3 study groups were susceptible to ATV. 76-78% of patients were susceptible to Kaletra. 33-37% of patients across all 3 treatment groups had 4 PI mutations or more. 39% of patients in the ATV/RTV group had 4 or more NRTI mutations; 45% in the ATV/SQV arm had 4 or more NRTI mutations; and 43% in the Kaletra group had 4 or more NRTI mutations.
Prior to week 24, 7 patients (6%) in the ATV/RTV arm, 14 patients (12%) in the ATV/SQV arm, and 6 patients (5%) in the Kaletra group discontinued. Adverse event: 3% in ATV/RTV; 4% in ATV/SQV; 2% in Kaletra. One patient in each of the ATV/RTV and ATV/SQV discontinued for treatment failure/lack of efficacy and 0 patients did so in Kaletra arm.
Mean viral load reduction was about the same in the ATV/RTV (-1.86 log) and Kaletra (-1.89 log) arms, but the viral load reduction was less in the ATV/SQV (-1.52 log).
VIROLOGIC RESPONSE THROUGH WEEK 24 (ITT: time to loss of virologic failure) Responses were similar in the ATV/RTV and Kaletra arms but were lower in the ATV/SQV group.
--<50 copies/ml: 42% in Kaletra arm and 39% in the ATV/RTV arm; 23% for ATV/SQV
--<400 copies/ml: 62% for Kaletra and 64% for ATV/RTV; 44% for ATV/SQV
Cd4 count increases were 90 cells in Kaletra arm, 83 in ATV/RTV arm, and 59 in ATV/SQV arm.
Triglycerides increased 31% in the Kaletra patients, remained the same in patients receiving ATV/RTV, and decreased 14% in patients getting ATV/SQV. Total cholesterol decreased 9% in the ATV/SQV group, 8% in the ATV/RTV group, and increased 3% in the Kaletra group. These differences were significant. HDL-C (good cholesterol) remained the same in the Kaletra group and decreased 7% and 1% in the ATV/RTV and ATV/SQV arms, respectively. LDL-C (bad cholesterol) decreased 10% and 11% in the ATV/RTV and ATV/SQV arms, respectively, and decreased 4% in the Kaletra group. Patients on lipid lowering therapy were excluded from this analysis.
Prior to the study 6% of patients in the ATV/RTV, 7% in the ATV/SQV, and 5% of patients in Kaletra arms received lipid lowering drugs. On study 7% of patients receiving ATV/RTV used lipid lowering drug vs 15% in the Kaletra group (p<0.005). 12% patients in ATV/SQV group used lipid lowering drug.
Diarrhea: 3% in ATV/RTV; 5% in ATV/SQV; 11% in Kaletra
Jaundice: 6% in ATV/RTV; 2% ATV /SQV; 0% Kaletra (no one withdrew from study due to jaundice)
Nausea: 2%, 7%, 2%, respectively
Vomiting: 0%, 4%, <1%, respectfully
Scleral Icterus (yellow eyes): 3%, 0%, 0%, respectfully
Total bilirubin: 45% in ATV/RTV; 19% ATV/SQV; <1% Kaletra
ALT: 3%, 4%, 3%, respectfully
AST: 3%, 2%, <1%