Atazanavir/ritonavir shows comparable efficacy to Kaletra at 96 weeks for PI-experienced patients

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The protease inhibitor atazanavir (Reyataz) boosted by low dose ritonavir achieves comparable rates of viral load suppression after 96 weeks to Kaletra (lopinavir/ritonavir) in patients who have experienced failure of at least one PI-containing regimen, according to results from the BMS 045 study presented today at the Seventh International Congress on Drug Therapy in HIV Infection in Glasgow.

The BMS 045 study randomised 358 patients to receive either atazanavir/ritonavir 300/100mg once daily or lopinavir/ritonavir (400/100mg) twice daily, plus tenofovir and one other nucleoside analogue selected by genotypic resistance testing. A third arm in the study, which assigned patients to receive atazanavir/saquinavir, was discontinued after the 24 week interim analysis showed outcomes to be inferior, and patients were offered the option to switch. Twenty four week results were presented at the Second International AIDS Society conference in Paris in 2003 (Click here for full report).

Ninety-sex week follow-up is available on 120 patients randomised to atazanavir and 123 patients randomised to lopinavir. Intent to treat analysis shows that 33% of the lopinavir group and 30% of the atazanavir group had viral load below 50 copies/ml by week 96, a non-significant difference.

Glossary

lipid

Fat or fat-like substances found in the blood and body tissues. Lipids serve as building blocks for cells and as a source of energy for the body. Cholesterol and triglycerides are types of lipids.

cholesterol

A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or ‘bad’ cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or ‘good’ cholesterol (which helps get rid of LDL).

intent to treat analysis

All participants in a clinical trial are included in the final analysis, in the groups they were originally assigned to, whether or not they actually completed their course of treatment. This method provides a better estimate of the real-world effect of a treatment than an ‘on treatment’ analysis.

triglycerides

A blood fat (lipid). High levels are associated with atherosclerosis and are a risk factor for heart disease.

 

resistance testing

Laboratory testing to determine if an individual’s HIV strain is resistant to anti-HIV drugs. 

By week 96 ten atazanavir-treated patients and nine lopinavir-treated patients had discontinued treatment due to adverse events. The nature of the adverse events causing treatment discontinuation was not stated.

Gastrointestinal adverse events of grade 2 severity or greater were significantly more frequent in lopinavir-treated patients (19 vs 9, p

Grade 3 or 4 elevations of unconjugated bilirubin were common among atazanavir-treated patients (53 cases), but infrequently resulted in severe clinical symptoms. Although jaundice was significantly more common in the atazanavir group (7 vs 0, p

A closer look at lipid changes

Although the study conclusions suggest that atazanavir had a more favourable effect on lipids than lopinavir, close examination of the data suggests that there is little clinically meaningful difference.

Lipid changes at week 96 were expressed as mean percentage changes from baseline rather than mean mg/dL changes from baseline; although the differences in mean percentage change were statistically significant for total cholesterol and triglycerides, the degree of increase or reduction may not be clinically meaningful in terms of cardiovascular risk, especially given that patients using lipid-lowering agents were censored from the analysis.

For example, whilst atazanavir-treated patients had a 7% reduction in total cholesterol from 188mg/dl at baseline (to a mean of 175mg/dl), lopinavir-treated patients had a 9% increase from 181mg/dL (to a mean of 197mg/dL), mean values remained within the average range. A similar pattern held true for triglycerides, whilst differences in LDL and HDL cholesterol were negligible and mean values remained within the normal range.

Among patients using lipid-lowering agents at baseline there was a modestly significant trend in favour of atazanavir. Six patients in the atazanavir group and five patients in the lopinavir group were receiving lipid-lowering treatment at baseline. By week 96 this number had risen to nine in the atazanavir group and 20 in the lopinavir group (p=0.05).

References

Johnson M et al. Long-term efficacy and durability of atazanavir (ATV) with ritonavir (RTV) or saquinavir (SQV) versus lopinavir/ritonavir (LPV/RTV) in HIV-infected patients with multiple virologic failures: 96-week results from a randomized, open label trial, BMS AI424045. Seventh International Congress on Drug Therapy in HIV Infection, Glasgow, abstract PL14.4, 2004.