Atazanavir: effect on lipids arouses interest

Atazanavir is an experimental protease inhibitor in development from Bristol-Myers Squibb. Formerly known as BMS-232632, atazanavir is a once daily drug, taken as one or two pills, without regard to food. Data thus far suggest that this drug may have a less pronounced effect on levels of cholesterol and triglycerides in the blood, a significant problem associated with other HIV drugs in this class.

Forty-eight week follow-up from a pivotal study comparing two doses of an atazanavir-based HAART regimen to one containing nelfinavir, in people new to treatment, were announced at a recent European HIV conference in Athens. This randomised study found no difference in viral load response between arms. At week 48, 65% in both atazanavir arms had viral load below 400 copies, compared with 58% of the nelfinavir group. The proportions with viral load below 50 copies were substantially smaller, at 31% in the atazanavir 400mg group, compared with 36% in the 600mg group and 38% in the nelfinavir group. CD4 cell increases were comparable at week 48, at around 210-240 cells above baseline.

Dose reduction in the 600mg group was necessary in 19 patients due to grade 4 bilirubin elevations (although only four cases of clinical jaundice were reported in this arm). The risk of bilirubin elevations in individuals receiving atazanavir is related to genetic susceptibility, and not all patients are at risk of this side effect, but the incidence of grade 3 or 4 hyperbilirubinemia was high in both atazanavir groups (32% in the 400mg group and 52% in the 600mg group).

No significant triglyceride or cholesterol elevations were seen in the atazanavir groups. At week 48, the mean percentage increase in total cholesterol for the atazanavir 400mg arm was 5%, a non-significant change from baseline, compared to 25% in the nelfinavir arm. Similar differences were seen when LDL cholesterol and triglycerides were analysed (5% versus 23%, and 7% versus 50% respectively).

Now two new trials are recruiting protease inhibitor experienced individuals in the UK, and abroad. The first compares atazanavir with two NRTIs, to lopinavir/ritonavir plus two NRTIs in people who have experienced virological failure on one protease inhibitor-containing regimen. The second is a randomised, open-label trial for people who have experienced failure of at least two anti-HIV treatment regimens which have contained drugs from all three classes, but have been unable to maintain an undetectable viral load. This study will test the safety and efficacy of atazanavir when taken in combination with other anti-HIV drugs, including tenofovir. Details of these trials, including participating UK centres are available here on aidsmap.com. A third trial, for people whose first-line NNRTI-containing regimen has failed, is due to open in December.