A switch from the protease inhibitor nelfinavir to the newer, unlicensed PI, atazanavir, results in significant reductions in lipid levels within 12 weeks, according to data presented today at the Sixth International Congress on Drug Therapy in HIV Infection, in Glasgow.
Atazanavir, which will not be known as Zrivada after all, has been associated with little or no lipid elevation in randomised studies so far. This study was designed to test whether atazanavir could also reduce lipid elevations associated with previous protease inhibitor treatment.
Rob Murphy of Northwestern University Hospital, Chicago, reported on AI424-044, a 346 person study of switching from nelfinavir to atazanavir. All individuals were receiving a nucleoside analogue backbone of d4T/3TC, and had already participated in AI424-008, a randomised comparison of atazanavir and nelfinavir in treatment-naïve patients.
Sixty three individuals in the nelfinavir arm of the 008 study switched to atazanavir (400mg once daily), out of 91 individuals originally randomised to nelfinavir. 283 atazanavir recipients were rolled over from the 008 study and continued their original assigned dose of the drug (400mg or 600mg once daily).
The median baseline viral load was 1.73 log copies/ml; 70% had viral load below 400 copies/ml. The median total cholesterol in patients who switched from nelfinavir was 204 mg/dL; after 12 weeks on ATV therapy total cholesterol had fallen significantly, to 165 mg/dL (a reduction of 16%) (p
Median fasting LDL cholesterol (`bad` cholesterol) was 137 mg/dL at baseline and 94 mg/dL after 12 weeks on ATV (a reduction of 21%) (p
32% of the nelfinavir group had total cholesterol above 240 mg/dL, the level at which intervention is recommended in US National Cholesterol Education Program Guidelines. After 12 weeks of atazanavir treatment, 10% had total cholesterol above 240mg/dL. 55% of patients had LDL cholesterol above 130 mg/dL, considered high by NCEP Guidelines, before switching from nelfinavir; this fell to 22% after 12 weeks of atazanavir treatment.
Lipid levels did not change significantly in the patients who continued to take atazanavir.
The authors noted that “lipid improvements of this degree may reduce cardiovascular risk and the need for dietary and pharmacologic interventions.” Indeed, the total cholesterol reductions seen in this study correspond quite closely to reductions seen in a randomised, placebo controlled study of pravastatin treatment in patients with HAART-associated hyperlipidemia, although the populations are not strictly comparable.
Three cases of jaundice associated with elevated bilirubin levels were seen following the switch to atazanavir, similar to the level seen in patients who continued with atazanavir during the same 12 week period. Bilirubin elevations not associated with jaundice remained less common in the switch group after 12 weeks on atazanavir (10% grade 3 / 4 elevations), when compared with those who had already received a minimum of 48 weeks atazanavir treatment in the previous study (23% in the 400mg group and 35% in the 600mg group).
Diarrhoea, reported by 52% of nelfinavir recipients in the previous study, was reported by only 2% of those who switched to atazanavir during their first 12 weeks on the new regimen.
Murphy R et al. A nelfinavir (NFV) to atazanavir (ATV) switch correlates with lipid improvements at 12 weeks: results from BMS AI424-044. Sixth International Congress on Drug Therapy in HIV Infection, Glasgow, abstract PL3.2, 2002.