Lipid Changes with Reyataz Are Significantly Less Than with Viracept Among Treatment-naïve HIV Patients

HAART has proved effective in suppressing HIV replication and improving clinical outcome . Low potency, variable pharmacokinetic characteristics, heavy pill burden, complex dosing requirements and metabolic toxicities, however, often limit the effectiveness of currently available protease inhibitor (PI)-based regimens, contributing to poor tolerability, suboptimal adherence and treatment failure .

Currently available PIs cause potentially serious metabolic complications, significantly elevating lipids and triglycerides, which   possibly contribute to lipodystrophy and increasing cardiovascular disease risk. The Adult AIDS Clinical Trials Group recommends that PI-related dyslipidemia be treated according to general population guidelines.

However, lipid-lowering agents may introduce drug-related complications, as current PIs alter the metabolism of many of these agents, and their use potentially introduces additional complexity to already complicated HAART regimens. T here is a need for effective PIs with simplified dosing without elevations in lipid concentrations.

The objective of the current study was to compare the efficiency and safety of Reyataz (atazanavir) and Viracept (nelfinavir) in treatment-naive patients.

Study participants were randomization to atazanavir 400 mg or 600 mg once daily or to nelfinavir 1250 mg twice a day, plus lamivudine and stavudine.

This was a blinded (to the atazanavir dose), 48-week trial in patients with HIV-1 RNA >/= 2000 copies/ml, CD4 cell count >/= 100 x 106cells/l. Primary end-point: change in HIV-1 RNA from baseline at 48 weeks. Secondary end-point: subjects with HIV-1 RNA < 400, and < 50 copies/ml, CD4 cell count changes, adverse events.

Study Results

The 467 randomized subjects had comparable baseline characteristics across treatments. With atazanavir 400 mg, 600 mg and nelfinavir, respectively, mean changes in HIV-1 RNA (log10 copies/ml) from baseline to 48 weeks were -2.51, -2.58, -2.31; HIV-1 RNA < 400 copies/ml [intent-to-treat population (ITT), non-completion = failure (NC = F)], 64%, 67%, 53%; HIV-1 RNA < 50 copies/ml (ITT NC = F), 35%, 36%, 34%; mean CD4 cell count increased comparably at 48 weeks (234 x 106, 243 x 106, 211 x 106cells/l).

Adverse events were similar across treatments with the exception of diarrhea (more frequent with nelfinavir) and jaundice (more frequent with atazanavir). Mean changes from baseline to 48 weeks were: fasting low density lipoprotein cholesterol, +5.2%, +7.1% and +23.2% (at 56 weeks) and fasting triglycerides (48 weeks), +7.2%, +7.6% and +49.5%, in the atazanavir 400 mg, 600 mg, and nelfinavir groups, respectively (P < 0.01, atazanavir versus nelfinavir).

The authors conclude, “Atazanavir is a potent, safe, well tolerated, and effective once-daily protease inhibitor with low pill burden (two capsules/day). Lipid changes with atazanavir were significantly less than with nelfinavir, however, clinical significance of these finding in terms of decreased cardiovascular risk is unknown.”

01/05/04

Reference

RL Murphy and others. Dose-ranging, randomized, clinical trial of atazanavir with lamivudine and stavudine in antiretroviral-naive subjects: 48-week results. AIDS 17(18): 2603-2614. December 5, 2003.

Suggested Further Reading

Squires K and others AI424-007: 48-week safety and efficacy results from a phase II study of a once-daily HIV-1 protease inhibitor (PI), BMS-232632. 8th Conference on Retroviruses and Opportunistic Infections. Chicago, February 2001 [abstract 15].

Piliero PJ, Cahn P, Pantaleo G, Gatell J, Squires K, Percival L, et al. Atazanavir: a once-daily protease inhibitor with a superior lipid profile-results of clinical trials beyond week 48. 9th Conference on Retroviruses and Opportunistic Infections. Seattle, February 2002 [abstract 706-T].