NRTI-Sparing Atazanavir/Efavirenz Regimens Suppress HIV but Raise Lipids

Concerns about long-term side effects associated with nucleoside reverse transcriptase inhibitors (NRTIs), such as lipoatrophy and mitochondrial toxicity, have prompted researchers to explore NRTI-sparing regimens.

Regimens that combine non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) can cause elevated blood fats, but the newer PI atazanavir (Reyataz) is associated with less lipid elevation than other drugs in its class.

As reported at the 46th ICAAC held last week in San Francisco, researchers conducted a multicenter, open-label study (BMS 121) in which 61 treatment-naive participants were randomly assigned to receive one of 2 doses of atazanavir/ritonavir (300/100 mg and 400/100 mg) plus 600 mg efavirenz (Sustiva), with no NRTIs.

Most participants were men (85%), with a mean age of 37 years; 49% were white and 43% were black. The median CD4 cell count was 305 cells/mm3, the median HIV viral load was 4.97 log10copies/mL, and all had normal fasting triglycerides (below 200 mg/dL).

Results

At Week 48, the mean viral load decrease was 3.24 log copies/mL.
In an intent-to-treat analysis, 75% of patients in the 300/100 mg atazanavir arm and 67% in the 400/100 mg arm achieved viral loads below 400 copies/mL, and 63% and 61%, respectively, below 50 copies/mL.
In an as-treated analysis, 92% and 96%, respectively, attained viral loads below 400 copies/mL, and 77% and 87% below 50 copies/mL.
Mean CD4 counts increased by 271 cells/mm3 and 250 cells/mm3, respectively.
The rates of Grade 2-4 treatment-related adverse events were 26% and 30%, respectively (all Grade 2).
The most common side effects were insomnia, rash, diarrhea, and dizziness.
12 patients discontinued the study prematurely (2 due to adverse events).
13% in the 300/100 mg arm and 40% in the 400/100 mg arm had Grade 3-4 bilirubin elevations.
7% and 10% in the 300/100 mg arm experience Grade 3-4 ALT and AST elevations, as did 7% and 3% in the 400/100 mg arm.
Fasting triglyceride levels increased by 48% in the lower-dose arm and by 63% in the higher-dose arm.
Total cholesterol rose by 29% and 32%, respectively in the 2 arms.
Fasting LDL ("bad") cholesterol increased by 11% and 13%, respectively.
HDL ("good") cholesterol rose by 54% and 45%, respectively.

Conclusion

The researchers concluded that, "Both atazanavir/ritonavir/efavirenz regimens were generally safe, well tolerated and demonstrated potent antiretroviral efficacy through 48 weeks."

They added that, "Increases in triglycerides, total cholesterol and LDL-cholesterol were observed in both arms and were accompanied by robust increases in HDL-cholesterol and decreases in TC:HDL and LDL:HDL ratios." They noted that lipid increases were greater than those seen in most previous studies using the same drugs.

Because deleterious triglycerides and LDL cholesterol rose along with protective HDL cholesterol, the researchers said that, "The long-term implications for cardiovascular health can not be assessed from this study."

Dupont Circle Physicians Group, Washington, DC; South Florida Clin. Res., Atlantis, FL; Bristol-Myers Squibb, Wallingford, CT; Central West Clin. Res., St. Louis, MO; Jemsek Clinic, Huntersville, NC; Health for Life Clinic, Little Rock, AR.

10/03/06

Reference
D Ward, L Bush, A Thiry, and others. Atazanavir/Ritonavir (ATV/r) and Efavirenz (EFV) NRTI-Sparing Regimens in Treatment-Naive Adults: BMS -121 Study. 46th ICAAC. San Francisco, CA. September 27-30, 2006. Abstract H-1057.

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