HIV and Hepatitis.com Coverage of the
4th IAS Conference on HIV Pathogenesis, Treatment and Prevenion (IAS 2007)
 July 22-25, 2007, Sydney, Australia

Once-daily Ritonavir-boosted Fosamprenavir (Lexiva) or Atazanavir (Reyataz), Both with Tenofovir/emtricitabine in Treatment-naive Patients: 48-week Results of the ALERT Trial 

In a poster exhibited at the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Sydney, Australia (July 22-25, 2007), Dr. Keith Pappa of GlaxoSmithKline presented 48-week data from the ALERT trial, an open-label, randomized study evaluating the safety and efficacy of once-daily fosamprenavir (Lexiva)/ritonavir 1400 mg/100mg versus once-daily boosted atazanavir (Reyataz) 300 mg/100mg, both in combination with tenofovir/emtricitabine 300 mg/200mg.

Study participants were antiretroviral-naïve with HIV RNA levels greater than 1,000 copies/mL. Substitutions were permitted for tenofovir/emtricitabine-related adverse events requiring discontinuation. The once-daily dose of fosamprenavir 1400 mg boosted with ritonavir 100 mg has not been previously studied.

Results

  • 106 patients were enrolled (53 per arm).

  • Results are reported as fosamprenavir/ritonavir vs atazanavir/ritonavir, respectively; all lipids were fasting.

  • Median baseline characteristics were plasma HIV RNA viral load 4.9 log10 copies/mL in both arms, triglycerides 120 vs 123 mg/dL, total cholesterol 160 vs 153 mg/dL, HDL cholesterol 35 vs 38 mg/dL, LDL cholesterol 95 vs 97 mg/dL, and total cholesterol/HDL ratio 4.4 in both arms,

  • Mean CD4 counts were 176 vs 205 cells/mm3.

  • 36% vs 40% had a glomerular filtration rate (GFR) by MDRD in the normal range (>/= 90 ml/min).

  • 12 total patients discontinued the study early, 8 vs 4 in the 2 arms.

  • At week 48, using an ITT missing or discontinuation=failure analysis, 75% (40/53) vs 83% (44/53) had viral load <50 copies/mL (P=0.34) and 79% (42/53) vs 87% (46/53) had viral load < 400copies/mL (P=0.30);

  • Using an ITT observed analysis, 89% (40/45) vs 92% (44/48) had viral load< 50 copies/mL (P=0.66) and 93% (42/45) vs 96% (46/48) had viral load < 400copies/mL (P=0.60).

  • Median lipid levels at week 48 were:

    • triglycerides 167 vs 133 mg/dL;
    • total cholesterol 179 vs 181 mg/dL;
    • HDL cholesterol 43 vs 48 mg/dL;
    • LDL cholesterol 99 vs 102 mg/dL.
    • total cholesterol/HDL ratio: 4.3 vs 3.5;

  • Mean CD4 change from baseline was +170 vs +183 cells/mm3.

  • 3 patients with baseline GFR 50-80 mL/min discontinued tenofovir/emtricitabine when GFR declined to <50 mL/min (confirmed).

  • Treatment-related grade 2-4 (moderate to severe) adverse events occurred in 15% vs 57%, with differences driven by atazanavir-related hyperbilirubinemia.

Conclusion

Based on these results, the authors concluded, “Both regimens demonstrated comparable virologic suppression through 48 weeks. Lipid changes were similar. [Patients taking] fosamprenavir/ritonavir had [a] lower percentage of treatment-related Grade 2-4 adverse experiences.”

Rush University Medical Center, Chicago, IL; Kaiser Permanente, Atlanta, GA; Orlando Immunology Center, Orlando, FL; University of Miami, Miami, FL; GlaxoSmithKline, Research Triangle Park, NC.

08/03/07

Reference
K Smith, W Weinberg, E DeJesus, and others. Once-daily ritonavir (100mg) boosting of fosamprenavir (FPV/r) or atazanavir (ATZ/r) with tenofovir  (TDF)/emtricitabine (FTC) in antiretroviral-naive HIV-infected patients: 48-week safety/efficacy results from COL103952 (ALERT). 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Sydney, Australia, July 22-25, 2007. Abstract (poster) WePeB023.