Once-daily 1400/100 mg Dose of Fosamprenavir/ritonavir (Lexiva) Is Virologically Effective and Causes Fewer Body Fat Changes than 1400/200 mg Dose

As with most other HIV protease inhibitors (PIs), ritonavir boosts plasma concentrations of the PI fosamprenavir (Lexiva). Fosamprenavir/ritonavir 1400/200 mg is the FDA-approved once-daily dose of this combination.

To decrease the risk of metabolic abnormalities associated with the standard dose, researchers evaluated the safety and efficacy of fosamprenavir/ritonavir 1400/100 mg -- half the usual ritonavir dose -- in treatment-naive HIV patients. Prior 24-week study results have suggested that once-daily fosamprenavir/ritonavir 1400/100 mg is virologically effective.

At the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Sydney, Australia (July 22-25, 2007), investigators presented 48-week results from the COL100758 study, an open-label trial in which 155 antiretroviral-naive patients were randomly assigned to receive either 1400/100 mg or 1400/200 mg once-daily fosamprenavir/ritonavir, along with abacavir/3TC 600/300 mg.

The study assessed antiviral efficacy and changes in regional fat mass and bone mineral density (BMD). Total body DEXA was obtained pre-treatment and at week 48. Median percent changes in fat were reported for upper limbs, lower limbs, and trunk. Clinically relevant (potentially detrimental) changes in fat mass were defined as >20% loss of limb fat and/or >20% gain of trunk fat.

Median percent change in total body BMD and lumbar spine (L-spine) BMD were reported, but L-spine BMD data were only available from centers with Hologic scanners.

Results

• 87 patients had paired baseline and week 48 DEXA scans (70 men, 50 non-white, median age 42 years).

• Median fat percent changes in the fosamprenavir/ritonavir 400/100 mg arm (n = 44) vs the fosamprenavir/ritonavir 400/200 mg arm (n = 43) were as follows:

- +7.0% vs +6.6% g, respectively, for upper limbs (P = 0.73);
- +3.1% vs +9.4% for lower limbs (P = 0.47);
- +6.3% vs +6.3% for trunk (P = 0.94).

• Clinically relevant fat changes were observed as follows:

- upper limbs: 11% vs 16% of patients, respectively.
- lower limbs: 9% vs 14%;
- trunk: 18% vs 30%.

• Median total body BMD (g/cm2) percent changes were -0.60% vs -0.94%, respectively (P = 0.11).

• L-spine BMD changes were -2.53% vs -0.80%, respectively, for the 35 patients with available data (P = 0.61).

• No patient had simultaneous limb fat loss >20% and trunk fat gain >20%.

Conclusion

The study authors concluded that after 48 weeks of treatment with once-daily fosamprenavir/ritonavir 1400/100 mg + abacavir/3TC, limb and trunk fat depots increased and BMD changes were small in both study arms. In addition, they noted, "Clinically relevant changes in regional fat occurred less frequently in patients assigned to fosamprenavir/ritonavir [1400/]100 mg."

University of North Carolina at Chapel Hill, Chapel Hill, United States, GlaxoSmithKline, Research Triangle Park, United States, Orlando Immunology Ctr, Orlando, United States, North Texas Infectious Disease Consultants, Dallas, United States, Comprehensive Care Center, Ft. Lauderdale, United States, Duke University, Infectious Diseases, Durham, United States.

08/14/07

Reference
D Wohl, T Lancaster, E DeJesus, and others. Determination of body composition changes by total body dual-energy x-ray absorptiometry after 48 weeks of treatment with once-daily fosamprenavir (FPV) boosted with two different doses of ritonavir(r) plus abacavir (ABC)/lamivudine (3TC): COL100758. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention. July 22-25, 2007. Sydney, Australia. Abstract (poster) TUPEB080.