Fosamprenavir (Lexiva) Works Well with 100 mg Ritonavir (Norvir) at 96 Weeks in Treatment-naive Patients

By Liz Highleyman

The use of ritonavir (Norvir) to boost blood levels of other protease inhibitors has improved the effectiveness and convenience of combination antiretroviral therapy, but ritonavir can cause metabolic side effects and adds to the number of pills a patient must take.

According to a study reported in the April 2009 issue of AIDS Research and Human Retroviruses (available in advance online), once-daily fosamprenavir (Lexiva) boosted with 100 mg ritonavir worked at least as well as a 200 mg boosting dose at 96 weeks in HIV patients starting treatment for the first time. (Results were previously presented at the 48th International Conference on Antimicrobial Agents and Chemotherapy [ICAAC] in October 2008, abstract H-1246).

As per the current prescribing information, the approved dose for treatment-naive adults is 1400 mg fosamprenavir plus either 100 mg or 200 mg ritonavir once-daily, or else 700 mg fosamprenavir plus 100 mg ritonavir twice-daily. Only the twice-daily dose is recommended for treatment-experienced patients.

In this open-label multicenter trial, investigators with the COL 100758 Study Team compared the efficacy and safety of once-daily fosamprenavir with 100 mg or 200 mg ritonavir.

A total of 115 treatment-naive participants with HIV viral load > 1000 copies/mL took 1400 mg once-daily fosamprenavir and were randomly assigned (1:1) to receive one of the 2 ritonavir boosting doses; everyone also received 600 mg/300 mg abacavir/lamivudine.

Most study participants (about 80%) were men, about half were African-American, and about 40% were white. At baseline, participants in both arms had similar viral loads (median 4.7-4.9 log10 copies/mL), but those in the 100 mg ritonavir arm had a somewhat higher CD4 count (259 vs 179 cells/mm3).

The primary endpoints were proportion of patients achieving a viral load < 400 copies/mL or discontinuing therapy for drug-related reasons at 48 weeks. Secondary endpoints were HIV RNA < 400 copies/mL at 24 and 96 weeks, and < 50 copies/mL at 24, 48, and 96 weeks.

Results

In an intent-to-treat missing = failure analysis at 96 weeks, significantly more patients in the 100 mg ritonavir arm had viral load < 400 copies/mL compared with the 200 mg ritonavir arm (78% vs 53%; P = 0.006).

For viral load < 50 copies/mL, the correspondence proportions were 66% vs 53%, respectively, which was not a statistically significant difference.

In an observed or as-treated analysis of 79 patients who completed 96 weeks, 98% in the 100 mg ritonavir arm and 94% in the 200 mg arm achieved HIV RNA < 400 copies/mL (not a significant difference).

For viral load < 50 copies/mL, the correspondence percentages were 83% and 94%, respectively (again, not significantly different).

The 100 mg and 200 mg ritonavir arms had a similar median change from baseline in CD4 count, 265 vs 260 cells/mm3.

Fewer patients receiving 100 mg ritonavir experienced virological failure (5 vs 8), and none developed major protease inhibitor resistance mutations.

Fewer participants in the 100 mg ritonavir arm discontinued treatment prematurely (12 vs 24 patients).

Overall, the types and frequencies of treatment-related moderate to severe (grade 2-4) adverse event were similar in the 2 treatment arms.

The most commonly reported grade 2-4 adverse events were diarrhea, headache, suspected abacavir hypersensitivity reaction, nausea, abdominal pain, fatigue, and rash.

Increases in total cholesterol levels (33 vs 35 mg/dL) and total cholesterol to HDL ratios (4.0 vs 4.1) were essentially the same in the 100 mg and 200 mg ritonavir arms.

The 100 mg ritonavir group, however, experienced a smaller increase in triglyceride levels (27 vs 48 mg/dL).

Based on these findings, the researchers concluded, "through 96 weeks, [fosamprenavir/100 mg ritonavir] was more effective and prompted less elevation in triglycerides than [fosamprenavir/200 mg ritonavir]."

"This data further supports the use of this simplified regimen in clinical practice for treatment-naive HIV patients," said Judith Ng-Cashin, MD, Vice President, Clinical Therapeutic Area, GlaxoSmithKline (manufacturer of fosamprenavir) in a press release issued by the company. "This regimen not only reduces the pill burden for patients therefore reducing costs, but may also enhance treatment adherence among patients."

Duke University, Durham, NC; Orlando Immunology Center, Orlando, FL; Texas ID Consultants, Dallas, TX; University of North Carolina at Chapel Hill, Chapel Hill, NC; GlaxoSmithKline, Research Triangle Park, NC.

4/03/09

Reference
CB Hicks, E Dejesus, LM Sloan, and others. Comparison of Once-Daily Fosamprenavir Boosted with Either 100 or 200 mg of Ritonavir, in Combination with Abacavir/Lamivudine: 96-Week Results from COL100758. AIDS Research and Human Retroviruses 25(4). April 2009 (Epub ahead of print). (Abstract).

Other Source
GlaxoSmithKline. Data Support Long-Term Safety and Efficacy of a Lower Dose of Ritonavir-Boosted LEXIVA in Treatment-Naive HIV Patients. Media announcement. March 30, 2009.