Boosted protease inhibitors are an effective component of combination antiretroviral therapy, but are associated with adverse effects including a negative impact on serum lipids and higher rates of myocardial infarction (Friis-Møller, 2007). Two studies presented on Monday examined the substitution of once daily raltegravir for boosted protease inhibitors.
The ODIS trial was presented by Eugenia Vispo from Madrid. HIV-infected persons receiving protease inhibitor-based regimens, with HIV-1 RNA <50 copies/ml for at least 24 weeks were randomly assigned to raltegravir 800mg daily, 400mg twice daily, or twice-daily dosing for 3 months followed by once-daily dosing. Of the 222 patients completing 24 weeks of raltegravir 6% of patients experienced virologic failure at 24 weeks; 12 (6.4%) in the QD and 1 (2.9%) in the BID arm (p=0.18). A predictor of failure included prior NRTI resistance, OR 28.45 (95% CI: 3.62-223.56). Persons receiving raltegravir once-daily were more likely to experience virologic failure, however this was not statistically significant (OR 2.33, p= 0.42). A benefit in lipid levels was noted with a reduction in total and LDL cholesterol of 10 mg/dl and 6 mg/dl respectively at 24 weeks after simplification to raltegravir.
The SPIRAL study presented by Jose Gatell of Barcelona, also examined the effect of switching patients on protease-based regimens to raltegravir. 286 patients receiving protease inhibitors for at least 6 months with HIV-1 RNA <50 copies/ml were randomized to raltegravir 400mg BID vs. continuing with the protease regimen. The patients were matched on the presence of lipid lowering agents. Switching to raltegravir was found to be non-inferior with 97% of the raltegravir group and 95% of the protease group free of virologic failure through week 48. A benefit in lipid levels was also noted in the raltegravir group with mean reductions from baseline seen of 22%, 11% and 6% for triglycerides, total cholesterol and LDL cholesterol. Switching to raltegravir appeared safe with no significant change in rates of adverse effects.
The two studies demonstrated non-inferior efficacy after switching from boosted-protease inhibitors to raltegravir, as well as showing a reduction in lipid levels. Switching to raltegravir may be an option for patients without prior NRTI resistance, however once-daily dosing appeared to perform less well when compared to twice-daily dosing.
References:
Friis-Møller, et al. N Engl J Med. 2007;326:1723-1735
Vispo E, Barreiro P, Maida I, Mena A, Blanco F.
Simplification from protease inhibitors to once or twice daily raltegravir: the ODIS trial. Abstract Presented July 18 at the XVIII International AIDS Conference, Vienna, Austria. Oral Abstract MOAB0102.
Martinez E, Larrousse, Llibre JM, Guttierraz F et al. Simplification of antiretroviral therapy by switching from ritonavir-boosted protease inhibitors to raltegravir in virologically suppressed HIV-1-infected patients (SPIRAL): a randomised open-label trial. Abstract Presented July 18 at the XVIII International AIDS Conference, Vienna, Austria. Oral Abstract MOAB0103.
07/19/10
PRN Report from AIDS 2010: Switch from Boosted-PI to Raltegravir is Non-inferior in Two Studies
Source: Reporting from Vienna, Austria for PRN News: Anita Radix MD, MPH and Susan Weiss FNP, AAHIVS