18th International HIV Drug Resistance Workshop Basic Principles & Clinical Implications June 9–13 2009, Fort Myers, Florida, USA

EFFICACY OF RALTEGRAVIR AND FACTORS ASSOCIATED WITH TREATMENT FAILURE IN A ROUTINE CLINICAL CARE SETTING: THE SWISS HIV COHORT STUDY

Antivir Ther 2009; 14 Suppl 1:A49 (abstract no. 45)

AU Scherrer¹, V von Wyl¹, CA Fux², M Opravil¹, HC Bucher³, A Fayet⁴, LA Decosterd⁴, B Hirschel⁵, HJ Furrer², D Mertz⁴, S Yerly⁵, T Klimkait³, B Ledergerber¹ and HF Günthard^1
1University Hospital Zürich and University of Zürich, Zürich, Switzerland; ²University Hospital Bern and University of Bern, Bern, Switzerland; ³University Hospital Basel and University of Basel, Basel, Switzerland; ⁴University Hospital Lausanne, Lausanne, Switzerland; ⁵Geneva University Hospital, Geneva, Switzerland

OBJECTIVES: Raltegravir (RAL) is the first substance of an entirely new drug class, the integrase inhibitors. Randomized clinical trials (BENCHMARK-1 and 2) showed remarkable viral suppression rates in patients on salvage therapy, but efficacy of RAL (400 mg twice daily) combined with an optimized background treatment (OBT) was not systematically studied in a routine clinical setting.

METHODS: We performed an intent-to-treat analysis for week 24 response (HIV RNA<50 copies/ml) using last observation carried forward imputation. Included were all patients receiving RAL within the SHCS. The following factors, potentially associated with treatment failure, were analysed: genotypic sensitivity score (GSS) of the OBT, RAL plasma concentration, HIV RNA at baseline, CD4 nadir and self-reported adherence. The GSS was calculated with Stanford algorithm. Drug levels were considered too low when falling below the 90% confidence interval (CI).

RESULTS: The study included 108 patients of whom 106 were still on RGV at week 24. At baseline, 71 (65.7%) had detectable (salvage patients) and 37 (34.3%) had undetectable (switch patients) viral loads (HIV RNA<50 copies/ ml). The predominant reason to switch was a regimen containing T20 (OR: 25.2 [95% CI: 9.0–70.3]). Median baseline log HIV RNA was 3.9 (IQR: 3.0–4.7) in salvage patients. Median baseline CD4 cell counts were 195 cells/µl and 342 cells/µl in salvage and switch patients, respectively. The overall response rate was 87.0% (95% CI: 79.2–92.7). The stratified response rates were 81.7% (95% CI: 70.7–89.9) and 97.3% (95% CI: 85.8–99.9), respectively. CD4 cell counts increased significantly by 75 cells/µl (t-test: P<0.001) and 49 cells/µl (t-test: P=0.006). Potential reasons for failure (n=14: 13 salvage and 1 switch) were a GSS<1 of the OBT (n=2), low RAL plasma concentrations (n=3), poor adherence (n=2), no follow-up HIV RNA (n=5) or unknown (n=2). Two patients had a genotypic resistance test performed while failing on RAL: one patient had the Q148R mutation and the other had no known RAL resistance-associated mutation.

CONCLUSIONS: Multiple factors were associated with RAL failures, such as low GSS of the OBT, low drug levels and poor adherence. Efficacy data from this routine clinical setting were comparable to previous published randomized controlled trials. Response rate in switch patients was very high. However, contrary to the SWITCHMRK-trials, 62% of our patients were kept on a boosted PI.

2009-06-09
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