[31] IMPACT OF BASELINE PROTEASE DRUG MUTATIONS ON VIROLOGICAL RESPONSE TO FOSAMPRENAVIR/RITONAVIR-BASED REGIMENS IN ANTIRETROVIRAL-EXPERIENCED PATIENTS (ZEPHIR STUDY)

14th International HIV Drug Resistance Workshop

7-11 June 2005, Québec City, Canada

IMPACT OF BASELINE PROTEASE DRUG MUTATIONS ON VIROLOGICAL RESPONSE TO FOSAMPRENAVIR/RITONAVIR-BASED REGIMENS IN ANTIRETROVIRAL-EXPERIENCED PATIENTS (ZEPHIR STUDY)

Antivir Ther. 10, Suppl 1:S33 (abstract no. 31)

I Pellegrin¹,G Coureau², D Neau³, D Lacoste³, E Lazaro³, HJA Fleury¹, MH Schrive¹, F Dabis², JL Pellegrin³, D Breilh⁴ and the GECSA
¹Department of Virology, Bordeaux University Hospital, Bordeaux, France ²INSERM U593, Bordeaux University Hospital, Bordeaux, France ³Department of Internal Medicine and Infectious Diseases, Bordeaux University Hospital, Bordeaux, France ⁴Department of Pharmacy, Bordeaux University Hospital, Bordeaux, France

OBJECTIVE: To assess the impact of HIV-1 mutations on virological responses to fosamprenavir/ritonavir (FosAPV/r)-based regimens in experienced HIV patients.

METHODS: Antiretroviral-experienced subjects with virological failure (HIV-RNA>1.7 log₁₀ copies/ml) were included in an observational cohort study and received a FosAPV/r (700 mg/100 mg twice daily)-based regimen. Sequencing of HIV-reverse-transcriptase and protease was performed at baseline. Virological success (VS) at month 3 was defined by HIV-RNA<1.7 log₁₀ copies/ml. FosAPV/r resistance-related mutations (FosAPV/r-score) were defined according to the French ANRS genotype-interpretation guidelines, that is FosAPV/r resistance if number of mutations was >6 among L10F/I/V, K20M/R, E35D, R41K, I54V, L63P, V82A/F/T/S, I84V or V32I+I47V or I50V.

RESULTS: FosAPV/r-containing regimen was initiated in 90 patients (M/F=68/22, median [25th–75th] age=45 [40–50] years). The median prior antiretroviral exposure was 9 [7–10] years with a median of 10 [5–16] previous lines of treatment. Eightyseven percent of patients were protease-inhibitor (PI)-experienced. At baseline, median CD4+ and HIV-1-RNA were 284 [150–387]/µl and 3.4 [3.5–4.9] log₁₀ copies/ml, respectively. Median number of PI-resistance mutations and FosAPV/r-score mutations were 8 [3–10] and 4 [2–5] (no I50V at baseline) respectively, and 5 [3–6] NRTI-related mutations. At M3, 24% of patients were considered VS. Median HIV-1-RNA decrease was -0.5 [-2.2;+0.2] log₁₀ copies/ml, CD4+ increase was +24 [-6;+84]/µl. When FosAPV/r-score was <4 vs ≥4 mutations, HIV-1-RNA decrease was -1.7 [-3.1;-0.6] vs -0.07 [-0.4;+0.3] log₁₀ copies/ml (P=0.001) and VS occurred in 47% vs 7% (P=0.004) of patients, respectively.

Failure was associated with the number of prior lines of treatment (P=0.02), baseline number of PI-resistance mutations (P=0.01), FosAPV/r-score (P=0.006) and NRTI-related mutations (P=0.05). Presence of following protease mutations at baseline were associated with failure: L10I (P=0.001), L33F (P=0.05), 54L/T/V (P=0.009), L63P (P=0.05), A71I/T/V/L (P=0.02), V82A/F/S/T (P=0.05) and L90M (P=0.008). Virological failure occured in the three patients with V32I+I47V baseline PI mutations. The response was significantly reduced in patients with >4 mutations among the seven defined in our study: HIV-1-RNA decrease was -1.8 [-3.0;-0.6] vs +0.07 [-0.4;+0.3] log₁₀ copies/ml (P=5.10-4) if <4 vs ≥4 mutations.

CONCLUSION: In highly experienced patients, FosAPV/r-score was predictive of virological response (<4 vs ≥4 mutations) at month 3. We found that L90M PI-mutation was associated with failure.

PRESENTING AUTHOR: I Pellegrin

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2005-06-07
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