14th International HIV Drug Resistance Workshop


7-11 June 2005, Québec City, Canada

CLINICAL VALIDATION OF ATAZANAVIR/RITONAVIR GENOTYPIC RESISTANCE SCORE IN PI-EXPERIENCED PATIENTS

Antivir Ther. 10, Suppl 1:S9 (abstract no. 7)

S Vora1, A-G Marcelin6, H Günthard2, P Flandre7, HH Hirsch3, P Vernazza4, H Furrer5, B Masquelier8, A Zinkernagel2, G Peytavin6, V Calvez6, B Hirschel1, L Perrin1, S Yerly1, and the Swiss HIV Cohort Study (SHCS)
1Geneva, University Hospital, Switzerland; 2Zurich, University Hospital, Switzerland; 3Basel, University Hospital, Switzerland; 4St-Gallen, University Hospital, Switzerland; 5Bern, University Hospital, Switzerland; 6Pitié-Salpêtrière Hospital, Paris, France; 7INSERM Unit 472, Paris, France; 8CHU Bordeaux, France

BACKGROUND: Virological response to ATV/RTV containing HAART in PI-experienced patients was used to develop a clinically relevant genotypic resistance score.

METHODS: We included 62 PI-experienced patients switched to ATV/RTV (300 mg ATV, 100 mg RTV, plus other ARVs) with HIV-1 RNA >1000 copies/ml at baseline and detectable ATV in plasma at month three (M3). The impact of baseline protease mutations on virological response (>1 log RNA decrease) at M3 was analysed using Fischer’s exact test. Mutations with prevalence >8% and P<20% were retained. Cochran- Armitage’s test was used to select the combination of mutations most strongly associated with the virological response (lowest P value). Robustness of the score was investigated using bootstrap re-sampling.

RESULTS: Median baseline viraemia and CD4 count were 4.3 log10 copies/ml and 226/mm3, respectively. Patients had been treated with a median of 7.5 ARV drugs including two PIs. At M3, 82% of patients had a virological response and 56% had RNA<50 copies/ml. The PI mutations associated with a reduced response were 10F/I/V, 16E, 33I/F/V, 46I/L, 54L/V/M/T, 60E, 62V, 71I/T/V/L, 82A/T, 84V, 85V, 90M and 93L. The strongest association with the virological response was found with the combination of 10F/I/V, 16E, 33I/F/V, 46I/L, 60E, 84V and 85V (P=8.0×10-9). Using this ATV resistance score, virological response was observed in 100%, 100%, 80%, 42%, and 0% of patients with 0, 1, 2, 3, ≥4 mutations, respectively. The number of active drugs was also associated with virological response (P=0.001). In patients with ATV resistance score ≥3, virological response was observed in 0%, 29% and 60% of patients with 0, 1 and 2–3 active drugs (P=0.024). Addition of the 90M to the previous score provides also a strong association with the virological response (P=8.7×10-9). The bootstrap analysis showed the robustness of both scores.

CONCLUSION: Most PI-experienced patients switched to ATV/RTV containing HAART had a virological response. The ATV/RTV resistance score predicts reduced response in patients with at least three mutations of a set of seven to eight mutations.

PRESENTING AUTHOR: A-G Marcelin

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2005-06-07
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