1st EACS RESISTANCE & PHARMACOLOGY WORKSHOP
October 25 - 29, 2003 Warsaw, Poland
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9TH EUROPEAN AIDS CONFERENCE (EACS) 1st EACS RESISTANCE & PHARMACOLOGY WORKSHOP October 25 - 29, 2003 Warsaw, Poland |
| 7.3 Phase III/IV Trials F6/9 - CLINICALLY RELEVANT INTERPRETATION OF GENOTYPE FOR RESISTANCE TO DIDANOSINE (VIDEX EC(R)) IN TREATMENT EXPERIENCED HIV INFECTED PATIENTS |
| (1) Pitié Hosp., Paris, France,2 St-Louis Hosp, Paris, France,3 BMS, Rueil, France |
Background: The antiviral efficacy of didanosine (ddI) and the impact of reverse transcriptase (RT) mutations in antiretroviral (ARV)-experienced patients (pts) have not been fully investigated.
Objective: To identify a clinically relevant genotypic score for resistance to ddI
Methods: Randomized, placebo controlled double-blinded study. Pts under stable ARV therapy and plasma HIV RNA > 1000 cps/ml were randomized (2:1) to add ddI or placebo (P) to their regimen for 4 weeks. Primary efficacy : mean change in plasma HIV RNA from baseline to week 4. Mutations in RT gene (IAS list) and the virological response to ddI were studied in the ddI group (non-parametric univariate analyses). Mutations with a p-value below 0.20 were retained for further analysis.
Results: 168 pts received either ddI (n= 110) or P (n=58). At baseline, median HIV RNA level (log10) : 3.8, median CD4 count : 378 cells/mm3, median nb of TAMs and NAMs : 3 and 4. The following mutations were selected : M41L, D67N, T69D, L74V, V118I, L210W, T215Y/F and K219E/Q. In ddI arm, at W4, median HIV RNA decrease from baseline in presence of L74V (n=9) was -0.1. Median HIV RNA decrease for the selected mutations (L74V excluded) is described in the table below:
| ddI | ddI | Placebo | Placebo | |
| Number of mutations | N | Median | N | Median |
| 0 | 29 | -0.97 | 12 | 0.09 |
| 1 | 13 | -0.82 | 3 | 0.23 |
| 2 | 13 | -0.63 | 13 | 0.05 |
| 3 | 13 | -0.60 | 10 | 0.08 |
| 4 | 12 | -0.30 | 5 | -0.41 |
| 5 | 10 | -0.23 | 3 | -0.04 |
| 6 | 1 | -0.02 | 3 | -0.05 |
| All | 92 | -0.61 | 49 | 0.06 |
In ddI arm, median decrease in presence of M184V (n=93) and K70R mutation (n=27) were respectively -0.6 and -0.9.
Conclusion: Genotype is strongly linked to viral response in NRTI-experienced patients receiving ddI. This study will help to develop a clinically relevant interpretation of genotype for ddI.
Presenting Author: Doctor Marcelin Anne-Genevieve, Service de Virologie - Hôpital Pitié Salpêtrière, 47-83 boulevard de l'hôpital, 75013, Paris, France, Phone: 33-1-42.17.75.14
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