588-T. Genotype, Phenotype, and Virtual Phenotype at Baseline and at Failure in Naďve Patients Included in a Randomized Trial (Rescombine Study)

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Session 77 Poster Session
Resistance Testing in Drug Selection
Session Time: 4:30-6:30 pm
Room 4E-F

588-T.

Genotype, Phenotype, and Virtual Phenotype at Baseline and at Failure in Naďve Patients Included in a Randomized Trial (Rescombine Study)
E. Ferrer*¹, D. Podzamczer¹, M. Arnedo², E. Fumero¹, J. L. Perez¹, M. J. Barbera¹, T. Pumarola², and J. M. Gatell²
¹Hosp. Bellvitge and ²Hosp. Clin.. Barcelona, Spain

Background: The objective was to determine genotypic and phenotypic resistance patterns at baseline and at failure in naďve patients receiving combivir plus nefinavir (NFV) or nevirapine (NVP).
Methods: Of 142 patients included in the combined study, 91 were enrolled in Spain and have stored baseline plasma samples. Samples of 18/19 patients (10 NFV, 8 NVP) developing a virological failure were also available, and 16 could be amplified. Genotype, Phenotype, and Virtual Phenotype were determined by Virco NV (Mechelen, Belgium) according to published protocols.
Results: In only 1 case (1%), 2 thymidine analog-associated mutations were detected at baseline (215Y and 41L). Of 16 failing patients (8 NFV, 8 NVP), in 9 patients (5 NFV, 4 NVP, 6 with poor adherence, and 3 who stopped therapy due to toxicity) no mutations were found, while genotypic and phenotypic resistance was observed in 7 patients (3 NFV, 4 NVP, 2 with apparent good compliance and 5 with irregular adherence). Of 3 NFV patients, the 3TC 184V mutation was detected in all of them, associated to 30N and 36I in 1 case. Of 4 NVP patients, only a NNRTI-mutation was detected in 3 cases (181C in 2 and 103N in one), while 103N and 184V mutations appeared in one case. No thymidine analog-associated mutations were detected in failing patients, except for 41L in 1 case. For mutant strains fold changes in IC50 ranged between >31 and >68 for NVP, >14 and > 25 for 3TC and > 21 for NFV. Phenotypic and virtual phenotypic patterns were in accordance to genotypic patterns in all cases.
Conclusions: Primary resistance is very uncommonly detected in our patients with chronic HIV infection. In more than half of failing patients, virologic failure was related to poor adherence and not to resistance. The presence of only NNRTI-related mutations was the predominant pattern in NVP failing patients, while the presence of 184V 3TC-related mutation was the predominant pattern in NFV failing patients. An absolute concordance between genotypic, phenotypic, and virtual phenotypic tests was found in this study.

Š2002 9^th Conference on Retroviruses and Opportunistic Infections