7th Conference on Retroviruses and Opportunistic Infections
 


Transmission of Dual and Triple-Class Drug-Resistant Viral Variants in Primary/Early HIV-1 Infection (PHI) in Montreal

J.-P. ROUTY*1, B. BRENNER1, H. SALOMON1, Y. QUAN1, A.-F. CAMPOS1, D. ROULEAU2, E. LEFEBVRE4, P. COTÉ4, R. LEBLANC4, C. TSOUKAS1, B. CONWAY3, R. SEKALY2, M.-A. WAINBERG1, and Investigators of the Quebec Primary Infection Study. 1McGill Univ., Montreal, Canada; 2Univ. of Montreal, Canada; 3Univ. of British Columbia, Vancouver; and 4Private Clin., Montreal, Canada

Objective: To analyze the prevalence of dual and triple class resistance to protease (PR), non-(NNRT) and nucleoside (NRT) reverse transcriptase (RT) inhibitors in patients with primary/early HIV-1 infection in Montreal, Canada.
Methods: Plasma and PBMCs from 87 patients from the Montreal PHI cohort from 1997 to 1999 were analyzed for their phenotypic and genotypic RT and PR drug resistant characteristics using tissue culture and TruGene TM HIV-1 assay systems (Visible Genetics Inc.).  Line probe assays (LIPA) were used to detect quasispecies variations in wild type and mutated RT codons.
Results: Prevalence of RT mutations were 8% (T215Y), 5% (M184V), 4% (T69D/A), 4% (K103N),  and for  PI were 10.5% (L10I), 4% (L90M) and 3% (V82A). The genotypic and phenotypic analyses were concordant in 85% of the cases. Primary dual and triple class resistance was found in 12 patients (14%), with 5% carrying NNRT and PR, 7% NRT and PR, and 2% NNRT, NRT and PR resistance.  In 3 well-documented cases, the genotypic profile of source persons showed transmission of delavirdine resistance (n=1) and efavirenz in 2 patients. Two of them carried viral strains with 16 and 18 different mutations, conferring multi-drug resistance to all commercially available drugs, except ddI and d4T. The unpredictable outcome of these  two patients will be presented.
Conclusion: The prevalence of dual and triple-class drug resistance is respectively 12% and 2%, which raises the concern of resistance testing in all primary/recent HIV-1 infected individuals.

Key Words: Drug resistance, Genotyping, Primary infection

 

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