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Session 56 Poster Session Acute Infection: Resistance, Fitness, and Transmission Session Time: 4:30-6:30 pm Room 4E-F

377-M. Replicative Fitness of MDR Viruses in Primary HIV-1 Infection M. Petrella*, B. Brenner, J. P. Routy, D. Moisi, M. Oliveira, M. Detorio, B. Spira, B. Conway, R. Lalonde, R. P. Sekaly, and M. A. Wainberg McGill AIDS Ctr., Lady Davis Inst., Montreal, QC, Canada Background: Persistence of dual and triple class multidrug (MDR) resistant viruses acquired during primary HIV infection (PHI) may affect virological and treatment outcomes. This study compares the genotypic evolution and fitness of MDR and wild-type viruses present in PHI. Methods: Longitudinal sequence analysis was performed on plasma or PBMC samples obtained from PHI patients with WT, single-class, or MDR infections. Changes in genotype and viremia were assessed in relation to relative viral fitness. Results: MDR infections persisted over the entire study period ranging from 1 to 5 years in the absence of antiretroviral (ARV) therapy similar to that observed in PHI with WT virus. This was unlike MDR infections in source partners where the typical pattern of WT outgrowth was observed within 12 weeks of treatment interruption. Viral isolates were obtained and expanded from PHI patients with WT or MDR infections. As expected, MDR viruses were replicatively unfit with severely compromised reverse transcriptase (RT) activity and were consistently out-competed by WT virus in dual infection experiments. Nevertheless, despite their replicative disadvantage, MDR viruses maintained levels of infectivity (TCID50), comparable to WT virus. Reintroduction of selective antiretroviral (ARV) drug pressure allows for minor MDR variants to re-emerge, overtaking WT virus. In some cases, MDR viruses were associated with low viremia. Conclusions: These results indicate that MDR viruses expressed following PHI can establish persistent infections despite their impaired replicative competence. In this context, genotypic analysis at the time of initial patient presentation will be an important consideration for optimization of ARV therapy.

©2002 9th Conference on Retroviruses and Opportunistic Infections