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Session 76 Poster Session HIV Resistance and Fitness Session Time: 4:30-6:30 pm Room 4E-F

572-T. High Prevalence of Insertions in HIV p6 PTAP Region in Drug Naïve Individuals Starting Antiretroviral Therapy: Potential Clinical Implications W. Dong, Z. Brumme, K. Chan, R. Hogg, M. V. O'Shaughnessy, J. S. G. Montaner, and P. R. Harrigan* British Columbia Ctr. for Excellence in HIV/AIDS, Vancouver, Canada Background: Insertions in the p6(Gag) PTAP motif have been shown to confer some reduced susceptibility to antiretrovirals. These insertions were identified in plasma virus of ~21% of patients treated with nucleoside analogs, but were reported to occur only very rarely in drug-naïve individuals. We wished to assess the prevalence and potential clinical implications of these PTAP insertions for initial antiviral therapy. Methods: This retrospective study involved 510 antiretroviral naïve individuals initiating therapy between June 1996 and August 1998. The presence of insertions was determined by RT-PCR amplification and DNA sequencing of plasma HIV. Time to virological failure (rebound of plasma viral load to 400 copies HIV-1 RNA/mL or greater) and to immunological failure (2 successive CD4+ cell counts below baseline) were assessed by Kaplan-Meier analysis on an intent to treat basis. Results: To date, data are available from 473 individuals. Insertions in the PTAP region were observed in 77 (16%) of these drug naïve patients. The most commonly observed insert was PTA (or APP, depending on the alignment chosen), though other insertions were also common. There was a trend toward both earlier immunological and virological failure in the overall population with PTAP insertions, but this was not statistically significant (p=0.15 or 0.24, respectively). This trend strengthened or became statistically significant when the analysis was restricted to those individuals filling 100% of their expected antiretroviral prescriptions within the first year (p=0.11 or 0.001, for virological or immunological failure, respectively, n=238 or 205). Conclusions: Insertions in the HIV gag PTAP region appear to be much more common (16% prevalence) in drug naive individuals than previously reported; these may therefore appear as natural polymorphisms. The trends for individuals harboring HIV with PTAP insertions to earlier treatment failure suggest that these insertions may be clinically relevant.

©2002 9th Conference on Retroviruses and Opportunistic Infections