756   Antiretroviral Drug Susceptibility and Response to Initial Therapy Among Recently HIV-Infected Subjects in North America.

S. J. Little*¹, J. P. Routy², E. S. Daar³, M. Markowitz⁴, A. C. Collier⁵, R. A. Koup⁶, B. Conway⁷, M. S. Saag⁸, E. Connick⁹, S. Holte¹⁰, L. Corey⁵, P. H. Keiser⁶, A. Mwatha¹⁰, K. Dawson¹¹, J. M. Whitcomb¹¹, N. S. Hellmann¹¹, and D. D. Richman^1,2.
¹Univ. of California San Diego, La Jolla;²McGill Univ. Health. Ctr., Montreal, Quebec, Canada;³Cedars-Sinai Med. Ctr., Los Angeles, CA;⁴Aaron Diamond AIDS Res. Ctr., New York, NY;⁵Univ. of Washington, Seattle;⁶Univ. of Texas, Dallas;⁷Viridae Clin. Sci. Inc., Vancouver, British Columbia, Canada;⁸Univ. of Alabama at Birmingham;⁹Univ. of Colorado Health Sci. Ctr., Denver;¹⁰Fred Hutchinson Cancer Res. Ctr., Seattle;¹¹ViroLogic, Inc., South San Francisco, CA; and¹²VA Med. Ctr., San Diego, CA.

Background:The objective of the study is to retrospectively evaluate antiretroviral (ARV) susceptibility to reverse transcriptase (RT) and protease inhibitors (PIs) and response to potent therapy for 408 treatment-naïve subjects with recent HIV infection from 8 North American cities (Birmingham, Dallas, Denver, Los Angeles, San Diego, Seattle, Montreal and Vancouver).

Methods:The ViroLogic PhenoSense HIV assay was used to assess ARV drug susceptibility, and ABI sequence analysis was used to evaluate the HIV pol region.

Results:The percentage of subjects with >10-fold reduced susceptibility to the non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI) has increased significantly during 1999-2000 (N = 108) compared to previous reports (1 vs. 7%, p = 0.001 and 2 vs. 6%, p = 0.05). No significant change in the frequency of reduced susceptibility to the nucleoside reverse transcriptase inhibitors (NRTI) was observed (p = 0.29). Overall, 8% of subjects identified after 1998 showed >10-fold reduced susceptibility to at least one ARV and 4% showed >10-fold reduced susceptibility to ARV in 2 or more different classes (i.e., multidrug resistant). Among all patients initiating potent NNRTI- or PI-based therapy (N = 182), the time to complete virological suppression (RNA <400) was significantly increased in patients with either >5- and >10-fold reduced susceptibility to one or more ARV at baseline (p = 0.005 and p = 0.04).

Conclusions:The prevalence of transmitted virus reduced susceptibility (both >5 and >10 fold) to both NNRTI and PI drugs has increased significantly compared to previous reports. These results support the use of resistance testing in the initial selection and management of ARV therapy in all newly infected patients.