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

368-M. Transmission and Transmissibility of Drug Resistant HIV-1 R. M. Grant*1,2, J. Kahn2, M. Warmerdam1, L. Liu2, C. J. Petropoulos3, N. S. Hellmann3, and F. Hecht2. 1Gladstone Inst. of Virology and Immunology, San Francisco, CA; 2Univ. of California, San Francisco; and 3ViroLogic, Inc., South San Francisco, CA Background: Primary drug resistance prevalence depends on the prevalence of exposure and transmissibility. Methods: 2 consecutive series of recently infected or drug-experienced subjects were referred from the same network of clinics in San Francisco. Recent infection was defined as an evolving serological test (WB, EIA, detuned EIA) or seroconversion in the past 12 months. Resistance was assayed genotypically (VGI) and phenotypically (ViroLogic). Transmissibility was defined as the prevalence of primary resistance divided by the prevalence of exposure, indexed using observed secondary resistance and treatment rates prevailing in the same region and time period. Results: 248 recently infected subjects were enrolled between July 1996 and July 2001, of which 225 (91%) had an evaluable genotype. There were no significant changes over time in gender, age, risk group, viral load, or CD4 count at diagnosis, or duration of infection. During the study period, genotypic primary resistance increased from 16.7 - 27.6% for any drug class, from 0 - 17% for NNRTI's (p=0.003), and from 0 - 10.3% for PI's (p=0.19). Primary genotypic resistance to NRTI's initially decreased from 25% to 6% in 1998-1999, then increased to 20% by 2000-2001 (p=0.03). Primary resistance to 2 drug classes increased from 1.5% to 13.5% (p=0.01). There was only 1 case of 3-class MDR primary resistance, detected in 2000. The prevalence of greater than 10-fold phenotypic resistance to NNRTI's increased from 0 to 8.8% (p=0.02). Subjects recently infected with drug resistant HIV-1 had higher CD4 counts after controlling for duration of infection (p=0.03). Secondary genotypic resistance among 263 drug-experienced patients referred from July 2000 to June 2001 was 60% for NRTI's, 39% for NNRTI's, 38% for PI's, and 15% for 3-drug class MDR HIV-1. There were differences in transmissibility of HIV-1 resistant to different classes of drugs (transmissibility: NNRTI > NRTI > PI >> 3-class MDR). Conclusions: Primary drug resistance is highly prevalent and rising in San Francisco, especially for NNRTI-resistant HIV-1. Transmissibility of drug resistant HIV-1 likely reflects replication capacity, partial viral load responses during resistant viremia, and/or tropism for genital tissues.

©2002 9th Conference on Retroviruses and Opportunistic Infections