Abstract

E-mail Abstract Author Add To Itinerary Session Search Abstracts Program

Session 24 Oral Abstract Session Antiretroviral Chemotherapy: Pathogenesis of Primary HIV Infection Session Time: Wednesday, 10 am - 12:30 pm Room 6A-B

11:00   95. Persistence of Transmitted Drug Resistance among Subjects with Primary HIV Infection not Receiving Antiretroviral Therapy S. J. Little*1, E. S. Daar2, S. Holte3, S. D. W. Frost1, J. P. Routy4, M. Markowitz5, A. C. Collier6, J. Margolick7, R. Koup8, B. Conway9, E. Connick10, M. Kilby11, T. Wrin12, C. J. Petropoulos12, N. S. Hellmann12, and D. D. Richman13 1Univ. California, San Diego; 2Cedars-Sinai Med. Ctr., Los Angeles, CA; 3Fred Hutchinson Cancer Res. Ctr., Seattle, WA; 4McGill Univ. Hlth. Ctr., Montreal, Quebec, Canada; 5Aaron Diamond AIDS Res. Ctr., Rockefeller Univ., New York, NY; 6Univ. of Washington, Seattle; 7Johns Hopkins Univ. Sch. of Publ. Hlth., Baltimore, MD; 8NIAID, NIH Vaccine Res. Ctr., Bethesda, MD; 9Univ. of British Columbia, Vancouver, Canada; 10Univ. of Alabama, Birmingham; 11Univ. of Colorado, Denver; 12ViroLogic, Inc., South San Francisco, CA; and 13VA Med. Ctr., San Diego, CA Purpose: To evaluate the persistence and altered replication capacity (fitness) of transmitted antiretroviral (ARV) resistant variants among untreated subjects with primary HIV infection. Methods: ARV drug susceptibility and replication capacity were measured using a single replication cycle assay (ViroLogic). ABI sequence analysis of pol was used to identify drug resistant mutations. Clonal analysis is in progress to evaluate the rate of reversion to wild type in these patients. Results: Baseline antiretroviral susceptibility results have been previously reported for 412 subjects from North America with primary HIV infection (8th CROI). Pretreatment susceptibility testing was performed a mean of 79 days after the estimated date of infection. The prevalence of >10-fold reduced susceptibility to one or more ARV did not differ among patients relative to elapsed time from infection (0-147 days). Longitudinal samples were analyzed from 6 subjects, identified a mean of 60 days post infection, with >10-fold reduced susceptibility at baseline who deferred ARV therapy during follow-up. In the 6 patients, the presence of >10-fold reduced susceptibility to one or more NNRTI at baseline was associated with the detection of K103N with or without Y181C. The median baseline viral load was 5.6 log10 copies/mL (range 4.9-6.2). Reversion of the K103N mutation was observed in only 1 subject (>117 days after baseline), while persistence of the K103N mutation was observed in the other 5 subjects during a median follow-up of 140 days (and 77, 130, 200, 242, and 296 days post infection). Mixtures of wild type (WT) and drug-resistant (R) strains at positions K103 and Y181 in reverse transcriptase were detected in 2 of the 5 patients at days 119 and 182 with an associated increase in NNRTI drug susceptibility. The replication capacity was reduced in 5 of the 6 subjects (approximately 50% of WT replication capacity) and did not improve significantly after detection of the WT/R mixture in 2 subjects. Conclusions: Transmitted K103N and Y181C drug resistance mutations are associated with reduced drug susceptibility and replication capacity. Transmitted NNRTI drug resistance in newly infected patients does not rapidly become undetectable in untreated patients, in contrast to the rapid reversion to WT virus described in patients with treatment-associated secondary drug resistance.

©2002 9th Conference on Retroviruses and Opportunistic Infections