[25] ANTIRETROVIRAL RESISTANCE AND RESPONSE TO INITIAL THERAPY AMONG RECENTLY HIV-INFECTED SUBJECTS IN NORTH AMERICA

5th International Workshop on HIV Drug Resistance & Treatment Strategies

4-8 June 2001, Scottsdale, Arizona

[TITLE:] ANTIRETROVIRAL RESISTANCE AND RESPONSE TO INITIAL THERAPY AMONG RECENTLY HIV-INFECTED SUBJECTS IN NORTH AMERICA

[AUTHOR(S):] SJ Little¹, S Holte², JP Routy³, ES Daar⁴, M Markowitz⁵, AC Collier⁶, RA Koup⁷, B Conway⁸, E Connick⁹, MS Saag¹⁰, A Mwatha², L Corey⁶, PH Keiser⁷, M Kilby¹⁰, K Dawson¹¹, JM Whitcomb¹¹, NS Hellmann¹¹ and DD Richman^1,12
¹ University of California, San Diego, Calif., USA; ² Fred Hutchinson Cancer Research Center, Seattle, Wash., USA; ³ McGill University Health Center, Montreal, Canada; ⁴ Cedar-Sinai Medical Center, Los Angeles, Calif., USA; ⁵ Aaron Diamond AIDS Research Center, New York, N.Y., USA; ⁶ University of Washington, Seattle, Wash., USA; ⁷ University of Texas, Dallas, Tex., USA; ⁸ Viridae Clinical Sciences, Vancouver, Canada; ⁹ University of Colorado, Denver, Col., USA; ¹⁰ University of Alabama, Birmingham, Ala., USA; ¹¹ ViroLogic, San Francisco, Calif., USA; and 12 VA Medical Center, San Diego, Calif., USA
Antivir Ther. 2001;6 Suppl 1:21

OBJECTIVE: To evaluate retrospectively antiretroviral (ARV) susceptibility to reverse transcriptase (RT) and protease inhibitors (PIs) and response to potent therapy for 389 treatment-naïve subjects with recent HIV infection from nine North American cities (Birmingham, Dallas, Denver, Los Angeles, New York, San Diego, Seattle, Montreal and Vancouver).

METHODS: The ViroLogic PhenoSense HIV assay was used to assess ARV drug susceptibility (n=389) and ABI sequence analysis (n=350) was used to evaluate the HIV genotype. These data have been updated since first presented at the 8th Conference on Retroviruses and Opportunistic Infections (February 2001).

RESULTS: The percentage of subjects with >10-fold reduced susceptibility to one or more ARV drugs has increased significantly during 1999–2000 compared to previous reports (4.6 versus 16.5%, P=0.002). Nucleoside RT inhibitors (NRTI) increased from 2.5 to 7%, non-nucleoside RT inhibitors (NNRTI) from 2 to 7%, and PIs from 0.4 to 8%. Multi-drug resistance (>10-fold reduced susceptibility to drugs in two or more classes) increased during this period from 1 to 6% (P=0.01). By comparison, the proportion of patient samples identified with one or more major drug resistance mutation were quite similar and increased from 5.3% (1995–1998) to 18.5% (1999–2000) (P=0.0001). Comparison of the average prevalence of high-level phenotypic resistance (>10- fold reduced susceptibility) and genotypic resistance (presence of one or more primary drug resistance mutations) throughout the study period (1995–2000), was 3.6 versus 7.8% for NRTIs, 3.1 versus 2.7% for NNRTIs and 2.3 versus 2.9% for the PIs, respectively. Among patients who initiated potent NNRTI- or PIbased therapy (n=199), the time to complete virological suppression (HIV-1 RNA <400 copies/ml) was increased in patients with >10-fold reduced susceptibility to one or more ARV at baseline (P=0.09). Correlation of additional treatment responses and baseline genotype and phenotype are in progress.

CONCLUSIONS: The prevalence of transmitted drug resistant virus has increased significantly for all three classes of drugs as assessed by both phenotype and genotype compared to earlier reports. These results support the use of resistance testing in the initial selection and management of ARV therapy in all newly infected patients.

PRESENTING AUTHOR: SJ Little

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