PATTERNS OF GENOTYPIC HIV DRUG RESISTANCE IN ONTARIO

C Swantee¹, C Major¹, R Remis², M Fearon¹, K Wu¹, A Bayoumi², A Rachlis², R Kort¹, F McGee¹, R Galli³, PR Harrigan³, S Read², Ontario HIV Genotyping Working Group
¹Ontario Ministry of Health and Long-Term Care, ²University of Toronto, Toronto, Ontario ³BC Centre for Excellence in HIV/AIDS, Vancouver, British Columbia

Objective: To evaluate patterns of HIV drug resistance and patient outcomes after implementation of a Pilot HIV Genotyping Program.
Methods: In January 2000, HIV genotyping was made available to HIV infected patients with evidence of treatment failure. Eligibility included failure of current ART on 2 successive viral load (VL) tests (VL>1000 c/ml). Specimens were tested by the BC Centre for Excellence in HIV/AIDS. Current ART, CD4, and VL were available at baseline and follow-up. We examined individual mutations and a “virtual phenotypic” assessment of ART resistance and assessed treatment changes and virologic outcome at >6 months after testing. Univariate, co-variate and survival analyses (SAS) were used to determine factors associated with time to undetectable VL after genotyping.
Results: As of June 2001, specimens from 991 individuals had been genotyped. The most common mutations were: RT region: 184V (53%), 41L (40%), 215Y (36%), 67N (35%), 103N (25%); Protease region: 10I (49%), 90M (46%), 77I (41%), 71V (35%), 36I (33%). The rate of resistance (for patients on specific drugs) was: 3TC 85%, EFV 83%, NVP 87%, DLV 68%, NFV 60%, IDV 59%, RTV 60%. Overall, 14% of individuals had no evidence of resistance to any ART, 0.8% to PI only, 17% to NRTI, 6% to NNRTI, 11% to NRTI/NNRTI, 26% to NRTI/PI and 17% to NRTI/NNRTI/PI. At >6 months after genotyping, the majority of individuals (78%) had changed therapy, of these, 54% experienced >0.5 log decrease in VL. Of the 507 individuals who switched to ³3 drugs for which they had no resistance (nonR) evident by genotyping, 67% experienced a >0.5 log decrease in VL (p<10^-5). Factors independently associated with achieving undetectable VL include: switching to ³3 nonR drugs (p<0.001), <5 mutations (p<0.001), VL at genotyping (p<0.001).
Conclusions: Resistance mutations and ART resistance are common in patients failing treatment. Using genotyping results to guide treatment changes will improve virologic outcome and may provide clinical benefit.