560-T. Influence of Genotypic Resistance on the Viral Load Response of 167 Patients on Lopinavir/r (LPV/r) including an Analysis of New Protease Inhibitor Resistant Mutations in 21 Patients who Failed

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Session 75 Poster Session
Resistance to Antiretroviral Chemotherapeutic Agents
Session Time: 4:30-6:30 pm
Room 4E-F

560-T.

Influence of Genotypic Resistance on the Viral Load Response of 167 Patients on Lopinavir/r (LPV/r) including an Analysis of New Protease Inhibitor Resistant Mutations in 21 Patients who Failed
M. Loutfy*¹, C. Thompson¹, M. Trpeski¹, C. Kovacs¹, A. Rachlis¹, J. Goodhew¹, G. Rubin¹, K. Gough^1,2, and S. Walmsley¹
¹Univ. of Toronto and ²St. Michael’s Hosp., Toronto, ON, Canada

Background: LPV has a high barrier to resistance. No specific mutations (muts) has been found to confer LPV resistance.
Methods:To determine the effect of resistance on VL response to LPV/r and to analyze the resistance of patients who have failed LPV/r, a retrospective study of patients in the LPV/r EAP in 4 Toronto HIV centres was done. To be included, patients must have a genotype prior to LPV/r and at least 1M F/U. The LPV mut score was defined as the number of muts at positions 10, 20, 24, 46, 53, 54, 63, 71, 82, 84, and 90. The proportion of patients who achieved a VL<50/mL at 4-6M was determined for various muts and LPV mut scores using an on-treatment analysis. Logistic regression (LR) was used to determine the effect of each additional PI mut in the LPV mut score. Changes in resistance were analyzed in patients who had genotyping after LPV/r.
Results:167 ARV-experienced patients were analyzed (98.2% PI-experienced). The mean number of PI muts was 4.8 (SD 3.1). The mean LPV mut score was 3.3 (SD2.1). 85.7% had a score of 0-5, 13.1% had a score of 6-7 and 1.2% had a score >7. 54.8% had the 90M mut and 1.8% had the D30N mut. By 4-6M, 40.5% with a LPV score of 0-5, 25.0% with a score of 6-7 and 0% with a score >7 achieved a VL,50/mL. Using LR, each additional mut in the LPV score increased the odds of VL failure by 1.26 (p=0.02). 26.7% of patients with and 52.4% without 90M achieved a V<50/mL at 4-6M (p=0.008). 21 patients who were VL non-responders had a genotype after LPV/r. 4 patients had no new PI muts. New primary PI muts were noted in 6 patients including 90M in 3 patients, and 82V in 4 ptatiens. Reviewing the drug histories, all of these muts may have been selected from previous PI use. Muts that would increase the LPV mut score by 1, 2 or >3 were observed in 5, 5, and 4 patients, respectively. 19 new secondary PI muts were found in 11 patients at sites 33 (5 patients), 36 (2 patients) 47 (3 patients), 48 (1 patient), 50 (2 patients), 73 (3 patients), and 77 (3 patients), and may have been selected by previous PI use in 15 cases. 33 other PI muts of uncertain significance were observed in 10 patients and occurred in >3 patients at sites 37, 55, 58, 52, and 93.
Conclusions: VL failure to LPV/r has a linear relationship w/ the LPV mut score. Presence of the 90M mut is predictive of failure. VL failure on LPV/r often selects for muts that may have developed under previous PI pressure. VL failure on therapy with LPV/r results in an increased LPV mut score in 2/3 of patients. The significance of new PI muts requires further study.