ZOLOPA AR, GONZALES M, RICE H, HERTOGS K, SHAFER R; Interscience Conference on Antimicrobial Agents and Chemotherapy (41st : 2001 : Chicago, Ill.).

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2001 Dec 16-19; 41: abstract no. I-1764.

Stanford University, Palo Alto, CA

Introduction: In the presence of protease resistance mutations 82A and 90M, SQV PT often reveals no or only modestly reduced susceptibility. We evaluated the response to SQV/RTV therapy in protease experienced patients with these mutations at baseline. METHODS: We identified protease inhibitor (PI) experienced patients who had the combination of protease mutations 82A/90M and were treated with SQV/RTV at a University clinic. All patients had baseline genotypes (ABI), PT (VIRCO) and viral load response measured over 24 weeks. We also evaluated follow up genotypes and PT while on SQV/RTV. RESULTS: We identified 11 patients with mutations 82A and 90M who received SQV/RTV 400mg/400mg BID. In addition to the mutations at codons 82 and 90 patients had a median of 9 differences from consensus B sequence (range 5 to 11). The median reduction in SQV susceptibility was 4.2 fold change (FC) (range 0.5->71). Only 2 patients had SQV IC50 FC >10, both had a 48V mutation. At week 4, median change in plasma HIV-1 RNA level was -0.38 log (range: +0.26 to -1.32 log). By week 24, all patients were within 0.33 log of baseline viral load or above. Follow up genotype while on SQV/RTV showed limited evolution. The most common new mutation was a G73S or C which developed in 5 patients, while L10I, L10F, 43N, G48V and I84V developed in 1 patient each. Similarly there was limited change in SQV PT while on SQV/RTV, median increase in IC50 FC was 0.75 (range 0.2 - 3.4). CONCLUSIONS: Patients harboring HIV-1 isolates with protease mutations at codons 82 and 90 often fail to respond to SQV/RTV (400/400mg bid) therapy despite the absence of high-level SQV resistance. This study suggests that patients treated with SQV/RTV after prior PI failure may require higher doses of SQV than that used in this cohort or that the clinical significance of SQV PT "cut-offs" be reconsidered.

Publication Types:

• Meeting Abstracts

Keywords:

• Codon
• Endopeptidases
• Genotype
• HIV Protease
• HIV Protease Inhibitors
• HIV-1
• Humans
• Mutation
• Phenotype
• Protease Inhibitors
• Ritonavir
• Saquinavir
• Viral Load
• genetics
• reverse transcriptase, Human immunodeficiency virus 1

Other ID:

• GWAIDS0029033

UI: 102268665

From Meeting Abstracts