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Impact of Phenotypic Antiretroviral Drug Resistance Testing on the Response to Salvage Antiretroviral Therapy (ART) in Heavily Experienced Patients D. MELNICK*1, J. ROSENTHAL1, M. CAMERON1, M. SNYDER1, S. GRIFFITH-HOWARD1, K. HERTOGS2, W. VERBIEST2, N. GRAHAM3, and S. PHAM3.
1Kaiser Permanente, Springfield, VA; 2Virco, Belgium; and 3Glaxo Wellcome Inc., Res. Triangle Park, NC Prospective 16 week pilot study to evaluate impact of phenotypic resistance testing on the response of patients failing PI-containing regimens to subsequent ART.
Methods: Patients failing PI-containing ART (HIV RNA >2,000 c/ml) were randomized to 1) a standard of care arm (SOC) - salvage ART chosen based on treatment history and clinical guidelines or 2) phenotypic resistance testing (PRT) arm - physicians had access to baseline phenotype results (AntivirogramTM). Patients were NRTI and PI-experienced (no restriction) but were NNRTI-naïve.
Results: 115 patients enrolled. Baseline median CD4 and HIV RNA were comparable between the study arms. Patients were heavily ART experienced as reflected by baseline phenotypic resistance to 41% of the drugs prescribed for salvage therapy. The mean number of active (sensitive) drugs prescribed was significantly greater in the PRT arm compared with the SOC arm (p = .0001) but was still less than 3. Greater mean HIV RNA decline was observed at week 4 in the PRT arm (-1.0 logs PRT vs -0.5 logs SOC, p=.137). A significant difference in mean change in CD4 count from baseline was apparent at week 12 (PRT= 53.1 vs SOC=11.2, p=.014). The proportion of patients reaching a virologic endpoint by week 16 was similar for both arms.
Conclusions: In this pilot study of heavily ART-experienced patients, access to baseline phenotype 1) did improve selection of active drugs, 2) enhanced decrease of HIV RNA from baseline at week 4, 3) improved CD4 count, but 4) did not sustain a long-term virologic response (16 weeks). This result is likely a consequence of the limited number of marketed active drugs (<3) available in 1997-8 for patients in either study arm.
Key Words: Antiretrovirals, Resistance, Salvage
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