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Association between phenotypic resistance and virologic response to mega-HAART regimen in patients from the Frankfurt HI

Association between phenotypic resistance and virologic response to mega-HAART regimen in patients from the Frankfurt HIV Cohort. V Miller, A Cozzi-Lepri, K Hertogs, P Gute, B Larder, S Bloor, C Rottmann, AN Phillips, S Staszewski. Introduction.

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Association between phenotypic resistance and virologic response to mega-HAART regimen in patients from the Frankfurt HI

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  1. Association between phenotypic resistance and virologic response to mega-HAART regimen in patients from the Frankfurt HIV Cohort V Miller, A Cozzi-Lepri, K Hertogs, P Gute, B Larder, S Bloor, C Rottmann, AN Phillips, S Staszewski

  2. Introduction • The Frankfurt HIV Cohort consists of all patients attending the clinic who have presented at least once since Jan 1, 1995 • data pertaining to antiretroviral history, immune status, HIV-1 viral load, HIV-associated clinical events and demographics are collected prospectively • patients with multiple treatment failures were treated with salvage regimen consisting of 6 or more antiretroviral drugs • phenotypic resistance tests were performed from stored plasma samples

  3. Patients & Methods • 50 patients met the definition criteria and the DAP requirements • viral load: Amplicor • resistance: Antivirogram (recombinant virus based phenotypic assay) • virologic failure: > 400 copies/week 24 window • statistical analysis: as described per DAP

  4. Study Population: Baseline characteristics Characteristic Median Range HIV RNA(log10 copies/ml) 5.52 3.40 - 6.70 CD4 cell count (cells/mm3) 95 2 - 587 Time on HAART (months) 18.3 1.7-53.5

  5. Summary of previous ART

  6. Susceptibility Status at Baseline

  7. On - Treatment Drugs

  8. Univariate Analysis: Odds ratio of virological failure DAFDAC NRTI sens/10 new drugs NRTI sens/4 PI sens/10 PI sens 4 sens/10 sens/4 RNA

  9. Multivariate Analysis: Odds ratio of virological failure DAFDAC Multivariate 1 Multivariate 2 RNA New Drugs Sens/4 RNA New Drugs Sens/10

  10. Multivariate Analysis: Odds ratio of virological failure DAF DAC Multivariate 3 Multivariate 4 RNA New Drugs NRTI Sens/4 PI Sens/4 RNA New Drugs NRTI Sens/10 PI Sens 10

  11. Conclusion • in this retrospective analysis based on a small group of extensively experienced patients, phenotypic resistance was a significant predictor of virologic response, independent of baseline viral load and previous antiretroviral history • either a 4-fold or a 10-fold cut-off provided significant independent information • in models looking at resistance within individual drug classes, resistance to PI was more predictive than resistance to NRTI

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