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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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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 HIV Cohort

V Miller, A Cozzi-Lepri, K Hertogs,

P Gute, B Larder, S Bloor,

C Rottmann, AN Phillips, S Staszewski

introduction
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
patients methods
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
study population baseline characteristics

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

univariate analysis odds ratio of virological failure
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

multivariate analysis odds ratio of virological failure
Multivariate Analysis: Odds ratio of virological failure

DAFDAC

Multivariate 1

Multivariate 2

RNA New Drugs Sens/4

RNA New Drugs Sens/10

multivariate analysis odds ratio of virological failure1
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

conclusion
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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