[10] A RANDOMIZED CONTROLLED TRIAL OF PHENOTYPIC RESISTANCE TESTING IN ADDITION TO GENOTYPIC RESISTANCE TESTING: THE ERA TRIAL

2nd International AIDS Society Conference on HIV Pathogenesis and Treatment

Paris, France - July 13 - 16, 2003

[TITLE:] A RANDOMIZED CONTROLLED TRIAL OF PHENOTYPIC RESISTANCE TESTING IN ADDITION TO GENOTYPIC RESISTANCE TESTING: THE ERA TRIAL

[AUTHOR(S):] C Loveday¹, DT Dunn², H Green², A Rinehart³ and P McKenna⁴ on behalf of the ERA Steering Committee
¹International Clinical Virology Centre, UK; ²MRC Clinical Trials Unit, UK; ³VircoLab Inc, USA; and ⁴Virco BVBA, Belgium

IAS Conf HIV Pathog Treat 2003 Jul 13-16;2nd: Abstract No. 10
Antiviral Therapy 2003; 8(Suppl. 1):S188

[ABSTRACT:] Background: Although clinical guidelines recommend the routine use of HIV drug resistance testing, they are not prescriptive on the choice between genotypic and phenotypic testing. We report on the clinical utility of phenotypic resistance testing in addition to genotypic resistance testing in patients with limited therapeutic options.

Methods: In the ERA (Evaluation of Resistance Assays) Trial, patients in whom therapy was failing were randomized to one of two parts depending on whether or not the clinician considered that a resistance test was essential for selecting the new regimen. In Part B (test was considered essential), all subjects had access to genotypic testing with rules-based interpretation (VIRCOGEN I™) at baseline and during follow-up and were randomized to have or not have access to phenotypic testing (ANTIVIROGRAM™ prior to the introduction of drug-specific cutoffs). The primary endpoint was change in plasma HIV RNA viral load (VL) between randomization and 12 months by an ‘intention-to-treat’ analysis.

Results: 311 patients were enrolled in Part B, of whom 152 were allocated to genotypic testing alone (G arm) and 159 to genotypic plus phenotypic testing (G+P arm). At baseline, mean VL was 4.23 log₁₀ copies/ml, mean CD4 count was 275 cells/mm³, and subjects had previous exposure to a mean of 7.7 ART drugs. The primary endpoint was evaluable in 283 (91%) subjects; the main reason for being missing was non-attendance at the clinic around 12 months. The mean reduction in plasma VL at 12 months was similar in the two arms (G: 1.37 log₁₀ reduction; G+P: 1.28 log₁₀ reduction; difference=0.08, SE=0.27, P=0.77); 35% of subjects in the G arm and 27% in the G+P arm had a VL of less than 50 copies/ml. There was no appreciable difference between the study arms in terms of the number of drugs, the number of ‘active’ drugs (as assessed by genotypic resistance) or the individual prescribed drugs following the initial test.

Conclusions: The ERA trial found no clear evidence of added value (in terms of virological response) of phenotypic resistance testing against a background of genotypic resistance testing in patients with limited therapeutic options.

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