Randy Lanier, of Glaxo Wellcome, reported how the "cut-offs" for phenotype resistance were different for the two phenotypic tests--ViroLogic's and Virco's (LabCorp). He suggests this difference could lead to confusion about the degree of resistance or sensitivity to abacavir.

The clinical utility of HIV resistance assays relies on their interpretation by physicians. One advantage of phenotyping over genotyping is that it provides a direct measure of the ability of the virus to grow in the presence of drug and permits a simple report of "fold resistance" over wild-type (WT) controls. However, small differences in these measurements or their interpretation may be important.

Lanier examined 3TC experienced subjects harboring virus with only the M184V mutation (ABI dideoxy terminator sequencing) who added ABC to background therapy of 3TC/ZDV after at least 3 months on 3TC/ZDV (N=31).

After 48 weeks on 3TC/ZDV/ABC, 23/31 (74%) subjects had <400 copies of plasma HIV-1 RNA (Roche Amplicor). Phenotype data was obtained at baseline using the Virco Antivirograrnë and/or Virologic PhenoSenseë assays. 17/20 (85%) samples evaluated by the Antivirograrnë were categorized as "sensitive" to ABC (<4 fold over WT) and 3/20 (15%) had "intermediate" sensitivity to ABC (4-10 fold). Notably, 3/3 subjects harboring isolates with "intermediate" sensitivity had plasma viral RNA <400 copies/ml at week 48 after addition of ABC. The cutoff for "decreasing susceptibility" for the PhenoSenseë assay is currently 2.5 fold for all drugs, corresponding to the inherent sensitivity of the assay. With this cutoff 14/17 (78%) baseline samples had "decreasing susceptibility" to ABC. The 14 patients with these samples had a 71 % response rate (<400 copies/ml) at week 48.

Patients harboring virus of intermediate or decreased susceptibility to ABC still achieve an optimal response to ABC in these studies. Clinically relevant cutoff values for individual anti-retrovirals must be established before phenotypic resistance tests can be effectively incorporated into routine clinical practice.