The VIRADAPT study was a prospective, randomized, controlled, open-label
study designed to evaluate the clinical utility of using a genotypic
resistance assay to assist in deciding which drugs to use in patients
failing therapy.
The study was conducted in four hospitals in southern France and
enrolled patients with HIV RNA levels >10,000 copies/mL despite at least 3
months PI therapy and 6 months NRTI therapy. Baseline characteristics are
shown in Table 1. One hundred and eight patients were randomized at a 1:2
ratio into two arms. Patients in the control arm were switched to a new
regimen based on standard of care practices and the physicianís best
clinical judgement. In the genotyping arm, physicians were given the
results of a genotypic resistance assay to assist them in deciding which
new drugs to use. Forty-three patients were randomized into the
standard of care/control arm and 65 into the genotyping arm. The study
began in early 1997 at which time an in-house genotypic assay was
performed, this was subsequently replaced with the TruGene TM genotypic
assay (Visible Genetics,Inc.).
Table 1.
Baseline Characteristics.
The patient population was very drug-experienced, with patients having
been on an average 3.9 NRTIs for an average duration of 39.5 months, and
1.8 PIs for 11.6 months. Three months after switching to their new
regimens,results showed a greater reduction in plasma HIV RNA levels in the
genotyping arm (-1.04 log10 copies/mL) than in the standard of care arm
(-0.46 log10 copies/mL) (Figure 1). This was statistically significant
(P=0.006). The percent of patients with viral load below the level of
detection (which was 200 copies/mL) was 29.2% in the genotypic arm versus
13.9% in the standard of care arm (p= 0.02) (Figure 2). Patients not
showing a reduction in viral load of at least 0.5 log10 copies/mL or not
dropping below 10,000 copies/mL were allowed to have their therapy
adjusted. This was done according to best clinical judgement in the
standard of care arm and with the help of a second genotypic assay at month
3 in the genotypic arm.
Figure 1 
Figure 2 
At month 6, viral load reductions continued to be greater in the
genotypic arm (-1.15 log10 copies/mL) than in the standard of care arm
(-0.67 log10copies/mL) (P=0.05). The percentages of patients with HIV RNA
levels < 200copies/mL were 32.3% and 13.9% in the genotyping and
standard of care arms, respectively. This did not reach statistical
significance (P=0.15).
Although patients in both arms had been on similar regimens before
beginning the study, patients in the genotyping arm were changed to a much
wider variety of individualized regimens than were patients in the standard
of care arm, who were switched to a few specific regimens. When the impact
of regimens containing specific drugs were compared, it was found that the
average viral load reduction seen for patients in the genotyping arm was
greater than that seen in the standard of care arm for the same new drugs.
For example, new regimens containing ritonavir + saquinavir resulted in an
average viral load reduction of 1.25 log10 copies/mL in the genotypic arm,
but only 0.65 log10 copies/mL in the standard of care arm (Figure 3). This
would suggest that it was the proper use of the drugs that resulted in the
greater viral load reduction and not only the characteristics of the drugs
themselves.
Figure 3 
Although this small pilot study leaves many questions unanswered, it
definitely suggests genotypic assays may have clinical utility in the
management of HIV-infected individuals.
