Benefits of genotypic testing confirmed in French clinic study

A French cohort study has shown that selection of an anti-HIV drug regimen by resistance testing is beneficial in patients who have failed previous regimens. The study, published in the March edition of HIV Medicine, produced similar results to previous randomised trials, and backs up recommendations for the routine use of genetic testing to select new treatment regimens.

The study also found that a new regimen is more likely to reduce HIV viral loads in patients with experience of fewer protease inhibitors, if it contains a new class of antiretrovirals, or if it contains two or more new drugs. It also concluded that the use of abacavir (Ziagen) or ritonavir-boosted lopinavir (Kaletra) were associated with better outcomes.

“Our prospective cohort study showed that, in patients failing antiretroviral therapy, the rate of virological response obtained by optimising therapy with the help of genotypic resistance testing was comparable to that obtained in clinical trials,” write the researchers.

The investigators from Paris analysed the outcomes of 344 HIV-positive patients who underwent genotypic resistance testing after treatment failure. One hundred and seventy-five (51%) of the patients had experience of all three major drug classes, with a median of three nucleoside analogue (NRTI) mutations, one non-nucleoside reverse transcriptase inhibitor (NNRTI) mutation and two protease inhibitor mutations per patient.

The median CD4 cell count was 274 cells/mm³ and viral load was 25,100 copies/ml after a median duration of 4.6 years of antiretroviral exposure.

Three months after starting an optimised regimen based on the genotypic test results, 188 (55%) of the patients had a viral load below 200 copies/ml or had experienced a fall in viral load of 1 log₁₀ or more. This remained stable to the six-month mark, when 182 patients (53%) were classified as having a virological response.

In a multivariate analysis, the investigators found that exposure to two or fewer protease inhibitors was associated with virological response (odds ratio [OR] = 1.8, p = 0.008), as was use of a new class of antiretrovirals (OR = 2.9, p = 0.006). Use of two or more new drugs (OR = 3.0, p < 0.001), abacavir (OR = 1.9, p = 0.03) or Kaletra (OR = 3.7, p < 0.001) were also independently associated with virological success.

The investigators explain the better outcomes in patients with experience of fewer protease inhibitors on the basis of their having less cross resistance between drugs within this class. In addition, “the benefits of using abacavir and lopinavir in our study were probably related to their antiviral activity on resistant viruses,” they write.