Benefits of genotypic testing confirmed in French clinic study

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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.

Glossary

resistance testing

Laboratory testing to determine if an individual’s HIV strain is resistant to anti-HIV drugs. 

genotypic resistance testing

In HIV, genotypic resistance tests are assays that identify mutations of the virus that can confer antiretroviral drug resistance. Resistance testing can be used to guide selection of an HIV regimen when initiating or changing antiretroviral therapy (ART). 

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

antiviral

A drug that acts against a virus or viruses.

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.

References

Fournier S et al. Factors associated with virological response in HIV-infected patients failing antiretroviral therapy: a prospective cohort study. HIV Med 6: 129-134, 2005.