Secondary mutations in HIV-1 protease predict treatment failure in naive patients

Drug-naive HIV-positive patients with secondary mutations in the protease region of HIV are significantly more likely than HIV-infected patients without these mutations to fail antiretroviral therapy at 24 weeks.

“If confirmed in independent studies, this result may justify the increased use of HIV genotyping in drug-naive patients requiring antiretroviral therapy” Dr Carlo F. Perno, of the University of Rome Tor Vergata, and colleagues suggest in the October 15th issue of the Journal of Infectious Diseases.

Dr Perno’s group examined the role of mutations in the protease and reverse-transcriptase regions of HIV in predicting virologic failure in 248 drug-naive, HIV-positive patients. All patients had just begun antiretroviral therapy with a multidrug regimen containing two reverse transcriptase inhibitors and at least one protease inhibitor.

“Virologic failure at 24 weeks correlated significantly with the number of protease region mutations in each patient. Secondary mutations at two sites in particular, codons 10 and 36, were the strongest predictors of virologic failure. According to the model estimate, patients with either mutation were at twice the risk of having virologic failure at week 24 than were patients with neither mutation,” the team writes. (p = 0.004).

And this risk remained even after accounting for other factors known to affect treatment failure, such as CD4 cell count and pretherapy viral load.

Both mutations were common, with mutations at codons 10 and 36 present in 39.3% and 40.0% of patients, respectively. Given this prevalence, Dr Perno and colleagues suggest that the mutations may represent natural polymorphisms in the HIV protease region.

“Further data are needed to confirm whether our results would persist in cohorts of naive patients from different geographic regions, who start therapy at different disease stages and who are infected with HIV subtypes different from those circulating in Italy,” the researchers add.

Dr Perno’s group concludes that “randomised studies are warranted to assess whether drug-naive patients with selected secondary mutations should be treated with a non-nucleoside reverse-transcriptase inhibitor-containing regimen or with a regimen containing dual protease inhibitors.”