Prevalence of mutations associated with drug resistance in antiviral naïve HIV-1 patients with acute and chronic infection.

M. C. Re^a, P. Monari^a, I Bon^a, M. Borderi^b, F. Chiodo^b. ^aSection of Microbiology and ^bSection of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Bologna, Via Massarenti 9-40138 Bologna (Italy).

Background: The routine determination of drug resistance in newly HIV-1 infected individuals documents a potential increase in the transmission of drug-resistant variants. Mutations correlated to HIV-1 resistance were analyzed by TruGene HIV-1 assay and by virtual phenotype in plasma samples from sixty two therapy naive HIV-1 infected Italian patients, to assess the presence of viral mutations in a cohort of HIV-1 infected patients never treated with anti-retroviral compounds. Material and Methods: Thirty eight individuals classified as “newly infected” (serocoversion time <12 months) and twenty four individuals with a long-lasting infection (seroconversion time ranging from 3 to 10 years) were enrolled in this study. Plasma were analyzed for the presence of HIV-RNA levels and mutations by Trugene HIV-1 genotyping assay and Virtual phenotype. Results: A limited number of relevant mutations associated with substantial resistance to reverse transcriptase and protease inhibitors were observed in naïve patients. In particular, three patients (4.8%) carried viral major mutations (T69D and M41L associated with reverse transcriptase inhibitors, whereas only one showed the presence of M46L correlated with partial resistance to some protease inhibitors (indinavir, ritonavir and amprenavir). In addition a large number of accessory mutations were detected in a high percentage of plasma samples. The clinical interpretation based on different approach to monitor resistance showed that Virconet interpretation was less “severe” in comparison with Trugene, suggesting that the results’ reading might have a different impact on the eventual use of drugs and need standardization among currently used sequencing methods. Conclusion: The prevalence of mutations associated with high level of resistance to antiviral compounds, even if in a very limited number of samples, suggest the need to continue drug resistance-monitoring in naive patients to gain a true picture of highly resistant HIV strains and to study new models able to optimize therapy protocols. Only data obtained following different therapy protocols, will suggest which results’ interpretation is valid in HIV patients.