The rationale for a study on HIV-1 reverse transcriptase mutations and outcome of antiretroviral therapy with two nucleoside analogs.

The development of resistance to antiretroviral drugs has been recognized as an important cause of treatment failure in HIV-1-infected patients; however the correlation between emergence of resistance and treatment failure has not been yet clearly defined. The high rate of viral replication, together with the lack of proof reading activity of HIV-1 reverse transcriptase, accounts for the rapid establishment of extensive genotypic variation, resulting in the emergence of viral mutants showing primary or secondary resistance to antiretroviral drugs. In this regard, phenotyping and genotyping allow the detection of drug resistance. Both tests have advantages and limitations compared to each other. The complete suppression of viral replication seems to be the best way to avoid occurrence of drug resistance, and viral loads below the limit of detection can be usually achieved by a combination of 3 antiretroviral drugs. In this scenario, the proportion of HIV-1-infected patients on dual therapy is still relevant in Italy. We believe that the study of this subset of individuals is very important, as resistance to nucleoside analogues may impair the outcome of a future triple therapy. In addition, this study could contribute to define the role of resistance assays in the management of HIV-1-infected patients.