The objective of the study by L.K. Naeger et al. (USA), was to determine the resistance profile to tipranavir in HIV-1 infected individuals who had previously received antiretroviral therapy. This work was carried out as part of a clinical study evaluating the efficacy and safety of tipranavir at week 24 of treatment. During the course of the work, the frequency of the virological response to treatment was determined taking into account the presence of primary mutations which determine the resistance to protease inhibitors and the sensitivity of the viral strain to tipranavir at the start of the study, as well as an analysis of the frequency of development of mutations that determine resistance to protease inhibitors during the treatment period. the specified drug.

According to the results, the frequency of development of the virological response to treatment with tipranavir was lower when the amino acids were replaced at positions I13, V32, M36, I47, Q58, D60 V82 and I84, or if the HIV strain had five mutations or more that determine resistance to protease inhibitors, at the start of the study.

In patients receiving tipranavir without concomitant use of enfuvirtide and infected with a strain of the virus who underwent five or more mutations causing resistance to protease inhibitors, by the time the study began, the antiretroviral response began to decline after 4 to 8 weeks of treatment. At the same time, in the patients taking enfuvirtide with tipranavir, at the 24th week of treatment, the viral load decreased by more than 1.5 log10 compared to the level at the start of the study, even in the presence five or more mutations that cause resistance to protease inhibitors.. A decrease in virologic response to treatment with tipranavir has occurred if an offset of more than 3 times the effective concentration of 50% (EC50) was observed in the phenotype of the isolate at the start of the study by compared to published data. Patients in whom tipranavir did not reduce the virological load were most often infected with viral strains with mutations L10I / V / S, I13V, L33V / I / F, M36V / I / L V82T, V82L and I84V.

According to the authors, the phenotypic and genotypic characteristics of the virus at the time of initiation of treatment make it possible to predict the probability of a virological response to the use of tipranavir in patients infected with HIV-1.