Grant: Travel Awards - Institute Community Support

Human immunodeficiency virus (HIV) remains a global public health issue. Although the epidemic has not yet been controlled, considerable progress in HIV treatment and prevention have been made during the last 20 years. In fact, new antiretroviral (ARV) drug classes are constantly being developed, such as the integrase-strand transfer inhibitors (INSTIs) that target the HIV-1 integrase (IN) enzyme. Clinical studies have shown that INSTIs can be used effectively against HIV-1 infection. To this day, no resistance mutation has been found in INSTI-naïve patients who were treated with the second-generation inhibitor dolutegravir (DTG). In a recent study involving DTG and a virus containing the mutation H51Y in the integrase protein, we have observed the emergence of a new mutation at position 262 (R262K). In this study we have characterized the addition of R262K to H51Y in regard to integrase activity and resistance to DTG in biochemical and cellular experiments. Although the virus ability to replicate was not affected and the integrase enzyme efficiency was impaired by the addition of the two mutations (R262K to H51Y), we observed an overall increase in the level of drug resistance against DTG. These observations support the fact that no DTG resistance mutations in the integrase coding sequence have been observed in the clinic yet due to their high fitness cost for the virus.