Resistance associated mutations in HIV-1 subtype C primary viruses after in vitro passage with integrase inhibitors raltegravir, elvitegravir and dolutegravir

The prevalence of HIV-1 integrase (IN) mutations associated with resistance to the first generation IN inhibitors (INI), raltegravir (RAL) and elvitegravir (EVG), and the next generation INI, dolutegravir (DTG) have not been adequately assessed in non-B subtypes. This study evaluated the resistance mutation profiles for RAL, EVG and DTG associated with in vitro drug resistance selection experiments with HIV-1 subtype C primary virus isolates. Six HIV-1 subtype C primary virus isolates, including three from antiretroviral drug-naive patients and three from patients failing a first-line regimen were grown in peripheral blood mononuclear cells (PBMCs) in the presence of increasing concentrations of RAL, EVG and DTG using standard methodologies. HIV-1 subtype C primary virus isolates grown under INI pressure mutate to contain the described major IN mutations, similar to what has been reported from patient clinical samples worldwide. DTG pressure induced a RAL and EVG drug-resistant mutation, warranting further studies to establish the benefit of DTG treatment in HIV-1 subtype-C-infected patients failing EVG or RAL-containing regimens.