Resistance to the most recent protease and non-nucleoside reverse transcriptase inhibitors across HIV-1 non-B subtypes

Limited data are available on resistance to etravirine, rilpivirine, darunavir and tipranavir in patients infected with HIV-1 non-B subtypes, in which natural polymorphisms at certain positions could influence the barrier and/or pathways to drug resistance. FASTA format sequences from the reverse transcriptase and protease genes recorded within the Spanish Drug Resistance database (ResRIS) were examined. From 8272 genotypes derived from 5930 different HIV-1 patients included in ResRIS, 5276 genotypes had complete treatment information. Overall, 85 were from antiretroviral-experienced subjects and 7.5 belonged to HIV-1 non-B subtypes: CRF02_AG, C, F and G being the most prevalent variants. For etravirine, only G190A was more prevalent in B than non-B subtypes, whereas V90I and V179E were more frequent in non-B than B subtypes. For rilpivirine, V108I and Y188I were more frequent in B than non-B subtypes, whereas V90I was more prevalent in non-B subtypes. Despite these differences, the overall prevalence of resistance did not differ significantly when comparing etravirine or rilpivirine in B versus non-B subtypes (11.3 versus 7.4, P0.13, and 10.5 versus 7.4, P0.23, respectively). Despite more frequent natural polymorphisms in non-B than B subtypes at tipranavir resistance positions, the prevalence of tipranavir resistance was greater in B than non-B subtypes (11 versus 4.3, P0.004), reflecting a greater antiretroviral exposure in the former. Darunavir resistance did not differ significantly when comparing B and non-B subtypes (5.8 versus 5.5, P0.998). The rate of resistance to the most recently approved protease and non-nucleoside reverse transcriptase inhibitors is low in antiretroviral-experienced patients, regardless of the HIV-1 subtype.