High level of multidrug resistance mutations in HIV type 1 pol gene and resistance-associated mutations to enfuvirtide (T-20) among antiretroviral-experienced patients from central Brazil

Abstract

HIV-1 resistance mutations to antiretroviral (ARV) drugs (nucleoside reverse transcriptase inhibitors, NRTI; nonnucleoside reverse transcriptase inhibitors, NNRTI; and protease inhibitors, PI) represent a challenge for sustainable virologic and immunologic responses. HIV-1 phylogenetic diversity and ARV resistance mutations associated with protease (PR) and reverse transcriptase (RT) were assessed among 48 ARV-experienced patients from Goiania/Goias, central west Brazil. The gp41 resistance mutations to the fusion inhibitor (T-20) were analyzed among multidrug-resistant (MDR) patients. PR, partial RT, and gp41 genes were amplified and sequenced from plasma RNA. HIV-1 subtype was assigned by phylogenetic analysis. ARV mutations in PR/RT were analyzed by the Stanford Database. T-20 resistance mutations in gp41 were identified by Stanford, the Los Alamos Database, and other sources. Subtype B represented 79.2% (38/48), subtype F1 4.2% (2/48), subtype C 2.1% (1/48), F1PR/BRT 8.3% (4/48), and BPR/F1RT 6.3% (3/48). Secondary drug resistance was observed in 79% (38/48): NRTI resistance (n = 1), NNRTI resistance (n = 1), PI + NRTI or NRTI + NNRTI resistance (n = 20), and PI + NRTI +NNRTI resistance, considered MDR (n = 16). Almost half of the MDR patients had viral loads bellow 10,000 copies/ml. The gp41 sequences from 14 MDR revealed one F1PR/BRT/F1ENV recombinant and 13 subtype BPR/BRT/BENV isolates. G36E, N42T, and N43S T-20 resistance mutations were observed in three MDR patients, two of them previously treated with T-20 and the other who had never used T-20. Our data among ARV-experienced patients showed a high proportion of drug-resistance mutations and MDR. T-20 resistance mutations were detected among MDR patients corroborating the importance of T-20 genotyping for clinical management and salvage therapy.