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.
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), F1(PR)/B(RT) 8.3% (4/48), and B(PR)/F1(RT) 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 below 10,000 copies/ml. The gp41 sequences from 14 MDR revealed one F1(PR)/B(RT)/F1(ENV) recombinant and 13 subtype B(PR)/B(RT)/B(ENV) 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.
Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiania/Goias, Brazil.
Ludimila Paula Vaz
LP
Cardoso
Mariane Martins de Araújo
MM
Stefani
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology; D001938:Brazil; D002648:Child; D024921:Drug Resistance, Multiple, Viral; D000077560:Enfuvirtide; D005260:Female; D005838:Genotype; D015700:HIV Envelope Protein gp41 / Q000235:genetics* / Q000494:pharmacology*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010446:Peptide Fragments / Q000494:pharmacology*; D010802:Phylogeny; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D017422:Sequence Analysis, DNA; D055815:Young Adult; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D012367:RNA, Viral; C514787:gp41 protein, Human immunodeficiency virus 1; D054302:pol Gene Products, Human Immunodeficiency Virus; D000077560:Enfuvirtide