Evaluation of primary resistance to HIV entry inhibitors among brazilian patients failing reverse transcriptase/protease inhibitors treatment reveal high prevalence of maraviroc resistance-related mutations.
Entry inhibitor is a new class of drugs that target the viral envelope protein. This region is variable; hence resistance to these drugs may be present before treatment. The aim of this study was to analyze the frequency of patients failing treatment with transcriptase reverse and protease inhibitors that would respond to the entry inhibitors Enfuvirtide, Maraviroc, and BMS-806. The study included 100 HIV-1 positive patients from one outpatient clinic in the city of Sao Paulo, for whom a genotype test was requested due to treatment failure. Proviral DNA was amplified and sequenced for regions of gp120 and gp41. A total of 80 could be sequenced and from those, 73 (91.3%), 5 (6.3%) and 2 (2.5%) were classified as subtype B, F, and recombinants (B/ F and B/C), respectively. CXCR4 co-receptor use was predicted in 30% of the strains. Primary resistance to Enfuvirtide was found in 1.3%, following the AIDS Society consensus list, and 10% would be considered resistant if a broader criterion was used. Resistance to BMS-806 was higher; 6 (7.5%), and was associated to non-B strains. Strikingly, 27.5% of samples harbored one or more mutation among A316T, I323V, and S405A, which have been related to decreased susceptibility of Maraviroc; 15% of them among viruses predictive to be R5. A more common mutation was A316T, which was associated to the Brazilian B strain harboring the GWGR motif at the tip of V3 loop and their derivative sequences. These results may be impact guidelines for genotype testing and treatment in Brazil.
Infectious Diseases Division, Federal University of São Paulo, São Paulo, Brazil. sabinoec@gmail.com
Cecília S
CS
Alencar
Anna S
AS
Nishiya
Suzete
S
Ferreira
Maria Teresa M
MT
Giret
Ricardo S
RS
Diaz
Ester C
EC
Sabino
D000328:Adult; D000554:Ambulatory Care Facilities; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001938:Brazil; D003510:Cyclohexanes / Q000494:pharmacology*; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics; D024882:Drug Resistance, Viral; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology; D023581:HIV Fusion Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D000077592:Maraviroc; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010446:Peptide Fragments / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D015995:Prevalence; D011533:Proviruses / Q000235:genetics; D017422:Sequence Analysis, DNA; D017211:Treatment Failure; D014230:Triazoles / Q000494:pharmacology*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
D019380:Anti-HIV Agents; C451732:BMS 806; D003510:Cyclohexanes; D004279:DNA, Viral; D015700:HIV Envelope Protein gp41; D023581:HIV Fusion Inhibitors; D017320:HIV Protease Inhibitors; D010446:Peptide Fragments; D010879:Piperazines; D014230:Triazoles; D054299:env Gene Products, Human Immunodeficiency Virus; D000077560:Enfuvirtide; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D000077592:Maraviroc