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

Autor(es)

Alencar, Cecilia S. ^[1] ; Nishiya, Anna S. ^[2] ; Ferreira, Suzete ^[2] ; Giret, Maria Teresa M. ^[3] ; Diaz, Ricardo S. ^[1] ; Sabino, Ester C. ^{[2, 4]}

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo, Div Infect Dis, Sao Paulo - Brazil

^[2] Fundacao Prosangue, Hemoctr, BR-05403000 Sao Paulo - Brazil

^[3] Univ Sao Paulo, Div Clin Immunol & Allergy, BR-05508 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Div Hematol & Hemotherapy, BR-05508 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: AIDS Research and Human Retroviruses; v. 26, n. 12, p. 1267-1271, DEC 2010.
• Citações Web of Science: 11

Resumo

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. (AU)

• Processo FAPESP: 04/15856-9 - Análise prospectiva das características virológicas e imunológicas em indivíduos com infecção recente pelo HIV-1 das cidades de São Paulo e Santos, SP
• Beneficiário: Ricardo Sobhie Diaz
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/52381-2 - Imunidade mediada por células em crianças infectadas pelo vírus da imunodeficiência humana
• Beneficiário: María Teresa Maidana Giret
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado