Differential Persistence of Transmitted HIV-1 Drug Resistance Mutation Classes

Autor(es):Mostrar menos -

Jain, Vivek ^[1] ; Sucupira, Maria C. ^[2] ; Bacchetti, Peter ^[3] ; Hartogensis, Wendy ^[1] ; Diaz, Ricardo S. ^[2] ; Kallas, Esper G. ^{[2, 4]} ; Janini, Luiz M. ^[2] ; Liegler, Teri ^[1] ; Pilcher, Christopher D. ^[1] ; Grant, Robert M. ^[5] ; Cortes, Rodrigo ^[2] ; Deeks, Steven G. ^[1] ; Hecht, Frederick M. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94143 - USA

^[2] Univ Fed Sao Paulo, Div Infect Dis, Sao Paulo - Brazil

^[3] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 - USA

^[4] Univ Sao Paulo, Div Clin Immunol & Allergy, BR-05508 Sao Paulo - Brazil

^[5] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 - USA

• Tipo de documento: Artigo Científico
• Fonte: Journal of Infectious Diseases; v. 203, n. 8, p. 1174-1181, APR 15 2011.
• Citações Web of Science: 86

Resumo

Methods. We studied participants with acute and/or early HIV infection and TDR in 2 cohorts (San Francisco, California, and Sao Paulo, Brazil). We followed baseline mutations longitudinally and compared replacement rates between mutation classes with use of a parametric proportional hazards model. Results. Among 75 individuals with 195 TDR mutations, M184V/I became undetectable markedly faster than did nonnucleoside reverse-transcriptase inhibitor (NNRTI) mutations (hazard ratio, 77.5; 95% confidence interval {[}CI], 14.7-408.2; P < .0001), while protease inhibitor and NNRTI replacement rates were similar. Higher plasma HIV-1 RNA level predicted faster mutation replacement, but this was not statistically significant (hazard ratio, 1.71 log(10) copies/mL; 95% CI, .90-3.25 log(10) copies/mL; P = .11). We found substantial person-to-person variability in mutation replacement rates not accounted for by viral load or mutation class (P < .0001). Conclusions. The rapid replacement of M184V/I mutations is consistent with known fitness costs. The long-term persistence of NNRTI and protease inhibitor mutations suggests a risk for person-to-person propagation. Host and/or viral factors not accounted for by viral load or mutation class are likely influencing mutation replacement and warrant further study. (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: 04/12316-3 - Tempo de persistência das mutações de resistência adquiridas por transmissão
• Beneficiário: Maria Cecilia Araripe Sucupira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado