Differential Persistence of Transmitted HIV-1 Drug Resistance Mutation Classes

• Autor(a) principal: Jain, Vivek
• Data de Publicação: 2011
• Outros Autores: Sucupira, Maria Cecilia Araripe [UNIFESP], Bacchetti, Peter, Hartogensis, Wendy, Diaz, Ricardo Sobhie [UNIFESP], Kallas, Esper Georges [UNIFESP], Janini, Luiz M. [UNIFESP], Liegler, Teri, Pilcher, Christopher D., Grant, Robert M., Cortes, Rodrigo [UNIFESP], Deeks, Steven G., Hecht, Frederick M.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNIFESP
• Texto Completo: http://dx.doi.org/10.1093/infdis/jiq167; http://repositorio.unifesp.br/handle/11600/33633

Methods. We studied participants with acute and/or early HIV infection and TDR in 2 cohorts (San Francisco, California, and São 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.