Differential Persistence of Transmitted HIV-1 Drug Resistance Mutation Classes

作者：Jain Vivek; Sucupira Maria C; Bacchetti Peter; Hartogensis Wendy; Diaz Ricardo S; Kallas Esper G; Janini Luiz M; Liegler Teri; Pilcher Christopher D; Grant Robert M; Cortes Rodrigo; Deeks Steven G; Hecht Frederick M^*

来源：Journal of Infectious Diseases, 2011, 203(8): 1174-1181.

DOI：10.1093/infdis/jiq167

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.

• 出版日期2011-4-15