Differential Persistence of Transmitted HIV-1 Drug Resistance Mutation Classes

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Jain, Vivek
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.
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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.
Journal of Infectious Diseases. Cary: Oxford Univ Press Inc, v. 203, n. 8, p. 1174-1181, 2011.