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Differential Persistence of Transmitted HIV-1 Drug Resistance Mutation Classes

2011; Oxford University Press; Volume: 203; Issue: 8 Linguagem: Inglês

10.1093/infdis/jiq167

ISSN

1537-6613

Autores

Vivek Jain, Maria Cecília Araripe Sucupira, Peter Bacchetti, Wendy Hartogensis, Ricardo Sobhie Diaz, Esper G. Kallás, Luiz Mário Janini, Teri Liegler, Christopher D. Pilcher, Robert M. Grant, Rodrigo Cortes, Steven G. Deeks, Frederick Hecht,

Tópico(s)

HIV/AIDS Research and Interventions

Resumo

Background. Transmitted human immunodeficiency virus type 1 (HIV-1) drug resistance (TDR) mutations can become replaced over time by emerging wild-type viral variants with improved fitness. The impact of class-specific mutations on this rate of mutation replacement is uncertain. 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 log10 copies/mL; 95% CI, .90–3.25 log10 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.

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