Differential Persistence of Transmitted HIV-1 Drug Resistance Mutation Classes

Differential Persistence of Transmitted HIV-1 Drug Resistance Mutation Classes

Author Jain, Vivek Google Scholar
Sucupira, Maria Cecilia Araripe Autor UNIFESP Google Scholar
Bacchetti, Peter Google Scholar
Hartogensis, Wendy Google Scholar
Diaz, Ricardo Sobhie Autor UNIFESP Google Scholar
Kallas, Esper Georges Autor UNIFESP Google Scholar
Janini, Luiz M. Autor UNIFESP Google Scholar
Liegler, Teri Google Scholar
Pilcher, Christopher D. Google Scholar
Grant, Robert M. Google Scholar
Cortes, Rodrigo Autor UNIFESP Google Scholar
Deeks, Steven G. Google Scholar
Hecht, Frederick M. Google Scholar
Institution Univ Calif San Francisco
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Abstract 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.
Language English
Sponsor National Institutes of Health/National Institute of Allergy and Infectious Diseases
Brazilian Programfor STD and AIDS, Ministry of Health
São Paulo City Health Department
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number National Institutes of Health/National Institute of Allergy and Infectious Diseases: T32AI060530
National Institutes of Health/National Institute of Allergy and Infectious Diseases: PO1AI071713
National Institutes of Health/National Institute of Allergy and Infectious Diseases: K24AI069994
National Institutes of Health/National Institute of Allergy and Infectious Diseases: P30 AI027763
National Institutes of Health/National Institute of Allergy and Infectious Diseases: UL1 RR024131
Brazilian Programfor STD and AIDS, Ministry of Health: 914/BRA/3014-UNESCO
São Paulo City Health Department: 2004-0.168.922-7
CAPES: PNPD/CAPES-2496/08
FAPESP: 04/15856-9
FAPESP: 04/12316-3
Date 2011-04-15
Published in Journal of Infectious Diseases. Cary: Oxford Univ Press Inc, v. 203, n. 8, p. 1174-1181, 2011.
ISSN 0022-1899 (Sherpa/Romeo, impact factor)
Publisher Oxford Univ Press Inc
Extent 1174-1181
Origin http://dx.doi.org/10.1093/infdis/jiq167
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000289168500018
URI http://repositorio.unifesp.br/handle/11600/33633

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