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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Differential Persistence of Transmitted HIV-1 Drug Resistance Mutation Classes

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Author(s):
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Jain, Vivek [1] ; Sucupira, Maria C. [2] ; Bacchetti, Peter [3] ; Hartogensis, Wendy [1] ; Diaz, Ricardo S. [2] ; Kallas, Esper G. [2, 4] ; Janini, Luiz M. [2] ; Liegler, Teri [1] ; Pilcher, Christopher D. [1] ; Grant, Robert M. [5] ; Cortes, Rodrigo [2] ; Deeks, Steven G. [1] ; Hecht, Frederick M. [1]
Total Authors: 13
Affiliation:
[1] Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, San Francisco, CA 94143 - USA
[2] Univ Fed Sao Paulo, Div Infect Dis, Sao Paulo - Brazil
[3] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 - USA
[4] Univ Sao Paulo, Div Clin Immunol & Allergy, BR-05508 Sao Paulo - Brazil
[5] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 - USA
Total Affiliations: 5
Document type: Journal article
Source: Journal of Infectious Diseases; v. 203, n. 8, p. 1174-1181, APR 15 2011.
Web of Science Citations: 86
Abstract

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. (AU)

FAPESP's process: 04/15856-9 - Prospective analysis of the virological and immunological characteristics in individuals with recent HIV-1 infection in the cities of São Paulo and Santos
Grantee:Ricardo Sobhie Diaz
Support Opportunities: Research Projects - Thematic Grants