Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
J Infect Dis. 2011 Apr 15;203(8):1174-81. doi: 10.1093/infdis/jiq167.

Differential persistence of transmitted HIV-1 drug resistance mutation classes.

Author information

  • 1HIV/AIDS Division, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA 94143, USA.

Abstract

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 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.

© The Author 2011. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

PMID:
21451005
[PubMed - indexed for MEDLINE]
PMCID:
PMC3107558
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk