title: Differential persistence of transmitted HIV-1 drug resistance mutation classes.
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.
authors: HIV/AIDS Division, San Francisco General Hospital, University of California, San Francisco, San Francisco, CA 94143, USA.
authors: Vivek
authors: V
authors: Jain
authors: Maria C
authors: MC
authors: Sucupira
authors: Peter
authors: P
authors: Bacchetti
authors: Wendy
authors: W
authors: Hartogensis
authors: Ricardo S
authors: RS
authors: Diaz
authors: Esper G
authors: EG
authors: Kallas
authors: Luiz M
authors: LM
authors: Janini
authors: Teri
authors: T
authors: Liegler
authors: Christopher D
authors: CD
authors: Pilcher
authors: Robert M
authors: RM
authors: Grant
authors: Rodrigo
authors: R
authors: Cortes
authors: Steven G
authors: SG
authors: Deeks
authors: Frederick M
authors: FM
authors: Hecht
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D015331:Cohort Studies; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral