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Phenotypic susceptibility to didanosine is associated with antiviral activity in treatment-experienced patients with HIV-1 infection.

AbstractOBJECTIVE:
We investigated the relationship between human immunodeficiency virus (HIV) phenotypic susceptibility to didanosine and the antiviral activity of didanosine (ddI) in the JAGUAR study.
METHODS:
Baseline plasma HIV phenotypic susceptibility to ddI was assessed using a phenotype assay of patients randomized to receive ddI or placebo for 4 weeks in addition to their current regimen. Phenotypic susceptibility scores (PSSs) were then calculated for each sample. Associations between PSS and week 4 reductions in plasma HIV-1 RNA load or virologic response were assessed using linear regression and Jonckherre's test and the Wilcoxon and Cochran-Armitage tests, respectively.
RESULTS:
In the ddI arm, a significant association between reduction in viral load and continuous PSS was observed (P<.0001). Using distinct categories, an increasing fold change (FC) in susceptibility to ddI was strongly associated with smaller reductions in plasma HIV-1 RNA load (P<.0001). The proportion of virologic responders was 83% (15/18) for patients with a ddI FC < or =1.3, 50% (33/66) for patients with an FC of 1.3-2.2, and 29% (4/14) for patients with an FC > or =2.2 (P=.0008). After we determined these findings, 3 ddI FC categories were defined using 1.3 and 2.2 as thresholds.
CONCLUSIONS:
The relationship between phenotypic susceptibility to ddI and reduction in plasma HIV-1 RNA load describes a continuum. The establishment of a lower clinical cutoff at 1.3 and an upper clinical cutoff at 2.2 are clinically relevant.
AuthorsPhilippe Flandre, Colombe Chappey, Anne Genevieve Marcelin, Kirk Ryan, Jen-Fue Maa, Mike Bates, Daniel Seekins, Marie Charlotte Bernard, Vincent Calvez, Jean Michel Molina
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 195 Issue 3 Pg. 392-8 (Feb 01 2007) ISSN: 0022-1899 [Print] United States
PMID17205478 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-HIV Agents
  • RNA, Viral
  • Didanosine
Topics
  • Anti-HIV Agents (pharmacology, therapeutic use)
  • Didanosine (pharmacology, therapeutic use)
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Endpoint Determination
  • HIV Infections (drug therapy, virology)
  • HIV-1 (drug effects, genetics)
  • Humans
  • Microbial Sensitivity Tests
  • Mutation
  • RNA, Viral (blood)
  • Species Specificity
  • Viral Load

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