Abstract | OBJECTIVE: 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.
|
Authors | Philippe Flandre, Colombe Chappey, Anne Genevieve Marcelin, Kirk Ryan, Jen-Fue Maa, Mike Bates, Daniel Seekins, Marie Charlotte Bernard, Vincent Calvez, Jean Michel Molina |
Journal | The Journal of infectious diseases
(J Infect Dis)
Vol. 195
Issue 3
Pg. 392-8
(Feb 01 2007)
ISSN: 0022-1899 [Print] United States |
PMID | 17205478
(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
|