| Abstract | BACKGROUND: Chemokine coreceptor use impacts both the natural history of human immunodeficiency virus type 1 (HIV-1) disease and the potential use of a new class of antiretroviral agents, the CCR5 inhibitors. METHODS: We analyzed HIV-infected patients who were screened for participation in Acquired Immunodeficiency Syndrome (AIDS) Clinical Trial Group protocol A5211, a phase 2b study of the investigational CCR5 inhibitor vicriviroc involving antiretroviral-experienced subjects. Screening CD4(+) cell count, HIV-1 plasma RNA level, HIV-1 genotype, and chemokine coreceptor use phenotype were determined. The univariate and multivariate association of subject characteristics with coreceptor use was assessed by logistic regression. RESULTS: Coreceptor use was determined for 391 subjects: 197 (50%) had virus that used the CCR5 coreceptor (the R5 group), 178 [corrected] (46%) had dual-tropic or mixed HIV-1 populations that used both CCR5 and CXCR4 coreceptors (the D/M group), and 16 (4%) had virus that used the CXCR4 coreceptor (the X4 group). The D/M group had a significantly lower median CD4(+) cell count than the R5 virus group (103 cells/ micro L vs. 170 cells/ mu L; P<.001). No other characteristics were independently associated. Among 118 subjects who entered A5211 having R5 virus, 12 (10%) had D/M virus according to the results of a second coreceptor test conducted prior to starting treatment with the study drug. CONCLUSIONS: Infection with dual-tropic or mixed HIV-1 populations that use both CCR5 and CXCR4 is common among highly treatment-experienced patients, but infection with virus using CXCR4 alone is uncommon. Subjects in the D/M group had significantly lower CD4(+) cell counts than subjects in the R5 group. Evaluating coreceptor use will be important in the clinical development of CCR5 and CXCR4 inhibitors. |
| Authors | Timothy J Wilkin, Zhaohui Su, Daniel R Kuritzkes, Michael Hughes, Charles Flexner, Robert Gross, Eoin Coakley, Wayne Greaves, Catherine Godfrey, Paul R Skolnik, Joseph Timpone, Benigno Rodriguez, Roy M Gulick
(Affiliation: Division of International Medicine and Infectious Diseases, Weill-Cornell Medical College, New York, NY, USA. tiw2001 at med.cornell.edu)
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| Journal | Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
(Clin Infect Dis)
Vol. 44
Issue 4
Pg. 591-5
(Feb 15 2007)
ISSN: 1537-6591 United States |
| PMID | 17243065
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
|
| Chemical References |
- Anti-Retroviral Agents
- Antigens, CD4
- Receptors, CCR5
- Receptors, CXCR4
|
| Topics |
- Acquired Immunodeficiency Syndrome
(diagnosis, drug therapy)
- Adult
- Analysis of Variance
- Anti-Retroviral Agents
(therapeutic use)
- Antigens, CD4
(analysis)
- Clinical Trials as Topic
- Cross-Sectional Studies
- Female
- Genotype
- HIV-1
(drug effects, genetics)
- Humans
- Logistic Models
- Male
- Middle Aged
- Patient Selection
- Probability
- Receptors, CCR5
(antagonists & inhibitors, metabolism)
- Receptors, CXCR4
(antagonists & inhibitors, metabolism)
- Viral Load
|
