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Who Will Benefit from CCR5 Inhibitors?
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".....presence of some CXCR4 tropism in an individual's viral population is thought to reflect more-aggressive disease.....but they do not prove that the CXCR4 viruses are the cause of progressive HIV disease. Importantly, a sizable proportion of patients retain pure CCR5 tropism even in advanced HIV infection".
More-advanced disease is correlated with a higher probability of mixed viral populations or dual-tropic virus.
When CCR5 inhibitors enter the marketplace in the near future, clinicians will need some guidance for selecting patients likely to benefit from these drugs. To this end, researchers evaluated clinical and epidemiologic data from patients screened for enrollment in a phase IIb trial of the CCR5 inhibitor vicriviroc.
The 391 subjects who provided samples for HIV coreceptor phenotype testing were all heavily treatment-experienced; 197 (50%) had virus that used CCR5 only, 16 (4%) had virus that used CXCR4 only, and 178 (46%) had dual-tropic virus or a mixed population. Median age was higher in the CCR5-tropic group than in the dual/mixed group (46 vs. 44 years), and white subjects were more likely than blacks to have CCR5-tropic virus; no differences were seen by sex. The CCR5 group had higher current CD4 counts (median, 170 vs. 103 cells/mm3), higher nadir CD4 counts (61 vs. 44 cells/mm3), and slightly lower viral loads (median, 4.5 vs. 4.7 log copies/mL) than did the dual/mixed group. On multivariate analysis, only current CD4-cell count remained a significant predictor of coreceptor phenotype.
The small group of patients with virus that used CXCR4 alone had significantly lower viral loads than did either of the other two groups, but no other epidemiologic or clinical factors were significantly associated with this phenotype. Number and pattern of resistance mutations did not vary among groups.
Comment: The presence of some CXCR4 tropism in an individual's viral population is thought to reflect more-aggressive disease. The data presented here (which are consistent with those of similar analyses) confirm this association, but they do not prove that the CXCR4 viruses are the cause of progressive HIV disease. Importantly, a sizable proportion of patients retain pure CCR5 tropism even in advanced HIV infection.
- Abigail Zuger, MD
Published in AIDS Clinical Care March 12, 2007
Citation(s):
Wilkin TJ et al. HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trial Group A5211. Clin Infect Dis 2007 Feb 15; 44:591-5.
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