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Mixed HIV Coreceptor Use Associated With Lower CD4 Count

nd in ACTG A5211. He suggests that the poorer prognosis associated with syncitium-inducing virus might indeed be due to the presence of dual-tropic virus: 'a tangle of assaults from both CCR5-using and CXCR4-using viral envelopes'.

He goes on to suggest that dual-tropic virus may be more destructive of the CD4 cell population than CXCR4-tropic virus because of its ability to infect a wider range of target cells than either type of single-tropic virus.

However, the analyses of the TORO studies and ACTG A5211 did not find an association between dual-tropic virus and higher viral load, as would be expected if this hypothesis is correct. But Melby argues that this may be explained by the greater sensitivity of the Trofile coreceptor assay used in each study when compared to previous research, using older assays that did suggest an association. The assay may be picking up the switch to dual-tropic virus earlier, at higher CD4 cell counts, he suggests.

The ACTG A5211 researchers point out that even at relatively high CD4 cell counts, a surprisingly large proportion of patients were found to have dual-tropic or CXCR4-using virus: 45% in the 200-350 cells/mm3 range and 29% in those with CD4 cell counts above 350 cells/mm3.

Thus, the researchers suggest that “assessment of coreceptor use may be a critical determinant of eligibility for treatment with the CCR5 and CXCR4 receptor inhibitors currently in clinical development”, noting that specialised tests may therefore be necessary before starting treatment with a chemokine-receptor blocking drug. “CD4 cell count alone cannot reliably predict coreceptor use”, they note.

The authors do not discuss the implications of dual-tropic virus for response to CCR5 antagonists. However a recent study of maraviroc in highly-treatment experienced patients with low CD4 cell counts who had dual-tropic or CXCR4-using virus has shown that while viral load suppression is not improve
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