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Mixed HIV Coreceptor Use Associated With Lower CD4 Count

for a phase 2b study of vicriviroc (study ACTG A5211) to determine whether their strains used CCR5 alone, CXCR4 alone, or both receptors to infect cells.

Of 391 individuals who had available results, Wilkin and colleagues report that 50% of people had a strain of virus that used CCR5 alone, 46% had a mixed or 'dual-tropic' viral population, while only 4% had virus that used CXCR4 alone. An analysis of other factors found that people with dual-tropic viral strains had lower CD4 counts than those with CCR5-using or CXCR4-using virus alone (103 cells/mm3 vs 170 and 161 cells/mm3 respectively, p<0.001).

Participants who had only CCR5-using viral strains were then eligible to participate in the drug trial. However, of 118 individuals who were eligible to enter the study, 10% had a dual-tropic strain by the time of study entry (a median interval of 37 days). The authors say they believe that this evidence of change in tropism is more likely to reflect the variability of the Trofile coreceptor assay used in the study rather than the speed at which tropism can switch in a treatment-experienced population.

Dual-tropic viral strains are found more commonly in treatment-experienced patients, and it has been suggested that CXCR4-using strains may develop due to antiretroviral treatment. Moreover, the authors suggest that the poorer prognosis associated with CXCR4-using viral strains might in fact be due to development of dual-tropic strains.

In an accompanying commentary, Thomas Melby of Trimeris, the company which developed the HIV entry inhibitor enfuvirtide (Fuzeon) concurs, noting a trend towards increasing frequency of dual-tropic virus with increasing treatment experience. He points to the high prevalence of dual-tropic virus in the TORO 1 and 2 studies of enfuvirtide, which also recruited highly treatment-experienced patients, and a similar association between dual-tropic virus and the lowest CD4 cell counts to the one fou
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