Prevalence of Coreceptor Use in Treatment-Naïve Patients
Treatment-naïve patients with more-advanced HIV infection were more likely to harbor dual-tropic virus at baseline than were those with less-advanced disease. Nevertheless, there was no appreciable difference in response to antiretroviral therapy based on coreceptor status.
Knowledge of HIV coreceptor use is becoming a clinically important topic as CCR5 inhibitors (e.g., maraviroc, vicriviroc, and aplaviroc) enter phase III testing. Although data are not yet available on whether these drugs are effective in patients whose HIV can use CXCR4 (X4), as well as CCR5 (R5), the best treatment responses are likely to be seen in patients with R5-only virus. One unanswered question is whether screening for coreceptor usage will be necessary before initiating treatment with this new class of drugs. In this large, industry-supported study, researchers evaluated the distribution of coreceptor usage among 1991 HIV-infected patients initiating potent combination antiretroviral therapy at the British Columbia Centre for Excellence in HIV/AIDS. Assessment of coreceptor usage was based on the most recent plasma sample collected before treatment initiation.
Of the 979 samples that could be typed, 178 (18.2%) included X4 variants; all but one demonstrated the presence of dual-tropic virus (both R5 and X4 variants). Patients with dual-tropic virus had higher pretreatment viral loads and lower baseline CD4-cell counts than those with R5-only virus; they were also significantly more likely to have had an AIDS-defining illness before initiating antiretroviral therapy. Dual-tropic virus was present in fewer than 10% of patients with baseline CD4 counts above 200 cells/mm versus more than 50% of those with counts below 25 cells/mm. On average, CD4-cell counts were three times lower in patients harboring X4 variants than in those with R5-only virus. However, after adjustment for factors that could affect treatment outcome, the presence of X4 variants was not independently associated with response to antiretroviral therapy.
If studies that include CCR5 inhibitors as part of combination antiretroviral therapy demonstrate that the presence of X4 virus is associated with diminished treatment response, then data from studies like this one will be critical for determining the appropriate use of this new class of agents. Tropism assays will likely be necessary to identify suitable candidates for CCR5 inhibitors, especially as CD4-cell counts fall. Given that dual-tropic virus is more common in patients with lower CD4-cell counts, CCR5 inhibitors may need to be positioned earlier in the sequence of antiretroviral agents to maximize their effect.
Published in AIDS Clinical Care September 28, 2005
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Treatment-naïve patients with more-advanced HIV infection were more likely to harbor dual-tropic virus at baseline than were those with less-advanced disease. Nevertheless, there was no appreciable difference in response to antiretroviral therapy based on coreceptor status.
Knowledge of HIV coreceptor use is becoming a clinically important topic as CCR5 inhibitors (e.g., maraviroc, vicriviroc, and aplaviroc) enter phase III testing. Although data are not yet available on whether these drugs are effective in patients whose HIV can use CXCR4 (X4), as well as CCR5 (R5), the best treatment responses are likely to be seen in patients with R5-only virus. One unanswered question is whether screening for coreceptor usage will be necessary before initiating treatment with this new class of drugs. In this large, industry-supported study, researchers evaluated the distribution of coreceptor usage among 1991 HIV-infected patients initiating potent combination antiretroviral therapy at the British Columbia Centre for Excellence in HIV/AIDS. Assessment of coreceptor usage was based on the most recent plasma sample collected before treatment initiation.
Of the 979 samples that could be typed, 178 (18.2%) included X4 variants; all but one demonstrated the presence of dual-tropic virus (both R5 and X4 variants). Patients with dual-tropic virus had higher pretreatment viral loads and lower baseline CD4-cell counts than those with R5-only virus; they were also significantly more likely to have had an AIDS-defining illness before initiating antiretroviral therapy. Dual-tropic virus was present in fewer than 10% of patients with baseline CD4 counts above 200 cells/mm versus more than 50% of those with counts below 25 cells/mm. On average, CD4-cell counts were three times lower in patients harboring X4 variants than in those with R5-only virus. However, after adjustment for factors that could affect treatment outcome, the presence of X4 variants was not independently associated with response to antiretroviral therapy.
If studies that include CCR5 inhibitors as part of combination antiretroviral therapy demonstrate that the presence of X4 virus is associated with diminished treatment response, then data from studies like this one will be critical for determining the appropriate use of this new class of agents. Tropism assays will likely be necessary to identify suitable candidates for CCR5 inhibitors, especially as CD4-cell counts fall. Given that dual-tropic virus is more common in patients with lower CD4-cell counts, CCR5 inhibitors may need to be positioned earlier in the sequence of antiretroviral agents to maximize their effect.
Published in AIDS Clinical Care September 28, 2005
Click here for AIDS Clinical Care subscription information.
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