HIV-1 strains using the CXCR4 co-receptor are suppressed with potent therapy

With disease progression, the HIV-1 viral population often shifts from strains that use T cell CCR5 (R5) co-receptor to those that use the CXCR4 (X4) co-receptor. However, highly active antiretroviral therapy (HAART) may cause a shift back to R5-using strains, which may help explain why antiretroviral agents are able to slow disease progression without uniformly suppressing plasma viraemia.

In a study reported in the February issue of the Journal of Clinical Investigation, Dr. Harold Burger from the New York State Department of Health in Albany and colleagues assessed the effects of HAART on the HIV-1 viral population in 15 women harbouring primarily X4-using strains at baseline.

The authors found that, with HAART, the predominant viral population shifted from X4- to R5-using strains. Furthermore, this change was independent of changes in plasma HIV-1 RNA level and CD4+ cell count.

“Understanding co-receptor usage during potent antiretroviral therapy is relevant to HIV-1 dynamics and the maintenance of viral suppression and clinical response,” the researchers point out.

Dr. Burger’s team believes that “co-receptor usage studies may have a role in virologic monitoring of patients on antiviral therapy particularly as drugs are developed that target R5 or X4 strains of HIV-1.” However, the investigators emphasize that “additional studies of viral variation, drug resistance, and co-receptor usage in well-characterized, treated patients are needed.”