Change from CCR5 to CXCR4 phenotype may affect immunologic responses

Some patients treated with antiretroviral therapy receive some immunologic benefit without significant virologic suppression. The full explanation for this observation is unknown but viral characteristics may play some role.

It is well known that co-receptor usage plays a significant role in HIV-1 disease progression. The initial, infecting strains of HIV-1 usually utilize CCR5 (R5), but later CXCR4 (X4) strains emerge and this change usually heralds CD4+ cell depletion and clinical deterioration.

In a study presented at the 41st ICAAC, researchers evaluated co-receptor utilization of serial primary HIV-1 isolates from 15 women (mean CD4+ T cell count 147 cells/mm3 and viral load 5.2 log10 copies/mL) with advanced disease who had predominantly X4 viruses. Twelve initiated therapy with HAART and three with two to three nucleoside analogues.

The analysis demonstrated a shift in the predominant viral population from X4 strains at baseline to the R5 strains after initiation of antiviral drugs (P<0.003). This shift from X4 to R5 happened very rapidly, in some patients within days of starting HAART, and was followed by a complete suppression of X4 viruses within two weeks of therapy.

In two women started on Combivir (zidovudine and lamivudine) and efavirenz (Sustiva/Stocrin) there was a complete shift from all X4 to all R5 over time, with X4 suppressed significantly within one week. In some women, the shift from X4 to R5 occurred despite a lack of full viral suppression and the most significant factor was being treated with at least two antiretroviral drugs.

The authors conclude: “Shifts in co-receptor usage may occur rapidly following the start of HAART and contribute to the clinical efficacy of anti-HIV drugs.” The significance and clinical utility of this finding are unclear. It is also not clear what is responsible for the shift and whether the cells infected with the more pathogenic X4 virus simply die more quickly than those infected with R5 virus and that this actually accounts for the apparent shift from X4 to R5.

H Burger and others. Preferential Suppression of CXCR4 Specific HIV-1 Strains by Antiviral Therapy and Dynamics of Response. Abstract I-1322.