Changes in CCR5 and CXCR4 expression and β-chemokine production in HIV-1-infected patients treated with highly active antiretroviral therapy

The effect of highly active antiretroviral therapy (HAART) on the expression of CCR5 and CXCR4 HIV coreceptors and the production of the β-chemokines regulated upon activation, normal T-cell expressed and secreted (RANTES), macrophage inflammatory protein (MIP)-1α, and MIP-1β has been investigated in 30 HIV-1-infected individuals during 12-36 months of therapy. CCR5 expression was increased in both CD4⁺ and CD8⁺ subsets, whereas CXCR4 expression was upregulated only in CD4⁺ cells. CCR5 levels normalized during 36 months of therapy and positively correlated with the levels of memory, CD95⁺, and HLA-DR⁺ T cells. In contrast, the frequency of CXCR4-expressing cells was not significantly modified by HAART, although a downregulation was observed early after starting treatment. CXCR4 levels were significantly associated with the frequencies of naive T cells and negatively correlated with plasma viral load, CD95, and HLA-DR expression. An increased production of both spontaneous and lectin-induced RANTES, MIP-1α, and MIP-1β was found at baseline in HIV-infected individuals. The spontaneous β-chemokines production was not modified by 12 months of HAART, although a significant reduction was seen during the first months of therapy. A transient decrease of lectin-stimulated RANTES production was also observed, whereas the reduction of lectin-induced MIP-1α persisted for up to 12 months of therapy. In contrast, MIP-1β secreted by phytohemagglutinin antigen-stimulated peripheral blood mononuclear cells progressively increased during HAART. In conclusion, our data indicate a normalization of CCR5 but not CXCR4 expression during suppressive therapy and changes in β-chemokine production that may play a part in dictating the efficiency of viral infection and consequently the disease course.