Expression of chemokine receptors CCR5 and CXCR4 on CD4+ T cells and plasma chemokine levels during treatment of active tuberculosis in HIV-1-coinfected patients.
The pathogenesis of persistently elevated plasma HIV viremia in patients coinfected with tuberculosis (TB) during anti-TB treatment in Africans remains unknown. We examined the expression of chemokine receptors CCR5 and CXCR4 on CD4+ T cells and plasma chemokine levels of macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, regulated on activation normal T expressed and secreted (RANTES), and stromal cell-derived factor (SDF)-1alpha among TB patients with HIV coinfection during the first 2 months of anti-TB treatment. During treatment of TB, the plasma HIV-1 load and CD4+ T-cell count remained unchanged. Levels of CCR5 and CXCR4 expression on CD4+ T cells as well as plasma levels of chemokines remained persistently elevated during anti-TB treatment. Persistently elevated plasma HIV viremia also paralleled persistently elevated expressions of activated CCR5+ or CXCR4+ CD4+ T cells. These results suggest that increased expression of CCR5 and CXCR4 on an activated CD4+ T-cell population coupled with persistently elevated chemokines may provide a suitable condition for continuous replication of HIV associated with TB coinfection. This, in turn, may contribute, at least in part, to the observed persistently elevated plasma HIV viremia in coinfected patients despite anti-TB treatment.
Ethio-Netherlands AIDS Research Project (ENARP) and Ethiopian Health and Nutrition Research Institute (EHNRI), Addis Ababa, Ethiopia. dawit@enarp.com
Dawit
D
Wolday
Belete
B
Tegbaru
Afework
A
Kassu
Tsehaynesh
T
Messele
Roel
R
Coutinho
Debbie
D
van Baarle
Frank
F
Miedema
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000276:immunology*; D000995:Antitubercular Agents / Q000627:therapeutic use; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000097:blood; D054377:Chemokine CXCL12; D018925:Chemokines / Q000097:blood*; D019743:Chemokines, CXC / Q000097:blood; D015658:HIV Infections / Q000150:complications* / Q000276:immunology* / Q000821:virology; D006801:Humans; D008213:Lymphocyte Activation; D019402:Macrophage Inflammatory Proteins / Q000097:blood; D019713:Receptors, CCR5 / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*; D014766:Viremia / Q000150:complications / Q000276:immunology / Q000821:virology; D014779:Virus Replication
D000995:Antitubercular Agents; C515255:CXCL12 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4