Immune activation in HIV-infected African individuals

Objective: Immune activation induced by chronic infections, dietary limitat ions, and poor hygienic conditions is suggested to be present in African HI V infection and is at the basis of the hypothesis that HIV infection in Afr ica could be prevalently associated with immunopathogenetic mechanisms. Ver y limited data are nevertheless available supporting this theory, and in pa rticular no data are reported on functional and phenotypic analyses perform ed on fresh peripheral blood mononuclear cells (PBMC) of African HIV-infect ed patients living in Africa. Design: Immunological and virological parameters were analysed in fresh PBM C of HIV-infected African and Italian patients with advanced HIV disease an d comparable CD4 and CD8 counts, sex, and age. Both functional (antigen- an d mitogen-stimulated cytokine production) and phenotypic (activation marker s; markers preferentially expressed by T helper (Th) type 2 cells or by mem ory and naive cells) analyses were performed. Results were compared with th ose of HIV-seronegative African and Italian controls. HIV plasma viraemia w as analysed by competitive polymerase chain reaction (PCR) and branched DNA techniques. Results: (1) The production of mitogen-stimulated IFN-gamma and TNF-alpha a s well as the production of env peptide-stimulated IFN-gamma, TNF-alpha, an d IL-10 are increased in African HIV infection; (2) the expression of activ ation and Th2-associated markers is augmented in African HIV infection as i s the memory/naive ratio; (3) mitogen-stimulated IFN-gamma and IL-10 produc tion, as well as the expression of activation and Th2-associated markers an d the memory/naive ratio, are augmented in African compared with Italian co ntrols; and (4) plasma viraemia is reduced in African compared with Italian HIV-infected individuals. Conclusions: These results, which are the first to be reported on fresh mat erial from African HIV-infected patients living in Africa, indicate that HI V disease is associated with an abnormal immune hyperactivation and may be accompanied in these patients by lower loads of virus, and show that such a ctivation is present even in HIV-seronegative controls. (C) 1998 Lippincott Williams & Wilkins.