EFFECT OF MYCOBACTERIUM-TUBERCULOSIS ON HIV REPLICATION - ROLE OF IMMUNE ACTIVATION

The prevalence of Mycobacterium tuberculosis (MTB)(3) has increased wo rldwide, in part due to the HIV epidemic, Epidemiology data have demon strated that HIV-infected individuals are more susceptible to MTB dise ase, which may lead to an acceleration in the progression of HIV disea se, The purpose of this study was to determine whether MTB modulates H IV infection in vivo and to delineate the mechanisms involved by using in vitro model systems, Plasma viral load was measured in HIV-infecte d individuals before, during, and after the development of MTB disease ; a 5- to 160-fold increase in viral replication was observed during t he acute phase of MTB disease, In order to evaluate the mechanisms inv olved in this MTB-induced HIV replication, we used an in vitro system of primary PBMC and lymph node mononuclear cells isolated from HIV-inf ected individuals. The data demonstrated that MTB induced HIV replicat ion in CD8(+) T cell-depleted lymphocytes from HIV-infected individual s with a history of purified protein derivative (PPD) positivity but n ot in those who were PPD negative; this induction of HIV replication c orrelated with the level of cellular activation. In an in vitro acute HIV infection model, MTB increased HIV replication in PBMC from health y donors with a history of PPD positivity, but not in PBMC from PPD-ne gative donors and this induction of viral replication also correlated with cellular activation. In conclusion, MTB increased HIV replication in vivo and in an in vitro model. This MTB-mediated viral production likely occurs through Ag-specific activation and infection of respondi ng T cells.