MORPHINE PROMOTES THE GROWTH OF HIV-1 IN HUMAN PERIPHERAL-BLOOD MONONUCLEAR CELL COCULTURES

Because morphine has been shown to alter the function of human T lymphoyctes and monocytes, we postulated that morphine would promote the growth of HIV-1 in these cells. To test this hypothesis, a coculture assay was used consisting of phytohemagglutinin (PHA)-activated peripheral blood mononuclear cells (PBMC) from normal donors and PBMC which had been infected with a viral isolate from an asymptomatic patient, HIV-1(AT). The growth of HIV-1(AT), as reflected by the concentration of p24 antigen in coculture supernatants, was markedly increased in cocultures that contained morphine. A bell-shaped dose-response curve was observed with three- to fourfold increased growth at a morphine concentration of 10-12 M. Augmentation of HIV-1(AT) growth by morphine required an interaction with the PHA-activated donor PBMC. Furthermore, potentiation of HIV-1(AT) growth by morphine was stereospecific and was antagonized by naloxone and β-funaltrexamine indicating involvement of an opiate receptor mechanism. These findings provide an additional explanation of how opiates could act as a cofactor in the pathogenesis of HIV-1 in intravenous drug users.