Cocaine amplifies HIV-1 replication in cytomegalovirus-stimulated peripheral blood mononuclear cell cocultures

Cocaine and CMV each have been suggested to promote the progression of HIV-1 infection. In the present study, the interaction of cocaine and CMV was investigated in a PBMC coculture assay in which release of HIV-1 p24 Ag into coculture supernatants was used as an index of HIV-1 replication. CMV was an effective activation signal for HIV-1 replication when PBMC from CMV- seropositive donors were used in the coculture assay, and cocaine markedly increased replication of HIV-1 in these cocultures. The synergistic activity of cocaine was reduced by neutralizing antibodies to TNF-α and by pentoxifylline, an inhibitor of TNF-α mRNA production. Also, antibodies to transforming growth factor-β (TGF-β) eliminated the amplifying effect of cocaine on HIV-1 replication, whereas antibodies to IL-6 were inactive. The potentiating effect of cocaine could be reproduced by addition of rTNF-α or rTGF-β to the cocultures of CMV-activated PBMC, although TGF-β was substantially more potent than TNF-α. The possibility that TNF-α may act indirectly through stimulation of TGF-β was suggested by the finding of reduced TGF-β levels in culture supernatants of PBMC that were treated with CMV and cocaine in the presence of antibodies to TNF-α. Thus, cocaine amplifies HIV-1 replication in cocultures containing CMV-activated PBMC via a mechanism that appears to involve both TNF-α and TGF-β. The results of this study support the possibility that cocaine and CMV could enhance HIV-1 replication and, thus, aggravate HIV-1-related disease.