Exploiting the apoptotic process for management of HIV: are we there yet?

CD4+ T cells die in individuals infected with HIV, either as a result of direct HIV infection or as uninfected "innocent bystanders". Possible mechanisms for bystander killing include generation of viral products such as Tat or gp120 and expression of death receptor ligands, such as FasL, that engage functional death receptors on uninfected cells. This review covers the sometimes conflicting in vitro and ex vivo studies that address these possible mechanisms of HIV-associated cell death. It is an intriguing possibility that manipulation of cell death processes, to decrease bystander death or increase death of infected cells, in patients infected with HIV might provide a useful adjunct to antiretroviral therapy.