INTERFERONS IN THE PERSISTENCE, PATHOGENESIS, AND TREATMENT OF HIV-INFECTION

Interferon (IFN) plays an important role in the treatment and pathogenesis of HIV disease. Recent studies show beneficial effects of IFN-alpha in the treatment of HIV-associated Kaposi's Sarcoma and early HIV-infection. Moreover, cell culture studies support these beneficial effects. HIV infection of monocytes is blocked by IFN-alpha administered at the time of viral challenge. The IFN-alpha-treated cells show no evidence of HIV infection. Viral gene products produced in monocytes infected with HIV then treated with IFN-alpha gradually decrease to baseline. Large quantities of proviral DNA are seen in the HIV-infected IFN-alpha-treated cells with little evidence for viral transcription suggesting true microbiological latency. While most viral infections of cells result in IFN production, HIV is a notable exception. Indeed, HIV does not induce monocytes to produce IFN-alpha and blocks its production following poly(I).poly(c) stimulation. This allows HIV yet another mechanism to evade an important host antiviral response. Paradoxically, the appearance of IFN activity in sera of HIV-infected patients is associated with disease progression, not resolution. Recent observations showing that the interaction between HIV-infected monocytes and PBMC results in the production of IFN-alpha-s with reduced anti-HIV activity may help explain this paradox. Thus, IFN-alpha plays an important but complex role in HIV disease. The elucidation of cellular factors that regulate the antiretroviral effects of IFN-alpha may lead to the development of novel therapeutic strategies for HIV infection.