NEVIRAPINE SYNERGISTICALLY INHIBITS HIV-1 REPLICATION IN COMBINATION WITH ZIDOVUDINE, INTERFERON OR CD4 IMMUNOADHESIN

Objective: To determine whether synergistic inhibition of HIV-1 replication would result from the in vitro use of nevirapine in combination with zidovudine, interferon (IFN)-alpha 2C, and CD4 immunoadhesin. Design and methods: The non-nucleoside reverse transcriptase inhibitor nevirapine (formerly BI-RG-587) was tested in combination with the other antiretroviral agents. Assays were performed on stimulated peripheral blood lymphocytes infected with HIV-1. Virus replication was assessed by the release of viral p24 antigen into culture supernatants. The median-effect principle was used to assess for synergistic interactions of the combined agents. Results: Zidovudine, IFN-alpha 2C and CD4 immunoadhesin, when used in combination with nevirapine, synergistically inhibited HIV-1 replication in human peripheral blood lymphocytes compared with each agent used alone. Some analyses were also consistent with additive effects, but antagonism was not noted. Conclusion: These in vitro findings provide a scientific basis for future trials with similar drug combinations.