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.


METHODS
The non-nucleoside reverse transcriptase inhibitor nevirapine (formerly BI-RG-587) was tested in combination with the other antiretrovial 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.


CONCLUSIONS
These in vitro findings provide a scientific basis for future trials with similar drug combinations.
Koup
R A
RA
University of Massachusetts Medical School, Department of Pediatrics, Worcester.
Brewster
F
F
Grob
P
P
Sullivan
J L
JL
D000998:Antiviral Agents / Q000494:pharmacology; D016860:CD4 Immunoadhesins / Q000494:pharmacology*; D004357:Drug Synergism; D005240:Feasibility Studies; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000494:pharmacology*; D019829:Nevirapine; D011725:Pyridines / Q000494:pharmacology*; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D014779:Virus Replication / Q000187:drug effects; D015215:Zidovudine / Q000494:pharmacology*
D000998:Antiviral Agents; D016860:CD4 Immunoadhesins; D007370:Interferon Type I; D011725:Pyridines; D011994:Recombinant Proteins; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D019829:Nevirapine; D054303:HIV Reverse Transcriptase