Inhibition of human immunodeficiency virus type 1 infection in vitro by combination of delavirdine, zidovudine and didanosine.
Delavirdine (DLV), a non-nucleoside reverse transcriptase inhibitor (RTI) of human immunodeficiency virus type 1 (HIV-1), was evaluated in two and three-drug combinations against acute and co-culture infections of HIV-1JRCSF in human peripheral blood mononuclear cells. DLV combined with didanosine (DDI) at 1:10 and 1:30 ratios were statistically synergistic (combination indices (CI) < 1) at > 75% inhibition levels. However, at 1:100 ratio, the interaction appeared to be additive. Three-drug combinations of zidovudine (ZDV), DLV, and DDI (at a ratio of 1:2:333) were synergistic at 50-99% inhibition levels. The three-drug group also showed significantly (P < 0.01) lower p24 levels in acute cultures than two-drug combination groups (DLV + ZDV, DLV + DDI, ZDV + DDI). In co-culture studies, the extent of viral inhibition was dependent on drug dose and the duration of treatment. Combination of DLV, ZDV, and DDI at IC95 concentration of the individual drugs showed complete inhibition of viral growth in co-culture after 19 days, but not after 7 or 12 days of treatment. The combinations studied did not show additive or synergistic drug toxicity. These data provide an in vitro basis for beneficial use of DLV in combinations with DDI and ZDV in HIV-1 infected patients.
Chong
K T
KT
Pharmacia & Upjohn Company, Kalamazoo MI 49001-0199, USA.
Pagano
P J
PJ
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002460:Cell Line; D004279:DNA, Viral; D020008:Delavirdine; D016049:Didanosine / Q000008:administration & dosage / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D015215:Zidovudine / Q000008:administration & dosage / Q000494:pharmacology*
D019380:Anti-HIV Agents; D004279:DNA, Viral; D007211:Indoles; D010879:Piperazines; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D020008:Delavirdine; D016049:Didanosine