Anti-human immunodeficiency virus interactions of SCH-C (SCH 351125), a CCR5 antagonist, with other antiretroviral agents in vitro.
SCH-C (SCH 351125) is a small-molecule antagonist of the human immunodeficiency virus type 1(HIV-1) coreceptor CCR5. It has in vitro activity against R5 viruses with 50% inhibitory concentrations ranging from 1.0 to 30.9 nM. We have studied anti-HIV-1 interactions of SCH-C with other antiretroviral agents in vitro. Synergistic interactions were seen with nucleoside reverse transcriptase inhibitors (zidovudine and lamivudine), nonnucleoside reverse transcriptase inhibitors (efavirenz), and protease inhibitors (indinavir) at all inhibitory concentrations evaluated. We have also studied antiviral interactions between the HIV-1 fusion inhibitor T-20 and SCH-C against a panel of R5 HIV-1 isolates. We found synergistic interactions against all the viruses tested, some of which harbored resistance mutations to reverse transcriptase and protease inhibitors. Anti-HIV-1 synergy was also observed between SCH-C and another R5 virus inhibitor, aminooxypentane-RANTES. These findings suggest that SCH-C may be a useful anti-HIV drug in combination regimens and that a combination of chemokine coreceptor/fusion inhibitors may be useful in the treatment of multidrug-resistant viruses.
Tremblay
Cécile L
CL
Massachusetts General Hospital, Infectious Diseases Unit, Harvard Medical School, Boston, Massachusetts 02114, USA.
Giguel
Françoise
F
Kollmann
Christopher
C
Guan
Yongbiao
Y
Chou
Ting-Chao
TC
Baroudy
Bahige M
BM
Hirsch
Martin S
MS
D019380:Anti-HIV Agents / Q000494:pharmacology*; D065100:CCR5 Receptor Antagonists; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004347:Drug Interactions; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests / Q000379:methods; D010091:Oximes; D010880:Piperidines; D011725:Pyridines / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D003497:Cyclic N-Oxides; D010091:Oximes; D010880:Piperidines; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; C438583:Ancriviroc