Anti-human immunodeficiency virus drugs are ineffective against Pneumocystis carinii in vitro and in vivo.
Human immunodeficiency virus (HIV) protease inhibitors (PIs) recently have been reported to be active against Pneumocystis carinii in cell culture. Twelve anti-HIV drugs were analyzed for their effects against rat P. carinii by an ATP cytotoxicity assay. Indinavir and saquinavir exhibited slight anti-P. carinii activity at concentrations above those that can be clinically achieved in serum; other PIs and nucleoside and nonnucleoside reverse-transcriptase inhibitors were inactive against the organism. Anti-HIV drugs, alone or in combination, did not materially reduce the organism count in the treatment of P. carinii pneumonia in immunosuppressed mice. Thus, anti-HIV drugs have little or no activity against P. carinii in these in vitro and in vivo systems. Caution should be used when interpreting reports of the susceptibility of P. carinii to anti-HIV drugs on the basis of in vitro testing only.
Walzer
P D
PD
Research Service, Veterans Affairs Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA. peter.walzer@med.va.gov
Ashbaugh
A
A
Collins
M
M
Cushion
M T
MT
D000284:Administration, Oral; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D017320:HIV Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019469:Indinavir / Q000008:administration & dosage / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000382:microbiology; D051379:Mice; D008809:Mice, Inbred C3H; D011010:Pneumocystis / Q000187:drug effects* / Q000302:isolation & purification; D016720:Pneumocystis Infections / Q000188:drug therapy*; D019258:Saquinavir / Q000008:administration & dosage / Q000494:pharmacology
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D019469:Indinavir; D019258:Saquinavir