indinavir-sulfate and Pneumocystis-Infections

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.

Topics: Administration, Oral; Animals; Anti-HIV Agents; Disease Models, Animal; Drug Therapy, Combination; HIV Protease Inhibitors; Indinavir; Lung; Mice; Mice, Inbred C3H; Pneumocystis; Pneumocystis Infections; Saquinavir

Since 1996, the introduction of protease inhibitors (PIs) has led to a dramatic decrease of human immunodeficiency virus-related Pneumocystis carinii pneumonia. This effect is clearly due, in large part, to the induction of immune reconstitution by highly active antiretroviral therapy (HAART). However, it is conceivable that PIs had other beneficial effects, including direct activity against Pneumocystis. In this study, the occurrence of specific aspartyl proteases in Pneumocystis is described. These protease targets seemed to be affected in vitro by antiretroviral PIs. These data suggest intriguing implications for the possible antipneumocystis benefit of receiving indinavir, ritonavir, nelfinavir, or saquinavir during HAART.

Topics: Animals; Cell Line; HIV Protease Inhibitors; Humans; Indinavir; Lung; Male; Microbial Sensitivity Tests; Nelfinavir; Pepstatins; Pneumocystis; Pneumocystis Infections; Rats; Rats, Sprague-Dawley; Saquinavir