Abbott Protease Inhibitor: Early Results Reported

Two separate placebo-controlled studies of ritonavir, the Abbott protease inhibitor, were reported December 7 in the NEW ENGLAND JOURNAL OF MEDICINE. Both reported good viral load and CD4 results.

A 32-week study in 84 patients in The Netherlands, Spain, and Australia, found the most sustained benefit at the highest dose tested -- 600 mg twice daily. The seven persons who completed the full 32 weeks at this dose had a median CD4 increase of 230 above baseline. The viral load reduction was reported as a mean of 0.81 logs (about a 6.5-fold, or 85%, reduction), but this number is clearly an underestimate; the study used the version of the Chiron branched DNA test which has a lower cutoff at 10,000 copies (4 logs), and since the high-dose group entered the study with a mean log copy number of 4.97, the test used could not possibly have recorded more than about a one-log decrease. A subset of high-dose patients measured with Roche PCR test, which has a much lower cutoff, found almost a 2-log drop in viral load, but complete data are not available. More problematic is the fact that 15 volunteers started the highest dose, and only 7 of them had 32-week measurements reported; a full accounting of the other
8 was not provided.

The lower doses tested (300, 400, and 500 mg twice daily) had results at four weeks which were about comparable to the 600 mg dose, but these results were not nearly as well sustained at 32 weeks.

The other study, in 62 patients for 12 weeks at five U.S. sites, tested doses of 200 and 300 mg three times daily. The median CD4 increase was 83 at week 12. Viral load decrease of 0.5 logs using the branched DNA test with a 10,000-copy cutoff; when the more sensitive PCR test was used for a subset of patients with values below the cutoff, the 12-week viral load reduction was about 1.1 logs.

The main side effects in the European study were nausea, circumoral paresthesia (abnormal sensation around the mouth), and certain blood-chemistry changes; the U.S. study also reported diarrhea, headache, and alterations in taste. These side effects were usually considered minor, and seldom required discontinuation of the drug.