New Drug Combinations May Improve Outlook in AIDS Patients

March 1, 1996
Volume 5, Issue 3

WASHINGTON--Studies of two new protease inhibitors, used in combination with currently available anti-HIV agents, show good results in reducing viral load. Furthermore, studies of a new test for determining viral load indicate a significant relationship between high viral load and faster disease progression.

WASHINGTON--Studies of two new protease inhibitors, used in combinationwith currently available anti-HIV agents, show good results inreducing viral load. Furthermore, studies of a new test for determiningviral load indicate a significant relationship between high viralload and faster disease progression.

All three studies were presented at the Third Conference on Retrovirusesand Opportunistic Infections, sponsored by the Infectious DiseasesSociety of America, the NIH, and the CDC.

The three-drug combination of indinavir (Merck's investigationalprotease inhibitor, Crixivan), AZT (Retro-vir), and 3TC (Epivir)reduced the amount of HIV in the blood by 99%, to undetectablelevels, in 24 of 26 patients, with effects lasting for up to 6months, said Dr. Roy Gulick of New York University. The studywas conducted at NYU and three other US hospitals.

In another study, which combined indinavir with AZT and ddI (Videx),HIV was reduced to undetectable amounts in 13 of 22 patients (59%)for 5 months. The most serious side effect was kidney stones,seen in 2% to 3% of patients.

Ritonavir Approved

In a large, 7-month international study, 13% of patients receivingthe protease inhibitor ritonavir had progressive HIV disease (ie,developed an AIDS-related disease or died) vs 27% of placebo patients,said Dr. John M. Leonard of Abbott Laboratories.

Mortality was 4.8% among 543 patients given ritonavir vs 8.4%among the 547 controls, a reduction of more than 50%. The studyinvolved many different drug combinations, since patients continuedto receive the anti-HIV drugs they were taking prior to entryinto the study.

Side effects associated with ritonavir use were predominantlynausea and other gastrointestinal problems.

Based on these studies, the FDA granted approval for ritonavirin record time. The agent, to be sold under the brand name Norvir,received full approval for use in patients with advanced diseaseand conditional approval for use in early HIV infection. Abbottwill perform additional studies on patients with early diseaseto determine if the agent can delay the onset of symptoms or prolongsurvival, and will perform tests in children.

An FDA advisory panel has also recommended approval of Merck'sCrixivan, and the agency is expected to act quickly on this drugas well.

New Test Measures Viral Load

At the University of Pittsburgh, investigators performed a newtest to measure viral load as well as the standard measurementof CD4 cells in samples from 181 HIV-infected men collected overa period of 10 years for an NIH study. The investigational test,developed by Chiron Diagnostics (Emeryville, Calif), is basedon branched DNA technology. The study, reported by Dr. John W.Mellors, found that baseline viral load powerfully predicted survivalwhile CD4 counts did not.

Dr. Mellors said that the risk of progression to AIDS after 7years was about 10% among those whose viral count was less than5,000/mL vs 60% for those with measurements of more than 34,500/mL.

Among the 43 patients whose viral count was less than 5,000/mL,there were no deaths at 5 years, compared with 28 deaths amongthe 43 patients with viral load greater than 34,500. Dr. Mellorsbelieves that timing and choice of therapy should be based onviral load as a measure of disease progression.