A combination of three antiretroviral therapies, including saquinavir (Ro 31-8959), an inhibitor of the proteinase enzyme needed by HIV to replicate, has shown activity in HIV-infected people, according to preliminary results of the study, AIDS Clinical Trials Group (ACTG) 229, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). These preliminary findings are being distributed to participating ACTG sites for their information. The data and additional analyses are being prepared for publication and will be submitted to a peer-reviewed journal.
This 302-patient study compared the safety and activity of the three-drug combination of saquinavir, zalcitabine (ddC) and zidovudine (AZT) to the combinations of saquinavir with AZT, and ddC with AZT. All patients had counts of CD4+ T cells ranging from 50 to 300 per cubic millimeter of blood and received AZT therapy for at least four months before enrollment. CD4+ T cells are crucial immune system cells.
The clinical effectiveness of the three-drug combination remains to be determined in future studies. The trial was not designed to detect differences in clinical progression of the patients on the three different therapy regimens. Therefore, standard clinical patient management should not be affected by this study, note the researchers.
In all three treatment groups, CD4+ T cell counts rose during the first eight weeks of study, but then gradually declined. The increase in CD4+ T cell counts was greatest in the three- drug combination group. In addition, the three-drug combination was significantly better than both of the two-drug combinations in decreasing viral load as measured by quantitative cell culture. Viral load is the amount of HIV in circulating blood. Results from other virological assays, such as plasma RNA, are pending. The associated reduction of viral load among patients receiving the three-drug combination appears to be sustained for the initial 24 weeks of the trial.
The type, severity and frequency of adverse experiences were similar in the three treatment regimens. The small number of AIDS-defining events and two deaths resulted from complications of advanced HIV infection and did not appear to be associated with the study therapies.
Patients were enrolled in the study from March to July 1993 and were randomly assigned to one of the three treatment arms. Neither the scientists nor participants knew which drug therapy a patient received.
The duration of therapy was originally scheduled to be 24 weeks. However, the study was later extended an additional 12-24 weeks to allow patients to remain on blinded therapy while the data from the first 24 weeks were analyzed. The preliminary results are based on the analysis from the first 24 weeks of therapy. Additional analyses will be performed. The therapies used 600 mg doses of saquinavir three times a day, 200 mg of AZT three times a day and/or 0.750 mg of ddC three times a day.
NIAID, a component of the National Institutes of Health, supports research on AIDS, tuberculosis and other infectious diseases as well as allergies and immunology. NIH is an agency of the U.S. Public Health Service, U.S. Department of Health and Human Services.
Prepared by: Office of Communications National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD 20892
Public Health Service U.S. Department of Health and Human Services