Investigators supported by the National Institute of Allergy and Infectious Disease (NIAID) have completed analysis of a multi-site clinical trial examining the safety and tolerability of two different regimens of combination drug therapy for patients with moderately advanced HIV disease and prior prolonged antiretroviral therapy.
AIDS Clinical Trials (ACTG) 241 compared the two regimens using virologic and immunologic parameters. Analysis of data revealed that, after 48 weeks of treatment, patients receiving a combination of nevirapine (NVP), didanosine (ddI) and zidovudine (AZT) appear to have better immunologic and virologic responses than patients who took a combination of AZT, ddI and a placebo. However, no major differences in HIV disease progression or survival could be detected within the limits of the study design.
The ACTG 241 researchers found that counts of CD4+ T cells, crucial immune system cells targeted by HIV, were 25 percent greater among patients receiving NVP/ddI/AZT compared to patients taking AZT/ddI after 48 weeks of treatment. Researchers detected differences between the two patient groups within eight weeks of their beginning therapy. The differences remained throughout 48 weeks of the study.
Study scientists used two methods to monitor HIV in the patients' blood, measuring viral infectivity in peripheral blood mononuclear cells (PBMC) and amounts of HIV-1 RNA in plasma. Both measures revealed that the patients receiving NVP/ddI/AZT had greater decreases in the amount of HIV in their blood, called viral load, during the first weeks of the study. Using the PBMC measure, investigators detected a decrease in viral load throughout the study. With the HIV-1 RNA test, these decreases were lost by 48 weeks.
Overall patients had no significant differences in rates of severe side effects from the therapies, although patients receiving the NVP/ddI/AZT therapy had significantly more severe skin rashes than patients taking AZT/ddI. The investigators attributed the rashes to NVP.
Conducted at 16 sites within the ACTG, the trial enrolled 400 HIV-infected adults with CD4+ T cell counts of 350 or less per cubic millimeter of blood who had previous single-drug or combination therapy with AZT, ddI or zalcitabine (ddC) for six or more months.
Both treatment regimens included oral doses of 600 milligrams (mg) a day of AZT and 400 mg/day of ddI. The triple drug regimen also used 400 mg of NVP daily (200 mg for the first two weeks). Neither the investigators nor the participants knew which regimen a patient received until the study ended.
AZT and ddI are licensed for the treatment of HIV infection. The drugs all inhibit a viral enzyme, reverse transcriptase, necessary for the replication and spread of HIV. NVP, an investigational medication, also inhibits reverse transcriptase, but appears to work on a different site of the enzyme.
When the study began in May 1993, the duration of treatment was to be 48 weeks. However, investigators extended the study to allow patients to receive therapy until the study was unblinded in November 1994. At that time, data for the first 48 weeks of therapy were analyzed from 398 patients. Richard T. D'Aquila, M.D., served as the study chair and Martin S. Hirsch, M.D., as co-chair. Both investigators are from Harvard University School of Medicine.
The ACTG, established in 1987, is one of NIAID's nationwide clinical trials network that conducts studies to evaluate the safety of new drugs, drug combinations and vaccines in adults and children at various stages of HIV disease. The ACTG has 57 units affiliated with major U.S. medical centers. NIAID conducted ACTG 241 in collaboration with Boehringer Ingleheim, Bristol-Myers Squibb and Burroughs Wellcome, manufacturers of the NVP, ddI and AZT, respectively.
NIAID, a component of the National Institutes of Health (NIH), 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.
For further information about ACTG 241 and other AIDS clinical trial, call 1-800-TRIALS-A, Monday through Friday, 9 a.m. to 7 p.m., ET.
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