On February 23, 1995, the NIAID AIDS Research Advisory Committee (ARAC) reaffirmed the need for the Institute to conduct a multicenter study to examine the effects of low- dose oral alpha interferon (LDOAI) therapy on the symptoms caused by HIV disease. The ARAC recommended that NIAID identify a different clinical trials mechanism in which to conduct study, giving consideration to the Division of AIDS Treatment Research Initiative (DATRI).
LDOAI products are used in the United States, particularly in communities of people of color. Some practitioners in these communities recommend LDOAI based on reports of its beneficial effect on symptoms associated with HIV infection, such as weight loss and the severity of opportunistic infections. However, several multicenter, randomized, placebo-controlled trials have yielded conflicting data on whether LDOAI is beneficial in relieving symptoms associated with HIV.
Because the data are conflicting and because of the important public health issues surrounding its use, NIAID has been, and remains, committed to conducting a study of LDOAI. Since July 1993, resources have been devoted to develop and conduct such a study with the NIAID Community Programs for Clinical Trials on AIDS (CPCRA). However, at its meeting on January 28,1995, the CPCRA Steering Committee voted against continuing the study within the CPCRA. According to Fred Gordin, M.D., Washington Regional AIDS Program and chair of the Steering Committee, reasons mentioned included concerns about; limited interest in LDOAI in communities served by the CPCRA sites, their ability to recruit patients for the study, limited scientific rationale for the study, and lack of resources to provide data management, statistical and monitoring support to the non- CPCRA sites, from which the majority of patients would come.
Balancing the concerns expressed by the leadership of the CPCRA with the identified need for a well-designed clinical trial that would provide information upon which to base decisions about treatment, ARAC recommended that NIAID proceed with the study, possibly utilizing the DATRI for implementation. Sites within both CPCRA and AIDS Clinical Trials Group (ACTG) that are interested in participating in the trial would have the ability to do so. In addition, three interested sites that are not currently part of an existing NIAID clinical trials program would participate in the trial: two Abundant Life Clinics in New York City and Washington D.C., and King Drew Medical Center in Los Angeles.
The need to explore research addressing LDOAI was first discussed at a meeting in October 1992, jointly sponsored by the National Medical Association (NMA) and NIAID. Following that meeting, and with the concurrence of ARAC, NIAID convened the Low-Dose Oral Alpha Interferon planning Group in December 1992 and March 1993. The group advised NIAID to pursue a study of LDOAI products to address the conflicting data concerning the claims made by practitioners. The group also recommended primary design elements and implementation steps that must be considered in a study.
The protocol team represents a complex collaboration, comprised of representatives from the CPCRA, ACTG, Division of AIDS, Food and Drug Administration, pharmaceutical sponsors, and community-based physicians most experienced with the use of LDOAI products in HIV-infected persons. The team has worked diligently over the last 18 months to design a prospective, randomized, double-blind, placebo-controlled trial of the three currently available oral alpha interferon products (Alferon U, Veldona U, and Ferimmune U). The development process involved two pilots studies, the first of which tested a novel patient questionnaire designed to assess symptoms reported to be relieved with LDOAI therapy. The second pilot study tested the ability of patients to take the three oral preparations simultaneously, as called for in the double-blind study design. Results from both of the pilot studies support moving forward with the current double-blind study design.
NIAID will now begin implementation of the trial. Jones Kumi, M.D., Mercy Hospital in Detroit, is the principal investigator and Wayne Greaves, M.D., Howard University in Washington, D.C., is co-principal investigator. The products will be provided by Pharma Pacific Management, Pty-LTD, Amarillo Cell Culture, Co., and Interferon Sciences, Inc., while funding for the trial will be provided by NIAID.Prepared by: