The IOM report indicates several areas of research that require additional resources. These areas and the relevant recommendations include: basic research in such areas as immunology, virology, and molecular biology (Recommendation 3.1); vaccine research program (Recommendation 3.2); behavioral research, especially basic behavioral research (Recommendation 3.9); nursing research for the care of people with HIV-related illness (Recommendation 3.11); mechanism-of-action studies for anti-HIV agents as part of drug development efforts (Recommendation 3.13); basic and applied research in the area of opportunistic infections (OIs) (Recommendation 3.14); pre-and post-doctoral training programs in a wide range of AIDS-related disciplines including molecular biology, virology, cell biology, immunology, epidemiology, behavioral sciences, infectious diseases, and clinical medicine (Recommendation 3.27); and a program on the biology of rhesus monkeys as part of the research resources (Recommendation 3.28). In some of the research areas for which the IOM report indicates additional resources are needed, expansion has already been implemented as demonstrated by the increased budget for nursing studies of HIV-infected patients, expansion of clinical trials for OIs and expansion of several animal resources programs. As part of the ongoing evaluation of these programs, these research programs will be periodically reviewed for progress and level of funding by their sponsoring ICDs as recommended by the IOM panel. Significant progress has been made in AIDS-related research in the last several years with funding appropriated by Congress. Progress has been made in gaining an understanding of the epidemiology of AIDS through a number of large cohort natural history studies. Progress in basic research has provided a basic understanding of HIV and its pathogenesis, which has permitted the development of specific therapeutic agents directed toward the prevention, treatment and control of HIV infection. The NIH-funded clinical trials efforts have evaluated the safety and efficacy of numerous potential therapies for the treatment of HIV infection and the opportunistic infections (OIs) and malignancies associated with HIV. Efforts to develop a safe and immunogenic vaccine for the prevention of HIV are ongoing with substantial progress being achieved. A description of the activities in each of these areas is described further in the following sections. EPIDEMIOLOGY - CHANGING PROFILE OF THE EPIDEMIC NIH-funded studies have demonstrated that the prevalence of AIDS continues to increase steadily in underserved populations at a rate that is disproportionate to the demographics of the U.S. population. Epidemiological studies indicate that HIV infection and AIDS are steadily increasing among several special populations that include minorities, intravenous drug users (IVDUs), and women and their offspring. Among women and children, AIDS is predominantly a disease of minorities. A brief listing of the major epidemiology and natural history studies funded by the NIH include: Multicenter AIDS Cohort Study (MACS)-behavioral correlates with disease transmission and progression, 6000 gay and bisexual men, started 1984. San Francisco Men's Health Study (SFMHS) Heterosexual AIDS Transmission (HATS) - includes minority women, children and IVDUS Women and Infant Transmission Study (WITS)-course of HIV in infected pregnant women and children, majority are IVDUS. Newark Perinatal Study - includes minority women, NICHD-NCI study on high level of anti-gp120 and low NCI SEER study showed increased incidence of non- NCI study showed decrease in expected incidence rate of NIAID-PAHO and Mexican Ministry of Health study on Recent activities reflecting the changing demographics indicated by natural history and epidemiological studies include: O O O Supplemental funding provided to the AIDS Clinical Trials Units (ACTUs) to increase participation of racial and ethnic minorities, IVDUS and HIV-infected pregnant women. Opportunity for full participation of women in almost Committees in the ACTG and CPCRA have been established to focus on the specific needs of women. Awards made to Howard University (Washington, D.C.), the University of Puerto Rico, and the University of Hawaii to develop infrastructure in order to begin clinical trials and compete successfully for an ACTU. National Conference on Women and HIV Infection held on December 13-14, 1990, to draft recommendations for research on special problems associated with HIV infection in women. NICHD and NIAID clinical trials in infants, children and pregnant women. Twenty clinical trials are currently evaluating 19 therapeutic agents. Collaboration with the National Institute on Drug Abuse to encourage increased participation of HIV-infected IVDUS at ACTUS and with the Human Resource and Service Administration (HRSA) to provide ancillary services to increase participation of pediatric patients at specialized ACTUS and Pediatric Centers. BASIC RESEARCH Basic research investigations supported and performed by the NIH have led to rapid and significant increases in the understanding of HIV. Similarly, the scientific understanding of HIV infection and AIDS is making significant contributions to resolving other basic scientific issues in the fields of virology, immunology, microbiology, animal models and molecular biology with important applications to clinical medicine. The influence of basic research on the scientific response to the AIDS epidemic includes: Early research on retroviruses facilitated the Advances in molecular biology allowed elucidation of genetic function of HIV. Previous advances in immunology allowed more rapid Previous advances in microbiology provided the basis for recognition and understanding of opportunistic infections. The molecular and behavioral aspects of transmission. The effects of AIDS research on non-AIDS areas includes: O Understanding of the function of the immune system. O Understanding of the mechanisms of gene expression. O Understanding of the blood-brain barrier. Development of sophisticated technology such as polymerase chain reaction (PCR) and new animal models of viral disease. Understanding of central nervous system pathology. Understanding of the transmission of sexually transmitted diseases. Understanding of the development of nervous and immune systems in children. Development of new strategies for targeted drug Development of new strategies for vaccine development. Changes in approaches to clinical trials and access to experimental therapeutics. DRUG DEVELOPMENT The discovery and development of safe and efficacious therapeutic modalities for the treatment, control and prevention of HIV infection and HIV-associated OIs and malignancies represent an urgent public health priority. malignancies represent the major causative agent resulting in mortality of AIDS patients. OIs and The NIH has established extensive intramural and extramural programs for the discovery and pre-clinical development of new agents for AIDS with academic centers and pharmaceutical establishments. Identification of each of these programs and a brief summary of their activities is outlined below: Developmental Therapeutics Program, Division of Cancer Treatment, NCI has contract resources for drug development with the capability for: Screening up to 27,000 compounds a year in a cell culture assay (40,000 compounds screened since 1987, with approximately 1 percent showing antiHIV activity). Providing developmental capacity for identified drugs including scale-up drug synthesis, drug dose formulation, pharmacology and toxicology for IND application. Developmental Therapeutics Branch, Division of AIDS, National Cooperative Drug Discovery Group-HIV. National Cooperative Drug Discovery Group-OI. Animal models for testing efficacy of drugs and combination therapies. NIGMS' Targeted Antiviral Program provides extramural NIH investigations using sophisticated techniques including: Nuclear Magnetic Resonance (NMR) X-ray crystallography Computer modeling Biophysical studies of proteins O The intramural AIDS Targeted Antiviral Program, Office of the Director, has developed a facility with highly sophisticated technologies. This facility is currently being utilized by 12 ICDs on 48 separate research programs. The program supports resources for: The Protein Expression Laboratory Computer modelling Synthesis of new compounds Screening Animal models X-ray crystallography Major Accomplishments of these programs include: O Discovery and development of AZT, ddI, ddC, d4T and CLINICAL TRIALS The NIH has the primary responsibility for the national clinical trials efforts for the evaluation of potential therapies for the treatment of HIV infection and its sequelae. The NIH, through its intramural and extramural programs, has developed a multifaceted approach for the evaluation of antiretroviral and anti-OI drugs. OIS represent the common cause of morbidity and mortality of AIDS patients. The objective of the NIH-funded clinical trials is to investigate new drugs valuable to the treatment for patients with HIV infection and HIV-associated opportunistic infections and malignancies. This represents an urgent public health priority. The goal is to develop innovative and effective new procedures for the diagnosis, prevention, and treatment of immunologically related diseases. * 12 adult ACTUS also have pediatric components Drugs evaluated for entry in NIH-funded clinical trials as of 1991: approximately 200 agents. Patients enrolled in NIH-funded clinical trials as of 1991: over 13,000. Pediatric patients enrolled in NIH-funded clinical O Pediatric NIH-funded clinical trials as of 1991: 20. |