HIV Therapy Recommendations Issued

Date: December 1, 1993
Source: National Institutes of Health (NIH)
Author: National Institute of Allergy and Infectious Diseases (NIAID)

HIV-infected patients and their physicians must be aware of the benefits, toxicities, limitations and knowledge gaps about antiretroviral drugs when making decisions concerning treatments, according to recommendations published in the Dec. 1 Journal of the American Medical Association from an independent panel of experts convened by the National Institute of Allergy and Infectious Diseases (NIAID).

Such information about the antiretroviral drugs zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC) is reviewed in the panel's recommendations. The panel developed the guidelines following a state-of-the-art meeting, June 23 to 25 at NIAID in Bethesda. Md. The panel's recommendations are neither federal nor NIAID policy.

Physicians are obliged to educate patients about clinically sound treatment options and their impact on a patient's quality of life," says Anthony S. Fauci, M.D., director of NIAID. "These recommendations reflect our current knowledge of antiretroviral drugs and will guide health care providers and patients in making treatment decisions for early, intermediate and late stages of HIV disease."

The recommendations present 12 clinical scenarios for patients with HIV followed by antiretroviral therapy suggestions and a rationale. The scenarios include HIV-infected patients without symptoms who have not had prior therapy, those with signs and symptoms of HIV-related disease who have not had prior therapy, clinically stable patients who tolerate initial AZT therapy, patients on AZT whose disease has progressed and patients who cannot tolerate therapy.

The panel's recommendations are less prescriptive than those from a previous state-of-the-art conference held in 1990. The 1990 guidelines recommended that HIV-infected patients whose count of the crucial immune system cell targeted by HIV, CD4+ T cells, had dropped to below 500 should begin taking AZT. A healthy adult has between 800 and 1,200 cells per cubic millimeter of blood. Since that time, other trials in specific situations have shown that ddI alone, ddC alone and ddI or ddC in combination with AZT have value as therapies as well.

The panel's recommendations also emphasize that the primary care provider has a responsibility to assess available support systems, assure appropriate integration into the health care system and provide early diagnosis, immunizations, preventive therapies for opportunistic infections and treatment.

Treatment of HIV infection and disease requires all the skills of the primary care physician," says Merle A. Sande, M.D., chair of the panel and chief of the medical services at San Francisco General Hospital. "Management of overall health status, counseling to reduce risk behaviors, provision of psychosocial support, assessment of quality-of-life issues and prevention of opportunistic infections all are in the domain of the clinician-patient relationship.

The HIV epidemic reminds practitioners that the finest expression of medicine lies in the optimal blend of science and the art of patient care."

In particular, the panel notes, available antiretroviral nucleoside therapies -- drugs like AZT, ddI and ddC -- have a role in the treatment of HIV infection, but the benefits are unfortunately limited.

"Early intervention for HIV disease does not necessarily imply early drug treatment, and physicians need to integrate up-to-date scientific knowledge with other relevant needs to improve patient care," Dr. Sande and the panel write.

During the conference, 14 published research studies were presented to and discussed with the panel by more than 30 investigators and clinicians involved in HIV research worldwide as well as members of the HIV-infected community and the public.

The 14 studies considered by the panel include: AIDS Clinical Trials group (ACTG) trials 016, 019, 114, 116A, 116B/117, 118 and 155; the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) 002; the Concorde Study; the Veterans Administration Study; Burroughs Wellcome Study 020; the Alpha Trial; the Bristol Myers Squibb Trial A1454-010 and several unpublished studies. Additionally, scientific presentations centered on HIV's resistance to drugs, how different strains of HIV influence the course of disease and markers of disease progression. ACTG and CPCRA are among NIAID's clinical trial networks.

The panelists included 18 physicians, investigators, statisticians and people living with HIV infection. In addition to Dr. Sande, the panel members were Charles Carpenter, M.D., Brown University, Providence, R.I.; C. Glenn Cobbs, M.D., VA Medical Center, Birmingham, Ala.; Robert W. Coombs, M.D., Ph.D., University of Washington, Seattle; Thomas R. Fleming, Ph.D., University of Washington, Seattle; Mitchell H. Gail, M.D., Ph.D., National Cancer Institute, Bethesda, Md.; Wayne L. Greaves, M.D., Howard University, Washington, D.C.; Martin S. Hirsch, M.D., Harvard University Medical School, Boston, Mass.; King K. Holmes, M.D., Ph.D., University of Washington, Seattle; Roberta Luskin-Hawk, M.D., Saint Joseph's Hospital, Chicago, Ill.; Donna Mildvan, M.D., Beth Israel Medical Center, New York, N.Y.; Charles Nelson, Morehouse School of Medicine, Atlanta, Ga.; John P. Phair, M.D., Northwestern University, Chicago, Ill.; Jay Sanford, M.D., Antimicrobial, Inc., Dallas, Texas; R. Gabriel Torres, M.D., St. Vincents Hospital and Medical Center, New York, N.Y.; Robert Schooley, M.D., University of Colorado Health Sciences Center, Denver; Robert Vasquez, Minority Taskforce on AIDS, New York, N.Y.; and Rebecca Denison, Women Organized to Respond to Life-Threatening Diseases, Oakland, Calif.

Reprints of the recommendations will be available from the AIDS Clinical Trials Information Service at 1-800-TRIALS-A.

NIAID, a component of the National Institutes of Health (NIH), supports investigators and scientific studies at universities, medical schools, hospitals and research institutions in the United States and abroad aimed at preventing, diagnosing and treating such illnesses as AIDS, tuberculosis, allergies and asthma. NIH is an agency of the U.S. Public Health Services, part of the U.S. Department of Health and Human Services.