HIV Therapy Guidelines Issued

Date: June 25, 1993
Source: National Institutes of Health (NIH)
Author: National Institute of Allergy and Infectious Diseases (NIAID)

An independent panel of experts, convened by the National Institute of Allergy and Infectious Diseases (NIAID), has released preliminary recommendations regarding the use of antiretroviral drugs in the care of adults infected with HIV. Final recommendations will be submitted in July to a peer-reviewed medical journal for publication.

The panel's recommendations are not federal or NIAID policy. Rather, the recommendations serve to guide health care providers treating adults with early, intermediate and late stages of HIV disease in using the antiretroviral drugs zidovudine (AZT), didanosine (ddI) and zalcitabine (ddC).

The panel's recommendations offer physicians guidance in working with their HIV-infected patients in the selection of appropriate therapies," says Anthony S. Fauci, M.D., director of NIAID. "With such advice and counsel, patients and their care givers can make the most informed decisions about whether to begin, change or combine therapies."

During the two-day state-of-the-art conference, held Wednesday and Thursday, June 23 and 24 at NIAID, 18 panel members heard presentations and discussion from more than 30 investigators and clinicians involved in HIV research worldwide as well as members of the HIV-infected community and the public.

The HIV epidemic has forced clinicians to recognize the limitations of medical technology and reminded us that the finest expression of medical practice still lies in the optimal blend of current science and the "art" of patient care," says Merle A. Sande, M.D., chair of the panel and chief of the medical services at San Francisco General Hospital.

We also recognize that no "average patient" exists. Some patients will do better, and others, worse, than what clinical studies would predict. Doctors and patients should work as a team to design a treatment strategy that is both clinically sound and appropriate for each individual patient's needs, priorities and circumstances of daily life," he adds.

In writing the recommendations, the panel emphasized the choice to accept or decline antiretroviral therapy ultimately rests with the patient. Moreover, the panel noted that early intervention does not necessarily mean just giving these drugs to stable HIV-infected patients who have not developed symptoms. Instead, early intervention involves primary medical care, including management of the patient's overall health status, and providing emotional and psychological support.

The recommendations for patients who have never before received antiretroviral therapy are:

For patients without symptoms whose CD4+ T cell counts are above or equal to 500/mm3, the panel recommends continued observation, and clinical and immunological monitoring, (measurement of CD4+ T cell counts) every six months.

For patients without symptoms whose CD4+ T cell counts are between 200 to 500/mm3 and who are stable over time, the panel recommends consideration of the following two options:

  1. initiation of antiretroviral therapy;
  2. continued observation and monitoring for clinical or laboratory evidence of deterioration, at which point antiretroviral therapy should be initiated.

For patients with CD4+ T cell counts between 200 to 500/mm3 who present with symptoms related to HIV disease, the panel recommends starting antiretroviral therapy.

When choosing an initial antiretroviral therapy:

Use AZT as first-line therapy in patients who have received no prior antiretroviral therapy. The recommended dose is 600 mg/day in divided doses.

The recommendation to initiate therapy with AZT applies to patients with or without symptoms, with CD4+ T cell counts between 200 to 500/mm3 or below 200/mm3, or to patients with severe AIDS-Related Complex or AIDS regardless of their CD4+ T cell counts.

Combination therapy with AZT and ddI or AZT and ddC also may be considered, although clinical trials have not conclusively demonstrated clinical benefit to date.

On changing initial therapy in patients who are tolerating an initial antiretroviral therapy:

In patients tolerating initial therapy, the panel recommends continuing AZT for patients who appear to be stable with CD4+ T cell counts above 300/mm3.

For patients who have CD4+ T cell counts below 300/mm3, the panel recommends consideration of two options:
  1. continuing AZT; or
  2. hanging to ddI.

The panel notes that the strongest data supporting a change in therapy to ddI were seen in patients who had been on AZT for four months or longer (median duration of 13 months prior AZT).

For patients who are intolerant to AZT, or who experience progression of disease despite AZT therapy:

In patients with CD4+ T cell counts between 200 to 500/mm3 and 50 to 200/mm3 who are intolerant of AZT, the panel recommends switching to ddI monotherapy. For AZT intolerant patients with CD4+ T cell counts of less than 50/mm3, the panel recommends switching to ddI or ddC monotherapy. Another option includes discontinuing antiretroviral therapy.

For patients with CD4+ T cell counts between 200 to 500/mm3 and 50 to 200/mm3 who show signs of clinical progression, the panel recommends initiating an alternative antiretroviral regimen. Options include monotherapy, for example with ddI, or initiation of combination therapy by adding a second agent, either ddI or ddC.

For patients with CD4+ T cell counts below 50/mm3 and who have evidence of disease progression, the panel recommends switching to an alternative monotherapy, either ddI or ddC. Other options include combination therapy.

For patients with CD4+ T cell counts above 500/mm3 who are taking AZT but experience intolerance, the panel recommends discontinuation of therapy.

During the conference, the panel heard presentations of data from 14 published studies including: 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.

NIAID previously held a SOTA conference in 1990, recommending that HIV-infected patients whose count of CD4+ T cells dropped to below 500 should begin taking AZT. Since that time, other trials have shown that ddI alone and ddI and ddC in combination with AZT have value as therapies as well. HIV targets CD4+ T cells, which are crucial to the function of the immune system. A healthy adult has between 800 and 1,200 cells per cubic millimeter of blood.

The panelists included 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.

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.