|EMBARGOED FOR RELEASE
Thursday, June 19, 1997
10:30 AM Eastern Time
Draft HIV/AIDS Treatment Guidelines Available
- Decisions on initiation of or changes in antiretroviral therapy
should be guided by monitoring the amount of virus in the
patient's blood (viral load) supplemented by information about the
patient's CD4+ T cell count and clinical condition.
- Viral load testing should generally be repeated at 3-4 month
intervals to evaluate the continuous effectiveness of therapy.
Treating Established Infection
- All patients with AIDS, as defined by the 1993 CDC Guidelines, or
with symptomatic HIV infection should be placed on antiretroviral
therapy regardless of viral load.
- Asymptomatic patients with CD4+ T cell counts of less than 500
or with HIV RNA levels greater than 10,000 copies (by bDNA test)
or greater than 20,000 copies (by RT-PCR test) should be offered
therapy. However, other considerations, such as drug toxicity and
willingness of the patient to start therapy and comply, will affect
the strength of the recommendation for therapy. These factors
are discussed at great length in the document. Some physicians
may choose only to monitor patients with 350-500 CD4+ T
cells/mm3 and low viral burdens.
- Some physicians would also treat patients with low but detectable
viral burdens and CD4+ T cell counts greater than 500; others
- A regimen of two nucleoside reverse transcriptase inhibitors and
one protease inhibitor is preferred to achieve maximal viral
- An alternative regimen may substitute nevirapine for the protease
inhibitor, but this is not considered optimal.
- If it is necessary to stop antiretroviral therapy for an extended
time, clinicians and patients should be advised to stop all
antiretroviral drugs simultaneously, rather than continuing one or
two drugs, to minimize the potential for encouraging resistant viral
Considerations for Changing a Failing Regimen
- It is important to distinguish between discontinuation of
combination therapy due to drug failure and discontinuation due to
- For drug toxicity, it is appropriate to substitute one or more
alternative drugs for the agent suspected of causing the toxicity.
- For drug failure, at least two drugs must be changed. Optimally,
three new drugs should be used in replacement of a failing
- Therapy should be changed only with the patient's full agreement
and compliance and after ruling out malabsorption of drug.
- Criteria for changing therapy include:
- a less than ten-fold reduction in viral load level by four
weeks following initiation of therapy.
- failure to suppress viral load to undetectable levels within
four to six months of beginning therapy.
- repeated detection of virus in plasma after initial suppression
to undetectable levels, suggesting the development of
- any reproducible significant increase from the lowest viral
- persistently declining CD4+ T cell counts.
- clinical deterioration.
- The document contains some suggested alternative therapeutic
regimens. Most suggested alternative drug regimens are still
investigational in nature. While these combinations may have
shown promise in smaller numbers of patients or be theoretically
reasonable, no clinical trial data exist as yet to show that these
regimens are broadly effective. Thus, clinicians, patients and
payers should weigh advantages and consequences before
choosing a regimen that is still undergoing evaluation in clinical
Considerations for Antiretroviral Therapy in the HIV-Infected
- Physicians should suspect HIV infection in all patients presenting
with some of the symptoms of the acute retroviral syndrome,
which are easily confused with the common flu.
- Patients without documented HIV infection should not be given
- Treatment, if used, must be aggressive to achieve maximal
antiretroviral effects and suppression of viral replication.
- Therapeutic regimens for acute HIV infection should include the
combination of two nucleoside inhibitors and one protease
inhibitor. The drugs should be started simultaneously.
- Once therapy is initiated, many experts recommend continuing to
treat indefinitely. Research is ongoing to determine if there is a
period after which therapy can be discontinued.
- Guidelines for determining optimal antiretroviral therapy and for
deciding to initiate therapy in pregnant HIV-infected women
should generally be the same as those for non-pregnant adults,
with the overriding consideration being for the mother's health.
- Risks to the fetus from effects of antiretroviral drugs are not well
understood. Some clinicians might choose to delay therapy until
after the first trimester of pregnancy, or, if the mother is already
on an antiretroviral drug regimen, to stop all drugs until the
- To date, the only drug that has been shown to reduce perinatal
transmission by approximately 70-80 percent is zidovudine (AZT).
The zidovudine must be administered beginning as early as
the 14th week of pregnancy and continued throughout pregnancy.
The mother must receive intravenous zidovudine during labor and
delivery, and the newborn must receive zidovudine
during the first 6 weeks of life. Regardless of the independent
indication for antiretroviral therapy in the mother, all HIV-infected
women should receive this preventive therapy during pregnancy.
Guidelines for the Use of Antiretroviral Agents in HIV-Infected
Adults and Adolescents and Report of the NIH Panel
to Define Principles of Therapy of
June 19, 1997
Questions and Answers
What is the Panel on Clinical Practices for HIV Treatment?
The Panel on Clinical Practices for Treatment of HIV Infection is a
three-year public-private partnership convened in December 1996 by
the Office of HIV/AIDS Policy, DHHS, and the Henry J. Kaiser Family
Foundation at the request of DHHS Secretary Donna E. Shalala. The
Panel's mission is to provide comprehensive descriptions of clinical
practices in the care of HIV-infected people and to provide
recommendations for treatment options to practitioners, patients, and
payers. The Panel developed the document, Guidelines for the Use
of Antiretroviral Agents in HIV-Infected Adults and Adolescents.
Anthony S. Fauci, M.D., director, National Institute of Allergy and
Infectious Diseases and John G. Bartlett, M.D., professor of medicine
and chief of infectious diseases at Johns Hopkins University School of
Medicine co-chair the Panel. The Panel includes federal, academic
and private sector experts in the clinical treatment and care of HIV-
infected people, as well as representatives of AIDS interest groups,
health policy groups and payer organizations.
What is the role of Kaiser Family Foundation?
The Henry J. Kaiser Family Foundation is a co-convener of the Panel
on Clinical Practices for Treatment of HIV Infection. The Foundation
provided funding for the meetings to develop the Guidelines and will
remain a partner in the Panel throughout its three-year duration.
What is the Panel to Define Principles of Therapy?
The Office of AIDS Research at the NIH convened the Panel to
Define Principles of Therapy of HIV Infection to review the current
state of knowledge of antiretroviral therapies and prepare a document
outlining principles that would guide therapy decisions. The expert
panel developed the document, Report of the NIH Panel to Define
Principles of Therapy of HIV Infection. Charles C. Carpenter, M.D.,
professor of medicine at Brown University School of Medicine chaired
the NIH panel.
What do the Principles and Guidelines contain and how do they
relate to one another?
The Report of the NIH Panel to Define Principles of Therapy of HIV
Infection outlines 11 principles based on current scientific knowledge
regarding HIV disease, its interaction with the immune system, and
implications for decisions in treating people infected with HIV. The
Report focuses specifically on such parameters as CD4+ T cell count
and the amount of HIV in a person's blood (viral load).
The Guidelines for the Use of Antiretroviral Agents in HIV-Infected
Adults and Adolescents contain recommendations for practitioners to
use in providing antiretroviral treatment to HIV-infected adults and
adolescents, in light of the new combination therapies and new ways
to monitor HIV disease progression. The Guidelines were developed,
in part, based on the Principles report. Together, the two documents
provide the scientific rationale for therapeutic strategies as well as
practical guidelines for implementing the strategies.
Are the Guidelines different from those prepared by other
The Guidelines represent a unique collaboration between the federal
and private sectors, independent of commercial interest, and reflect
the current knowledge regarding treatment of retroviral infections.
Such knowledge evolves rapidly with the identification of new
potential treatments. Unique to the Guidelines is the accompanying
Principles document, which provides the scientific rationale.
What key areas do the Guidelines cover?
Key areas include: 1) use of testing for plasma HIV RNA (ribonucleic
acid) levels and CD4+ T cell count in guiding decisions for therapy; 2)
testing to establish infection; 3) therapy in patients with asymptomatic
infection; 4) therapy in advanced disease; 5) special considerations
for treatment in patients with advanced disease; 6) interruption of
therapy; 7) criteria for changing therapy and alternative treatment
options; 8) therapy for acute HIV infection; and 9) considerations for
antiretroviral therapy in women who are HIV-infected and pregnant.
What are the major recommendations regarding treatment?
In general, the Guidelines recommend treating patients relatively
early and with an aggressive combination drug regimen including
protease inhibitors. Unless a change in therapy is necessary due to
drug toxicity, adding or changing just one drug at a time in treatment
may allow HIV a head start in becoming resistant to the drug, and is
therefore not recommended. The Guidelines recommend starting
treatment with three drugs and changing at least two drugs when
there is reason to consider other therapeutic strategies, such as when
HIV levels in the blood increase.
Therapy with only two drugs, in general, is considered less than
optimal; all monotherapy is contraindicated. The exception to this is
the use of zidovudine (AZT) to prevent perinatal transmission in
pregnant women who otherwise do not require antiretroviral therapy
for their own treatment.
The Guidelines recommend that physicians regularly measure their
patients' CD4+ T cell levels and viral loads to determine whether a
change of therapy is needed, and they note that viral load
determination is the most important factor to consider in monitoring
Explain the treatment rating system used in the Guidelines.
Each therapeutic recommendation is accompanied by a rating that
includes a letter and a Roman numeral. (See Table I. in the
Guidelines.) The letter indicates the strength of the treatment
recommendation (from "A: strong, should always be offered" to "E:
should never be offered") and the Roman numeral reflects the evidence
for the recommendation (from "I: at least one randomized trial with
clinical endpoints" to "III: expert opinion").
According to the Guidelines, should everyone be on
Combination therapy is most effective at reducing HIV RNA load.
Once the patient and physician have decided that antiretroviral
therapy is indicated, treatment should be aggressive to meet the goal,
consistent with the Principles, of suppressing viral load to
undetectable levels. Therefore, three-drug therapy is the preferred
choice, and any drug regimen that does not achieve maximal viral
suppression is not optimal.
Do the Guidelines enable any physician to determine treatment
for HIV-infected people?
The recommendations in the Guidelines are not intended to substitute
for the judgment of a physician who is expert in the care of
HIV-infected individuals. The Panel underscored that, when possible, the treatment
of patients should be directed by a physician with extensive experience in
the care of HIV-infected people. When this is not possible, the physician
should have access to such expertise through consultations.
What role should the patient play in considering the Guidelines?
The Panel emphasized the necessity of an informed and close
partnership between patient and clinician with ongoing patient
counseling and education. The multidrug regimens are complicated
and require close monitoring by the physician and a strong
commitment on the part of the patient.
Do the Guidelines contain recommendations for treatment of
pediatric HIV infection?
No. The Panel decided that the issues regarding pediatric HIV
infection and treatment are extensive and should be addressed in a
Will there be updates to the Guidelines?
Once the final Guidelines are completed and issued, the
DHHS/Kaiser Family Foundation Panel on Clinical Practices for
Treatment of HIV Infection will update the Guidelines periodically as
Where can I get copies of the document?
The draft Guidelines for the Use of Antiretroviral Agents in HIV-
Infected Adults and Adolescents and the Report of the NIH Panel to
Define Principles of Therapy of HIV Infection are both announced in
The Federal Register, following which there is a 30-day public-comment
period. The draft documents are available from the National
AIDS Clearinghouse (1-800-458-5231) and on the Clearinghouse
Web site (http://www.cdcnac.org) and from the HIV/AIDS Treatment
Information Service (Phone: 1-800-448-0440; FAX: 1-301-519-6616;
TTY: 1-800-243-7012) and on their Web site (http://www.hivatis.org).
After consideration of the comments, both documents will be
published in the Centers for Disease Control and Prevention (CDC)
Morbidity and Mortality Weekly Report. A second publication is
planned in a peer-reviewed medical science journal.
Where do I send in comments?
Mail comments to: The HIV/AIDS Treatment Information Service,
P.O. Box 6303, Rockville, MD 20849-6303.