Draft DHHS Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents

Press Briefing

June 19, 1997

Natcher Building, National Institutes of Health

Statement by: Anthony S. Fauci, M.D.

Director, National Institute of Allergy and Infectious Diseases

Co-Chair, Panel on Clinical Practices for Treatment of HIV Infection

I would like to thank all of you for coming out to Bethesda this morning as we unveil two important draft documents related to the care of HIV-infected people. As has been discussed, the first of these documents, generated by an NIH panel chaired by Dr. Charles Carpenter of Brown University, delineates the underlying scientific principles, based on our current understanding of HIV pathogenesis, that guide the treatment of HIV infection.

I am joined by Dr. John Bartlett of Johns Hopkins to introduce a complementary document, the DHHS Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. These draft guidelines were developed by a panel convened in December of 1996 by the Department of Health and Human Services and the Henry J. Kaiser Family Foundation, at the request of Secretary Shalala.

Dr. Bartlett and I co-chaired this panel and have had the privilege of working with approximately thirty knowledgeable and dedicated panel members from government, academia, industry and the HIV/AIDS community. The panel has a 3-year mandate to sequentially address and update various aspects of the clinical care of HIV-infected individuals.

Let me provide you with a little background before I get to the meat of the guidelines. During primary HIV infection the virus replicates rapidly and spreads throughout the body, particularly to the lymph nodes and related organs. The immune system is able to curtail viral replication to a greater or lesser degree, but some virus invariably escapes immune containment, producing a chronic, persistent infection. Indeed, HIV actively replicates throughout the course of HIV disease, even when a patient may feel perfectly well. In most patients, replication accelerates over time, leading to the destruction of the immune system. The level of HIV replication is striking: billions of HIV particles may be produced and cleared from an individual's body each day.

We have recently learned that the amount of virus in the plasma is intimately related to the risk of a person developing AIDS or dying. In the Multicenter AIDS Cohort Study, Dr. John Mellors and his colleagues demonstrated that the level of HIV in an individual's plasma soon after infection -- the so-called viral "set point" -- is highly predictive of the rate of progression of HIV disease in that person; that is, patients with high levels of virus are much more likely to get sicker, faster, than those with low levels of virus. This information was published last year in the journal Science; just this week, the MACS researchers published follow-up data in the Annals of Internal Medicine that fortify this concept.

These and other findings have provided the rationale for aggressive antiretroviral therapy for HIV-infected people, as well as for routinely using newly available blood tests to measure viral load when initiating, monitoring and modifying anti-HIV therapy. Today, the central tenet of antiretroviral therapy is to reduce the amount of HIV in the body to the lowest possible level for as long as possible, with the goal of forestalling disease progression.

Ten years ago, we had only one therapeutic option -- single-drug therapy with AZT -- which conferred a modest benefit on AIDS patients that was short-lived because of the emergence of drug resistance. Approximately 3 years ago, two-drug therapy was shown to have a clinical benefit for HIV-infected patients with moderate immunodeficiency.

Now, as most of you know, we have an armamentarium of 11 approved antiretroviral drugs in the United States. In the past two years, a number of clinical trials have demonstrated that triple-drug combinations that include protease inhibitors can reduce plasma levels of HIV to undetectable levels in many HIV-infected individuals. Several different drug combinations have been shown to provide either virologic or clinical benefit to patients, albeit in the relatively short-term.

With the flood of new data from scientific meetings and publications, and the current availability of a large number of new antiretroviral drugs, considerable uncertainty exists among many patients and their physicians regarding the optimal approach to the treatment of HIV infection. In particular, questions repeatedly arise about when to initiate therapy, which drugs to use, how to monitor the effects of therapy, when to change drugs, and which drugs to change to.

Since there are few, if any, clinical trials with long-term clinical endpoint results that have come to fruition, there was a clear need for a coherent set of flexible treatment guidelines upon which patients and their physicians could rely as they engage in the complex task of the treatment of HIV infection.

To address this need, our panel came together at the behest of Dr. Shalala to synthesize the recent advances, and develop the specific treatment recommendations which are being released today for public comment and which will be elaborated upon in the next three years.

The guidelines are summarized in Table 5 of the document, which indicates that decisions on initiating or changing antiretroviral therapy should be guided by monitoring the viral load, supplemented by information gained from the CD4+ T cell count.

All patients with AIDS or symptomatic infection should be placed on antiretroviral therapy, regardless of viral load.

Asymptomatic patients with CD4+ T cell counts lower 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 prognosis for disease-free survival, drug toxicities and willingness of the patient to start therapy and comply, will affect the strength of the recommendation for therapy. These factors and many others are discussed at great length in the document. Finally, based on the principle that continuous viral replication results in ongoing immunological decline, some physicians would treat patients with low but detectable viral burdens and CD4+ T cells greater than 500; others would not. Again, the document discusses some of the considerations to be weighed in this decision-making process.

The panel's preferred regimen of antiretroviral drugs to achieve maximal viral suppression is a combination of two nucleoside reverse transcriptase inhibitors and one protease inhibitor.

The new draft guidelines reflect the current state of knowledge regarding the HIV disease process and the use of antiretroviral drugs, and will be updated periodically to reflect changes in the rapidly evolving field of AIDS research. As part of our panel's three-year mandate, we plan to develop additional guidelines related to the care of HIV-infected children, immunization in HIV infection, and other key issues. I would stress that the current guidelines are not intended to substitute for the judgment of a physician expert in the care of HIV-infected individuals. Instead, they should be used in the context of an ongoing dialogue between patient and clinician, including discussion of the many uncertainties in HIV therapy. In this regard, although we are hopeful, we do not yet know for certain whether early treatment of asymptomatic, HIV-infected individuals will have long-term clinical benefits, or if cumulative toxicity and the development of drug resistance will ultimately outweigh the benefits of aggressive therapy for some patients.

What happens next? After a 30-day public comment period, and following consideration of comments and suggestions, the draft guidelines will be revised and published in the Morbidity and Mortality Weekly Report of the Centers for Disease Control and Prevention and subsequently in a peer-reviewed medical journal.

Dr. Bartlett and I, as well as Dr. Goosby and Dr. Carpenter, will be happy to answer any questions that you may have.