Updated guidelines for treating HIV disease in adults that take into account the availability of new antiretroviral drugs and expanded therapy choices were released today by an international group of AIDS specialists.
Reported in the new issue (January 19) of The Journal of the American Medical Association, the recommendations represent the consensus of a 17-member physician panel of the International AIDS Society-USA. The panel was first convened in 1995 with the mission of developing treatment guidelines for health care providers that would set a standard of care for HIV. Since then, the panel has reviewed the recommendations annually, and a revised version was last issued in July 1998.
The most important changes in the new recommendations are:
* The decision to initiate therapy must be individualized for each patient. The widespread use of potent antiretroviral therapies in recent years has had a significant impact on quality of life and survival of people infected with HIV. However, with these important advances has also come the recognition of the difficulties with the current regimens, including the emergence of long-term side effects of the drugs. These issues suggest that deferral of therapy may sometimes be advantageous.
* Choices for initial regimens have expanded. At least three new drugs became available in the past year. Recommended combinations include (1) a protease inhibitor and two nucleoside reverse transcriptase inhibitors (nRTIs), (2) a nonnucleoside and two nRTIs, and (3) two protease inhibitors (where one is used to enhance the pharmacologic properties of the other) and two nRTIs.
* Assessing and supporting patient adherence to the prescribed antiviral regimen are critical to successful therapy. Drugs and regimens with more convenient administration requirements (e.g., twice daily dosing) are now available to help in this area.
"In the mid-90s, emerging clinical and basic science data supported a theoretical case for HIV eradication within 2-3 years through early and aggressive antiretroviral drug therapy that would completely suppress viral replication," said Paul Volberding, MD, chair of the IAS-USA board and a University of California, San Francisco professor of medicine. "Now we know that eradication with drug therapy alone is not a realistic goal at this time. Our new recommendations take this into consideration along with long-term survival."
Volberding is senior author of the JAMA paper and also serves as director of the UCSF Positive Health Program at San Francisco General Hospital Medical Center.
"Since our last recommendations in 1998 were announced, three effective new drugs have become available and new ways of combining drugs are in common use, greatly increasing the opportunity for positive treatment outcomes in our patients," emphasized Charles C. J. Carpenter, MD, chair of the panel, first author of the JAMA paper, and professor of medicine at Brown University.
"Now with more convenient drug administration schedules and carefully individualized treatment plans, most patients with HIV infection can live fully active and productive lives," he said.
The new guidelines are limited to therapies approved by the U.S. Food and Drug Administration and available in 1999, according to Volberding. Other highlights of the treatment recommendations are:
* When to initiate antiretroviral therapy Physicians and patients must weigh the risk and benefits of starting therapy and make individual informed decisions. When to initiate therapy and what regimen to choose are crucial decisions, otherwise future options may be severely compromised. Ultimate long-term success may be a function of the aggregate effectiveness of sequential therapies, the panel noted.
Therapy is generally recommended for patients with a confirmed plasma HIV RNA level (viral load) above 30,000 copies per milliliter, irrespective of CD4 cell count, and for patients with CD4 cell counts below 350, irrespective of HIV RNA level.
* Initial therapy
Recommendations for specific combination of drugs cannot be made. Choice of a
regimen should be individualized based on its potency, tolerability, and
adverse effects.
Dual protease inhibitor combinations are increasingly being used because they offer pharmacologic and adherence benefits and improved efficacy. Data has shown ritonavir can be used effectively with saquinavir, indinavir, and amprenavir. Also, much more data support the initial use of non-nucleoside RTIs in place of protease inhibitors. These combinations, regardless of the specific class of drug used, can offer potential for increased potency and reduced pill burden, dose frequency, cost, and meal-time restrictions.
* Monitoring therapy
Both CD4 cell and HIV RNA levels are important for evaluating treatment
response. The HIV RNA levels should decrease rapidly after therapy is
initiated. Failure to achieve a target level of less than 50 copies/ml after
about 16 to 24 weeks should raise concern about poor adherence, inadequate drug
absorption, or drug resistance. Increases in CD4 cell counts reflect
reconstitution of the immune system.
* Changing therapy /regimen
A decision to change therapy must be balanced by consideration of the
likelihood that another regimen will achieve control of viral replication or be
better tolerated. The panel also pointed out, however, that there is little
direct
experience with comparative retroviral drug potency, even within drug classes,
and changes in a successful regimen should be approached cautiously.
* Stopping therapy
Based on clinical and immunologic benefit in patients with advanced disease
and few or no remaining antiretroviral options, it is reasonable to continue
treatment as long as possible.
IAS-USA is a national not-for-profit organization based in San Francisco that provides information and education for physicians involved in HIV/AIDS care. IAS-USA is not affiliated with the worldwide IAS, based in Sweden.
The panel for the newly released guidelines, in addition to Volberding and Carpenter, included: David A. Cooper, MD, DSc, University of New South Wales; Margaret A. Fischl, MD, University of Miami; Jose M. Gatell, MD, PhD, University of Barcelona; Brian G. Gazzard, MA, MD, Chelsea and Westminster Hospital, London; Scott Hammer, MD, Columbia University; Martin S. Hirsch, MD, Harvard Medical School; Donna M. Jacobsen, BS, IAS-USA; and David A. Katzenstein, MD, Stanford University.
Also, Julio S. G. Montaner, MD, St. Paul's Hospital, Vancouver; Douglas D. Richman, MD, UC San Diego; Michael S. Saag, MD, University of Alabama at Birmingham; Mauro Schechter, MD, PhD, Universidado Federal do Rio de Janeiro; Robert T. Schooley, MD, University of Colorado; Melanie A. Thompson, MD, AIDS Research Consortium of Atlanta; Stefano Vella, MD, Instituto Superiore de Sanita, Rome; and Patrick G. Yeni, MD, Hopital Bichat-Claude Bernard X. Bichat Medical School, Paris.
Journal
JAMA