Updated treatment guidelines for HIV infection announced by international panel of AIDS experts

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.