IAC: New Goals Set for HIV Salvage Therapy

TORONTO, Aug. 14 -- Even in HIV-infected patients who have tried and failed several drug regimens, the goal should still be to reduce the virus to undetectable levels, according to guidelines issued here.

"In the case of individuals with multidrug resistant virus and high degrees of treatment experience, regimens should be defined that can drive the virus to undetectable levels," said Scott M. Hammer, M.D., of Columbia's College of Physicians and Surgeons in New York.

Until now, the goal of so-called salvage therapy has been to reduce the level of HIV in a patient's bloodstream by a factor of 10, Dr. Hammer said at the 16^th International AIDS Conference.

The new guidelines were published simultaneously online in the Journal of the American Medical Association and will appear in the Aug. 16 issue. They are the seventh collection of treatment suggestions issued by the International AIDS Society -- USA, a San Francisco-based non-profit organization with the goal of educating American healthcare providers about HIV and AIDS.

Dr. Hammer said new drugs in existing classes, such as the protease inhibitor Prezista (darunavir), and medications in new classes, such as the fusion inhibitor Fuzeon (enfuvirtide), are the key to the new goal.

The panel urged that a second regimen should include "at least two and preferably three new agents" that are active against the resistant virus.

In 60% to 65% of cases of salvage therapy, Dr. Hammer said, it will be possible to make the levels of HIV undetectable, defined as fewer than 50 copies of HIV RNA per milliliter of blood.

In essence, doctors should try to hit a home run rather than settling for a single, said Stefano Vella, M.D., director of drug research and evaluation for Italy's national health agency. Dr. Vella was a member of the international panel that developed the guidelines.

The confusingly named organization is not related to the International AIDS Society, which is the organizer of the International AIDS Conference and directs a range of anti-HIV activities around the world.

International experts reviewed published, peer-reviewed literature on HIV/AIDS to come up with the new guidelines, which counsel doctors on when to begin treatment, what medications to use for initial therapy, when to change the treatment regimen, and what new regimen to choose.

The development of new drugs illustrates the continual refinement of the treatment options, Dr. Hammer said, but the recommendations for initial therapy remain essentially unchanged.

Symptomatic HIV should always be treated, the panel said, as should HIV infection in which the CD4 cell count is at or below 200 cells per microliter of blood.

But for CD4 cell counts between 200 and 500 cells per microliter, Dr. Hammer said, the panel said the physician's judgment should come into play.

The regimen for initial treatment is also essentially unchanged -- a combination of two nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor.

The favored non-nucleoside reverse transcriptase inhibitor is Sustiva (efavirenz), but there are a range of choices for the protease inhibitor and the nucleoside reverse transcriptase inhibitors, Dr. Hammer said. "The choice is really up to the provider," he said, taking into account the patient's history.

The panel said treatment response should be monitored by keeping an eye on the viral load, adding that a confirmed rebound should trigger a careful evaluation of the patient's adherence to the treatment regimen. CD4 cell count should be monitored at the same time.

On the other hand, the panel said, routine resistance testing isn't recommended, but if a patient is following a failing regimen, it should be done while the patient is still on the regimen.

Routine therapeutic drug monitoring to look at the levels of medications in a patient's system "remains controversial" because there's no evidence that it improves clinical outcomes and is not recommended, the panel said.

The guidelines for changing therapy remain "pretty classical," Dr. Hammer said: Doctors should change initial therapy if the regimen is failing because of resistance, or if it is inconvenient, intolerable or toxic.

While the panel was not compensated for its work and the study itself was financed by the IAS-USA, members reported previous financial links with Abbott, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Merck, Gilead, Schering Plough, and Boehringer Ingelheim, and several other drug companies.