Guidelines shed light on identifying failed regimens
Guidelines shed light on identifying failed regimens
Making regimens affordable is a growing concern
The new federal guidelines for HIV treatment discuss at length the considerations and consequences of a failing drug regimen resulting from regimen interruption, noncompliance, or resistance. However, the alternative options they offer are based on limited studies, they warn.
The federal panel cites several factors for consideration, including a patient’s recent clinical history and physical examination, viral loads measured on two separate occasions, and changes in CD4 count. It also notes the importance of distinguishing between the need to change therapy due to drug failure vs. drug toxicity. For drug failure, the regimen should be entirely changed to drugs that have not previously been taken. For drug toxicity, it is appropriate to substitute one or more alternative drugs.
Fight back quickly, thoroughly
The federal panel advises physicians to change as many elements of the regimen as possible when viral levels begin to creep up and the treatment regimen begins to fail, because the virus has become resistant to the therapy.
"The major difference here is that we used to give drugs until we saw a patient develop a new complication of AIDS and then change the therapy," says John Bartlett, MD, a panel member and professor of medicine at Johns Hopkins University. "We can’t afford to wait until that happens because it means that the drug has already become ineffective. Once the virus escapes, you’ve lost the regimen."
The guidelines issued by the International AIDS Society USA (IAS) last month note that "in the case of treatment failure, the guiding principle should be to try to change all drugs in the regimen or at least to include a minimum of two new drugs in the revised regimen.1 The practice of adding a single drug to a prior insufficiently suppressive regimen is strongly discouraged."
Criteria for changing therapy cited by the federal panel include:
• less than 10-fold (1 log) reduction in viral load by four weeks following start of therapy;
• failure to suppress viral load to undetectable levels within four to six months;
• repeated detection of virus after initial suppression to undetectable levels;
• declining CD4 counts measured on two separate occasions.
The IAS panel notes that "ideally, any confirmed detectable HIV RNA levels is an indication to change therapy, in order to prevent drug-resistance." In practice, however, the panel says it may be more realistic to await an increase of 2,000 to 5,000 copies before changing therapy.
The federal panel points to the paucity of data for specific strategies for changing therapies. However, it goes beyond the IAS guidelines by positing a theoretical framework for making those decisions and providing the treatment options available for consideration. (See excerpt from federal guidelines, inserted in this issue.)
For some patients, changing to a new regimen is not an option because of prior antiretroviral use, toxicity, or intolerance. For the patient whose viral load is detectable but remains clinically stable, the federal guidelines suggest the option of delaying changes in therapy until new and more potent agents are developed. Because these decisions are some of the most complex in HIV treatment, the federal panel also recommends that clinicians without specialized training in HIV seek assistance from experienced AIDS providers through consultation or referral.
Early treatment may help eradicate virus
Another group of patients posing difficult treatment decisions are those identified with primary or acute infection. Anywhere between 50% and 90% of patients experience the flu-like symptoms of acute retroviral syndrome and are candidates for early treatment. While the justification for such early treatment within the first months of infection is theoretical, the rationale is based on results in several dozen patients showing that the virus can remain undetectable for more than two years with combination therapy. Because treatment during primary infection may offer the greatest opportunity to eradicate HIV from the body, clinicians are urged to maintain a high level of suspicion for its symptoms.
Although the federal guidelines do not mention the controversial proposals to treat high-risk sexual exposures to HIV with preventive therapy, the IAS points out that the Centers for Disease Control and Prevention is developing guidelines for post-exposure prophylaxis. With limited data on the efficacy and side effects of this treatment, clinicians should hesitate to offer it right now, the panel adds.
The federal recommendations are now open for 30 days of public comment, after which the guidelines will be reviewed and published in the Morbidity and Mortality Weekly Report and another peer-reviewed medical journal.
"These guidelines don’t have any legal or regulatory clout," says Eric Goosby, director of the office of HIV/AIDS policy in the Department of Health and Human Services. "But they have the power to set the standard of care."
Approximately 150,000 to 180,000 HIV-infected people in the United States currently receive triple therapy. That number represents only half of the people with HIV who are receiving care. However, an estimated 350,000 people HIV-infected aren’t receiving care either because they don’t know they are infected or because they can’t get access to care. Triple therapy costs between $10,000 and $12,000 per year, and questions remain as to how managed care organizations and federal insurance programs will allocate resources for the treatment.
"Triple therapy compares favorably when you look at cost per year of life preserved," Bartlett notes. "In fact, what we are advocating compares favorably with mammography screening, renal dialysis, and cardiac bypass surgery."
Goosby notes that with AIDS treatments, the compensation issue is complex and is not unique to HIV infection. "The payment issues with AIDS therapies have implications on the compensation for all chronic progressive diseases," Goosby says. "These are complex issues that need to be addressed, and the federal government will be at the forefront."
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