IAS: Undetectable Viral Load Must Be Goal in HIV treatment

SYDNEY, July 23 -- Doctors and patients should not be content with keeping human immunodeficiency virus (HIV) at low levels, but should seek to optimize treatment to suppress virus to undetectable levels.

"Low level virus is no longer an acceptable option," said Charles Hicks, MD, of Duke University, at an industry-sponsored symposium held in conjunction with the International AIDS Society meeting here.

Dr. Hicks reviewed studies indicating that patients who had detectable levels of HIV continued to develop resistance mutations to the point that, after 12 months, 30% had lost the option to use a drug that they had never taken because they'd developed resistance.

"It has become quite clear that getting patients to a goal of less than 50 copies/ml of virus is strongly associated with good outcomes," he said. "Despite enormous improvements in the management of HIV-infected persons, cure is beyond our reach in 2007. As a result, long-term viral control, which in turn allows immune restoration, has become the goal of treatment for all patients."

Dr. Hicks illustrated the goal by describing a patient who had been treated with antiretroviral drugs since 1995 - including monotherapy, dual therapy and combination highly active antiretroviral therapy. He had developed virus with a substantial number of resistance-associated mutations and in the course of more than 10 years of therapy had never had an undetectable viral load.

To optimize his treatment, doctors put together a cocktail of five drugs that resulted in an undetectable viral load and a substantial increase in CD4-positive cells, an indication of an improved immune system.

Dr. Hicks said that this patient - who was resistant to three classes of HIV drugs - represents the goal of HIV treatment in 2007: "With the availability of better agents, including new classes, long-term viral suppression is increasingly possible even for these patients."

A key to being able to select the right drugs is performing resistance testing, said Eric Daar, M.D., of the University of California, Los Angeles and chief of HIV Medicine at Harbor-UCLA Medical Center.

In areas of the world where resistance testing is available, Dr. Daar said, doctors have a choice of using genotype, phenotype, or "virtual" phenotype testing. Each of those has advantages and disadvantages, he said, requiring physicians to practice the art of medicine.

"Achieving the goal of an undetectable viral load requires the full assessment of the patient's treatment history and drug resistance pattern," he said.

"Resistance testing is an invaluable tool in defining the likelihood of response to new drugs in existing classes. New classes of drugs complement those in existing classes but must be used with caution to preserve future treatment options," Dr. Daar said.

The treatment of patients with HIV infection should begin as soon as possible, said Jens Lundgren, M.D., director of the Copenhagen HIV Programme. While there has been continuing debate as to what level of CD4 cells is the threshold for beginning treatment, Dr. Lundgren said that in most cases patients generally don't present for treatment until their CD4 count is below 250 - a low threshold for starting treatment.

He reviewed results of the SMART Study [NEJM 2006] that considered whether a strategy of drug conservation or viral suppression was best for patients. The drug conservation cohort allowed patients to stop antiretroviral treatment when their CD4 count increased to more than 350 cells/ml. They restarted antiretrovirals if the CD4 count dropped below 250 cells/ml. The other patients stayed on treatment regardless of CD4 count.

Dr. Lundgren noted that the trial was halted in favor of continued viral suppression because patients in the drug conservation group experienced double the rate of opportunistic infections or death (p