IAPAC Sessions 2003 End with Focus on Monitoring Bio-medical Data, HIV Drug Resistance Testing, and Body Shape and Lipid Abnormalities

Sponsored by the International Association of Physicians in AIDS Care (IAPAC), HIV/AIDS physician thought-leaders gathered in Chicago last week at an annual forum to discuss and debate a host of contentious HIV treatment Issues. These  included adherence to therapy, the monitoring of Bio-medical data and the morphologic and metabolic changes often referred to as “lipodystophy.”

Monitoring Bio-Medical Data and Testing for Drug Resistance

Delegates at the morning session of the IAPAC Sessions 2003 discussed an issue at the center of the complexity involved with Highly Active Antiretroviral Therapy (HAART): testing how antiretroviral medications are interacting with a patient’s bio-chemistry and the human immunodeficiency virus (HIV) with which he or she is infected.

IAPAC sponsors this annual gathering because physicians need a forum at which to discuss the unknown factors they face in treating their HIV-infected patients. This morning’s session pointed out that need, as delegates and presenters discussed technologically advanced diagnostic tests that may be sensitive beyond clinicians’ ability to accurately interpret their meaning and alter a patient’s treatment.

Therapeutic Drug Monitoring (TDM)

Eugene D. Morse (University at Buffalo), a pharmacologist, described an emerging new option for diagnostic testing of the effects of highly active antiretroviral therapy (HAART) in patients. According to Morse, Therapeutic Drug  Monitoring (TDM) detects at a very precise level how HAART medications interact with each other and with the patient’s body.

But interpreting that data, as Morse and several delegates asserted, remains quite difficult.

Mark Dybul (National Institutes of Health), who sits on the US Department Health and Human Services (DHHS) HIV treatment guidelines committee that might someday make recommendations on this emerging tool, asked clinicians to describe how they had used TDM in their practices, or would have used it if it were available. They mentioned cases in which there was a potential for liver problems and patients on so-called “salvage” therapy who are resistant to most available HIV-treating drugs. Morse confirmed that this last usage was particularly appropriate and common.

Until TDM is somehow simplified, however, delegates asserted that it would be of limited clinical use. Several commented on the fact that a pharmacologist is needed to interpret the data at all, and many times the interpretations are not readily translatable into better treatment decisions.

Resistance Testing

There were differences and similarities in the discussion of resistance testing, a process that determines whether a patient’s HIV has mutated into a form that is no longer affected by a particular antiretroviral medication. Resistance testing is now common practice among clinicians, but, as with TDM, the interpretation of the data provided is highly variable and its usefulness in determining HAART regimens is also not clear.

David Katzenstein (Stanford University) presented data showing that patients whose physicians use resistance testing have HIV that is only very slightly better controlled than those who do not. He also showed that the world experts on interpreting resistance data only really agree on the meaning of a result about 60 percent of the time.

While the DHHS does not currently recommend resistance testing for patients who have never received HAART, nearly all the assembled delegates said that they use the resistance tests for that purpose. The reason to test a “treatment naive” patient is that strains of HIV already resistant to particular types of drugs can be passed from one person to another. Diane V. Havlir (University of California San Francisco), co-chair of the IAPAC Sessions 2003, said that the existence of drug-resistant HIV in the general population is reason enough to test every new patient for resistance.

Need for Widespread Use of Resistance Testing?

Havlir said the need to monitor for such resistant strains overcome the barriers of cost associated with the testing that some delegates expressed as reason to use the tests sparingly. “Think about all the things we thought we know about this virus that we’ve been wrong about.”

Other delegates disagreed. Referencing Katzenstein’s presentation of data that showed little clinical impact of resistance testing, one delegate expressed that resistance testing was widely over-used for all patients, whether treatment naïve or experienced. He asked, “Why are we spending hundreds of millions of dollars on this technology?”

Side Effects of HIV and HAART

In the afternoon, physicians at the IAPAC Sessions 2003 discussed the ubiquitous but poorly understood morphologic and metabolic complications associated with HIV and the highly active antiretroviral therapy (HAART) that is used to treat it. Such side effects include diabetes and abnormal fat distribution.

These complications occur in a relatively high percentage of patient's taking HAART, the treatment therapy that prevents HIV's destruction of their immune systems. Seven percent have diabetes, 57 percent have dangerously high cholesterol, and as many as half have abnormal fat distribution.

Potential Causes: Aging, HIV and Drug Therapy

Because of such difficulties, Hadigan predicted that clinicians might be treating morphologic and metabolic complications until such time as new medications are developed that do not cause them--which she thought would eventually happen. Faced with this possible reality, delegates discussed strategies for treating these complications, including medications for cholesterol levels, drugs that aid insulin sensitivity, and plastic surgery for altered body and facial characteristics.

However, Hadigan, along with session moderator Kathleen Mulligan (University of California, San Francisco), encouraged clinicians to also consider non-drug interventions for these complications. Getting more exercise, quitting smoking, and modifying diet can have a good effect. Such options warrant special consideration, they said, because patients being treated for HIV are already asked to take a large number of pills each day and, as delegates discussed yesterday, often have difficulty adhering to complex multi-pill regimens.

Without dismissing the importance of treating morphologic and metabolic complications, Renslow D. Sherer (University of Chicago Hospitals), co-chair of the IAPAC Sessions 2003, suggested that "perhaps we focus on these things too much." He pointed out the complications may be serious, but a significant percentage of patients do not suffer from them, they are generally manageable, and the ability to use HAART to add years to patients lives should not, by comparison to on-going difficulties, be discounted.

"Let's not forget how we've reduced mortality," he said.

05/19/03