• Management of Patients With Virologic Failure (Abstract 405)
  Authored by Judith Falloon, M.D.
  Symposium: Non-abstract driven session

In this talk, Dr. Falloon reviewed the current challenges to defining and addressing one of the greatest issues in ensuring the long term health of those with HIV infection: managing HIV rebound despite treatment. She began by defining viral rebound, as it is clear from multiple prior studies that viral suppression is the ideal way to ensure a durable CD4 cell recovery.

There are data that have shown stable CD4 counts even with partial virus rebound -- this is clear from work done by several groups over the past few years. However, it is also likely that this partial rebound leads to only a temporary recovery, and that over time, while growing, HIV continues to augment its degree of resistance to the drugs that are used, allowing it to accelerate CD4 destruction. Dr. Falloon noted that there is no clear threshold at which HIV is growing, but not creating, new mutations and thus stated that at least for now, we should strive for a viral load below detection.

Dr. Falloon did discuss the issue of defining exactly what a viral load below detection means. It is clear that over the years, our technology has improved, and this has changed what we refer to as "below detection." This technologic improvement can continue still -- even beyond what is now considered the standard, which is currently below 50 copies. However, since a definition of below detection is used to define a durable response, these improvements in our testing can then redefine someone who now has viral suppression as someone with detectable viremia -- and the question is whether this means that this person is actually in viral failure -- since, at this point, those with virus replication (detectable viremia) are considered at risk for rebound. It is clear that since we don't eradicate HIV -- we can always find it with some test -- defining the degree of suppression needed to maintain a durable response will be among the challenges for the future. For now, a viral load below 50 copies has worked well to define this group.

Over the past several years, studies have shown less degrees of success when switching from one regimen to the next. This is due, at least in part, to the problem of HIV resistance, and has led to a general approach of switching as soon as possible after rebound, as long as there is at least one regimen available that is likely to drive HIV down to below 50 copies. Otherwise, there is less urgency in the switch when going from one partially suppressive regimen to another.

We have learned that failure is not random, but can be predicted by a few well-defined factors, including low initial CD4 counts, high baseline viral load, a history of an AIDS-defining illness, and current injection drug use. The latter is a marker primarily for erratic medication adherence, likely to be the primary reason we see viral rebound.

However, other reasons include low drug levels based on other issues, such as drug-drug interactions or individual differences in how these drugs are absorbed and processed. There are studies that suggest that drug level monitoring may help; however, these studies are still considered preliminary by many, and have left an ongoing controversy in the field about the use of drug level testing.

Less controversial is the use of resistance testing. Defining what mutations HIV has made can certainly help define which agents are more or less active. Ongoing challenges here include defining the best interpretation of these mutations, including the incorporation of drug levels. For at least some drugs, we can "boost" the amount of drug present, which can overcome low levels of HIV resistance. Knowing how to interpret these patterns, given these drug level changes, is one of the key agendas in the field of resistance testing. It is clear, however, that one of the best predictors for the success of a new regimen is the number of active drugs in that regimen, and this activity is defined by resistance testing.

Is there a role for stopping treatment prior to a switch? At this point, several studies have been completed, and most have suggested that there is no established benefit to this strategy as currently implemented. However, one study conducted in France did show a benefit to the interruption, and there is much interest in assessing what may have been different in that study population to ensure that there is no missed opportunity to improve outcomes with this particular intervention.

Dr. Falloon summarized her talk with the following issues. If there are no new drugs, or no apparently new active drugs to change to, then there is little reason to switch, except for toxicity reasons. In addition, if there is only one new agent, it is generally considered best to wait for at least one new agent, if at all possible, since one new drug rarely provides a durable response. Nevertheless, there are ways to maintain health while awaiting a second drug, including prophylaxis for opportunistic infections, as clearly there are new and potent agents in active drug development.