Monitoring of treatment can help prevent ART resistance
Sustained treatment interruption is worst
The next step that HIV clinicians should take in improving their patients' HIV treatment adherence is to match patients to the optimal adherence strategies for each person, an adherence expert and HIV researcher says.
HIV providers should use better monitoring strategies and pick the right regimen for the right person and identify a treatment failure before it occurs, says David Bangsberg, MD, MPH, a senior scientist with the Massachusetts General Hospital and Harvard Medical School, Harvard Initiative for Global Health, in Cambridge, MA.
"What we're saying is each regimen has a certain type of pattern of adherence that leads to drug resistance," Bangsberg says.
"We need to understand what those patterns are for each regimen," Bangsberg adds. "We've made progress in that area, but there's a lot more to learn."
Research continues to show that sustained and repeated antiretroviral (ART) treatment interruptions result in viral rebound.1
One recent study also shows that patients with moderate adherence can still achieve virologic control, so long as they haven't missed doses over a sustained interval.1
HIV clinicians need to come up with strategies that more precisely monitor an individual's adherence patterns, Bangsberg says.
"Different people miss their medications in different ways," he notes. "With more precise measuring strategies we can understand what these patterns are at individual patient levels and pick the best regimen for them."
The problem has been that HIV providers have been trying to manage HIV care without a good strategy for managing adherence, Bangsberg says.
"It's like managing hypertension without a blood pressure test," he adds.
There are adherence tools available, but none are perfect. They include the following, Bangsberg suggests:
- Tools for looking at pharmacy refill behavior;
- Web-based strategies for asking patients how they're taking medication on a regular basis;
- Electronic devices that measure how they take medication and transmit that information to a central server.
For providers who would like to individualize their HIV treatment adherence for each patient, the ideal scenario would be to have real-time, objective adherence monitoring, Bangsberg says.
"So you'll know when each patient is taking a dose," he explains. "At any point in time, you'd know, based on the patient's pattern and level of adherence, what the patient's probability is of biologic failure."
If the patient's level or pattern of adherence reaches the point where the probability of biologic failure crosses a threshold, then it should set off a red flag that this patient is at risk, Bangsberg says.
Then, HIV clinicians could provide the patient with an adherence intervention.
"The patient might need a more detailed counseling session by telephone or in person," Bangsberg says. "Or, in extreme cases, this could lead directly to observed therapy."
The counseling session might provide insight into the problem, such as whether the missed doses are due to medication side effects or some other factor.
"Then you could tailor that person's medication to a regimen that reduces side effects and matches that person's individual adherence behavior," Bangsberg says.
For this individualized adherence strategy to work, the HIV clinician will need access to state-of-the-art technology, he notes.
"There are pillbox organizers that have micro-switches that connect to a modem," Bangsberg says. "It's put into a computer program that determines a person's type of adherence behavior."
This is very new technology, and there is only now an emerging technology that can do all that Bangsberg describes.
"We know there's such a close relationship between adherence and virologic failure that by detecting lapses in adherence, you could intervene before virologic failure occurs," Bangsberg says.
For example, HIV/AIDS patients who have treatment interruptions might fall into two categories: in the first, they stop taking their medications over an extended period of time, due to side effects, socioeconomic changes, or health payer problems.
The second category includes people who might miss an occasional dose every so often.
"We've found that for people in new treatment, if they miss their doses all at once then they're at much greater risk for virologic rebound than if they miss occasional doses over time," Bangsberg says. "The risk is at 50% for rebound after a 15-day interruption — so half of the people who had that interruption would have virologic rebound."
The probability is quite low of virologic rebound after the first, second, and third day of interruption. So this is where a clinician's close monitoring can make a huge adherence difference, Bangsberg explains.
"If you have real-time monitoring, and you have 5,000 patients in your clinic, but one patient goes two-to-three days without taking his medications, then you could call up that patient and see what is wrong and intervene before they have a rebound," Bangsberg says. "You would have a window of maybe five days."
The five-day window gives clinicians time to provide an adherence intervention and prevent virologic rebound, he adds.
"If you can detect it in real time you can find out the problem, and creative case managers could make a lot of progress in solving the problem for that individual patient," Bangsberg says.
Likewise, if real-time monitoring shows that a patient is missing the occasional dose, maybe 5% of ART doses, then the clinician would know that it's probably not going to be a resistance problem, and no intervention is necessary, he adds.
"With modest improvements in technology and a little clearer understanding of the relationship between adherence and virologic failure, this could revolutionize HIV treatment," Bangsberg says. "Instead of responding to virologic failure after it occurs, you could prevent resistance before it happens."
Reference:
- Parienti JJ, Das-Douglas M, Massari V, et al. Not all missed doses are the same: sustained NNRTI treatment interruptions predict HIV rebound at low-to-moderate adherence levels. PloS ONE. 2008;3(7):e2783.
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