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Doing more than testing and switching

May 2002
William Check, PhD

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A number of measures in addition to resistance testing and regimen switches are needed to combat the rise of drug-resistant HIV-1 strains.

Primary resistance—carried by the virus strain a patient was infected with, and secondary resistance—acquired during treatment, are becoming frequent:

• 12 percent of a sample of newborns in New York state had genotypic resistance mutations early after birth.
• Half of all Americans under care for HIV infection carry viruses resistant to standard antiretroviral drugs.
• In the United Kingdom, primary resistance was detected in 27 percent of a cross-section of patients infected in 2000.

To reduce the spread of primary resistance, prevention will be a key, with emphasis on reducing unsafe sexual practices. A recent study found that "Any decrease in per contact risk of HIV transmission due to HAART use appears to have been counterbalanced or overwhelmed by increases in the number of unsafe sexual episodes."

To decrease the rise of secondary resistance, some physicians are delaying potent therapy as long as possible. "We are moving to a more conservative approach" to therapy, says Dr. Charles Boucher, clinical virologist at University Hospital in Utrecht, the Netherlands. "We used to say, start early and hit hard. But newer clinical data say you can wait fairly long without losing options and avoid toxicity and reduce costs." So far only observational data support this notion. And, Dr. Boucher notes, it has a major drawback-more patients are walking around who could transmit virus.

"When we had drugs that were not as robust as the current ones, we had to start earlier to have a good result," says Dr. Robert Schooley, head of the infectious diseases division at the University of Colorado Health Sciences Center. "Now we have a bit more confidence that potent regimens work later. And the immune response is quite resilient in most people. Having said that," he cautions, "you do sacrifice some degree of success by waiting. And in some people the immune response is not as resilient."

An even more controversial approach now under investigation is structured treatment interruption—stopping therapy for a few weeks or months. Theoretically, susceptible viral strains should outgrow resistant virus during this period. But in one such trial reported a few months ago, multiply resistant virus appeared when therapy was resumed. Dr. Graeme Moyle, associate director of HIV research at Chelsea and Westminster Hospital, London, calls this "archived resistance"—persistence of mutations based on taking a drug many years ago. "This result tells us that resistant viruses are not disappearing when we stop treatment," Dr. Moyle says. They are only decreasing below the detectable level of resistance tests. "Current tests consistently underestimate the amount of resistance that is present in the patient's viral swarm," Dr. Moyle says.