Drug Resistance Not Always to Blame When HIV Treatment Fails

From the WebMD Archives

Jan. 11, 2000 (Atlanta) -- HIV treatments fail for more reasons than previously recognized, according to two new studies in this week's edition of the Journal of the American Medical Association. However, new tests may be able to expand the number of treatment options remaining to patients whose first anti-HIV drug regimen no longer works.

When combination HIV therapy fails, doctors usually assume one of two things: Either the virus has developed the ability to resist the drugs, or the patient has not taken the drugs as prescribed. The studies show that for patients in whom treatment stops working soon after it is begun, resistance to the most potent drugs in the combination is not usually the problem.

"There are many reasons why drug regimens fail patients," Diane V. Havlir, MD, lead author of one of the studies, tells WebMD. "Resistance testing might help define the optimal therapy for a patient in that situation. Not all of the drugs in a treatment regimen might be resistant to HIV."

"The cause of the failure in this trial seems to be related to problems with adherence ... and is related to the potency of the drugs," Françoise Brun-Vézinet, MD, PhD, lead investigator of the second study, tells WebMD.

Both research teams point to their findings as evidence -- not proof -- that only the drugs to which HIV has developed resistance need to be replaced in a failing regimen. Brun-Vézinet and Havlir both warn that this is a risky proposition, but that it is worth testing in the face of limited treatment options.

Brun-Vézinet insists that drugs that are hard for patients to take can be just as ineffective as drugs to which HIV has developed resistance. "We need very simple drugs to take," says the director of the virology laboratory at Bichat-Claude Bernard Hospital, Paris. "What we learned very early is that this is a chronic infection; patients will take the drugs all their lives. The pharmaceutical companies need to push efforts to make anti-HIV drugs very easy to take. We need to support patients and to help patients to take drugs in appropriate fashions. That means that we need to have some unique person in the clinical department who will be devoted to helping patients to take the drugs. It is a very important problem because it is a reason for treatment failure."

In an interview to provide objective comment, Mark Feinberg, MD, PhD, tells WebMD that there is an urgent need to study the exact reasons why patients sometimes find it impossible to take anti-HIV drugs exactly as directed -- even when their lives depend on it.

"These studies validate much of what we know, mainly that adherence to antiviral treatment is important, but that it is influenced by the ease of taking the retroviral regimen," says Feinberg, associate director of the Emory Atlanta Center for AIDS Research. "The easier they are the more people will take them. By more careful evaluation of people not responding we will be able to determine the cause of that. Not all early failure is due to resistance to all drugs, nor is it all due to people not taking the drugs."

Feinberg notes that the studies do not definitively answer these questions but in fact underscore the growing complexity of managing HIV disease. He suggests that doctors who do not see a large number of patients with HIV may find it difficult to keep up with new developments.

"Given that the field moves so rapidly and the optimal strategies require so much information, it makes it increasingly hard for people without expertise to take care of people with HIV," he says. "They just cannot do the best job. It does add credence to the argument that people with HIV should be taken care of by specialists, because I don't know that this is going to get any simpler."

Vital Information:

  • HIV treatments can fail for many reasons, according to the results of a new study.
  • Resistance testing could help to better define the best regimen for a patient, as the virus may not be resistant to all the drugs being taken.
  • Pharmaceutical companies also need to make drugs easier to take, so that patients can more easily adhere to their regimen, according to one of the researchers