Although antiretroviral drugs work remarkably well in reducing the viral load of HIV, the regimens that accompany them are often so complicated that one quarter of patients don't adequately adhere to them.

Non-adherence is an issue in treating most diseases. But with HIV, non-adherence has more consequences than the usual short-term loss of treatment effectiveness -- it leads to emergence of drug-resistant strains of the disease, resulting in permanent loss of effectiveness. Not only does the patient suffer, but so perhaps does the greater society, which may then be subjected to more drug-resistant strains of HIV.

UCSF faculty members Margaret Chesney , professor of medicine at SFGH and co-director of the Center for AIDS Prevention Studies; Paul Volberding, UCSF professor of medicine, director of UCSF Center for AIDS Research and director of AIDS program and medical oncology at SFGH; and Frederick Hecht, assistant clinical professor of medicine, UCSF AIDS Program at SFGH, discussed this increasingly salient issue last week at the Dean's Research Seminar titled "Adherence: The Achilles' heel of antiretroviral treatment for HIV?" Their conclusion: adherence is very important to prevent breakthroughs of HIV disease, yet non-adherence is common.

For close to a decade, Volberding and Chesney have been studying adherence issues as they relate to HIV and AIDS. They say that since 1996, when antiretrovirals began to be widely used, HIV drug regimens have become more complex and demanding, and that no precedent exists for such intensive drug therapy to be taken on an ambulatory basis for an indefinite period of time.

Adherence is especially difficult for people who are homeless, marginally housed or substance abusers. Because some antiretrovirals need to be refrigerated or taken according to very specific instructions, these UCSF researchers suggest that partnering with other AIDS-related service programs, and using a new initiative that the University hopes to develop with the City of San Francisco to establish action centers where people can gain access to antiretrovirals, might improve adherence.

But even for educated people with resources, adherence is difficult to achieve and maintain.

Volberding told of an HIV-positive man who became his patient after already being on triple combination therapy. After eight months under Volberding's care, the patient realized that he had been mistakenly taking one pill three times a day instead of the required three pills three times a day. Because the regimens are so complicated, it is easy to understand how a patient might get confused and, Volberding said, it is increasingly difficult to go over all the information about drug regimens with patients in the short time periods allotted for patient visits through managed care.

Chesney suggested that either clinicians or others on the health care team, including nurses and pharmacists, spend more time with their patients explaining the drugs, their side effects and the importance of adherence. It has been shown that poor adherence is directly associated with the complexity of drug regimens, the number of specific medications that are prescribed and the extent to which an assigned regimen interferes with daily life, Chesney said.

The number-one reason people do not adhere, Chesney said, is that people simply forget, followed by sleeping through a dose, being away from home and changing their routine. Depression is an across-the-board factor in people missing their medications for all diseases, accounting for 10% of all patients, Chesney said.

In fact, the three major factors that predict breakthrough of HIV are failure to adhere to drug regimens for treating HIV, high initial viral load and prior resistance to HIV medications.

A study conducted at SFGH by Hecht, Chesney and others found that non-adherence predicts viral load detection. The team surveyed half of all clinic sessions at the SFGH AIDS clinic from January 1997 through February 1997, measuring self-reported adherence in the three days prior. They found that for people who missed no doses in the previous three days, two-thirds had undetectable viral loads. For those who adhered 80 to 99% of the time, approximately 60% had undetectable viral loads. For those who adhered less than 80%, approximately 35% had undetectable viral loads.

Research has found that people who adhere less than 80% of the time are at high risk for a breakthrough of disease. Chesney and Hecht are currently studying what percentage above 80% adherence is required for antiretroviral treatment to be effective.

Chesney said the steps clinicians can take to improve adherence are to clarify and simplify the regimen, identify reminders or cues for taking medication and provide treatment for depression, if applicable. Chesney said they will be implementing some of these interventions at SFGH in a clinical trial format to see if they improve adherence. She also said that they are using HIVInsite to distribute adherence information to clinicians and patients alike.

Chesney, Volberding and Hecht stressed that different UCSF departments, health services programs and city agencies need to collaborate in order to stem this potential personal and public health threat of non-adherence. "There's an immediate need for a multidisciplinary effort," Chesney said. "We need to conduct critical research to maximize adherence in order to enhance the clinical benefit to patients and to prevent the spread of multi-drug resistant HIV to the public."

Links:

Strategies to Establish and Maintain Optimal Adherence

Compliance: How Physicians Can Help

by Paula Murphy

1st appeared 3/17/98

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