Adherence to Anti-HIV Therapy

By Kevin King, M.D.

Adherence to antiretroviral therapy is one of the greatest problems that HIV-infected patients and physicians face. Both the short-term and long-term success of antiretroviral therapy are determined to a great extent by careful adherence to any given antiretroviral regimen. Poor adherence may simply lead to the lack of the intended beneficial effect as measured by the viral load and the CD4+ (helper) T-cell count. More importantly, poor adherence may lead to the development of antiretroviral resistance. Resistance may develop quickly and is usually considered to be irreversible.

Drug resistance means that an individual's unique HIV is resistant to the suppressive effect of the drug. Because of the similarity of drugs within a class of antiretroviral drugs, resistance to one drug may in fact be indicative of resistance to several or all drugs in that class, a phenomenon known as "cross-resistance." Cross-resistance is a particularly great concern with the HIV protease inhibitors.

It is now known that an individual may be primarily infected with a drug-resistant virus, and even with multi-drug resistant HIV

(MDR-HIV). A case of primary infection with MDR-HIV was recently reported in the New England Journal of Medicine (Hecht F et al,

NEJM, 339:5 Jul 30 1998). This means that poor adherence may not only affect the individual patient, but the entire community of people at risk for HIV.

Why is meticulous adherence so difficult? Many aspects of antiretroviral therapy make adherence challenging. First, antiretroviral therapy at this time is considered to be a life-long obligation. Furthermore, it appears the only effective antiretroviral therapy involves combinations with a minimum of three different antiretroviral drugs. These drugs must be taken at precise intervals, usually two or three times a day. Several of the drugs have dietary requirements, such that they must be taken with or without food. Antiretroviral drugs are also very expensive. A typical combination of three drugs costs over $1000 a month. Finally, and perhaps most importantly, is the issue of unpleasant side effects. With all these barriers, the fact that anyone is able to consistently and successfully take these drugs is amazing.

What can be done to promote adherence? First of all, the doctor and patient must communicate at great length. Information should flow in both directions; that is, from doctor to patient and from patient to doctor. A provider who has just met a patient should not just write out three prescriptions for antiretroviral drugs and leave the room. The unanswered questions and doubts that are left behind will turn into adherence/resistance problems that will affect us all.

Antiretroviral therapy emergencies are rare. A doctor and patient may need several visits over several weeks to know each other well enough to initiate antiretroviral therapy with confidence of long-term success. A patient with a serious substance abuse problem or severe depression may require treatment of this problem prior to initiating antiretroviral treatment.

Both the doctor and the patient must clearly understand the goal of antiretroviral therapy. Simply put, the goal is to prevent or delay HIV-related immune suppression and its complications, including clinical disease and death. As these goals are only measurable retrospectively, surrogate markers including plasma viral load and CD4+ T-helper cell count serve as day-to-day measures of success.

Many people are concerned about how antiretroviral therapy will affect their quality of life. Preventing all the complications of immune suppression is the ultimate improvement in quality of life. It is essential to remember this long-term benefit when trying to weigh all of the benefits and burdens of antiretroviral therapy.

Patients may have strong beliefs about particular drugs. These beliefs should be elicited by the doctor and taken seriously, even if they seem irrational. For instance, some people may have had friends or lovers who died while taking AZT, and are consequently convinced that the drug caused the death. Trying to persuade such a person to take AZT may therefore be counter-productive. On the other hand, a patient may have had a close personal relationship with someone whose life seems to have been saved by a particular drug. The preconception may be used to beneficial effect.

Quality of life concerns vary from person to person. Some are afraid to allow co-workers to know they are HIV-infected, and are afraid to take their drugs to work. Prescribing a three-times-daily regimen should be avoided for these people. Other patients do not care how many pills they take or how many times a day they must take them, but will not tolerate any diarrhea. For still other people, the only insurmountable adherence issue is trying to take a pill on an empty stomach.

The key here is flexibility on the part of both the physician and the patient. A patient who insists that only a regimen involving one pill taken once a day with no side effects would be acceptable, will not find an effective regimen of antiretroviral drugs. Likewise, a physician who insists that every patient has to be on ddI or ritonavir will encounter a lot of non-adherent patients. For antiretroviral naive patients especially, there are numerous options for effective antiretroviral therapy.

It must be emphasized that adherence cannot be assumed or taken for granted. Both the physician and the patient must acknowledge and address all the problems that lead to poor adherence. This process should begin prior to treatment initiation, and continue as long as the patient is on treatment. Finally, I have referred to the physician as the primary partner in promoting adherence. In fact, nurses, pharmacists and community educators all have important roles to play in promoting adherence to these complex regimens of anti-HIV drugs. N