Medication Adherence In The HIV/AIDS Patient:
Evaluation And Intervention

Alan M. Tennenberg, M.D., M.P.H.
Alan Tennenberg, M.D. is HIV Section Chief and Clinical Assistant Professor
at the University of Florida Health Science Center / Jacksonville.

In 1995, the number of HIV related deaths in Florida peaked at 4,336. Since then the Florida Department of Health reports that HIV-related deaths in the state have dropped 65 percent. In 1998, 1530 HIV related deaths were reported. Dramatic reductions in the rates of opportunistic infections have also occurred. Most of these decreases can be attributed to the advent and widespread use of highly aggressive anti-retroviral therapy (HAART), including protease inhibitors. HAART has made it possible to control HIV replication and disease progression by driving HIV plasma viremia down to undetectable levels.

Adherence to HAART is critical to achieve these benefits. Adherence, though, is confounded by complex treatment regimens involving multiple medications taken at incongruous dosing intervals. The medications can have major side effects and may be difficult to tolerate. Medication compliance must occur in order to achieve successful HIV therapy.

It is necessary to understand the degree of medication adherence needed to effectively and durably control HIV replication; or, conversely, how many doses of medication can be missed before treatment response is adversely impacted. One study using an electronic medication event monitoring system (MEMS) looked at virological failures on HAART as a function of adherence to treatment.1 Forty-five patients were studied. Treatment failure was defined as an HIV-1 RNA of >400 copies/ml. Adherence to treatment at a level of 95% or better was associated with a failure rate of 19%. With adherence of 90-95%, the failure rate increased to 36%. As adherence dropped to 86-90%, the failure rate rose to 50%, and with <70% adherence, the failure rate increased to 94%. This study directly relates better adherence to greater reduction in HIV viral load. Electronic medication event monitoring caps record the time and date that the pill bottle is opened. Data does not disclose how many pills were removed when the bottle was opened or if the pills were taken as instructed. Thus, true adherence may be lower than indicated by surveillance.

Non-adherence to HIV medications allows for a higher viral load translating into a higher likelihood of progression to AIDS.2 Reduction in viral load results in a decrease of opportunistic infections,3 hospitalization, progression to AIDS, and HIV-related morbidity. Poor adherence results in increased plasma viremia with its associated increase in morbidity and mortality. Suboptimal treatment of HIV infection, due to a poor treatment regimen or non-adherence to a potent regimen, breeds HIV that is resistant to the antiretroviral agents. Cross-resistance also exists between antiretroviral agents in same class. Therefore, therapeutic options for drug resistant HIV can be limited. The best chance for effective HIV therapy lies with the first treatment course. Once resistance has developed, success rates are more limited, particularly if adherence issues are not resolved.

The reasons for non-adherence to HAART include patient, disease, treatment, and provider factors. No consistent connection between medication adherence and demographics such as age, gender, race, occupation, and socioeconomic status has been demonstrated. An association between alcohol and drug use and poor adherence can also not be consistently demonstrated.

Among important patient characteristics are the levels of insight into the disease process and the impact treatment will have on the course of the illness. If the patient does not believe that treatment will be of benefit, there is less motivation to adhere. The patient's fear of side effects or belief in the ability to control side effects may also be a factor. Another important patient factor is the presence or absence of a support network of friends, family, or partner. Supporting individuals can give encouragement and allay psychologic conditions such as depression and anxiety, which also affect compliance, as may the level of trust and confidence the patient has in the doctor and the entire healthcare team.

Treatment or disease factors relate to characteristics of the treatment or the illness that generate barriers to adherence. One example is the complexity of the treatment regimen. This includes the number of medications, the number of doses taken each day, and the number of pills taken at each dose. Some medications, such as didanosine, need to be taken on an empty stomach, and others, such as saquinavir should be taken with food. It can be challenging to keep the specifics of the treatment regimen straight. The medications can also be associated with serious side effects, such as nausea, vomiting, diarrhea, and neuropathy that can be serious deterrents to adherence. Individuals with unstable living circumstances may not be able to properly and safely store their medicines. Individuals who work may not be able to carry their medications with them and may not have a private place to take them out of view of their co-workers.

Provider factors also play an important role. The health care providers must see their patients as partners in the treatment plan. Time must be taken to educate the patient about the treatment, side effects, and the disease process. Attempts should be made to tailor the treatment regimen to a particular patient's lifestyle and attitudes about treatment. The providers must recognize the aforementioned patient factors, and prescribe appropriately. Importantly, the provider should not impose treatment on a patient who expresses reluctance or unwillingness, even if the patient meets the treatment criteria. Similarly, it may be reasonable to delay switching to a new regimen if the patient expresses unwillingness or hesitation. It is rarely an emergency to initiate HAART, and time spent exploring the reasons for the patient's hesitation may improve the chances of treatment success through better adherence.

Assessing and addressing poor adherence in the clinical setting can be a challenge. At the Boulevard Comprehensive Care Center, the HIV clinic for the Duval County Health Department and University of Florida Infectious Diseases Division in Jacksonville, we have initiated a program that is designed to accomplish these goals. The program is comprised of nurses and a social worker, with a pharmacist on location for consultation. The adherence team utilizes a variety of means to identify patients who are at risk for poor adherence. They then intervene in a manner tailored to the patient's specific needs. The program is available to provide medication education and adherence counseling for all clinic patients with HIV/AIDS.

Patients can be referred to the program for a variety of reasons. A brief screening questionnaire is administered at every clinic visit. This screening tool asks patients to identify their antiretroviral medications from a list, then write in how many times per day each medication is taken and how many pills at each dose. They are also asked to recall how many doses were missed in the preceding 24 hours and 48 hours, and if they take each medication with food or on an empty stomach. The questionnaire is brief, taking only moments to complete. Patients who do not know this basic information about their HAART are given a detailed adherence consultation by our adherence team.

Patients can also enter the program when they initiate HAART for the first time or change to a new antiretroviral regimen. A consultation is recommended whenever new medications are begun. In the event of virological failure, an adherence assessment is indicated to identify and intervene prior to the initiation of a new regimen. In addition, a pattern of missed clinic visits or missed prescription refills can also trigger a review and evaluation. Any member of the healthcare team can initiate internal referral to the program, or the patient can self-refer. Other events that may impact adherence, such as hospitalization, incarceration, acute illnesses, homelessness, depression, domestic violence, and mental illness arel also monitored.

Interventions vary and are tailored to the patients' individual needs. All patients are offered a basic level of service. This includes a printed medication schedule complete with color pictures of their pills, a personal log to track their own viral load and t-cell count, and a pill box. They also receive detailed education on their medications, including side effects and dietary restrictions. They learn more about how their medications can help them, the importance of adherence, and general information about what to do for any adverse event including running out of pills.

Advanced interventions can also be instituted depending upon patient preference and need, as assessed by the adherence program team. For example, if the adherence difficulties are connected to complexity or side effects of the drug regimen, consultation can be made with the pharmacist, nutritionist or doctor. A treatment dry run can be tried utilizing placebo, so that the patient can become accustomed to taking the medications as prescribed prior to confronting the side effects.

If the issues revolve around social supports, isolation, illiteracy, housing, poverty, or transportation, the team can call upon a social worker, case managers, and support groups. When the problems are with memory or organization, memory aids can be used, including beepers or watches that will alarm when it is time to take medication and display the name of the pill and the number to be taken. Messages about clinic visits and pharmacy pick-ups can also be displayed. Telephone reminder calls or home visits may be utilized in difficult cases.

Additionally, a peer support network is being established to meet our patients' needs. It will consist of people living with HIV/AIDS who volunteer to serve as "buddies" for other HIV positive individuals. The peer counselors can lend personal support that may be beyond the scope of the healthcare team. They can give advice on how to live with HAART from a personal perspective and may be available when the clinic staff is not. Patients may discuss issues with a peer that they are uncomfortable addressing with clinic staff.

Lastly, mental health and substance abuse issues often cause or contribute to adherence problems. To counter these barriers, we can access mental health counselors and refer to a psychiatrist. Our social worker also has experience working with and modifying high-risk behaviors.

Adherence issues in the HIV positive individual are complex. Ongoing evaluation of patients is important to identify the problems. Early intervention is needed in order to stave off antiretroviral resistance. It is also important to have specialized services available that are easily accessible. Comprehensive HIV treatment centers can benefit by having a wide range of services available on-site. Importantly, the HIV/AIDS practitioner should not be afraid to temporarily suspend HAART while adherence issues are being tackled. This will preserve the effectiveness of the medications and maintain options for future treatment.

REFERENCES

  1. Paterson DL, et al. Abstract I-172, 38th ICAAC, San Diego, September 1998.
  2. Mellors JW, Muņoz A, Giorgi JV, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med. 1997; 126(12):946-54.
  3. Palella FJ, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med. 1998; 338:853-60.

Jacksonville Medicine / August, 1999

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