Adherence: The Achilles Heel of Anti-retroviral Therapy

Introducing the speaker for HIVAN's first Invited Presentation (held in the Athlone Skinner Conference Room at Natal University's Durban campus), the Centre's Director of Social and Behavioural Sciences, Professor Eleanor Preston-Whyte, welcomed Professor Gerald Friedland of Yale University's School of Medicine.

She said that it was fortuitous for HIVAN to have a researcher of Prof Friedland's eminence to address staff from various schools, departments and service organisations on all campuses on this important topic. All those present were invited to participate in the brainstorming session scheduled to follow Prof Friedland's scan of the relevant literature, with the aim of planning a pilot research project tailored to focus on probable needs in KwaZulu-Natal and of establishing a paradigm for the integration of biology and behaviour in ART.

Friedland proceeded to describe his involvement at the clinical interface between the bio-behavioural aspects of the HIV/AIDS epidemic, explaining that the issue of adherence to Anti-Retroviral Therapy (ART) highlights, as a paradigm, the significance of this interface.

His presentation covered the definition, importance, measurement, components and determinants of adherence to ART, as well as a review of previous and proposed interventions and strategies, and a perspective on the topic within a South African context.

DEFINITION:

"Adherence" used to be called "compliance", but the latter term tended to imply that the patient was required to bend to the will of the healthcare provider. The contemporary view is that the dynamic should be one involving a shared decision, although it is felt that the concept would be better described as a "therapeutic alliance". "Adherence", then, means the extent to which a person's behaviour corresponds with medical advice, i.e. the ability to take medication as prescribed (as opposed to not at all, too little, too much or intermittently).

IMPORTANCE:

Adherence can be regarded as a highly significant determinant of the biologic, clinical and public health outcomes of ART, as poor adherence is a major cause of ART failure, of ART resistance, and of continued risky behaviour and transmission of resistant organisms. These pitfalls and concomitant negative outcomes are well-known in studies of other diseases such as tuberculosis.

HIV/AIDS is the only modern disease that requires such protracted therapy, and without the expertise and resources to evaluate and support adherence, ART can be ineffective, wasteful and dangerous. Adherence is, therefore, a process that needs careful study, and in the developing world context, this is a crucial and immediate area for research.

Studies in the US show that from 1982 to 1994, AIDS became the leading cause of death among the 25-44 years age group. With the introduction of ART, the trend flattened for approximately two years, and then showed a decrease by 1998 (although this decline occurred with ART being used in conjunction with other supportive interventions). At least three potent drug combinations have to be taken, some with toxicity and side-effects, making the regimen unpleasant to follow, but with the goal being to inhibit viral replication.

Failure to follow the ART regimen precisely can result in hospitalisation, new opportunistic infections, death, and transmission across the population. The durability of adherence is marred by pill-fatigue, change in life circumstances and long-term toxicities (although study in this area is insufficient).

MEASUREMENT:

Indirect measurement relies on:
* the clinician's estimate;
* the pill count (announced or unannounced);
* MEMS caps (a computer chip fitted inside the cap of the pill bottle that records the time and frequency of opening, a very expensive and non-foolproof mechanism);
* pharmacy refills;
* self-report (which Friedland believes is best as it strikes at the heart of the clinician-patient alliance, ensuring honesty, requiring the correct posing of questions, and being more valuable as to the assimilation of behavioural information);
* the biologic and clinical outcome (e.g. seeing a decline in the viral load, a decrease in hospitalisation)

Direct measurement relies on:
* Testing drug levels (although this provides incomplete information as it only indicates the intake of the day before the test, is an expensive route and inaccurate, because the half-lives of the dfiferent drugs vary). Testing of drug levels can be undertaken using hair and nail samples, displaying the cumulative effects of the medication, but Friedland felt that this was an "esoteric" method.

Question: How reliable is self-report in terms of efficacy?
Friedland's response: Self-report should be balanced with a test of the viral load. A current method of testing the validity of self-report involves the patient's anonymous completion of a questionnaire covering a seven-day "total recall" period; in an experimental stage is a three-day version of this record, which also asks "How many pills did you MISS?", thereby giving permission to the patient to disclose any lack of adherence and offering a list of options for explaining such non-adherence.

COMPONENTS AND DETERMINANTS:

These factors are only really known in the context of the developed world:

* patient characteristics: demography of age, sex, race/tribe/language, socio-economic status;
* Information, knowledge and cognition;
* Motivation: beliefs, depression, drug use;
* Behaviour skills: pill-taking, scheduling;
* provider-expertise, trust;
* regimen: simplicity, toxicity, disruption
* disease stage
* clinical setting

Friedland noted that by and large, the older the patient, the more successful the level of adherence. Recently published research (in the JAIDS, by Altice, Mostashari, Thompson and Friedland) on the Acceptance of and Adherence to ART, studied the topic in a subject community of prisoners and revealed that the issues of trust in the physician and mistrust of the medication are very important, as are the factors of side-effects, social isolation and the complexity of the regimen.

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