Antiretroviral Therapy in HIV-infected Adults: Adherence to Therapy

Many studies have cited an association between poor adherence and incomplete viral suppression. In one study, 84 patients were assessed after six months of antiretroviral therapy. A significant association was observed between adherence and virological suppression (P < .001). The authors concluded that a high level of adherence to therapy was important for virological success; below 95% compliance, failure rates increased rapidly. This trial suggested that a few missed doses can have a detrimental effect on clinical outcomes.

The level of adherence necessary for achievement of viral suppression in HIV-infected patients is far higher than the level needed in other chronically ill patients. Patient adherence outside of clinical trials can even be lower than that seen in study patients.
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Determinants of patients’ adherence to medication regimens are complex and multifactorial; some factors include (1) patients’ characteristics (e.g., eating habits and schedules), (2) health providers and the system of care, (3) the patient-provider relationship, and (4) the HAART regimen.

Few patient characteristics have been consistently associated with low levels of medication adherence and poor treatment outcomes. Demographic characteristics (e.g., race, ethnicity, sex, age, and socioeconomic status) generally do not predict adherence, even though some sociodemographic factors have been associated with nonadherence in individual trials. Some factors that have been among the strongest correlates of poor adherence are intravenous drug use, depression, missed clinic appointments, and a high pill burden.

Many initiatives have been explored to increase patient adherence to drug therapy, including (1) multidisciplinary medication counseling, (2) trial medication runs involving pill substitutes, and (3) timing devices that serve as dose reminders. Some studies indicate that pharmacists can improve patient adherence and can be influential in treating HIV.

Even though current efforts toward eradication of HIV seem bleak, the treatment of HIV infection as a chronic manageable disease has become the foundation of HIV therapeutics. Support for this approach comes from the ability of HAART to suppress viral replication and from the apparent ability of the immune system to rebuild itself during effective therapy.

The current theory on immune system reconstitution includes three phases:

1. After an effective antiretroviral regimen is initiated, there is a redistribution of T cells from lymphoid tissues, generally within the first months after HAART has begun. This redistribution is responsible for a rapid increase in CD4 counts.
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2. There is a movement toward normalization of the CD4 repertoire by an expansion of clones that are under-represented before treatment and a reduction in size of the expanded one.

3. After about six months of effective therapy, there is an expansion of naive T cells.

An exciting result of this finding is that the apparent reduction in diversity in the T-cell repertoire is not irreversible. Patients who need prophylaxis for opportunistic infections who have attained durable increases in CD4 counts and viral load suppression can often safely discontinue prophylaxis. The degree to which the immune system can rebuild itself.

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