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1.0 The role of adherence in HIV disease

The dramatic reduction in HIV-associated morbidity and mortality since the widespread introduction of Highly Active Antiretroviral Therapy (HAART) is well-recognised in all countries where such therapies have been made available1. However, it is also noted that extremely high levels of adherence to such therapies, which may often be complex in terms of pill burden, dietary restrictions and dosing frequency, are required to ensure optimal treatment benefit.

In the presence of sub-optimal therapy, HIV selects for resistance rapidly2, in part due to rapid and error-prone replication3, but often aided by the low genetic barrier of several antiretroviral agents to resistance4 5. In addition, the pharmacokinetic properties of many of the current agents are likely to contribute to this unforgiving therapeutic environment, resulting in the necessity for such high levels of adherence.

Though effective adherence levels have not been fully defined for HAART, levels of adherence below 95% have been associated with poor virological and immunological6 response. Other data suggest that levels of 100% achieve even greater benefit7 8.

These high adherence levels are by no means universal amongst HIV patients. Although there are many difficulties in measuring adherence levels (as discussed in section 5.0), data from the UK have demonstrated that 8% of subjects missed a dose the previous day, 15% in the previous week, and approximately 50% in the previous month9. These levels of adherence are nonetheless substantially higher than those observed for other chronic illnesses, where around 50% of individuals are reportedly adherent to therapy10.

Adherence has been rightly called the Achilles heel of antiretroviral therapy11; the consequences of low adherence are serious for the individual, for public health, and for the optimal use of limited health care resources:

  • For the individual, lower levels of adherence are associated with the development of viral resistance, treatment failure, and increased risk of disease progression 12 13 14. Upon such treatment failure, current treatment guidelines recommend switching to a new combination regimen which may include more agents, be more complex, and be associated with new or unknown toxicity. The prognosis for individuals who have experienced multiple treatment failures is uncertain.

  • From a public health perspective, the increase in prevalence of resistant virus as a result of (amongst other reasons) low adherence is likely to result in an increase in transmission of resistant virus to newly infected individuals. Data from the UK15 and the USA16 suggest such primary resistance is increasing, and that acquired resistance has a negative effect on subsequent HAART response17.

  • From a health economics perspective, low adherence will result in increased use of second-line and salvage regimens, which are in general more expensive than initial regimens. In addition, since low adherence is associated with an increased risk of disease progression, the cost of treating opportunistic complications will have a negative impact on the established cost-benefit of HAART.