| THE IMPORTANCE
OF ADHERENCE |
|
In recent years, advances in HIV therapeutics have
changed the nature of HIV/AIDS disease, so that it is
now viewed as a chronic manageable infection. However,
one of the crucial determinants of effective therapy
is a patient's level of adherence to the antiretroviral
regimen. This is due to factors associated with HIV
viral dynamics and limitations of current pharmacotherapy.
In fact, data indicate that near-perfect adherence is
required for a maximal response to HIV therapy.
Cessation of antiretroviral treatment and even brief
periods of erratic adherence may result in rapid rebound
of plasma viremia, selection of drug-resistant HIV strains
and significant damage to the immune system. Another
danger is the risk of transmission of multidrug-resistant
virus. Moreover, non-compliance also imparts both direct
and indirect costs including the cost of drugs and the
subsequent use of healthcare resources that could have
been avoided had adherence been good.
The figure above describes the relationship
between adherence and emergence of resistant virus.
From this figure, it is clear that only 100% adherence
minimizes the probability of resistance developing,
and that incomplete adherence greatly compromises the
efficacy of antiretroviral therapy (AIDS 1999; 13 (Suppl.
1): S61-71).
Several factors have been associated with lack of adherence
(Table 1) (Clin Infect Dis 2000; 30 (Suppl 2): S171-6).
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Table 1:
Factors reported to negatively affect adherence in
HIV-infected patients
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Patient Factors
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Medication Factors
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Other Factors
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Substance abuse (alcohol, drugs)
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Dose frequency of more than twice a day
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Poor doctor-
patient relationship
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Male sex
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Pill burden
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System of healthcare
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Youth
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Food requirements
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Active depression
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Inability to take medication
when away from home
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Lower level of education
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Type of drug
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Extreme anxiety
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Side effects
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Extreme pain
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No change in
health status
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Also, in a study conducted by Ostrop et al, subjects who
were prescribed antiretroviral therapy were asked to rank
difficulties experienced that may affect adherence (Table
2). The most important of these seem to be difficulties
in remembering the afternoon dose, inconvenient timing,
scheduling around food and adverse effects (Ann Pharmacotherapy
2000;34:703-9). |
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Table 2: Barriers to adherence identified
by patients
|
| Rank |
Barrier |
Score |
| 1. |
Difficulty remembering
- morning dose
- afternoon dose
- evening dose |
85
04
61
26 |
| 2. |
Inconvenient timing |
76 |
| 3. |
Difficulty scheduling around food |
54 |
| 4. |
Adverse effects |
38 |
| 5. |
Difficulty scheduling around sleeping |
22 |
| 6. |
Size and number of medications |
15 |
| 7. |
Storage specifications |
10 |
|
8.
|
Hydration requirements with indinavir |
04 |
| 9. |
Difficulty with discreet administration |
03 |
| Note: Higher the score,
the more it is considered to be a barrier to adherence |
In this regard, it would be advantageous to combine all
3 drugs into a single formulation, so as to ensure that
all 3 are taken as prescribed. Moreover, choosing drugs
which have a simple, twice-daily dosing schedule, irrespective
of food, would further ensure compliance.
Hence, the fixed-dose formulation of stavudine + lamivudine
+ nevirapine is proposed as a means of achieving this
end.
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"The simplification
of current antiviral regimens, without the loss of potency,
is essential to achieving the goal of complete adherence.
Maximizing the long-term benefit of highly active antiretroviral
therapy requires knowledge of the technical and biologic
aspects of HIV therapeutics, but necessitates an understanding
of the behavioral aspects of therapeutics as well."
AIDS 1999; 13 (suppl 1): S61-72 |
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