A significant minority of individuals taking combinations of anti-HIV drugs selectively miss doses of specific drugs, American researchers have found. Writing in the November 1st edition of the Journal of Acquired Immune Deficiency Syndromes investigators from Denver report that 15% of individuals didn’t adhere to all the components of their anti-HIV treatment regimen and that these patients were significantly more likely to progress to AIDS or death than individuals who had uniformly good adherence to all their anti-HIV drugs.
It is well known that for anti-HIV therapy to work effectively an exceptionally high level of patient adherence – 95% or better – is required. Many patients do not achieve this goal and although there has been a lot of research into adherence to antiretroviral therapy, most has focused on a single summary of overall pill-taking. “In clinical practice”, comment the investigators, “it is not uncommon for patients to report missing individual components of their regimen.”
Therefore the investigators conducted a retrospective analysis looking at 322 patients’ adherence to the individual components of anti-HIV treatment regimen.
These patients received antiretroviral therapy between 1997 and 2002 and adherence was measured by looking at prescription refill data. An individual was classified as having selective drug adherence is there was a difference of 5% or more between two components of an antiretroviral regimen lasting at least 60 days.
The 322 patients in the study had received 438 individual anti-HIV treatment regimens. A total of 48% of these combinations contained a protease inhibitor, 38% a non-nucleoside reverse transcriptase inhibitor (NNRTI) and 10% nucleoside analogues (NRTIs) only.
Overall, the level of adherence was 90% - high but nevertheless below the 95% or better necessary to achieve the best results from antiretroviral therapy. Unsurprisingly, the patients with the best adherence were most likely to have a viral load below 400 copies/ml.
Selective drug taking occurred in 47 patients (15%) and involved 51 (12%) treatment regimens. Combinations including protease inhibitors were significantly more likely to involve selective drug taking than those involving NNRTIs (8% versus 7%, p = 0.002).
A low baseline CD4 cell count was found to be significantly associated with selective adherence. For every 100 cells/mm3 fall in baseline CD4 cell count, the odds of selective drug taking increased by 1.3.
The investigators also found that 61% of treatment combinations with selective drug taking involved side-effects compared to 34% of combinations with non-selective adherence, a difference which was highly statistically significant (p
Patients who took their HIV medication three times a day were four times more likely to selectively miss doses of particular drugs than patients with less frequent dosing. The investigators also found that only 9% of patients taking their first or third regimen had selective adherence compared to 19% of patients taking their second regimen, a statistically significant difference (p = 0.009).
Patients who selectively missed drugs needed to change their first HIV treatment regimen sooner than patients who took all their medication (1.3 years versus 2.7 years, p = 0.02).
In addition, the investigators found that patients with selective drug taking had a poor clinical outcome. The frequency of AIDS-defining events or death was 12.9 per 100 patient years in patients who selectively took their treatment compared to just 4.4 per 100 patient years amongst patients with adherence to all their anti-HIV drugs. This difference was statistically highly significant (p
The investigators also found a factor that was associated with good overall adherence. Patients who took a fixed combination pill as part of their treatment regimen were 50% less likely to be affected by selective adherence. The authors comment, “our findings speak to the potential value of fixed-dose combination dosage forms in ensuring uniform adherence to medications.”
Gardner EM et al. Selective drug taking during combination antiretroviral therapy in an unselected clinic population. J Acquir Immune Defic Syndr 40: 294 – 300, 2005.