Assuming that a regimen would be easier to adhere to just because it is once-daily could mean that other important factors affecting adherence are neglected, according to a study published in the July 1st edition of the Journal of Acquired Immune Deficiency Syndromes. Investigators found that multiple factors, including a high pill burden, side-effects and dietary restrictions, rather than just dosing frequency, impact on adherence. The study also found that of seven HAART regimens currently in use, the one which patients perceived as the easiest to adhere to was a twice-daily regimen consisting of two pills a day, without any dietary restrictions.
Once-daily HAART regimens are becoming increasingly available and are viewed by many as a means of improving patient adherence to their anti-HIV treatment. Other factors known to be associated with adherence include the number of pills in a regimen, dietary restrictions and pill size. Most studies have only looked at the impact of a single factor on adherence; accordingly, in a study funded by the pharmaceutical company GlaxoSmithKline, investigators designed a cross-sectional study evaluating the relative impact on adherence of ten simultaneously considered factors known to have an impact on adherence. Individuals were also asked to say how easy they perceived adherence to be to seven once- or twice-daily HAART regimens in current use.
A total of 299 HIV-positive individuals who were taking HAART were recruited to the study in six US cities in April 2002. Data were collected using a questionnaire in small groups with a trained facilitator.
Individuals had a median age of 43 years, 76% were men, 45% African American, 37% white, 15% Hispanic, and 3% Asian. Sex between men was the main mode of HIV infection (57%). Most of the patients (55%) had started HAART before 1999, and 63% had been on three or more different treatment regimens. Almost three-quarters of individuals reported missing at least one dose of their anti-HIV treatment regimen in the previous three months, with 10% saying they had missed nine or more doses.
Side-effects caused by anti-HIV drugs were widely reported, particularly pain in the limbs or joints (44%), nausea (44%), numbness in the limbs (38%), headache (38%) and lipodystrophy (26%).
Individuals were asked which of ten attributes of a HAART regimen affected adherence. The ten attributes were: total number of pills per day, dosing frequency, side-effects, dietary restrictions, pill size, number of prescription refills required, number of payments required, number of prescriptions, number of medicine bottles, and a bedtime dose.
Each of these ten attributes was reported to have an impact on adherence to some degree. The factors having the greatest impact were total number of pills per day (importance score of 14%), dosing frequency (13%), side-effects (12%), diet restrictions (11%) and pill size (10%).
The features of a regimen predicted to be most helpful in promoting adherence included two pills per day taken as a single dose, no dietary restrictions, small pills, dispensed as one prescription with one payment, in a single medicine bottle, requiring a single refill.
However, when patients were asked to evaluate seven currently used HAART regimens, including both once-daily and twice-daily dosing, the regimen perceived to be the easiest to adhere to was a twice-daily regimen, involving two pills a day, with no food restrictions, involving a single prescription and repeat prescription, one medicine bottle, and one payment.
The regimen which individuals said they would find it hardest to adhere to also involved two daily doses, but with a total of 13 pills, five of which needed to be taken with food. The regimen also involved three prescriptions, three refills, three medicine bottles, and three payments.
Currently used once-daily regimens were not, overall, anticipated to promote adherence to a greater extent than some of the twice-daily regimens in current use.
“This study found that pill count, dosing frequency and [side-effects] had the greatest impact on patients’ perceived ability to adhere to antiretroviral medication regimens. Furthermore, the study suggests more clearly than prior surveys that multiple attributes of dosing complexity are important potential barriers to adherence [and] shows the importance of understanding patient preferences and perceptions in designing the ideal HAART regimen,” comment the investigators. They add that making a treatment decision on a single perceived adherence advantage of a regimen, such as once-daily dosing, may not take full account of individuals’ preferences.
The investigators note that their study has limitations, including the complexity of the questionnaire provided to patients. The questionnaire also asked the study members to assume that all the regimens were equally potent.
Further information on this website
Adherence - factsheet
Adherence - booklet in the information for HIV-positive people series (pdf)
Instability associated with non-adherence in HAART-treated HIV-positive New Yorkers - news story
High pill burden means poorer adherence but adherence no role in viral load blips - news story
Stone VE et al. Perspectives on adherence and simplicity for HIV-infected patients on antiretroviral therapy. Journal of Acquired Immune Deficiency Syndromes 36: 808-816, 2004.