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Atazanavir is Associated with Better Patient Adherence: Long-Term Follow-Up Data from BMS 041 and 044 Studies
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Reported by Jules Levin
In a poster at the 9th European AIDS Conference, October 25-29, Warsaw, Poland, researchers from Bristol Myers Squibb reported these study results comparing adherence to Reyataz vs nelfinavir in phase II studies. This report contains contents of poster.
Ying Wu, PhD; Linda Odeshoo, MA; Uche Iloeje, MD; Jayanti Mukherjee, PhD;
Anne Cross, PhD; Michael Giordano, MD. Pharmaceutical Research Institute, Bristol-Myers Squibb Company, Wallingford, CT, USA
The objective of this study is to evaluate patient-reported adherence on atazanavir-containing regimens compared to other regimens.
STUDY POPULATION AND DESIGN
BMS 041 study
- Subjects on phase 2 study 007 were followed in the open-label study 041.
- Combined with 2 NRTIs, mostly didanosine (DDI) and stavudine (D4T), subjects on previous atazanavir-containing regimens were switched to atazanavir 400 mg, QD. Subjects on nelfinavir 750 mg, TID, continued on nelfinavir.
BMS 044 study
- Subjects on phase 2 study 008 were followed in the open-label study 044.
- Combined with 2 NRTIs, mostly lamivudine (3TC) or stavudine (D4T), subjects on nelfinavir 1250 mg, BID, switched to atazanavir 400 mg, QD. Subjects on atazanavir 400 mg or 600 mg continued on with their previous regimens.
Long-term safety and efficacy data of atazanavir are being collected in roll-over studies, BMS 041 and BMS 044.
- Patient self-reported adherence data were also collected at baseline, mid-study, and final study visit.
This analysis reports adherence results at baseline and mid-study in 041 and 044.
STUDY METHODS
Adherence was measured using a self-administered questionnaire, developed by the Multicenter AIDS Cohort Study investigators. Since the questionnaire is only available in English, it was administered among English-speaking subjects only.
The questionnaire assesses drug use patterns during a four-day recall period. Questions include:
“According to your doctor, how many times a day should you take the medication?”
“How many times did you take the medication...yesterday?...2 days ago?...3 days ago?...4 days ago?”
“Is this pattern of use typical of your recent use of the medication?” “Was there any time in the last 4 days that you took fewer pills per dose than were prescribed?”
The published algorithm was used for scoring. Level of adherence was dichotomized as adherent or non-adherent. A subject was included in the non-adherent group when one of the following criteria were met:
(1) the participant reported taking his medication fewer times than prescribed in the last 4 days; or
(2) the participant always took his medication at the times prescribed in the last 4 days, but this was not a typical pattern; or
(3) the participant took fewer pills per dose than prescribed. Any response indicating less than perfect adherence by this algorithm would lead to categorization in the non-adherent group.
Drug-Based Analysis: The above algorithm was used to determine whether the subject was adherent on each of the drugs they were receiving.
Regimen-Based Analysis: An overall analysis by subject was conducted.
- If a subject was adherent on all the drugs he/she was taking, the subject was classified as adherent.
Medication data reported by the subject during study visit were used to determine the drugs being received.
RESULTS
Given the language limitation, a subset of the 041, 044 population was included in this analysis. In study 041, there were 103 subjects in atazanavir 400 mg arm and 35 subjects in the nelfinavir 750 mg arm. In study 044, there were 66, 66, and 30 subjects in the three study arms (atazanavir 400 mg, atazanavir 600 mg, and nelfinavir switching to atazanavir when entering 044, respectively).
Baseline adherence data in these two studies reflect at least a 48-week prior treatment experience, as patients were rolled over from the phase 2 studies.
Selected characteristics of subjects who completed adherence questionnaire in studies 041 and 044 were summarized below.
Summary
- At entry into 041, 83% of the ATV group and 78% of the NFV group were adherent (X 2 p-value not significant). At mid-study, 86% of the ATV group and 59% of the NFV group remained adherent. The difference was highly significant (X 2 p<0.005).
- In study 044, 71, 78, and 74% were adherent at entry. After 12 weeks of therapy, adherence rate remained stable at 79, 85, and 76%, respectively.
CONCLUSIONS BY AUTHORS
These data suggested that patients on atazanavir-containing regimens had better adherence in these studies than that of the end of their phase II.
In 041, adherence to atazanavir-containing regimens was high and durable compared to nelfinavir. While adherence is known to be dynamic and decreases over time, the durability of atazanavir adherence is especially important.
In 044, switching from nelfinavir to atazanavir maintained high adherence rate.
DISCUSSION BY AUTHORS
Adherence is critical in achieving HAART’s potential. High adherence, 95% or higher, is needed for successful virologic control and non-adherence is one of the most important factors for treatment failure. Substantial amount of data are available to highlight the importance of adherence. In Paterson et al.’s study, a clear association between adherence and viral control was demonstrated.4 Bangsberg et al. estimated that every 10% increase in adherence can result in a 28% decrease in risk of progression to AIDS.
Adherence can be measured in several ways, including patient-administered questionnaire, MEMS, or pill count. While self-reports can be biased, in this study we used a validated questionnaire. In Kleeberger et al.’s study, viral load data was measured and found to be correlated with adherence data, supporting the validity of the questionnaire.
This study has several limitations, such as small size, and data derived only from English-speaking subjects. Long-term data on these two cohorts, data from week 48, however, are needed to further confirm these trends.
Nevertheless, these data suggest that atazanavir-containing regimens, with atazanavir’s low pill burden and a QD dosing frequency, appear to offer a better option for patient to improve their adherence and potentially their clinical outcomes. (Editorial note: tolerability may also be a factor in the results).
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