Assessing the impact of implementing multiple adherence measures to antiretroviral therapy from dispensing data: a short report

Figures & data

Box 1. Definitions for different methods to estimate adherence to multiple antiretrovirals.

Measures of adherence	Definitions
1) Exposure to three or more antiretrovirals at the same time	${\displaystyle \frac{Numberofdaysthepatientiscoveredbyatleastthreeantiretrovirals\left(eg.,antiretroviralAANDantiretroviralBANDantiretroviralC\right)}{Totaltimeperiod}}$ If patients are using more than 3 antiretrovirals, any combination of 3 medicines is sufficient for considering a covered day, with exception of the enhancer’s ritonavir and cobicistat
2) Exposure to at least one antiretroviral	${\displaystyle \frac{\begin{array}{c}Numberofdaysthepatientiscoveredbyanyantiretroviral(eg.,antiretroviralAOR\\ antiretroviralBORantiretroviralC),\mathrm{w}\mathrm{i}\mathrm{t}\mathrm{h}\mathrm{e}\mathrm{x}\mathrm{c}\mathrm{e}\mathrm{p}\mathrm{t}\mathrm{i}\mathrm{o}\mathrm{n}\mathrm{o}\mathrm{f}\mathrm{t}\mathrm{h}\mathrm{e}\mathrm{e}\mathrm{n}\mathrm{h}\mathrm{a}\mathrm{n}\mathrm{c}\mathrm{e}{\mathrm{r}}^{\mathrm{\prime }}\mathrm{s}\mathrm{r}\mathrm{i}\mathrm{t}\mathrm{o}\mathrm{n}\mathrm{a}\mathrm{v}\mathrm{i}\mathrm{r}\mathrm{a}\mathrm{n}\mathrm{d}\mathrm{c}\mathrm{o}\mathrm{b}\mathrm{i}\mathrm{c}\mathrm{i}\mathrm{s}\mathrm{t}\mathrm{a}\mathrm{t}\end{array}}{Totaltimeperiod}}$
3) The lowest number of days covered per antiretroviral	${\displaystyle \frac{NumberofdaysthepatientiscoveredbyantiretroviralA}{Totaltimeperiod}}$ = A% ${\displaystyle \frac{NumberofdaysthepatientiscoveredbyantiretroviralB}{Totaltimeperiod}}$ = B% ${\displaystyle \frac{NumberofdaysthepatientiscoveredbyantiretroviralC}{Totaltimeperiod}}$ = C% The lowest adherence will be taken as the final adherence rate. If patients are using more than 3 antiretrovirals, all antiretrovirals are considered for the calculation, with exception of the enhancer’s ritonavir and cobicistat.
4) Average of days covered over all antiretrovirals	$\begin{array}{rl}& {\displaystyle \frac{NumberofdaysthepatientiscoveredbyantiretroviralA}{Totaltimeperiod}+}\\ & {\displaystyle \frac{NumberofdaysthepatientiscoveredbyantiretroviralB}{Totaltimeperiod}+}\\ & {\displaystyle \frac{{\displaystyle \frac{NumberofdaysthepatientiscoveredbyantiretroviralC}{Totaltimeperiod}}}{Totalnumberofantiretroviralsused}}\end{array}$ If patients are using more than 3 antiretrovirals, all antiretrovirals are considered for the calculation, with exception of the enhancer’s ritonavir and cobicistat.
5) The highest number of days covered antiretroviral	${\displaystyle \frac{NumberofdaysthepatientiscoveredbyantiretroviralA}{Totaltimeperiod}}$ = A% ${\displaystyle \frac{NumberofdaysthepatientiscoveredbyantiretroviralB}{Totaltimeperiod}}$ = B% ${\displaystyle \frac{NumberofdaysthepatientiscoveredbyantiretroviralC}{Totaltimeperiod}}$ = C% The highest will be taken as the final adherence rate. If patients are using more than 3 antiretrovirals, all antiretrovirals are considered for the calculation, with exception of the enhancer’s ritonavir and cobicistat.
Sensitivity analyses
3-day grace period	Each individual is granted up to 3 days to obtain an additional refill after the end of the supply of the previous prescription. For the purpose of adherence calculations, days under the grace period are considered covered days.
Loss to follow up censoring	Each individual is censored after the end of the supply of the last antiretroviral prescription dispensed within the follow-up period (360 days). For example, if a person refills her last prescription 180 days after the index date, has no supply left, and the prescription filled has a duration of 60 days, the total time period considered for adherence calculation will be 240 days (180+60) instead of 360 days. However, if the supply of the last prescription filled surpasses 360 days, the follow-up period is censored at 360 days.

Table 1. Descriptive statistics of the measures of adherence estimated from pharmacy dispensing claims (N = 2,042).

Criteria for adherence measures	Mean % PDC (SD)	Median % PDC (IQR)	Individuals meeting the adherence threshold (PDC ≥ 80%) N (%)
1) Exposure to ≥ 3 antiretrovirals at the same time	89.6 (16.4)	96.4 (87.2, 99.7)	1,708 (83.6)
With a 3-day grace period	90.7 (15.8)	97.8 (88.9, 100.0)	1,731 (84.8)
Censoring loss to follow up	92.6 (11.9)	98.0 (90.6, 100.0)	1,798 (88.0)
2) Exposure to at least one antiretroviral	90.4 (15.5)	96.9 (88.1, 100.0)	1,746 (85.5)
With a 3-day grace period	91.5 (15.2)	98.3 (90.0, 100.0)	1,766 (86.5)
Censoring loss to follow up	93.4 (11.1)	98.3 (91.4, 100.0)	1,831 (89.7)
3) The lowest number of days covered per antiretroviral	77.0 (29.8)	93.3 (60.0, 99.2)	1,368 (67.0)
With a 3-day grace period	78.1 (29.7)	94.9 (61.4, 100.0)	1,387 (67.9)
Censoring loss to follow up	79.9 (28.8)	95.1 (70.8, 100.0)	1,447 (70.9)
4) Average of days covered over all antiretrovirals	84.7 (18.7)	93.6 (75.0, 99.2)	1,397 (68.4)
With a 3-day grace period	85.8 (18.5)	95.0 (75.8, 100.0)	1,421 (69.6)
Censoring loss to follow up	87.8 (15.9)	95.6 (78.6, 100.0)	1,503 (73.6)
5) The highest number of days covered per antiretroviral	89.6 (16.2)	96.7 (86.7, 100.0)	1,706 (83.6)
With a 3-day grace period	90.6 (15.9)	97.8 (88.3, 100.0)	1,727 (84.6)
Censoring loss to follow up	92.5 (12.1)	98.1 (90.0, 100.0)	1,790 (87.7)

PDC: Proportion of Days Covered, IQR: Interquartile range.

Table 2. Descriptive statistics of the measures of adherence estimated from pharmacy dispensing claims according to antiretroviral regimen in their first dispensing (N = 2,042).

Criteria for adherence measures	Median % PDC (IQR)	p-value*	Individuals meeting the adherence threshold N (%)	p-value**
1) Exposure to ≥ 3 antiretrovirals at the same time		< 0.001		0.002
Single-tablet regimen	96.9 (88.3, 100.0)		989 (85.9)
Multi-tablet regimen	95.8 (84.4, 99.4)		719 (80.8)
2) Exposure to at least one antiretroviral		0.117		0.254
Single-tablet regimen	96.9 (88.4, 100.0)		994 (86.3)
Multi-tablet regimen	96.7 (87.5, 99.7)		752 (84.5)
3) The lowest number of days covered per antiretroviral		< 0.001		< 0.001
Single-tablet regimen	94.7 (69.2, 99.7)		818 (71.0)
Multi-tablet regimen	90.8 (43.6, 98.3)		573 (64.4)
4) Average of days covered over all antiretrovirals		< 0.001		< 0.001
Single-tablet regimen	94.7 (69.2, 99.7)		824 (71.5)
Multi-tablet regimen	91.1 (72.3, 98.4)		573 (64.4)
5) The highest number of days covered per antiretroviral		0.057		0.363
Single-tablet regimen	96.8 (87.2, 100.0)		970 (84.2)
Multi-tablet regimen	96.4 (85.3, 99.7)		736 (82.7)

PDC: Proportion of Days Covered, IQR: Interquartile range.

* Wilcoxon test for comparisons between people on single vs. multi-tablet.

** Chi-square test for comparisons between people on single vs. multi-tablet.

Figure 1. Example of results provided in the three tabs of the web application to visualise patterns of medicine use and adherence estimates at the individual and populational level (Interactive tool available at https://adherencehiv.shinyapps.io/Application). A: Patterns of medicine use by patient ID: This tab enables identifying gaps in refills, changes in treatment and the results for adherence calculations for individual people based on each measure (Example for Patient ID 1). B: Cohort adherence results by different measures: This tab allows evaluating the impact of each measure and the implemented scenario on adherence estimates for the entire cohort. The tool also shows the absolute number of people identified as non-adherents to assist in selecting the appropriate measure (Example for base case scenario). C: Cohort adherence results by measure used and selected characteristics: This tab presents adherence results stratified by selected characteristics at index date according to each measure (Example for regimen type).