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O riginal R esearch
Teresa L Kauf 1
Keith L Davis 2
Stephanie R Earnshaw 2
E Anne Davis 3
1
Department of Pharmaceutical
Outcomes and Policy, College
of Pharmacy, University of Florida,
Gainesville, FL, 2RTI Health Solutions,
Research Triangle Park, NC,
3
Independent consultant, Pittsboro,
NC, USA
Introduction
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http://dx.doi.org/10.2147/PPA.S28482
Mortality and morbidity associated with HIV disease are dramatically reduced through
the use of combination antiretroviral therapy (ART), commonly comprised of two
nucleoside reverse transcriptase inhibitors (NRTIs) and either a non-NRTI (NNRTI)
or a protease inhibitor (PI).1,2 The latter is often boosted with a low-dose of the PI,
ritonavir (Norvir, Abbott Laboratories, Abbott Park, IL). ART regimens containing a
boosted PI may consist of up to four separate pills, with several dosing frequencies
and requirements. However, more compact ART regimens can be created by taking
advantage of fixed-dose combination (FDC) products which consist of two or more antiretroviral drugs in a single tablet.
Since the introduction of the first FDC antiretroviral product, FDCs have become
a mainstay in the treatment of HIV. The chief advantage of FDCs lies in simplifying a
patients regimen. In addition to reducing pill burden, many FDCs also have reduced
dosing frequency and/or dosing requirements compared to other drugs in the FDCs
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Adherence measure
The primary outcome evaluated in this study was treatment
adherence to the non-NRTI-backbone regimen component
as measured by the medication possession ratio (MPR).
A recent systematic literature review found MPR to be the
most widely adopted measure in published claims-based
analyses of medication adherence (57% of all studies).17
MPR is generally defined as the proportion of days within an
observation period covered by the total days supply obtained
for a particular study drug within the observation period:
MPR =
NRTI Combo
(%)
(%)
650
100.0
1947
100.0
550
100
84.6
15.4
1597
350
82.0
18.0
96
278
205
62
9
14.8
42.8
31.5
9.5
1.4
329
920
534
142
22
16.9
47.3
27.4
7.3
1.1
263
237
62
69
19
40.5
36.5
9.5
10.6
2.9
1106
404
114
82
241
56.8
20.8
5.9
4.2
12.4
635
8
7
97.7
1.2
1.1
1895
28
24
97.3
1.4
1.2
231
35.5
699
35.9
145
266
22.3
40.9
249
915
12.8
47.0
1.2
84
4.3
119
357
174
370
18.31
54.92
26.77
56.92
14
13
137
185
162
248
296
547
245
100
570
0.7
0.7
7.0
9.5
8.3
12.7
15.2
28.1
12.6
5.1
29.28
0.88
0.96
502
459
426
355
0.170
0.261.00
77.2
70.6
65.5
54.6
0.82
0.86
1269
1126
953
766
0.20
0.081.00
65.2
57.8
49.0
39.3
0.92
1.0
565
542
514
478
242
0.168
0.031.0
86.9
83.4
79.1
73.5
37.2
0.85
0.98
1460
1362
1250
1103
522
0.245
0.0051.0
75.0
70.0
64.2
56.7
26.8
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Statistical analysis
MPR=0+1FDC+2Xi+, and
(1)
ADHERENT=0+1FDC+2Xi+.
(2)
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Results
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Original sample
N = 23,047
FDC group
n = 2,998
n = 1,860
Initiated alternative
therapy before study
therapy
n = 18,981
n = 1,574
n = 15,715
n = 1,568
n = 14,492
n = 978
n = 3,550
n = 876
n = 3,261
n = 651
n = 2,143
n = 650
Days supply
unavailable
n = 1,947
Figure1 Sequential application of study inclusion and exclusion criteria to the IHCIS sample.
Note: *Alternative therapy use refers to the use of a non-study drug within the group (eg, the use of Epzicom by the NRTI Combo group).
Abbreviations: FDC, fixed-dose combination; IHCIS, Integrated Health Care Information Services; NRTI, nucleoside reverse transcriptase inhibitor.
Discussion
Evidence from clinical trials and observational studies in
a variety of therapeutic applications supports the ability of
FDC products to improve adherence to therapy, compared
to separate pills.7,9,19,20 To our knowledge, this is the first
study to empirically quantify the spillover effect of FDCs
in improving adherence to another regimen component.
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Treatment group
FDC
N
Lamivudine + stavudine
Lamivudine + tenofovir
Tenofovir + emtricitibine
Tenofovir + didanosine
Lamivudine + abacavir
Stavudine + didanosine
Lamivudine + didanosine
Lamivudine + zidovudine
Tenofovir + abacavir
Stavudine + abacavir
Tenofovir + stavudine
Other combinations
NRTI Combo
(%)
(%)
500
377
188
125
113
104
91
70
67
62
53
197
25.7
19.4
9.7
6.4
5.8
5.3
4.7
3.6
3.4
3.2
2.7
10.1
29.9
8.2
40.3
0.62
21.1
637
72
987
3
248
32.7
3.7
50.7
0.15
12.7
31.2
24.8
10.3
7.9
9.1
4.8
2.8
1.7
1.2
0.9
1.1
0.6
0.2
3.5
757
215
279
28
224
29
20
21
1
1
157
93
7
115
38.9
11.0
14.3
1.4
11.5
1.5
1.0
1.1
0.1
0.1
8.1
4.8
0.4
5.9
Note: *For the NRTI Combo group, the third NRTI initiated must be different from
either of the two NRTIs initiated.
Abbreviations: NRTI, nucleoside reverse transcriptase inhibitor; PI, protease
inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; EI, entry inhibitor;
ART, antiretroviral therapy; FDC, fixed-dose combination.
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Continuous MPR
MPR $ 90%
MPR $ 95%
Parameter
estimate (SE)
P value
Odds ratio
95% CI
Odds ratio
95% CI
0.0155 (0.0132)
0.0133 (0.0116)
0.2406
0.2545
1.40
1.21
1.051.86
0.951.53
1.47
1.25
1.121.94
0.991.57
0.0047 (0.0125)
0.0173 (0.0134)
0.0257 (0.0189)
0.0822 (0.0420)
0.7042
0.2010
0.1729
0.0507
0.90
1.04
0.95
1.47
0.701.16
0.791.37
0.641.40
0.603.58
0.86
0.98
1.13
1.67
0.671.11
0.751.29
0.771.66
0.703.96
0.0236 (0.0127)
0.0258 (0.0189)
0.0404 (0.0205)
0.0043 (0.0153)
0.0733 (0.0293)
0.0631
0.1739
0.0489
0.7784
0.0125
0.68
1.37
1.48
1.07
2.93
0.530.89
0.912.01
0.942.32
0.781.45
1.615.31
0.65
1.00
1.24
0.90
2.19
0.500.84
0.681.46
0.811.89
0.671.22
1.203.98
0.0065 (0.0141)
0.0091 (0.0136)
0.0180 (0.0266)
0.6445
0.5052
0.4998
1.17
0.95
1.12
0.871.57
0.721.27
0.651.94
1.18
0.98
1.27
0.891.58
0.741.30
0.742.17
0.0698 (0.0843)
0.1324 (0.0630)
0.1309 (0.0624)
0.1625 (0.0626)
0.1405 (0.0617)
0.0854 (0.0616)
0.0419 (0.0602)
0.0356 (0.0604)
0.0026 (0.0614)
0.0152 (0.0140)
0.4077
0.0355
0.0361
0.0095
0.0229
0.1657
0.4859
0.5553
0.9664
0.2780
0.74
0.40
0.47
0.34
0.38
0.57
0.87
0.80
1.09
1.26
0.153.55
0.121.33
0.141.56
0.101.14
0.121.24
0.171.87
0.272.77
0.252.57
0.333.60
0.941.69
0.52
0.56
0.56
0.50
0.54
0.82
1.18
0.97
1.38
1.14
0.102.65
0.171.81
0.171.81
0.151.62
0.171.73
0.7360
0.383.67
0.313.02
0.434.43
0.861.52
0.0100 (0.0124)
0.0095 (0.0493)
0.0177 (0.0650)
0.4180
0.8477
0.7856
1.36
1.23
0.79
1.041.77
0.413.68
0.193.32
1.55
1.30
0.64
1.202.00
0.453.77
0.162.53
0.1164 (0.0242)
0.0177 (0.0103)
0.1623 (0.0834)
0.0731 (0.0182)
0.0476 (0.0153)
0.0147 (0.0095)
,0.0001
0.0861
0.0518
,0.0001
0.0019
0.1217
10.56
1.11
0.74
4.83
1.72
0.98
4.0927.25
0.911.35
0.163.52
2.957.91
1.272.33
0.811.19
9.74
1.12
0.62
5.45
2.21
1.01
4.0623.35
0.931.36
0.132.87
3.368.84
1.642.97
0.841.23
Abbreviations: ART, antiretroviral therapy; CI, confidence interval; EI, entry inhibitor; FDC, fixed-dose combination; HMO, health maintenance organization; MH, mental
health; MPR, medication possession ratio; NRTI, nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; PI, protease inhibitor;
POS, point of service; PPO, preferred provider organization; SA, substance abuse; SE, standard error.
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Acknowledgments
The authors thank Christopher M Blanchette for his
contributions to this study. This work was funded by
GlaxoSmithKline Inc (Research Triangle Park, NC). The
individual authors contributions to the work are as follows:
TLK led the study design, interpretation of results, and
writing. As corresponding author, TLK takes full responsibility for the entirety of the content of the manuscript.
KLD conducted all data analysis and contributed to the
interpretation of results and writing. SRE assisted with
study design and contributed to the interpretation of results.
EAD provided the data source for the study and contributed
to the study design.
Disclosures
This study was funded by a contract between GlaxoSmithKline
Inc (Research Triangle Park, NC), which manufactures
abacavir sulfate, zidovudine, lamivudine, and various
combinations of these drugs, and RTI Health Solutions
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References
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