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Adherence to Antiretroviral Therapy in Sub-Saharan Africa and North America: A Meta-analysis

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Adherence to antiretroviral therapy is a powerful predictor of survival for individuals living with human immunodeficiency virus (HIV) and AIDS. Concerns about incomplete adherence among patients living in poverty have been an important consideration in expanding the access to antiretroviral therapy in sub-Saharan Africa. To evaluate estimates of antiretroviral therapy adherence in sub-Saharan Africa and North America. Eleven electronic databases were searched along with major conference abstract databases (inclusion dates: inception of database up until April 18, 2006) for all English-language articles and abstracts; and researchers and treatment advocacy groups were contacted. Study Selection and Data Abstraction To best reflect the general population, studies of mixed populations in both North America and Africa were selected. Studies evaluating specific populations such as men only, homeless individuals, or drug users, were excluded. The data were abstracted in duplicate on study adherence outcomes, thresholds used to determine adherence, and characteristics of the populations. A random-effects meta-analysis was performed in which heterogeneity was examined using multivariable random-effects logistic regression. A sensitivity analysis was performed using Bayesian methods. Thirty-one studies from North America (28 full-text articles and 3 abstracts) and 27 studies (9 full-text articles and 18 abstracts) from sub-Saharan Africa were included. African studies represented 12 sub-Saharan countries. Of the North American studies, 71% used patient self-report to assess adherence; this was true of 66% of the African assessments. Studies reported similar thresholds for adherence monitoring (eg, 100%, >95%, >90%, >80%). A pooled analysis of the North American studies (17,573 patients total) indicated a pooled estimate of 55% (95% confidence interval, 49%-62%; I2, 98.6%) of the populations achieving adequate levels of adherence. Our pooled analysis of African studies (12,116 patients total) indicated a pooled estimate of 77% (95% confidence interval, 68%-85%; I2, 98.4%). Study continent, adherence thresholds, and study quality were significant predictors of heterogeneity. Bayesian analysis was used as an alternative statistical method for combining adherence rates and provided similar findings. Our findings indicate that favorable levels of adherence, much of which was assessed via patient self-report, can be achieved in sub-Saharan African settings and that adherence remains a concern in North America.
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. 2006;296(6):679-690 (doi:10.1001/jama.296.6.679) JAMA
Edward J. Mills; Jean B. Nachega; Iain Buchan; et al.
Africa and North America: A Meta-analysis
Adherence to Antiretroviral Therapy in Sub-Saharan
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REVIEW
Adherence to Antiretroviral Therapy
in Sub-Saharan Africa and North America
A Meta-analysis
Edward J. Mills, PhD, MSc
Jean B. Nachega, MD, MPH
Iain Buchan, MD, FFPH
James Orbinski, MD, MA
Amir Attaran, DPhil, LLB
Sonal Singh, MD
Beth Rachlis, BSc
Ping Wu, MBBS, MSc
Curtis Cooper, MD, MSc
Lehana Thabane, PhD, MSc
Kumanan Wilson, MD, MSc
Gordon H. Guyatt, MD, MSc
David R. Bangsberg, MD, MPH
A
NTIRETROVIRAL THERAPY
(ART) has improved the
health of many human im-
munodeficiency virus (HIV)
positive individuals who otherwise
would have died. Treatment efficacy re-
lies, however, on sustained adher-
ence, which constitutes a serious chal-
lenge to those receiving ART.
1,2
The
regimens are often complicated and can
include varying dosing schedules, di-
etary restrictions, and adverse effects.
3
Consistently high levels of adherence
are necessary for reliable viral suppres-
sion
4,5
and prevention of resistance,
6
dis-
ease progression,
7
and death.
8
Access to ART is limited for the ma-
jority of individuals living with HIV/
AIDS in sub-Saharan Africa. The World
Health Organization’s initiative to have
3 million individuals receiving ART
by 2005 (“3 by 5”) has yet to meet its
planned provision of care timelines,
leaving more than two thirds of the
global number of individuals needing
care worldwide without access to ART.
9
Author Affiliations are listed at the end of this article.
Corresponding Author: Edward J. Mills, PhD, MSc,
Centre for International Health and Human Rights
Studies, 1255 Sheppard Ave E, North York, Ontario,
Canada, M2K1E2 (emills@cihhrs.org).
Context Adherence to antiretroviral therapy is a powerful predictor of survival for
individuals living with human immunodeficiency virus (HIV) and AIDS. Concerns about
incomplete adherence among patients living in poverty have been an important con-
sideration in expanding the access to antiretroviral therapy in sub-Saharan Africa.
Objective To evaluate estimates of antiretroviral therapy adherence in sub-Saharan
Africa and North America.
Data Sources Eleven electronic databases were searched along with major confer-
ence abstract databases (inclusion dates: inception of database up until April 18, 2006)
for all English-language articles and abstracts; and researchers and treatment advo-
cacy groups were contacted.
Study Selection and Data Abstraction To best reflect the general population,
studies of mixed populations in both North America and Africa were selected. Studies
evaluating specific populations such as men only, homeless individuals, or drug users,
were excluded. The data were abstracted in duplicate on study adherence outcomes,
thresholds used to determine adherence, and characteristics of the populations. A random-
effects meta-analysis was performed in which heterogeneity was examined using mul-
tivariable random-effects logistic regression. A sensitivity analysis was performed us-
ing Bayesian methods.
Data Synthesis Thirty-one studies from North America (28 full-text articles and 3
abstracts) and 27 studies (9 full-text articles and 18 abstracts) from sub-Saharan Africa
were included. African studies represented 12 sub-Saharan countries. Of the North
American studies, 71% used patient self-report to assess adherence; this was true of
66% of the African assessments. Studies reported similar thresholds for adherence moni-
toring (eg, 100%, 95%, 90%, 80%). A pooled analysis of the North American
studies (17 573 patients total) indicated a pooled estimate of 55% (95% confidence
interval, 49%-62%; I
2
, 98.6%) of the populations achieving adequate levels of ad-
herence. Our pooled analysis of African studies (12 116 patients total) indicated a pooled
estimate of 77% (95% confidence interval, 68%-85%; I
2
, 98.4%). Study continent,
adherence thresholds, and study quality were significant predictors of heterogeneity.
Bayesian analysis was used as an alternative statistical method for combining adher-
ence rates and provided similar findings.
Conclusion Our findings indicate that favorable levels of adherence, much of which
was assessed via patient self-report, can be achieved in sub-Saharan African settings
and that adherence remains a concern in North America.
JAMA. 2006;296:679-690 www.jama.com
©2006 American Medical Association. All rights reserved. (Reprinted) JAMA, August 9, 2006—Vol 296, No. 6 679
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Although sub-Saharan Africa repre-
sents only 10% of the world’s popula-
tion, it represents 77% of women with
HIV, 79% of AIDS deaths, and 92% of
the world’s AIDS orphans.
10
There has
been concern that African patients,
many of whom live in poverty and lack
formal education, will have subopti-
mal adherence to ART, which could
lead to the development and spread of
drug resistence.
11,12
Are concerns of poor adherence in
Africans justified? No study has per-
formed a systematic meta-analysis of ad-
herence levels in Sub-Saharan Africa.
We conducted a systematic review of
available ART adherence data in both
Africa and a resource-rich setting, North
America, to determine the level of ad-
herence in emerging African treat-
ment programs relative to the more es-
tablished North American programs.
METHODS
Eligibility Criteria
Prospective studies assessing adher-
ence rates as a primary or secondary
outcome (ie, noninterventional) in gen-
eral HIV populations in North America
and Africa were included. Studies had
to have reported a threshold for adher-
ence monitoring (eg, 100%, 95%,
90%, 80%). Studies were ex-
cluded if they reported adherence as a
mean of all doses taken by the com-
bined group of participants; were con-
ducted in countries outside North
America and Africa; contained experi-
mental interventions to promote ad-
herence because these studies do not
reflect existing clinical settings
13
;oras-
sessed only specific groups (eg, drug us-
ers, children, homeless individuals, ho-
mosexuals, men or women only)
14,15
because the focus was adherence
rates in general populations of HIV-
positive individuals.
Search Strategy
In consultation with an information spe-
cialist (Pearl Raju, PhD, Centre for In-
ternational Health and Human Rights
Studies, Toronto, Ontario), 3 of the au-
thors (E.M., B.R., P.W.) developed
search strategies. First, search terms that
may indicate adherence (eg, adherence,
compliance, pill counts, Medication Event
Monitoring System [MEMS], directly ob-
served) were identified. The searches
combined these terms with Medical Sub-
ject Headings for HIV and were con-
ducted from May 2005 to April 18, 2006,
independently, in duplicate (B.R., P.W.).
MEDLINE via PubMed, EMBASE, Coch-
rane CENTRAL, AIDSLINE, AMED,
CINAHL, TOXNET, Development and
Reproductive Toxicology Hazardous
Substances Databank, Psych-info, and
Web of Science were searched with the
inclusion dates of the inception of the
individual database up until April 18,
2006, except for AIDSLINE, which was
searched from inception up until 2000
when its new citations ended. The Web
sites of major HIV conferences also were
searched, specifically all International
AIDS Society conferences (up to Rio de
Janeiro, Brazil, in July 2005) and all Con-
ferences on Retroviruses and Opportu-
nistic Infections (up to Denver in Feb-
ruary 2006). Lay publications and Web
sites were also searched including the
Canadian AIDS Treatment Informa-
tion Exchange publications, Me´decins
sans Frontières, AIDS Treatment News,
and Google. Individual clinical research-
ers and AIDS cohort trial groups were
contacted via e-mail and telephone (BC
Centre for Excellence in HIV/AIDS,
International AIDS Society, and Me´-
decins sans Frontières) and asked if
they were aware of any unpublished
studies.
Study Selection
Using a predefined protocol (available
from corresponding author on re-
quest), 2 investigators (E.M., P.W.),
working independently, scanned all of
the abstracts and obtained the full text
of articles and reports from nongovern-
mental organizations that indicated or
suggested a measurement of adherence
had been achieved. After obtaining the
full reports of the candidate studies
(either a full peer-reviewed article, con-
ference abstract, or non–peer-reviewed
article), the same reviewers indepen-
dently assessed eligibility. Reviewers
were not blinded to study authors, study
conclusions, and outcomes because
blinding has been shown to have little
effect on systematic reviews.
16
To ob-
tain the full information regarding con-
ference abstracts, the studies’ authors
were contacted via e-mail and tele-
phone. After all potentially relevant full-
text articles and abstracts were identi-
fied, 2 of the authors (E.M., P.W.) and
a member of the study team (Dugald
Seely, ND, MSc, University of Toronto,
Toronto, Ontario) met to achieve con-
sensus regarding eligibility.
Data Extraction
Between May 1, 2005, and April 23,
2006, data extraction was conducted in-
dependently, in duplicate, using a stan-
dardized form. Data abstractors col-
lected information about the study
country, study populations (age and
sex), participant ethnicity (as classi-
fied in the original study), sample size,
methods of adherence measurement,
and outcomes. When more than 1 ad-
herence measurement was used, data
on all measures used were extracted and
the most objective method was cho-
sen for this analysis (eg, MEMS). Ad-
herence measurements were defined
in the studies as primary adherence
thresholds. No studies reported exclu-
sions of patients due to adherence lev-
els prior to the study. However, in 8
studies, data are only reported for
patients who completed the adher-
ence assessments. In this case, only the
data for study completers were used.
Data on study settings (eg, nongovern-
mental organization clinic, specialist
clinic) and predictors of ART adher-
ence (eg, adherence threshold, use of
MEMS, quality of assessment) were ab-
stracted. Finally, where available, data
were abstracted regarding whether pa-
tients receiving ART paid for it or re-
ceived the therapy for free. Data on
populations’ disease state were not ab-
stracted due to large heterogeneity of
each study population. The data were
entered into an electronic database such
that duplicate entries existed for each
study; when the 2 entries did not match,
we reached consensus through discus-
sion and if necessary requested third-
META-ANALYSIS OF ADHERENCE TO ANTIRETROVIRAL THERAPY
680 JAMA, August 9, 2006—Vol 296, No. 6 (Reprinted) ©2006 American Medical Association. All rights reserved.
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party arbitration. We considered study
quality according to whether studies
used multiple measurement tools to as-
sess adherence (n=9) and when appli-
cable considered loss to follow-up of
greater than 20% of the study sample
as being poor (n=10).
Data Analysis
To assess interrater reliability on inclu-
sion of the articles and abstracts, the
statistic, which provides a measure of in-
terobserver agreement independent of
chance, was used.
17
Descriptive analy-
ses were used to compare the number
of full-text articles published over time.
To determine if complexity of regi-
mens might yield differing adherence
rates, a z test was used for the pooled
North American adherence rates prior
to and after 2002, the year when the Af-
rican studies first appeared in print.
Thresholds for adherence were consid-
ered as greater than or equal to the cut-
off levels. To determine pooled propor-
tions of study participants adherent to
individual study measurement thresh-
olds, the variances of the raw propor-
tions (r/n) were stabilized using a
Freeman-Tukey–type arcsine square
root transformation
18,19
: y=arcsine[
(r/(n 1)]arcsine [
(r 1)/(n 1)],
with a variance of 1/(n 1), where n is
the denominator for population size. The
I
2
statistic was calculated as a measure
of the proportion of the overall varia-
tion in adherence that was attributable
to between-study heterogeneity.
20
We
anticipated large heterogeneity consid-
ering the varied populations, health care
delivery systems, and course of the epi-
demic. The DerSimonian-Laird random-
effects method was used to pool the
transformed proportions,
21,22
which rec-
ognizes and anchors studies as a sample
of all potential studies, and incorpo-
rates an additional between-study com-
ponent to the estimate of variability. Ran-
dom-effects logistic regression was used
to explore this heterogeneity and to com-
pare continents after adjusting for the
potential confounding due to adher-
ence thresholds (100%, 95%, 90%,
80%); assessment criteria (self-
reported, pharmacy refills); whether the
study participant paid for ART; loss to
follow-up (20%); and clinic settings
(outpatient, nongovernmental organi-
zation). For any missing data on covar-
iates, the authors of the articles were con-
tacted and when there was no response,
these studies were considered nega-
tive. A sensitivity analysis was also con-
ducted to examine the impact of these
negative studies on the meta-regres-
sion. The unadjusted and regression-
adjusted estimates and odds ratios were
calculated by continent. Separate pooled
analyses were conducted of all studies
using the same cutoff thresholds for ad-
herence. For sensitivity analysis, we con-
firmed that a Mann-Whitney U test gave
results consistent with those of the other
methods used to compare continents.
The sensitivity analysis was conducted
using a Bayesian random-effects model
with an alternative logit transforma-
tion in addition to Monte Carlo Markov
Chain simulations of variability.
23
For-
est plots were created for each conti-
nent, showing individual study propor-
tions with Clopper-Pearson confidence
intervals (CIs) and the overall DerSim-
monian-Laird pooled estimate. Each in-
dividual study in the forest plot repre-
sents the proportion of the study
population meeting the threshold for ap-
propriate adherence, as defined in the
original studies. Results are reported as
combined adherence proportions with
95% CIs. All P values are exact and
P.05 was considered significant. Analy-
ses were conducted using StatsDirect
version 2.5.2 (StatsDirect Ltd, Cheshire,
England), which was developed by 1 of
us (I.B.), Stata version 9.0 (StataCorp,
College Station, Tex), and OpenBUGS
version 2.1 (http://www.mathstat
.helsinki.fi/openbugs/).
RESULTS
From the initial searches (May-
November 2005), 136 relevant ab-
stracts of full text articles were identi-
fied. Of these, 60 studies passed the first
screening. There was near perfect agree-
ment between the reviewers on the in-
clusion of 28 full-text articles and 2 ab-
stracts addressing North American
studies and 7 full-text articles and 15
abstracts addressing African studies
(=0.91). In a search update (April 18,
2006), 1 abstract addressing adher-
ence in North American settings, 2 full-
text African studies, and 3 abstracts ad-
dressing adherence in African settings
were identified. Agreement on ab-
stract inclusion was perfect. A flow dia-
gram of studies included in the analy-
sis is detailed in F
IGURE 1.
The characteristics of the North
American studies
3,4,24-52
appear in
TABLE 1. All full-text articles and ab-
stracts were published in English. Of the
28 full-text articles reporting on stud-
ies conducted in North American set-
tings,
3,4,24-47
26 were from the United
States and 2 were from Canada.
48,49
Of
the 3 abstracts reporting on studies con-
ducted in North American settings, 2 as-
sessed US populations
50,51
and 1 as-
sessed a Canadian population.
52
The
characteristics of the African stud-
ies
53-79
appear in TABLE 2. Of the 9 full-
text articles reporting on studies con-
ducted in Africa, 2 were from South
Africa,
53,54
2 were from Nigeria,
55,56
1 was
from Uganda,
57
1 was from Senegal,
58
1
was from Cameroon,
59
1 was from
Botswana,
60
and 1 was from Malawi.
61
Of the 18 abstracts reporting on stud-
ies conducted in African settings, 2 were
from Nigeria,
62,63
4 were from South
Africa,
64-67
5 were from Uganda,
68-72
1 was
from Malawi,
73
1 was from Rwanda,
74
1
was from the Democratic Republic of
Congo,
75
2 were from Burkina Faso,
76,77
1 was from Cote d’Ivoire,
78
and 1 was
from Tanzania.
79
Study Characteristics
Full-text studies conducted in North
America enrolled a median of 220 pa-
tients (interquartile range [IQR], 130-
683). This was largely unchanged when
combined with the 3 North American
abstracts (median, 219 patients; IQR,
116-683). Full-text studies conducted
in Africa enrolled a median of 109 pa-
tients (IQR, 60-263) and when the 18
African abstracts were included, the me-
dian was 100 patients (IQR, 60-270).
Four abstracts were missing data
65,67,71,77
;
3 on loss to follow-up and 4 on pay-
ment of ART.
META-ANALYSIS OF ADHERENCE TO ANTIRETROVIRAL THERAPY
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Twenty-two (71%) of the North
American studies assessed adherence us-
ing patient-reported adherence levels
over a specified period. Three studies
(10%) used pharmacy claims. Three
studies (10%) in North America used the
MEMS to assess adherence. Two stud-
ies (6.5%) used a mix of patient report-
ing and clinician observations and 1
study (3%) used clinic staff reporting.
Eighteen (66%) of the 27 studies assess-
ing adherence in African settings used pa-
tient-reported adherence over a speci-
fied period. Three studies (11%) used
pharmacy claims and 6 studies (22%)
used a mix of patient reporting of pill
counts and clinician observations.
Adherence Threshold
Measurements
Fifteen North American studies de-
fined adherence as 100% during the
measurement period.* Nine North
American studies assessed adherence as
greater than 95%,† 4 as greater than
90%,
29,35,37,48
and 3 as greater than
80%.
25,28,31
Eleven African studies as-
sessed adherence as 100%,‡ 11 as
greater than 95%,§ 2 as greater than
90%,
53,78
and 3 as greater than 80%.
55,58,66
Thresholds defined to assess adher-
ence were not systematically different
across settings.
Time Trends
Included studies assessing ART adher-
ence in North America began in 1998
and continued to the present. There was
no difference in the pooled effect size
for North American studies between
studies published prior to 2002 (n=4)
and studies published since 2002
(n= 27) (P=.52). We were unable to
identify studies assessing ART adher-
ence in Africa prior to 2002 that met
our inclusion criteria.
Meta-analysis
Our primary meta-analyses aimed to de-
termine the overall proportion of pa-
tients in each continent meeting the
threshold measurements used in the
specific studies. The combined conti-
nent analysis indicates adherence of
64% (95% CI, 59%-70%; I
2
, 98.7%).
FIGURE 2 displays a forest plot of all
North American studies and F
IGURE 3
displays a forest plot of all African
studies. When we pooled abstracts
with full-text articles, North Ameri-
can studies (31 studies; 17 573
patients total) yielded a pooled esti-
mate of 55% (95% CI, 49%-62%; I
2
,
98.6%) and African studies (27 stud-
ies; 12 116 patients total) yielded a
pooled estimate of 77% (95% CI,
68%-85%; I
2
, 98.4%), indicating a
significantly (P.001) higher level of
ART adherence in Africa. North Ameri-
can full-text articles (28 studies) had
a pooled proportion of 57% (95% CI,
49%-64%; I
2
, 98.9%) and African full-
text articles (9 studies) had a pooled
proportion of 71% (95% CI, 62%-
79%; I
2
, 91.6%); the superior ART ad-
herence rate in Africa remained
(P=.02). The Bayesian sensitivity analy-
sis provided an alternative statistical
manner to evaluate pooled propor-
tions and were largely similar to the
pooled random-effects analysis of 55%
(95% CI, 49%-62%) adherence in North
America and 81% (95% CI, 72%-87%)
adherence in Africa. The Mann-
Whitney U analysis in case of scale
transformation problems with arcsine
*References 3, 24, 26, 30, 32, 36, 38, 40, 42-47, 51.
†References 4, 27, 33, 34, 39, 41, 49, 50, 52.
‡References 56, 59, 61, 64, 71, 72, 74-77, 79.
§References 54, 57, 60, 62, 63, 65, 67-70, 73.
Figure 1. Flow Diagram of North American and African Studies Included in Analysis
58 Studies Included in Analysis
31 North American
28 Full-Text Articles
3 Abstracts
27 African
9 Full-Text Articles
18 Abstracts
96 Full-Text Articles Reviewed by
Individual Researchers for Eligibility
81 North American
15 African
136 Abstracts of Full-Text Articles
Identified in Electronic Databases
113 North American
23 African
25 Excluded (Reported Adherence
in Specific Populations)
22 North American
3 African
36 Excluded (Used Specific Population
or Measured Adherence Using
Mean Adherence Rather Than
Proportions)
31 North American
5 African
40 Excluded Based on Exclusion Criteria
32 North American
8 African
35 Studies Eligible by Consensus
of Researchers and Included
in Analysis
28 North American
7 African
21 Abstracts Identified at International
Conference
3 North American
18 African
2 Full-Text African Studies Identified
in Electronic Database
60 Full-Text Articles Reviewed by
Research Team for Eligibility
50 North American
10 African
META-ANALYSIS OF ADHERENCE TO ANTIRETROVIRAL THERAPY
682 JAMA, August 9, 2006—Vol 296, No. 6 (Reprinted) ©2006 American Medical Association. All rights reserved.
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Table 1. Characteristics of North American Studies*
Source
No. of
Participants
Characterisics of Study Population
Assessor
Adherence, %;
Threshold for Measurement
Female,
% Ethnicity, % Age, y
Acri et al,
24
2005 106 29 Black, 26
Hispanic, 32
41 (13-69)† Patient 100; Did not miss any doses over past month
Becker et al,
25
2002 3788 31 NA NA Pharmacy claim 80; No. of days drug taken/365
Castillo et al,
48
2004‡ 788 18.1 NA 37 (30-45)† Pharmacy claim 90; No. of months medication dispensed/No. of
months of follow-up
Cook et al,
26
2001 219 28 Black, 24
Hispanic, 15
NA Patient 100; Did not miss dose in previous 24 h
Diamond et al,
27
2005
874
(683 in Analysis)
12 Hispanic, 37
Black, 16
37 (21-73)† Patient 95; No. of pills taken/pills prescribed in past
week
Eldred et al,
28
1998 244
(207 in Analysis)
37 Black, 85 NA Medical record 80; Total dose of medication in previous week
(total No. of capsules of medication taken in
past week)
Ferguson et al,
3
2002 149 12.8 Black, 34 39 (8.6)§ Patient 100; Missed 1 dose in the past 4 wk
Gebo et al,
29
2003 196 32 Black, 78 37.5 (NA)§ Patient 90; No. of doses taken over past 2 wk
Gifford et al,
30
2000 133 14 Black, 22
Hispanic, 11
NA Patient 100; NA
Graney et al,
31
2003 57 22.8 Black, 82.5 35 (23-46) Patient
Heckman et al,
32
2004
329
(272 in Analysis)
92 Black, 18
Hispanic, 3
Native American, 1
40.9 (18-70) Patient 100%; Based on past 7 d
Hinkin et al,
33
2004 148 17 Black, 70
Hispanic, 9
44.2 (7.7)§ MEMS #
Ingersoll and
Heckman,
34
2005
120
(46 in Analysis)
38 Black, 83
Native American, 2
40.4 (NA)§ Patient 95; Composite adherence score of 3
Johnson et al,
35
2005 2765 24.4 Black, 49.4 42 (7.6)§ Patient 90; No. of pills taken/No. of pills prescribed over
prior 3 d
Kalichman et al,
36
2005
391
(255 in Analysis)
NA Black, 71 41 (NA)§ Patient 100; Based on previous 7 d
Levine et al,
37
2005 222 20 Black, 68 43.8 (7.2)§ MEMS 90; No. of the doses taken/No. of doses
prescribed in 4-wk study period
Mohammed et al,
38
2004
273 70.7 Black, 60.1 38.6 (19-66) Patient 100; Based on past 7 d
Paterson et al,
4
2000 99
(81 in Analysis)
NA Black, 20.8 40 (21-62)† MEMS 95; No. of doses recorded/total No. of doses
prescribed
Penedo et al,
39
2003 116 45 Black, 37
Hispanic, 33
39.2 (8.7)§ Patient 95; No. of doses taken/No. of doses prescribed
in past 4 d
Power et al,
40
2003 73 47 Black, 23 40.3 (6.9)§ Patient 100; Based on past 4 d
Russell et al,
41
2004 130 3.8 Black, 15.4
Hispanic, 5.4
37.2 (7.2)§ Clinic staff 95; Based on a combined adherence regimen
Schneider et al,
42
2004
554 15 Black, 14.5
Hispanic, 6.9
41.6 (7.7)§ Patient 100; Aggregate adherence score of 100 includes
taking all medication in previous 7 d
Tesoriero et al,
43
2003
435 48.6 Black, 47.9
Hispanic, 32.2
43.1 (NA)§ Patient 100; Based on past 3 d
Tucker et al,
44
2003 1910 22 Black, 32 NA Patient 100; Based on past 7 d
Wagner et al,
45
2002 80
(40 in Analysis)
NA Black, 35
Hispanic, 16
Native American, 3
39 (21-64) Patient 100; Based on past 3 d
Weiss et al,
46
2003 997 38.4 Black, 47.9
Hispanic, 32.9
NA Patient 100; Based on past 3 d
Wilson et al,
47
2001 454 28 Nonwhite, 37 42 (NA)§ Patient 100; Based on past 7 d
Wood et al,
49
2003‡ 1422 ** NA 37.1 (31.9-44.0)† Patient or
physician
95; Total amount of medication dispensed to
patient would last to follow-up during first year
Montessori et al,
52
2000‡,††
886 13.5 NA NA Pharmacy claims 95; No. of months prescriptions dispensed/No.
of months of follow-up in first year
Robertson et al,
51
2006††,‡‡
37 31 NA NA Patient 100; Based on past 4 d
Temoshok and
Wald,
50
2004††
131 44 Black, 91 42.4 (NA)§ Patient 95; NA
Abbreviations: MEMS, Medication Event Monitoring System; NA, data not available.
*Studies are from the United States unless otherwise indicated.
†Expressed as median (range).
‡Study is from Canada.
§Expressed as mean (SD).
Expressed as mean (range).
¶Adherence of 80 or greater on a scale of 100 coded for dosage.
#Adherence defined as 95% or greater of prescribed medication during a 4-week
period.
**There were 224 females in this study.
††This study was published as an abstract.
‡‡Data missing on payment of antiretroviral therapy and on loss to follow-up.
META-ANALYSIS OF ADHERENCE TO ANTIRETROVIRAL THERAPY
©2006 American Medical Association. All rights reserved. (Reprinted) JAMA, August 9, 2006—Vol 296, No. 6 683
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remained significant (P.001). The ad-
justed odds ratio of ART adherence in
African studies in relationship to ART
adherence in North America, indepen-
dent of the thresholds used, is 3.0 (95%
CI, 2.6-3.6). The odds ratio, adjusted
for all other potential covariates, is 2.5
(95% CI, 1.9-3.3).
TABLE 3 displays the pooled propor-
tions of each continent adjusted for
thresholds. As anticipated, we found
large heterogeneity across study analy-
ses. In multivariable analyses (T
ABLE 4),
heterogeneity was examined by conti-
nent, adherence threshold (100%,
95%, 90%), and use of more than 1
adherence measure. North American
studies using MEMS to assess ART ad-
herence had a reduced but nonsignifi-
cant level (P=.08) compared with other
North American studies that did not use
MEMS. Free access to care was not
associated with higher ART adherence
in Africa (16 studies; 74% [95% CI,
Table 2. Characteristics of African Studies
Source Country
No. of
Participants
Characteristics of
Study Population
Assessor
Adherence, %;
Threshold for Measurement
Female,
% Age, y
Byakika-Tusiime et al,
57
2005
Uganda 304 53 39 (NA)
a
Patient 95; No. of doses taken/No. of doses
prescribed in last 3 d
Idigbe et al,
55
2005 Nigeria 44 56 34.5 (30-60)
b
Patient 80; Based on period between clinic visits
Iliyasu et al,
56
2005 Nigeria 263 NA NA Patient 100; Based on previous 7 d
Laurent et al,
58
2002 Senegal 58 44.8 41.5 (30-46)
b
Patient
c
Laurent et al,
59
2004 Cameroon 60 68 34.5 (29-40.5)
d
Patient 100; Based on past 7 d
Orrell et al,
53
2003 South Africa 289
(278 in Analysis)
43 33.4 (8.7)
a
Pharmacy refill
and pill count
90; Medication dispensed minus pills returned/
No. of pills prescribed over 48 wk
Nachega et al,
54
2004 South Africa 66 71 36.1 (10.1)
a
Patient 95; No. of pills taken/No. of pills prescribed in
previous month
Weiser et al,
60
2003 Botswana 109 50 NA Patient or clinician 95; Based on previous year of missing 1
dose in 10-d period or 1 dose/wk
van Oosterhout et al,
61
2005
Malawi 176 55 39 (22-71)
b
Patient or file record 100; Did not miss any dose in prior day, week,
or month
Adedayo et al,
62
2005
e
Nigeria 689 36 32 (NA)
b
Patient 95; NA
Boileu et al,
77
2005
e
Burkina Faso
and Mali
270 65.2 NA Patient 100; Based on past 7 d
Brown et al,
64
2004
e
South Africa 50 NA NA Patient 100; Based on past 7 d
Byakika et al,
69
2005
e
Uganda 44
(28 in Analysis)
71.4
f
29.5 (13.5)
a
Pill count, patient,
or VAS
95; Based on 3-d report
Daniel et al,
63
2004
e
Nigeria 53 60.4 40.5 (NA)
a
Patient 95; Based on past 7 d
Darder et al,
67
2004
e,g,h
South Africa 192 NA NA Patient
i
Eholie et al,
78
2004
e
Cote d’Ivoire 308
(304 in Analysis)
47.4 NA Pharmacy refill 90; Based on proportion of prescribed doses
taken over 7 d
Ferris et al,
65
2004
e,g
South Africa 74 58.1
j
37 (NA)
a
Patient 95; Based on past 4 d
Hosseinipour et al,
73
2004
e
Malawi 141 52 NA Patient 95; NA
Karcher et al,
68
2004
e
Uganda 76 53.9
k
NA Patient 95; NA
Muganzi et al,
70
2004
e
Uganda 530 NA NA Patient or pill count 95; Based on majority of prescribed
medication taken
Okongo et al,
71
2004
e,g,h
Uganda 100 58 33.4 (NA)
a
Patient or pill count 100; Based on consistent medication regimen
Omes et al,
74
2004
e
Rwanda 95 NA NA Patient or VAS 100; Based on last 3 d (self-report) and the last
month (VAS)
Nachega et al,
66
2005
e
South Africa 7812 56 NA Pharmacy claim 80; No. of months patients submitted
claims/No. of months since began taking
antiretrovirals
Ramadhani,
79
2006
e
Tanzania 150 63 NA Patient 100; NA
Shihab et al,
72
2004
e
Uganda 84 50 38.6 (8.2)
a
Patient 100; Based on past 2 wk
Traore et al,
76
2004
e
Burkina Faso 120
(80 in Analysis)
NA NA Patient 100; Based on past month
Tu et al,
75
2004
e
Democratic
Republic
of Congo
30 NA NA Patient or pill count 100; Based on 3-mo period
Abbreviations: MEMS, Medication Event Monitoring System; NA, data not available;
VAS, visual analog scale.
a
Expressed as mean (SD).
b
Expressed as median (range).
c
Adherence based on 80% or greater of prescribed dose taken on the basis of the
patients’ statements to their physician at each monthly visit.
d
Expressed as mean (range).
e
This study was published as an abstract.
f
Of the total population in this study, 14.3% were children; mean (SD) age, 1.5 (3.0) years.
g
Data missing on payment of antiretroviral therapy.
h
Data missing on loss to follow-up.
i
Adherence based on 95% or greater dose taken at 1, 3, and 12 months.
j
Of the total population in this study, 5.4% were Asian.
k
Of the total population in this study, 6.6% were children.
META-ANALYSIS OF ADHERENCE TO ANTIRETROVIRAL THERAPY
684 JAMA, August 9, 2006—Vol 296, No. 6 (Reprinted) ©2006 American Medical Association. All rights reserved.
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64%-82%]) than North America (24
studies; 82% [95% CI, 67%-93%])
(P=.33).
COMMENT
The findings from this systematic
review and meta-analysis suggest that
ART adherence among sub-Saharan
African patients in early treatment pro-
grams are favorable, although it should
be noted that the complexity of treat-
ment regimens is potentially greater in
North America, which should be con-
sidered when interpreting the data.
This suggests that concerns about sub-
optimal adherence are not supported
by the data and such concerns should
not contribute to delayed access to
treatment. While these data are prom-
ising, these relatively high levels of
adherence may decline as treatment
access expands. The African studies in
these analyses were conducted in
patients with early access to limited
therapy and are possibly not generaliz-
able to the larger HIV epidemic in
Africa. Furthermore, most African
studies include patients during early
therapy when they are experiencing
dramatic increases in health status and
before they develop long-term adverse
effects of therapy. While expectations
of poor levels of adherence in Africa
appear to be thus far unwarranted,
efforts to sustain adherence in Africa
and elsewhere remain important goals
to optimize outcomes for individuals
and global HIV treatment.
Strengths of this systematic review in-
clude explicit eligibility criteria and con-
duct of a comprehensive search that
identified a number of eligible articles
not published or available on elec-
tronic databases. We attempted to con-
tact all of the articles’ authors, how-
ever only 36 provided appropriate
contact information. Thirty-two au-
thors (89%) responded and clarified
that adherence rates were correct as ab-
stracted. Independent reviewers as-
sessed eligibility and agreement was
high. In keeping with the large hetero-
geneity across studies, we used the
random-effects model to pool propor-
Figure 2. Pooled Proportion of Patients in North American Studies Adhering to Antiretroviral Therapy
Source
Full-Text Articles
Proportion Adherent
(95% CI)
Acri et al,
24
2005 0.45 (0.36-0.55)
Becker et al,
25
2002 0.26 (0.25-0.27)
Castillo et al,
48
2004 0.65 (0.62-0.69)
Cook et al,
26
2001 0.86 (0.81-0.90)
Diamond et al,
27
2005 0.74 (0.71-0.78)
Eldred et al,
28
1998 0.56 (0.49-0.63)
Ferguson et al,
3
2002 0.35 (0.27-0.43)
Gebo et al,
29
2003 0.71 (0.64-0.77)
Graney et al,
31
2003 0.56 (0.42-0.69)
Gifford et al,
30
2000 0.50 (0.41-0.58)
Heckman et al,
32
2004 0.50 (0.44-0.56)
Hinkin et al,
33
2004 0.33 (0.26-0.41)
Ingersoll and Heckman,
34
2005 0.30 (0.18-0.46)
Johnson et al,
35
2005 0.68 (0.66-0.70)
Kalichman et al,
36
2005 0.56 (0.50-0.62)
Levine et al,
37
2005 0.44 (0.38-0.51)
Mohammed et al,
38
2004 0.66 (0.60-0.71)
Paterson et al,
4
2000 0.30 (0.20-0.41)
Penedo et al,
39
2003 0.72 (0.63-0.80)
Power et al,
40
2003 0.74 (0.62-0.84)
Russell et al,
41
2004 0.83 (0.76-0.89)
Schneider et al,
42
2004 0.43 (0.39-0.47)
Tesoriero et al,
43
2003 0.46 (0.41-0.51)
Tucker et al,
44
2003 0.46 (0.44-0.49)
Wagner et al,
45
2002 0.53 (0.36-0.68)
Weiss et al,
46
2003 0.66 (0.63-0.69)
Wilson et al,
47
2001 0.42 (0.37-0.47)
Wood et al,
49
2003 0.57 (0.55-0.60)
Abstracts
Montessori et al,
52
2000 0.57 (0.54-0.60)
Robertson et al,
51
2006 0.68 (0.50-0.82)
Temoshok and Wald,
50
2004 0.54 (0.45-0.63)
No. Adherent/
Total No.
48/106
985/3788
514/788
188/219
508/683
116/207
52/149
139/196
32/57
66/133
136/272
49/148
14/46
1887/2765
143/255
98/222
179/273
24/81
84/116
54/73
108/130
238/554
200/435
888/1910
21/40
655/997
191/454
816/1422
504/886
25/37
71/131
Country
United States
United States
Canada
United States
United States
United States
United States
United States
United States
United States
United States
United States
United States
United States
United States
United States
United States
United States
United States
United States
United States
United States
United States
United States
United States
United States
United States
Canada
Canada
United States
United States
Combined 0.55 (0.49-0.62)
0 0.2 0.4 0.6 0.8 1.0
Proportion Maintaining Adherence (95% CI)
Size of data markers is proportional to sample size. The combined data marker indicates the DerSimmonian-Laird combined proportion of all North American studies.
CI indicates confidence interval.
META-ANALYSIS OF ADHERENCE TO ANTIRETROVIRAL THERAPY
©2006 American Medical Association. All rights reserved. (Reprinted) JAMA, August 9, 2006—Vol 296, No. 6 685
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tions. We used random-effects logis-
tic regression to account for the ex-
tent of differences between populations
and examined a priori defined vari-
ables to explain the heterogeneity.
The main limitation of our review is
in the quality of the studies. There is
no gold standard for evaluating adher-
ence to medication.
80
Patient recall and
pill counts have inherent biases in their
measurement.
81
However, proportion-
ately, both continents used a similar
number of patient recall and pill counts
to evaluate adherence, thereby mak-
ing our analysis as valid as the policies
to provide care in North America. There
were only 3 studies that assessed ad-
herence using the MEMS and these
were in North America.
4,33,37
These stud-
ies reported a nonsignificant pooled re-
duction in ART adherence compared
with self-reported studies of 19%, which
is in keeping with expectations that self-
report may exaggerate adherence. We
found large heterogeneity across the
meta-analyses as we had expected. We
were able to explain heterogeneity
across several outcomes. There are uni-
dentified factors either related to popu-
lations, drug regimens, or methodologi-
cal features that may have a large impact
on either apparent or real adherence.
Setting aside the pooled estimates, all
but 2 African studies had more than
50% of all patients meeting the thresh-
old for appropriate ART adherence.
Furthermore, despite our extensive
searching and contact with organiza-
tions providing care in North America
and Africa, as well as reviewing other
review articles,
82,83
which have ad-
dressed several of our included stud-
ies, it is possible that we have missed
some unpublished studies assessing
ART adherence. We cannot know the
extent to this limitation because fun-
nel plots do not apply in noninterven-
tion-based studies. Finally, our analy-
sis was based on studies across a great
spectrum of geographical and eco-
nomic locations. It is possible that po-
litical or sociodemographic status can
affect adherence rates. These data were
rarely available in the included stud-
ies and while a more detailed analysis
comparing regions would be informa-
tive in determining which factors within
Africa influence ART adherence, it
References 54, 57-60, 63-65, 67, 68, 70, 73-76, 84.
Figure 3. Pooled Proportion of Patients in African Studies Adhering to Antiretroviral Therapy
No. Adherent/
Total No.
207/304
38/44
142/263
51/58
52/60
175/278
58/66
59/109
92/176
593/689
38/50
139/270
25/28
42/53
168/192
148/304
57/74
134/141
52/76
519/530
97/100
90/95
3908/7812
125/150
65/84
30/30
24/80
Country
Uganda
Nigeria
Nigeria
Senegal
Cameroon
South Africa
South Africa
Botswana
Malawi
Nigeria
South Africa
Burkina Faso and Mali
Uganda
Nigeria
South Africa
Cote D’Ivoire
South Africa
Malawi
Uganda
Uganda
Uganda
Rwanda
South Africa
Tanzania
Uganda
Democratic Republic
of Congo
Burkina Faso
Proportion Adherent
(95% CI)
0.68 (0.63-0.73)
0.86 (0.73-0.95)
0.54 (0.48-0.60)
0.88 (0.77-0.95)
0.87 (0.75-0.94)
0.63 (0.57-0.69)
0.88 (0.78-0.95)
0.54 (0.44-0.64)
0.52 (0.45-0.60)
0.86 (0.83-0.89)
0.76 (0.62-0.87)
0.51 (0.45-0.58)
0.89 (0.72-0.98)
0.79 (0.66-0.89)
0.88 (0.82-0.92)
0.49 (0.43-0.54)
0.77 (0.66-0.86)
0.95 (0.90-0.98)
0.68 (0.57-0.79)
0.98 (0.96-0.99)
0.97 (0.91-0.99)
0.95 (0.88-0.98)
0.50 (0.49-0.51)
0.83 (0.76-0.89)
0.77 (0.67-0.86)
1.00 (0.88-1.00)
0.30 (0.20-0.41)
0.77 (0.68-0.85)
0 0.2 0.4 0.6 0.8 1.0
Proportion Maintaining Adherence (95% CI)
Source
Full-Text Articles
Byakika-Tusiime et al,
57
2005
Idigbe et al,
55
2005
IIiyasu et al,
56
2005
Laurent et al,
58
2002
Laurent et al,
59
2004
Orrell et al,
53
2003
Nachega et al,
54
2004
Weiser et al,
60
2003
van Oosterhout et al,
61
2005
Adedayo et al,
62
2005
Brown et al,
64
2004
Boileu et al,
77
2005
Byakika et al,
69
2005
Daniel et al,
63
2004
Darder et al,
67
2004
Eholie et al,
78
2004
Ferris et al,
65
2004
Hosseinipour et al,
73
2004
Karcher et al,
68
2004
Muganzi et al,
70
2004
Okongo et al,
71
2004
Omes et al,
74
2004
Nachega et al,
66
2005
Ramadhani,
79
2006
Shihab et al,
72
2004
Tu et al,
75
2004
Traore et al,
76
2004
Combined
Abstracts
Size of data markers is proportional to sample size. The combined data marker indicates the DerSimmonian-Laird combined proportion of all African studies. CI indi-
cates confidence interval.
META-ANALYSIS OF ADHERENCE TO ANTIRETROVIRAL THERAPY
686 JAMA, August 9, 2006—Vol 296, No. 6 (Reprinted) ©2006 American Medical Association. All rights reserved.
by guest on June 24, 2008 www.jama.comDownloaded from
would not change the primary finding
that treatment programs in Africa have
thus far had relatively high levels of ad-
herence even accounting for this het-
erogeneity.
Recognizing these limitations, the
consistent difference of ART adher-
ence in North America and Africa raises
the question as to why early opinions
may have underestimated adherence
among Africans. This sentiment was ex-
pressed at high levels of international
agency decision making.
85
Reports in-
dicate that individuals living in pov-
erty in North America had suboptimal
adherence in the range of 56% to
67%.
86,87
These data may have been in-
terpreted to mean that poverty is a risk
factor for incomplete adherence and
that individuals living in extreme pov-
erty would then have lower levels of ad-
herence. The barriers to adherence
among impoverished individuals in
North America appear, however, to be
due to poor patient-clinician relation-
ships, untreated depression, sub-
stance abuse, and other factors that are
common among poor individuals in the
North American setting rather than
poverty itself.
5
It appears that the in-
teractions between such factors and
ART adherence in Africa may be quite
different. Specific factors that can cor-
relate with poverty are at play in re-
duced adherence and poverty itself is
not the only determinant.
To date, the most important and
prevalent factors that have been re-
ported to negatively affect adherence in
sub-Saharan Africa are cost,
54,59,88,89
not
disclosing HIV status to a loved one or
fear of being stigmatized,
54,60
alcohol
abuse,
90
and difficulty in following com-
plex drug regimens.
59,91
Studies report
that the majority of patients receiving
ART have disclosed their HIV status to
family or friends
92,93
and that those who
have not appear to do worse with
therapy.
54,60
Such patients are likely to
have frequent treatment interruptions
due to the fact that tablets must be hid-
den and therefore not taken in the pres-
ence of others. Encouraging voluntary
HIV status disclosure in a community
with access to ART may result in im-
proved uptake of voluntary counseling
and testing, help decrease the stigma,
and improve adherence.
The findings of this analysis have
implications for clinicians in both con-
tinents. We have shown that there are
patients in both settings that have sub-
optimal adherence and that factors
beyond poverty play an important role.
Clinicians should therefore proac-
tively inquire with patients about cur-
rent barriers or facilitators of adher-
ence to HIV medications. We have
previously identified that important
barriers to ART adherence in both the
developed and developing world
included forgetfulness, a lack of under-
standing of treatment benefits, sever-
ity of adverse events, and the level of
complexity of the drug regimen.
90
Although the success of interventions
to improve adherence is modest to
Table 3. Pooled Adherence Rates Across Thresholds for North American and African Studies
No. of
Studies
Pooled
Summary
Proportion, %
(95% CI)* I
2
,% P Value†
Adequate adherence for full-text articles only
North America 28 57 (49-64) 98.9
Africa 9 71 (62-79) 91.6
.02
Adequate adherence for full-text articles
and abstracts
North America 31 55 (49-62) 98.6
Africa 27 77 (68-85) 98.4
.001
Adequate adherence for abstracts only
North America 3 57 (54-60) 4.3
Africa 18 80 (68-89) 98.9
.001
100% Adherence
North America 15 56 (49-63) 95.8
Africa 11 76 (62-87) 96.7
.004
95% Adherence
North America 9 55 (45-65) 96.7
Africa 9 82 (73-90) 96.3
.001
90% Adherence
North America 4 63 (54-70) 90.9
Africa 2 56 (42-69) 91.6
.41
80% Adherence
North America 3 45 (22-70) 97.9
Africa 3 75 (44-96) 97.1
.15
1 Adherence measure
North America 5 65 (55-75) 95.8
Africa 5 91 (72-100) 97.0
.003
Abbreviation: CI, confidence interval.
*All summary proportions use a random-effects pooled model.
†A z test of the pooled estimate was used to test for differences between continents.
Table 4. Multivariable Random-Effects Logistic Regression*
Variable Coefficient (95% CI) OR (95% CI) P Value
Africa 0.91 (0.64 to 1.19) 2.5 (1.9 to 3.3) .001
100% Adherence 0.85 (0.16 to 1.54) 2.3 (1.2 to 4.7) .02
95% Adherence 0.94 (0.26 to 1.63) 2.6 (1.3 to 5.1) .006
90% Adherence 0.90 (−0.13 to 1.94) 2.5 (0.9 to 7.0) .87
1 Adherence measure 0.68 (0.29 to 1.08) 2.0 (1.3 to 2.9) .001
Clinic setting 0.37 (−0.09 to 0.85) 1.5 (0.9 to 2.3) .12
Paying for treatment 0.19 (−0.05 to 0.45) 1.2 (0.9 to 1.6) .13
Loss to follow-up −0.41 (−0.66 to 0.16) 0.7 (0.3 to 1.4) .10
MEMS −1.00 (−1.93 to −0.08) 0.4 (0.2 to 0.7) .03
Abbreviations: CI, confidence interval; MEMS, Medication Event Monitoring System; OR, odds ratio.
*A priori defined covariates were used. Four abstracts
65,67,71,77
included in the analyses were missing data (3 on loss to
follow-up and 4 on payment of ART).
META-ANALYSIS OF ADHERENCE TO ANTIRETROVIRAL THERAPY
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date,
94
the use of patient-directed inter-
ventions and innovative reminder sys-
tems may be desirable for some patients.
Although the World Health Organi-
zation’s “3 by 5” initiative aims to in-
crease access to ART throughout sub-
Saharan Africa, the goal is far from being
achieved. In all of the sub-Saharan Af-
rican countries included in our analy-
ses, estimates of access to ART remain
severely limited. For example, the
World Health Organization estimates
indicate that as of June 2005, the pro-
portion of patients requiring urgent ac-
cess to ART and currently receiving
therapy was 56% in Botswana, 10% in
Burkina Faso, 15.8% in Cameroon,
5.4% in Cote d’Ivoire, 3.2% in the
Democratic Republic of Congo, 13.6%
in Malawi, 8% in Nigeria, 26.5% in
Rwanda, 12.5% in South Africa, 3.2%
in Tanzania, and 56% in Uganda.
95,96
Given the apparent relatively high
level of ART adherence in Africa, one of
the most controversial program com-
ponents in developing countries is
whether there is a need for intensive
interventions such as directly observed
therapy of ART (DOT-ART). Through
observation of a patient actually taking
a dose, by a close family member or
friend to whom the patient has volun-
tarily disclosed their HIV status, DOT-
ART is proposed to influence patient out-
comes. Indeed, in settings with high HIV
status disclosure rates, community-
based DOT-ART with a patient-
nominated treatment accompagnateur or
supporter
97-99
has been reported to be fea-
sible and helps to improve or maintain
high levels of ART adherence. How-
ever, because patient outcomes may be
confounded by a constellation of ser-
vices provided by the program, com-
munity support, or other factors, the
effectiveness of community-based DOT-
ART still needs to be confirmed in well-
conducted randomized trials, which are
under way in several African countries.
Alternatively, long-term, clinic-based
DOT-ART is not likely to be feasible due
to the lifelong nature of HIV treatment
and long transportation distances in rural
settings. Patients who do not disclose
their HIV status due to fear of stigma,
discrimination, or violence will need
other adapted and culturally sensitive
innovative adherence support if they
prove to be poorly adherent to ART.
The findings of this analysis have im-
portant policy implications. First, the
expectation of poor adherence in Africa
is not an evidence-based rationale for
delaying the expansion of ART pro-
grams in resource-poor settings. Sec-
ond, given the average relatively high
levels of adherence in resource-poor set-
tings documented in this analysis, the
focus (or priority) must now be to
maintain these ART adherence rates by
increasing access to affordable ART and
establishing reliable drug supply and
distribution networks from the phar-
macy to the individual patient. Third,
understanding culturally specific bar-
riers to adherence will be important in
developing evidence-based interven-
tions targeted at the individuals with
poor ART adherence.
HIV/AIDS is the most difficult pub-
lic health challenge the world cur-
rently faces. However, adherence to
ART in Africa may not be the chal-
lenge that many predicted. Policies de-
signed to combat this pandemic must
be based on sound and timely evi-
dence. Formulating policies based on
assumptions, without seeking evi-
dence, may leave millions of individu-
als without effective interventions.
Author Affiliations: Centre for International Health and
Human Rights Studies, Toronto, Ontario (Drs Mills and
Singh); Department of Clinical Epidemiology and Bio-
statistics, McMaster University, Hamilton, Ontario (Drs
Mills, Thabane, and Guyatt); Department of Medi-
cine, Division of Clinical Pharmacology, University of
Cape Town, Cape Town, South Africa (Dr Nachega);
Northwest Institute for Bio-Health Informatics, Medi-
cal School, University of Manchester, Manchester, En-
gland (Dr Buchan); St Michael’s Hospital (Dr Orbin-
ski), Department of Medicine (Dr Wilson), University
of Toronto, Toronto, Ontario; Centre for Global Health
(Dr Attaran), Division of Infectious Diseases, Ottawa
Hospital (Dr Cooper), University of Ottawa, Ottawa,
Ontario; Department of International Health (Dr
Nachega), MPH Program (Dr Singh), Johns Hopkins
University, Bloomberg School of Public Health, Balti-
more, Md; Department of Medicine, Wake Forest Uni-
versity, Winston-Salem, NC (Dr Singh); British Co-
lumbia Centre for Excellence in HIV/AIDS, St Paul’s
Hospital, Vancouver (Ms Rachlis); Department of Epi-
demiology, London School of Hygiene and Tropical
Medicine, London, England (Dr Wu); and Epidemiol-
ogy and Prevention Interventions Center, San Fran-
cisco General Hospital, University of California, San
Francisco (Dr Bangsberg).
Author Contributions: Dr Mills had full access to all
of the data in the study and takes responsibility for
the integrity of the data and the accuracy of the data
analysis.
Study concept and design: Mills, Nachega, Orbinski,
Attaran, Rachlis, Wilson, Guyatt, Bangsberg.
Acquisition of data: Mills, Nachega, Rachlis, Wu,
Bangsberg.
Analysis and interpretation of data: Mills, Nachega,
Buchan, Singh, Rachlis, Wu, Cooper, Thabane, Guyatt,
Bangsberg.
Drafting of the manuscript: Mills, Nachega, Buchan,
Orbinski, Attaran, Singh, Rachlis, Cooper, Guyatt,
Bangsberg.
Critical revision of the manuscript for important in-
tellectual content: Mills, Nachega, Buchan, Orbinski,
Attaran, Singh, Rachlis, Wu, Cooper, Thabane, Wilson,
Guyatt, Bangsberg.
Statistical analysis: Mills, Nachega, Buchan, Rachlis,
Wu, Cooper, Thabane, Guyatt.
Obtained funding: Mills.
Administrative, technical, or material support: Mills,
Singh, Rachlis, Guyatt, Bangsberg.
Study supervision: Mills, Nachega, Orbinski, Wilson,
Guyatt, Bangsberg.
Financial Disclosures: Dr Nachega received grant sup-
port or funding, honoraria (including honoraria for con-
tinuing medical education), travel grants, and lecture
sponsorships from GlaxoSmithKline, Bristol-Myers
Squibb, and Aspen Pharmaceuticals.
Funding/Support: Dr Mills is supported by the On-
tario HIV Treatment Network and the Canadian In-
stitutes for Health Research. Dr Nachega is sup-
ported by grants AI005535901 and K23A106858201
from the US National Institutes of Health. Dr Wilson
is supported by the Canadian Institutes for Health Re-
search. Dr Bangsberg is supported by grants
AA015287, MH54907, and AI27763 from the US Na-
tional Institutes of Health and by the Doris Duke Chari-
table Foundation. The Ontario HIV Treatment Net-
work provided financial support for this study.
Role of the Sponsor: The agencies had no role in the
conduct of the study; collection, management, analy-
sis, and interpretation of the data; and preparation,
review, or approval of the manuscript.
Acknowledgment: We thank Pearl Raju, PhD (Cen-
tre for International Health and Human Rights Stud-
ies, Toronto, Ontario), and Dugald Seely, ND, MSc
(University of Toronto, Toronto, Ontario), for assis-
tance with searching and arbitration. They did not re-
ceive compensation for their work. We also thank the
authors of the original studies for assistance and clari-
fications.
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690 JAMA, August 9, 2006—Vol 296, No. 6 (Reprinted) ©2006 American Medical Association. All rights reserved.
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... Various adherence levels and associated factors were documented by previous studies conducted in different countries. For example, the ART adherence level was 55% in North America and 77% in resource-limited countries of SSA (10). Whereas, in Ethiopia, according to a systematic review of different studies, the adherence level varies from the lowest 34.8% to the highest 95.8% (11). ...
... The finding of this study is higher than adherence levels found in Yirgalem Hospital (74.2%) (27), in Jimma Hospital (72.4%) (28), and Wolaita-Sodo Hospital (74.4%) (29) in Ethiopia. It is also higher than adherence levels documented by some studies in Nigeria (73.4%) (30), at Sokodẻ Hospital in Togo (78.4%)(31), a systematic review in sub-Saharan Africa (77.0%) and in North America (55%) (10), and in Brazil (62.8%) (32). The differences in adherence levels reported by the different studies might again be due to differences in study design, adherence measurement indicators used, and patients' socio-demographic characteristics across studies. ...
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Background: Adherence to antiretroviral therapy (ART) has paramount advantages for programmatic success, including its good treatment outcomes and reduced risk of resistant viral strains transmission to the general population. There is limited evidence on the magnitude and associated factors of adherence to ART among adult PLWHA attending highly active ART (HAART) at Adare General Hospital, Southern Ethiopia. Objective: This study aimed to determine the magnitude and associated factors of adherence to ART among adult PLWHA attending (HAART) at Adare General Hospital, Southern Ethiopia. Methods: A hospital-based cross-sectional study was conducted from January 01/2018 to February 30/2018 at Adare Hospital. The participants were 370 adult people living with HIV/AIDS taking ART and who were selected by systematic random sampling technique. The data were collected by trained health professionals using a pre-tested interviewer-administered structured questionnaire. The data collected was entered into a computer and analysed using SPSS version 19. Descriptive statistics and multiple logistic regressions were applied. The significance level of association was considered at p-value <0.05. Results: The magnitude of retrospectively self-reported combined adherence (measured by dose, schedule and dietary instructions) to ART in the past seven days before the interview was 80.3%. In multivariate analysis, Sidaamu Afoo language (AOR=0.5, 95%CI: 0.21-0.99), monthly income <1,000 Ethiopian Birr (AOR=0.08; 95%CI: 0.03-0.26), not disclosing HIV status to others (AOR=0.18; 95%CI: 0.07-0.50), taking ART pills comfortably while others looking (AOR=6.0; 95%CI: 2.54-13.91) and no utilisation of reminders (AOR=0.08; 95%CI: 0.03-0.21) were factors significantly associated with combined adherence. Forgetfulness and not wanting to take ART while others are looking were major reasons to miss pills. Conclusion: Adherence to ART among adult PLWHA attending HAART at Adare Hospital was suboptimal, but still comparable with that of resource-limited settings. To maximise treatment success, considering emphasised translation to Sidaamu Afoo language, encouraging patients to be involved in any income-generating system and to reveal their HIV status for others is helpful. [Ethiop. J. Health Dev. 2020; 35(2):000-000]
... High pill burden, frequent hospital visits, side effects, and dosing restrictions are reasons that lead to fatigue and non-adherence (35). Other psychological factors which may hinder adherence include mental health issues, drug abuse, cognitive decline, and absent-mindedness (36,37). Poverty, underdevelopment, and food insecurity are systemic issues which have impeded patient adherence (19,(37)(38)(39). ...
Article
Background: Human immunodeficiency virus (HIV) drug resistance is the ability of HIV to mutate such that it reduces the ability of antiretroviral drugs to block virus replication. This can lead to suboptimal treatment outcomes, treatment failure and continued community transmission of drug resistant HIV strains. The rapidly rising HIV drug resistance rates in low- and middle-income countries pose a critical challenge to ending the HIV epidemic. In Southeast Asia, where national surveillance of HIV drug resistance is lacking, there is an urgent need to understand this public health issue to effectively curb HIV. Methods: Literature review and interviews with key informants across Southeast Asia were conducted to understand the trends of HIV drug resistance in Southeast Asia, including prevalence rates, factors causing drug resistance, and policy strategies for combating HIV drug resistance. Results: HIV drug resistance prevalence rates in Southeast Asia were generally low to moderate. The key determinants of HIV drug resistance identified relate to barriers undermining treatment adherence and retention, particularly geographical access and the cost of travelling for treatment, stigma and discrimination, and the lack of patient confidentiality at health facilities. Most Southeast Asian countries have adapted WHO treatment guidelines and were in the process of transiting to using antiretroviral drugs with higher genetic barriers to resistance. However, resource constraints and limited laboratory capacity have hindered their ability to conduct routine viral load monitoring for all patients and testing of HIV drug resistance. Conclusions: Most Southeast Asian countries are making progress in managing HIV drug resistance. However, to achieve the UNAIDS global target of maximal viral load suppression in 90% of all people receiving antiretroviral therapy, Southeast Asian countries need to address barriers to treatment adherence and retention, expand viral load testing coverage and drug resistance testing availability, and make dolutegravir available as a treatment option.
... [2,3] However, ART has to be taken as a lifelong therapy and its success depends on continual adherence to the medication regimen. [4,5] ART has improved the health of many HIV positive individuals who would have died due to this infection. [6,7] This evidence was shown in the annual number of HIV/ AIDS deaths which declined from 2.5 million in 2005 to 0.67 million in 2017. ...
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ABSTRACT Objectives: Adherence to antiretroviral therapy (ART) is an important factor required to suppress viral activities and its load in the human body. There are identified factors that determine adherence to ART and these factors have been noticed based on environments. This study compared predictors of ART adherence between the urban and rural centers within the same State in Nigeria. Material and Methods: The study was a cross-sectional analytic study involving 322 participants. Data were analyzed using Statistical Package for the Social Sciences version 20. Descriptive and inferential statistics were done with the data collected. Results: There were more adherent participants in the urban than the rural center in a ratio of 2.2:1. There was also significant difference in the predictors of adherence to ART in these two centers. The factors that were not present in both centers were: Stigma experience, family support, and sex. Conclusion: Predictors of treatment adherence vary between the urban and rural treatment centers even within the same senatorial district of a state. Therefore, it is advisable to always determine factors that predicts adherence to ART which would serve as a guide to proper treatment of the patient.
... Evaluating health outcomes for ALWHIV is critical because when they are virally suppressed, they are far less likely to spread the virus (20), and more likely to live healthier lives (21), especially during adolescence when their health, a possible explanation for the null overall study group effect on the adherence (except at 24-months), viral load, physical health and sexual risk-taking intentions outcomes. Lastly, the inclusion criteria for the Suubi + Adherence study required ALWHIV to be aged 10-16 at baseline, prescribed ART medication, and receiving HIV care and treatment at one of participating clinics. ...
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150/150 words. We examined the 5-year impact of an economic empowerment (EE) intervention on: adherence, viral suppression, sexual risk-taking intentions (primary); and physical health, educational and economic (secondary) outcomes among adolescents living with HIV in Uganda. The Suubi + Adherence study (2012–2018) randomized clinics to: (1) Control group, n = 19 clinics, n = 344 participants; (2) intervention group which received matched savings accounts, mentorship, financial management and, business development training, n = 20 clinics, n = 358 participants. Participants completed post-baseline assessments at 12-, 24-, 36-, and 48-months. No significant differences in viral load, sexual risk-intentions and physical health perception were observed. The intervention group had better adherence (at 24-months) (Contrast=-0.28; 95% CI: -0.55, -0.004), higher school enrolment (OR = 2.18; 95% CI:1.30, 3.66); reported savings OR = 2.03 (1.29, 3.18) and higher savings (Contrast = 0.40; 95% CI:0.10, 0.70) than controls at 48-months. The EE intervention was efficacious in improving adherence, school enrolment, and economic outcomes creating opportunities for improved overall health among adolescents living with HIV.
... Evidence indicated that when ART adherence is below 95%, patients are susceptible to developing drug resistance and lower immunity [35]. The pooled proportion of ART adherence in sub -Saharan Africa countries was 75% [47]. This means sub-Saharan Africa countries had poor ART adherence. ...
Article
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United Nations program on HIV/AIDS 90-90-90 ambitious goal recommends 90% of people living with HIV and taking antiretroviral therapy should achieve viral suppression by 2020. However, virological failure is still a global public health problem, especially in sub-Saharan African countries. Thus, this systematic review and meta-analysis aimed at estimating the burden of virological failure and its associated factors among peoples living with HIV in sub-Saharan Africa. We searched Google Scholar, PubMed, Cochrane Library, and Scopus for studies that reported virologic failure and its associated factors. I-squared statistics and Egger's statistical test were used to detect heterogeneity and publication bias respectively. The pooled prevalence of virological failure was estimated using the DerSimonian-Laird random-effects model. Sensitivity analysis was done to check the presence of outlier results included in the studies. The estimated pooled prevalence of virological failure was 1.7.25%. Lower Adherence to ART drugs,longer ART duration, lower CD4 count,and being co-infected with TB were significantly associated with the pooled estimate of virological failure.Virological failure was found to be high in sub-Saharan Africa. Adherence, duration of ART, CD4 + count, and TB co-infection were the significant factors associated with the pooled estimate of virological failure. Therefore, to achieve the 90-90-90 target and sustainable development goal 3 policymakers should design mechanisms to improve ART adherence, and early detecting and prevent opportunistic infections such as TB.
... Evidence indicated that when ART adherence is below 95%, patients are susceptible to developing drug resistance and lower immunity [35]. The pooled proportion of ART adherence in sub -Saharan Africa countries was 75% [47]. This means sub-Saharan Africa countries had poor ART adherence. ...
... [11][12][13] Furthermore, adherence to ART and its determinants differ across regions and population groups, necessitating contextspecific non-adherence profiles. 14,15 Most studies show that adherence to ART is higher in children compared to other groups, with near-perfect rates of 95% seen in about 80% of the HIV-infected children. 16,17 All women (including pregnant women) are at a higher risk of non-adherence than men, 18 and studies on pregnant women show discrepancies depending on location (rural or urban) and healthcare setting (public or private). ...
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Background: Since the scale-up of antiretroviral therapy (ART) services in Burkina-Faso, achieving an AIDS-free generation depends on optimal ART adherence. However, no data exists on the population group differences on the level of ART adherence in Burkina-Faso. This study analyzes ART adherence among pregnant-and breastfeeding-women, non-pregnant women, and men in Burkina-Faso. Methods: From December 2019 to March 2020, a cross-sectional study among adult HIV-infected patients in Burkina-Faso, belonging either to the active file or the Prevention of Mother-To-Child Transmission programs was conducted. An analysis was performed and adherence was measured based on the number of times, patients did not meet the number of doses prescribed and did not take the ART treatment in the month prior to the survey. Logistic-regression models were used to identify factors associated with poor ART adherence and the adjusted odds ratios (aORs) with their 95% confidence intervals (95% CI) were reported. Results: The prevalence of good adherence was higher in the group of pregnant-and breastfeeding-women (86.6%, n = 112) compared to the other groups (73.1%, n=1017 in non-pregnant women and 72.0%, n = 318 in men). No association was found between ART adherence and the socio-demographic, clinical, and therapeutic characteristics of pregnant-and breastfeeding-women and men groups. However, non-pregnant women with a high level of education (aOR = 1.70; 95% CI: 1.16-2.49), having ever belonged to a support group (aOR= 1.47; 95% CI: 1.07-2.04), not having income-generating occupations (aOR= 1.53; 95% CI: 1.11-2.12), and in advanced clinical stage (aOR= 1.42; 95% CI: 1.06-1.91) were more susceptible to have poor adherence compared to their pairs. Conclusion: Findings showed a large difference in ART adherence among pregnant-and breastfeeding-women, non-pregnant women and men and highlight the need for differentiated healthcare delivery according to population while specifically considering addressing the interest in early initiation of treatment and the benefit of support groups meeting.
... 10−13 There is a specific group of patients that do not follow to antiretroviral medications and include adolescents, 10 pregnant women, 11 and others in high-, middle-, and low-income countries. 11,12 Other barriers to adherence have been reported, including forgetfulness, stigma, adverse drug reactions, and competing responsibilities. 12−14 Long-acting (LA) injectable ARVs, potentially administered less frequently or on monthly basis, have the capability to follow the particular drug therapy and increase opportunities for therapeutic or prophylactic treatment. ...
Article
The focus of present work was to synthesize prodrugs of dolutegravir (DTG) for ultra-long delivery purpose. The prodrug was synthesized by esterification of hydroxyl group with carboxyl group of fatty acid (lauric or myristic acid). The prodrugs were characterized by differential scanning calorimetry, X-ray powder diffraction, nuclear magnetic resonance, Fourier transformed infrared, near infrared-chemical imaging, pH-solubility, partition coefficient, and stability (solid and liquid). Stability studies were performed by exposing the powder drugs to 40°C/75% RH for three months and buffer solutions at room temperature for 72 h. The prodrugs and drug were formulated into in-situ implant using biodegradable polymer. Thermal, spectral, and diffractometric data indicated formation of new chemical and solid forms. Formation of prodrugs resulted in lowering of melting point of DTG from 191.1°C to 163.7 and 140.7°C for DTG-Laurate and DTG-Myristate prodrugs, respectively. A decrease in solubility of 18.2-115.9 and 124.5-1594.9 folds was observed for DTG-Laurate and DTG-Myristate, respectively compared to DTG. Similarly, the prodrugs were highly lipophilic compared to DTG. Solid-state and pH-stability profiles of DTG and prodrugs were comparable. Implant formulation released 60.1% in 77 days compared to 95.6% in 35 days in the case of DTG-Myristate and DTG, respectively. In summary, combining prodrug and drug delivery approaches can be utilized for delivering drug for ultra-long period.
Article
Background Antiretroviral therapy (ART) has potential to eliminate perinatal HIV infections, but adherence to ART in late pregnancy and postpartum is often suboptimal. Intimate partner violence (IPV) may influence non-adherence among perinatal women living with HIV (WWH), but few quantitative studies have examined this over time or explored mechanisms for this association. Methods We used secondary data from a parent trial in Johannesburg comprising WWH from the control arm (n=63) and WWH ineligible for the trial (n=133). Trained nurse researchers administered questionnaires at first antenatal visit on past-year psychological, physical, and/or sexual IPV (WHO instrument), socio-demographics (age, food security, education), and perinatal common mental symptoms of depression (Hospital Anxiety and Depression Screener-d); anxiety (HADS-a); post-traumatic stress disorder (PTSD; Harvard Trauma Questionnaire). At endline visit 2-4 months postpartum, nurse researchers assessed self-reported ART adherence using a visual analog scale (with ≥95% considered “good”). We fitted structural equation models (SEM) in MPlus to explore direct and indirect effects of IPV on ART adherence. Results Of 196 perinatal WWH, 53.1% reported IPV exposure at baseline. The majority of participants (85.7%) had good perinatal ART adherence. In adjusted models, IPV at baseline was associated with halved odds of good adherence (aOR=0.51, 95%CI=0.20-0.96). IPV was associated with higher adjusted odds of probable depression (aOR=4.64), anxiety (aOR=2.85), and PTSD (aOR=3.42). In SEM, IPV had a direct (standardized coef=-0.22) and indirect effect (coef=-0.05) on ART via common mental disorders. The total effect of IPV on perinatal adherence was of moderate size (coef= -0.27) and the model had good fit (CFI=0.972; TLI=0.969; RMSEA=0.045; SRMR=0.076). Conclusion IPV was longitudinally associated with perinatal ART non-adherence in part due to its relationship with mental health symptomology. Addressing IPV within clinical care has potential to improve perinatal mental health, maternal HIV outcomes, and HIV-free infant survival.
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La simulation est devenue dans la dernière décennie un outil essentiel du traitement statistique de modèles complexes et de la mise en oeuvre de techniques statistiques avancées, comme le bootstrap ou les méthodes d'inférence simulée. Ce livre présente les éléments de base de la simulation de lois de probabilité (génération de variables uniformes et de lois usuelles) et de leur utilisation en Statistique (intégration de Monte Carlo, optimisation stochastique). Après un bref rappel sur les chaînes de Markov, les techniques plus spécifiques de Monte Carlo par chaînes de Markov (MCMC) sont présentées en détail, à la fois du point de vue théorique (validité et convergence) et du point de vue de leur implémentation (accélération, choix de paramètres, limitations). Les algorithmes d'échantillonnage de Gibbs sont ainsi distingués des méthodes générales de Hastings-Metropolis par leur plus grande richesse théorique. Les derniers chapitres contiennent un exposé critique sur l'état de l'art en contrôle de convergence de ces algorithmes et une présentation unifiée des diverses applications des méthodes MCMC aux modèles à données manquantes. De nombreux exemples statistiques illustrent les méthodes présentées dans cet ouvrage destiné aux étudiants de deuxième et troisième cycles universitaires en Mathématiques Appliquées ainsi qu'aux chercheurs et praticiens désirant utiliser les méthodes MCMC. Monte Carlo statistical methods, particularly those based on Markov chains, are now an essential component of the standard set of techniques used by statisticians. This new edition has been revised towards a coherent and flowing coverage of these simulation techniques, with incorporation of the most recent developments in the field. In particular, the introductory coverage of random variable generation has been totally revised, with many concepts being unified through a fundamental theorem of simulation There are five completely new chapters that cover Monte Carlo control, reversible jump, slice sampling, sequential Monte Carlo, and perfect sampling. There is a more in-depth coverage of Gibbs sampling, which is now contained in three consecutive chapters. The development of Gibbs sampling starts with slice sampling and its connection with the fundamental theorem of simulation, and builds up to two-stage Gibbs sampling and its theoretical properties. A third chapter covers the multi-stage Gibbs sampler and its variety of applications. Lastly, chapters from the previous edition have been revised towards easier access, with the examples getting more detailed coverage. This textbook is intended for a second year graduate course, but will also be useful to someone who either wants to apply simulation techniques for the resolution of practical problems or wishes to grasp the fundamental principles behind those methods. The authors do not assume familiarity with Monte Carlo techniques (such as random variable generation), with computer programming, or with any Markov chain theory (the necessary concepts are developed in Chapter 6). A solutions manual, which covers approximately 40% of the problems, is available for instructors who require the book for a course. oui
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Background: Medication nonadherence in the treatment of chronic diseases compromises the effectiveness of therapy. Little information is available about the extent of medication adherence or determinants of medication adherence in HIV disease, an issue of increasing importance in this new therapeutic era of combination antiretroviral therapy. Methods: We studied 244 HIV-infected Medicaid-insured patients attending an HIV hospital-based clinic regarding the extent of and predictors of adherence to antiretroviral therapy and Pneumocystis carinii pneumonia (PCP) prophylaxis. Patients were asked to report medications being taken, patterns of use, and knowledge and attitudes about HIV therapies. Medical record report of type, dose, and frequency of medication was compared with self-report using the kappa statistic. Urine sulfamethoxazole assay was obtained from patients prescribed sulfamethoxazole-trimethoprim. Results: Among patients prescribed antiretroviral therapy, 60% reported greater than or equal to 80% adherence in the previous 7 days; 49% reported greater than or equal to 80% adherence with PCP prophylaxis in the previous seven days. Seventy-nine percent of patients who reported taking daily sulfamethoxazole-trimethoprim had detectable urinary sulfamethoxazole. In multivariate analysis, greater than or equal to 80% adherence to antiretroviral therapy was associated with taking medication less than or equal to twice a day (odds ratio [OR] = 1.44; 95% confidence interval [CI], 1.01, 1.96), being likely to take medication when not at home, (OR = 1.41; 95%CI, 1.04, 2.00) and patients' belief in their ability to adhere to therapy (OR = 1.57; 95%CI, 1.13, 2.17). For PCP prophylaxis, greater than or equal to 80% adherence was associated with presence of family (OR = 2.39; 95%CI, 1.01, 5.63) and patients' belief in their ability to adhere to therapy (OR = 2.87; 95%CI, 1.44-1.78). Sociodemographic characteristics and belief in the efficacy of medications were not associated with adherence. Conclusions: A relatively low level of adherence to antiretroviral therapy and PCP prophylactic regimens was found. Although our results are principally from patients receiving antiretroviral monotherapy, these findings may have important implications for patients receiving highly active antiretroviral therapy (HAART). Decreasing the complexity of antiretroviral regimens, and working with patients to modify identified barriers to adherence may improve effectiveness of medications and prolong survival.
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Objective: To examine the predictors of antiretroviral adherence among HIV-infected adults, with a particular focus on advancing age, neuropsychological dysfunction, and substance abuse. Design: Prospective observational design. Methods: Participants were 148 HIV-infected adults between the ages of 25 and 69 years, all on a self-administered antiretroviral regimen. Medication adherence was tracked over a one-month period using an electronic monitoring device (medication event monitoring system caps). All participants completed a comprehensive battery of neuropsychological tests as well as a structured psychiatric interview. Results: The mean adherence rate for the entire cohort was 80.7%, with older patients (≥ 50 years) demonstrating significantly better medication adherence than younger patients (87.5 versus 78.3%). Logistic regression analyses found that older patients were three times more likely to be classified as good adherers (defined as ≥ 95% adherent). Neurocognitive impairment conferred a 2.5 times greater risk of poor adherence. Among the older patients, those who were classified as poor adherers performed significantly worse on neuropsychological testing, particularly on measures of executive function and psychomotor speed. Current drug abuse/dependence, but not current alcohol abuse/dependence, was also associated with sub-optimal medication adherence. Conclusion: Although older age is associated with higher rates of antiretroviral adherence, older participants who were cognitively impaired showed disproportionate difficulty in adequately adhering to their medication regimen. As such, efforts to detect neuropsychological dysfunction, particularly among older patients, and a thorough assessment of substance abuse, appear to be essential for the effective treatment of HIV-infected adults.
Chapter
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Two models for study-to-study variation in a meta-analysis are presented, critiqued and illustrated. One, the fixed effects model, takes the studies being analysed as the universe of interest; the other, the random effects model, takes these studies as representing a sample from a larger population of possible studies. With emphasis on clinical trials, this paper illustrates in some detail the application of both models to three summary measures of the effect of an experimental intervention versus a control: the standardized difference for comparing two means, and the relative risk and odds ratio for comparing two proportions.