AIDS Care
Psychological and Socio-medical Aspects of AIDS/HIV
ISSN: 0954-0121 (Print) 1360-0451 (Online) Journal homepage: https://www.tandfonline.com/loi/caic20
Improved long-term antiretroviral treatment
outcomes amongst patients receiving communitybased adherence support in South Africa
Geoffrey Fatti, Eula Mothibi, Najma Shaikh & Ashraf Grimwood
To cite this article: Geoffrey Fatti, Eula Mothibi, Najma Shaikh & Ashraf Grimwood (2016)
Improved long-term antiretroviral treatment outcomes amongst patients receiving
community-based adherence support in South Africa, AIDS Care, 28:11, 1365-1372, DOI:
10.1080/09540121.2016.1191605
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AIDS CARE, 2016
VOL. 28, NO. 11, 1365–1372
http://dx.doi.org/10.1080/09540121.2016.1191605
Improved long-term antiretroviral treatment outcomes amongst patients
receiving community-based adherence support in South Africa
Geoffrey Fatti, Eula Mothibi, Najma Shaikh and Ashraf Grimwood
Kheth’Impilo, Cape Town, South Africa
ABSTRACT
ARTICLE HISTORY
Retaining high levels of patients in care who are virally suppressed over long treatment periods has
been an important challenge for antiretroviral treatment (ART) programmes in sub-Saharan Africa,
the region having the highest HIV burden globally. Clinic-linked community-based adherence
support (CBAS) programmes provide home-based adherence and psychosocial support for ART
patients. However, there is little evidence of their longer-term impact. This study assessed the
effectiveness of CBAS after eight years of ART. CBAS workers are lay healthcare personnel
providing regular adherence and psychosocial support for ART patients and their households
through home visits addressing household challenges affecting adherence. A multicentre cohort
study using routinely collected data was undertaken at six public ART sites in a high HIVprevalence South African district. Patient retention, loss to follow-up (LTFU), viral suppression
and CD4 cell restoration were compared between patients with and without CBAS, using
competing-risks regression, linear mixed models and log-binomial regression. 3861 patients were
included, of whom 1616 (41.9%) received CBAS. Over 14,792 patient-years of observation, the
cumulative incidence of LTFU was 37.3% and 46.2% amongst patients with and without CBAS,
respectively, following 8 years of ART; adjusted subhazard ratio (CBAS vs. no CBAS) = 0.74 (95%
CI: 0.66–0.84; P < .0001). Amongst patients on ART for 6.5–8 years, proportions not achieving viral
suppression were 11.4% and 19.4% in patients with and without CBAS, respectively; adjusted risk
ratio = 0.47 (95% CI: 0.26–0.86; P = .015). Annual CD4 cell increases from baseline were 62.8 cells/
µL/year and 51.5 cells/µL/year amongst patients with and without CBAS, respectively, after 6.5
years or more (P = .034). After adjustment, annual CD4 cell recovery was 15.1 cells/µL/year (95%
CI: 2.7–27.6) greater in CBAS patients (P = .017). ART patients who received CBAS had improved
long-term patient retention, viral suppression and immunological restoration. CBAS is an
intervention that can improve longer-term ART programme outcomes in resource-limited settings.
Received 18 September 2015
Accepted 16 May 2016
KEYWORDS
Antiretroviral treatment;
community-based adherence
support; South Africa; HIV;
outcomes; lay health workers
Introduction
Excellent adherence to antiretroviral treatment (ART) is
vital for treatment success, to prolong survival and to
prevent the development of drug resistant mutations
(Nachega et al., 2011). Long-term data show that adherence tends to wane with time, and sustained efforts are
required to ensure good long-term adherence to ART
(Nachega, Mills, & Schechter, 2010).
Sub-Saharan Africa remains the region with the highest burden of HIV globally, having 71% of all people living with HIV (UNAIDS, 2014b). The impact of ART has
made dramatic improvements in life expectancy in many
sub-Saharan countries (UNAIDS, 2015). However, sustaining patient retention over long treatment periods
has been a particular challenge to ART programmes,
with a recent meta-analysis reporting average 5-year
retention at 56% (Fox & Rosen, 2010, 2015). Viral suppression also decreases over increased treatment
durations, with a review indicating only 63% of patients
achieve viral suppression (by intention-to-treat) after 24
months (Barth, van der Loeff, Schuurman, Hoepelman,
& Wensing, 2010). Rising levels of HIV drug resistance
is also occurring (Aghokeng et al., 2011; Hamers, Sigaloff, Kityo, Mugyenyi, & de Wit, 2013). As primary
healthcare facilities delivering ART have become increasingly overburdened with the large number of ART
patients, the quality of clinic adherence counselling has
reduced and increasing numbers of patients have
become lost to follow-up (LTFU) (Bekker et al., 2014;
Cornell et al., 2010).
To address these challenges, and considering the
severe shortage of professional healthcare workers in
the region (Bärnighausen, Bloom, & Humair, 2007), lay
community-based health worker programmes have
been established to support sub-Saharan ART patients.
CONTACT Geoffrey Fatti
geoffrey.fatti@khethimpilo.org
Supplemental data for this article can be accessed at 10.1080/09540121.2016.1191605.
© 2016 Informa UK Limited, trading as Taylor & Francis Group
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G. FATTI ET AL
A review of these programmes has shown favourable
impact on short-term ART programme outcomes
(Wouters, Van Damme, van Rensburg, Masquillier, &
Meulemans, 2012). However, there are little available
data of the longer-term outcomes of ART programmes
in the region, and evidence regarding the longer-term
impact of community-based support programmes is
particularly lacking.
South Africa has the world’s largest ART programme
with over 2.6 million people who have initiated ART
(UNAIDS, 2014b). The aim of this study was to assess
the longer-term effectiveness of a clinic-linked community-based adherence support (CBAS) programme for
ART patients in a high HIV prevalence district of
South Africa. Clinical, immunological and virological
outcomes were compared after eight years of ART
between patients who received and did not receive
CBAS at six public healthcare facilities.
Methods
CBAS intervention
CBAS workers are clinic-linked, lay healthcare personnel
who provide adherence support through addressing psychosocial barriers to adherence amongst ART patients,
and undertake home visits and refer to social services
and others to address these challenges (see programme
description, supplemental online material). Support
starts from the time of pre-ART preparation and continues throughout long-term care. During the initial
home assessment, household issues are assessed including tuberculosis (TB) screening and HIV testing status
of household members. The psychosocial barriers to
adherence including nutrition security, substance
abuse, depression, domestic violence, non-disclosure
and stigma are assessed and addressed. Issues affecting
adherence are discussed at clinic multidisciplinary team
meetings, and interventions agreed by the team are
implemented by the CBAS worker or social worker.
Following the first visit, patients are visited weekly for
a month, and then on a monthly basis. Once stable,
patients are visited at least quarterly. CBAS workers provide one-on-one counselling regarding adherence and
psychosocial problems, and follow-up on progress
made regarding referrals to social workers. Health promotion education and symptom screening for TB and
opportunistic infections is performed, with referral to
clinics if indicated. CBAS workers also advise on medication storage and do adherence checks. Where patients
are not comfortable with home visits or if they work,
adherence and psychosocial support is provided at the
clinic.
CBAS workers have a specific geographic area which
they support. Each worker is assigned 80–120 patients,
and tracks patients with a paper-based diary. Visit
details, including interventions, are recorded by the
CBAS worker and captured electronically by clinicbased data capturers. Patients who default clinical visits
are also traced by CBAS workers. Each community
worker reports to an area coordinator who oversees the
work quality through audits and home visits with the
community worker.
Study design and setting
A multicentre cohort study utilising routine clinical data
was conducted at six ART facilities in iLembe district,
KwaZulu-Natal, South Africa. All facilities are primary
healthcare facilities. Two facilities are located in rural
areas and the remainder are in urban/semi-urban
areas. In 2012, the district antenatal HIV prevalence
rate was 37.4% (South African National Department of
Health, 2013). All facilities are supported by Kheth’Impilo, a non-governmental organisation that supports
the South African Department of Health. Kheth’Impilo
provides clinical staff and innovations to strengthen public health systems.
Inclusion criteria, outcomes and definitions
Adults with CD4 cell counts ≤200 cells/µL and/or a
World Health Organization (WHO) stage IV defining
illness were eligible to start ART as per the 2004 South
African national treatment guidelines (South African
National department of Health, 2004). From April
2010, ART eligibility criteria were expanded to include
adults with CD4 cell counts ≤350 cells/µL if they were
pregnant or diagnosed with active TB (South African
National department of Health, 2010).
All adults (≥16 years of age) not previously enrolled
for ART starting triple-drug ART between 1 January
2005 and 30 September 2010 with documented date of
birth, gender and date of starting ART were included.
Database closure was 30 September 2014.
Patients were allocated to receive CBAS during the
pre-treatment preparation period by the community
area co-ordinator if community workers were active
in the area of the patients home, community worker
capacity was available, and if consent was obtained.
Clinical and socioeconomic factors were not criteria
in the choice of allocation of patients to receive
CBAS or not. For analyses, patients were assigned to
the CBAS group if they were allocated to and received
support from a named CBAS worker since the start of
ART. Receipt of CBAS was captured in the clinical
AIDS CARE
database by clinic-based data capturers following the
ART initiation visit. All patients (CBAS and nonCBAS) received three group training sessions regarding HIV education and adherence prior to starting
ART.
Outcome measures were: patient retention in care
eight years after starting ART, LTFU after 8 years,
reported all cause-mortality, proportions of patients
not achieving viral suppression (viral load ≥400
copies/mL) amongst patients having a viral load
measurement between 6.5 and 8 years after starting
ART, and CD4 cell slope amongst patients with a
recorded baseline CD4 cell count and one or more
measurements between 6.5 and 8 years of ART. Patient
losses (patient attrition) was defined as a combined
endpoint of mortality or LTFU. Patient deaths were
recorded as reported to clinic healthcare workers. All
patients visited the clinic on a frequency determined
by clinic professional staff (generally monthly), and a
patient was defined as LTFU if no visits to the clinic
occurred for 180 days or more (Chi et al., 2011).
Patients transferring to other facilities were censored
on the date of last clinic visit. Laboratory measurements were performed by the South African National
Health Laboratory Service.
Data collection and statistical methods
Individual-level clinical data were collected prospectively
by designated site-based data capturers at each patient
clinic visit using standardised custom-designed electronic databases, which were regularly pooled to a central
data warehouse using standard operating procedures.
Regular data cleaning and quality control procedures
were implemented.
1367
Baseline characteristics were compared between
groups using the Wilcoxon rank-sum and Pearson’s χ 2
tests for continuous and categorical data, respectively.
Outcome analyses were by intention-to-treat ignoring
subsequent changes in exposure status. Kaplan–Meier
estimates, the logrank test and multivariable Cox’s proportional hazards regression were used to analyse time
till patient attrition and retention in care. Time to mortality and LTFU were analysed using cumulative incidence functions and competing-risks regression using
the method of Fine and Gray (1999; Schoni-Affolter
et al., 2011). The number needed to treat to prevent a
case of LTFU were calculated as appropriate for timeto-event outcomes (Altman & Andersen, 1999). Multivariable log-binomial regression was used to analyse
viral suppression on ART. Mixed-effects linear models
were used to analyse CD4 cell slope (Boscardin, Taylor,
& Law, 1998). Separate models were produced for CD4
cell increases from the start of ART, and using the six
month CD4 cell count as a baseline.
The following a priori specified covariates that were
plausible confounders were eligible to be included in
multivariable regression models to control for confounding: baseline age, gender, baseline CD4 cell count, baseline WHO clinical stage, baseline TB treatment, year of
starting ART, pregnancy when starting ART, time on
ART, urban/rural site. Covariates were included in multivariable models where their inclusion produced a ≥10%
shift in the point estimate of the prime exposure variable
(receipt of CBAS) (Maldonado & Greenland, 1993).
Modification of the effect of CBAS on outcomes was
assessed by stratifying effect measures by plausible modifiers. Data were analysed using Stata (TM) version 13.1
(Statacorp, College Station, TX, USA). Permission for
the study was granted by the University of Cape Town
Health Research Ethics Committee.
Results
Figure 1. Kaplan–Meier estimates of patient retention in care
after starting ART amongst patients who received and did not
receive CBAS.
3861 patients were included, of whom 1616 (41.9%)
received CBAS and 2245 (58.1%) did not. Characteristics
of patients included at the start of ART are shown in
Table 1. Patients who received CBAS had a higher proportion with advanced (stages III or IV) WHO clinical
stage disease (610/1225; 48.6%) compared to patients
who did not receive CBAS (643/1665; 38.6%);
P < .0001. Patients who started CBAS had a higher
proportion who received concomitant TB treatment at
baseline. A slightly higher proportion of patients who
received CBAS were from rural settings.
The total observation time was 14,792 patient-years.
During the study period, 50/1616 (3.1%) and 77/2245
(3.4%) patients who received and did not receive
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G. FATTI ET AL
Table 1. Characteristics of patients at the start of ART.
Median age, years (IQR)
(n = 3861; 0% missing)
Male gender, n (%)
(n = 3861; 0% missing)
Median CD4 cell count, cells/µL (IQR)
(n = 3762; 3% missing)
CD4 cell count < 100 cells/µL, n (%)
(n = 3762; 3% missing)
WHO stage
(n = 2920; 24% missing)
Stages I and II, n (%)
Stages III and IV, n (%)
Baseline TB, n (%)
(n = 2766; 28% missing)
Pregnancy amongst women, n (%)
(n = 2005; 22% missing)
Year of starting ART, median year (IQR)
(n = 3861; 0% missing)
Rural clinics, n (%)
(n = 3861; 0% missing)
With CBAS
(n = 1616)
Without CBAS
(n = 2245)
P-value
34.9 (29.8–41.4)
35.2 (29.6–43.1)
.62
504 (31.2%)
773 (34.4%)
.035
149 (98–193)
151 (100–188)
.48
409 (25.7%)
541 (25.0%)
.62
<.0001
645 (51.4%)
610 (48.6%)
124 (8.3%)
1022 (61.4%)
643 (38.6%)
139 (10.9%)
.022
47 (5.3%)
54 (4.8%)
.58
2009 (2007–2010)
893 (55.3%)
2009 (2008–2010)
1115 (49.7%)
<.0001
.001
Note: CBAS, community-based adherence support; WHO, World Health Organization; ART, antiretroviral treatment; IQR, interquartile range.
Figure 2. Cumulative incidence of loss to follow-up after starting
ART amongst patients who received and did not receive CBAS.
CBAS, respectively, were reported as having died
(P = .56). A further 404/1566 (25.8%) and 655/2168
(30.2%) of patients who received and did not receive
CBAS, respectively, were LTFU (P = .003). Following 8
years of ART, the Kaplan–Meier estimates of patient
retention amongst patients with and without CBAS
were 61.8% and 56.8%, respectively (P < .0001) (Figure
1). After controlling for confounding, overall patient
attrition was reduced by 25% amongst patients who
received CBAS, adjusted hazard ratio=0.75 (95% CI:
0.66–0.86; P < .0001) (Figure 3).
After 8 years of ART, the Fine and Grey cumulative
incidence estimates of LTFU were 37.3% and 46.2%
amongst patients who received and did not receive
CBAS, respectively (P < .0001) (Figure 2). After controlling for confounding, LTFU was reduced by 26%
Figure 3. Adjusted outcome measures (patients with CBAS vs.
patients without support). Estimates for attrition, loss to followup, and unsuppressed viral load are adjusted hazard ratio,
adjusted subhazard ratio, and adjusted risk ratio, respectively.
Horizontal bars are 95% confidence intervals.
amongst patients who received CBAS, adjusted subhazard ratio (asHR)= 0.74 (95% CI: 0.66–0.84; P < .0001)
(Figure 3) (see table, supplemental online material).
The reduction in LTFU associated with CBAS was particularly evident amongst patients with advanced clinical
disease, asHR=0.58 (95% CI: 0.47–0.73; P < .0001); and
amongst pregnant women, asHR = 0.34 (95% CI: 0.12–
0.98; P = .045). The numbers needed to treat to prevent
one case of LTFU after two years was 10.4 (95% CI:
7.3–18.2). Mortality was equivalent between patients
with and without CBAS; asHR=0.88 (95% CI: 0.61–
1.25; P = .48).
Amongst patients on ART for 6.5 years-8 years, the
proportions who had unsuppressed viral loads (utilising
AIDS CARE
1369
the most recent available measurement). Figure 4 shows
modelled CD4 cell trajectories. Median annual CD4 cell
slopes from baseline amongst patients with and without
CBAS were 62.8 cells/µL/year (IQR: 35.3–87.6) and 51.5
cells/µL/year (IQR: 26.7–71.1), respectively (P = .034)
(see figure, supplemental online material). After adjustment for covariates, annual CD4 increase since starting
ART was 15.1 cells/µL/year (95% CI: 2.7–27.6) greater
amongst CBAS patients (P = .017) (crude difference =
13.6 cells/µL/year [95% CI: 1.0–26.3; P = .034]) (see
table, supplemental online material). Using the CD4 cell
measurement at 6 months as a baseline, the adjusted
annual CD4 slope between 6.5 and 8 years of ART was
19.1 cells/µL/year (95% CI: 3.5–34.8) greater amongst
CBAS patients (P = .016).
Discussion
Figure 4. Modelled CD4 cell trajectories from: (a) CD4 cell count
at the start of ART, and (b) CD4 cell count 6 months after starting
ART. The number of patients with one or more CD4 cell count
measurements during each preceding one year period is
indicated.
the most recent measurement) in patients who received
and did not receive CBAS were 11.4% (95% CI: 8.0%15.5%; n = 299 patients; proportion suppressed=88.6%)
and 19.4% (95% CI: 11.1%–30.5%; n = 72 patients;
proportion suppressed =80.6%), respectively (P = .067).
After controlling for confounding, the risk of having
an unsuppressed viral load on long term ART was
significantly lower amongst patients who received
CBAS; adjusted risk ratio=0.47 (95% CI: 0.26–0.86;
P = .015) (Figure 3) (crude risk ratio=0.58 [95% CI:
0.33–1.03; P = .064]) (see table, supplemental online
material).
CD4 cell analyses were performed amongst patients
with recorded CD4 cell counts at the start of ART and
one or more measurement between 6.5 and 8 years of
ART. Median CD4 cell increases from baseline amongst
patients with and without CBAS were 425 cells/µL
(IQR: 243–596; n = 288 patients) and 350 cells/µL (IQR:
178–483; n = 50 patients), respectively (P = .025) (using
This study provides unique data on the longer-term
impact of CBAS for ART patients in a very high HIV
prevalence setting in sub-Saharan Africa. Patients who
received CBAS had improved retention and viral suppression up till 8 years of ART, and improved longterm immunological restoration.
The effect of CBAS is likely mediated through a variety of mechanisms: Firstly, improved understanding of
HIV and the importance of adherence through counselling improve motivation and behaviour skills related to
ART adherence (Fisher, Fisher, Amico, & Harman,
2006). Secondly, greater disclosure, reductions in
perceived stigma, and improvement in psychosocial
problems likely contribute to improved adherence
(Hodgson et al., 2014; Lowther, Selman, Harding, & Higginson, 2014). Thirdly, community support widens the
“community safety net” and harnesses social capital, a
powerful social force determining ART patient retention
(Foster, 2007; Hickey et al., 2015; Ware et al., 2009).
Patient retention is one of the most important determinants of the impact of ART programmes, and has
been an important challenge in sub-Saharan Africa
(Fox & Rosen, 2015). LTFU is the most important
cause of patient attrition. Psychosocial support through
home visits act as powerful prevention action against
patient attrition (Wouters et al., 2012). CBAS workers
also actively trace defaulting patients in the community,
which has been shown to improve ART outcomes
(Kabore et al., 2010), and is a service which may otherwise be unavailable.
ART patients need to be empowered to self-manage
their chronic illness in low-income settings (Wouters
et al., 2012). Patient empowerment encompasses a wide
range of educational and counselling activities to increase
patients’ chronic disease management skills. Without
1370
G. FATTI ET AL
these, patients are more likely to discontinue treatment and
clinic visits or to develope viral rebound, particularly as
treatment adherence tends to wane with increasing duration of treatment (Nachega et al., 2010). Overburdened
staff in under-resourced primary healthcare settings have
a limited understanding of their counselling role, and are
constrained in being able to deliver the patient-centred
care to empower patients to improve their chronic disease
management skills (Stein et al., 2008).
CBAS is an important link between primary healthcare facilities and the community, integrates and streamlines delivery of treatment and holistic patient care, and
aids the decentralisation of ART delivery to the community (Decroo et al., 2013). CBAS meets the emerging
need associated with chronic HIV care, where due to
the crippling shortage of professional healthcare workers
and the growing caseload of people needing to be maintained on ART, professional workers roles are becoming
progressively limited to technical medical and nursing
tasks (Wouters et al., 2012). The UNAIDS Strategy of
reaching 90–90–90 by 2020 (UNAIDS, 2014a) will
require South Africa to have over 5 million people on
ART. Reaching 90% retention with 90% viral suppression will be very challenging and may more likely be
attained with an emphasis on CBAS and the rollout of
chronic treatment clubs at facilities and in communities.
This data provides evidence of the efficacy of this community-based approach to adherence and requires consideration if South Africa is to reach these targets.
Challenges faced by the CBAS programme include the
rural context of many patient’s residences and long distances between the home and clinic with inadequate
transport systems; poor baseline patient knowledge
regarding HIV/AIDS, and cultural preferences for traditional medication.
The strengths of the study include that prospective,
individual-level cohort data were collected enabling controlling for patient-level factors associated with outcomes. A consistency of improved outcomes (patient
retention, LTFU, viral suppression and immunological
restoration) in the intervention group was observed.
Limitations of the study include the non-random allocation of patients to groups with the potential for selection bias and unmeasured or residual confounding.
Patients were allocated to receive the intervention on
the basis of availability of community workers, geography of patient’s residence, and patient consent. As consent was required to receive CBAS, it is possible that
consenting patients were more committed to treatment
and were more likely to have disclosed their HIV status
to family members. The proportions of patients who
declined CBAS (or who opted to receive CBAS in the
clinic instead of at home) were not available in the
dataset. In addition, the use of routine data may have
resulted in information bias. Of note, however, is that
nonrandomised studies of this type of intervention
using routine health systems data are more pragmatic
and suitable in low-income settings, as randomised
experiments are costly, and suitable and feasible for
only a small proportion of HIV interventions (Thomas,
Curtis, & Smith, 2011). Also, the pre-study probability
of these findings was high, as the results concur with
studies of shorter-term outcomes (Fatti, Meintjes, Shea,
Eley, & Grimwood, 2012; Wouters et al., 2012).
Although it was expected as part of the programme
that all patients commencing CBAS were to receive
long-term CBAS after commencing CBAS, the duration
of support that all patients included in the study actually
received was not able to be determined from the available
data. In addition, ascertainment of patient deaths
through linkage of data with the national death registry
was not conducted, and data capturers were not blinded
as to the group allocation of patients.
In conclusion, CBAS is an intervention associated
with improved clinical, virological and immunological
ART outcomes over eight years of patient treatment in
a high HIV-prevalence, resource-poor setting in South
Africa. Further research is needed to quantify the costeffectiveness of CBAS. Future randomised studies may
provide greater rigour as to the effectiveness of this intervention. Further scale-up of similar programmes should
be considered to support the large number of patients
who are starting ART in Africa and other areas where
the professional healthcare workforce is limited.
Acknowledgements
The authors wish to acknowledge patients included in the
study, the Department of Health of KwaZulu-Natal, the Global
Fund to Fight AIDS, Tuberculosis and Malaria, the United
States Agency for International Development, and the Presidents Emergency Plan for AIDS Relief.
Disclosure statement
No potential conflict of interest was reported by the authors.
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