INT J TUBERC LUNG DIS 20(4):430–434 PERSPECTIVE

Q 2016 The Union

http://dx.doi.org/10.5588/ijtld.15.0360

Re-inventing adherence: toward a patient-centered model of

care for drug-resistant tuberculosis and HIV

M. R. O’Donnell,*†‡ A. Daftary,‡§ M. Frick,¶ Y. Hirsch-Moverman,†# K. R. Amico,**

M. Senthilingam,†† A. Wolf,* J. Z. Metcalfe,‡‡ P. Isaakidis,§§ J. L. Davis,¶¶ J. R. Zelnick,##
J. C. M. Brust,*** N. Naidu,‡ M. Garretson,† D. R. Bangsberg,††† N. Padayatchi,‡ G. Friedland¶¶‡‡‡
*Division of Pulmonary Allergy and Critical Care Medicine, Columbia University Medical Center, New York,
†
Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, USA;
‡
Centre for the AIDS Programme of Research in South Africa, South African Medical Research Council TB HIV
Pathogenesis Extramural Unit, Durban, South Africa; §Dalla Lana School of Public Health, University of Toronto,
Toronto, Ontario, Canada; ¶Treatment Action Group, New York, #International Center for AIDS Care and Treatment
Programs, Mailman School of Public Health, Columbia University, New York, New York, **Department of Health
Behavior and Health Education, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA;
††
University of Cape Town, Cape Town, South Africa; ‡‡Division of Pulmonary and Critical Care Medicine,
University of California, San Francisco, California, USA; §§Médecins Sans Frontières, Mumbai, India; ¶¶Yale
University School of Public Health, New Haven, Connecticut, ##Touro College Graduate School of Social Work, New
York, New York, ***Montefiore Medical Center & Albert Einstein College of Medicine, Bronx, New York,
†††
Harvard Medical School, Boston, Massachusetts, ‡‡‡Yale University School of Medicine, New Haven,
Connecticut, USA

SUMMARY

B A C K G R O U N D : Despite renewed focus on molecular Medication adherence and care for drug-resistant TB-
tuberculosis (TB) diagnostics and new antimycobacte- HIV could be improved by fully implementing team-
rial agents, treatment outcomes for patients co-infected based patient-centered care, empowering patients
with drug-resistant TB and human immunodeficiency through counseling and support, maintaining a rights-
virus (HIV) remain dismal, in part due to lack of focus based approach while acknowledging the responsibility
on medication adherence as part of a patient-centered of health care systems in providing comprehensive care,
continuum of care. and prioritizing critical research gaps.
O B J E C T I V E : To review current barriers to drug-resis- C O N C L U S I O N : It is time to re-invent our understanding
tant TB-HIV treatment and propose an alternative of adherence in drug-resistant TB and HIV by focusing
model to conventional approaches to treatment support. attention on the complex clinical, behavioral, social, and
D I S C U S S I O N : Current national TB control programs structural needs of affected patients and communities.
rely heavily on directly observed therapy (DOT) as the K E Y W O R D S : drug-resistant TB; HIV; medication
centerpiece of treatment delivery and adherence support. adherence; patient-centered care

APPROXIMATELY 1.5 MILLION people are living countries, the proportion of DR-TB patients with
with multidrug-resistant tuberculosis (MDR-TB) HIV co-infection ranges between 7% and 23%.4,5
worldwide. While the overall TB epidemic is very Treatment of DR-TB in low- and middle-income
slowly being brought under control, the number of settings is fraught with clinical, operational and social
TB patients with drug-resistant TB (DR-TB) contin- challenges. Patients with DR-TB/HIV take an average
ues to rise. In 2013 alone, the World Health of six antimycobacterial medications for .18 months
Organization (WHO) estimated that 480 000 indi- in addition to lifelong antiretroviral therapy (ART).
viduals developed MDR-TB, an increase of 80% Treatment is often centralized, and involves social
from 2000 estimates.1 Globally, MDR-TB is associ- marginalization, family isolation, difficult and pain-
ated with human immunodeficiency virus (HIV) ful treatment regimens, dual stigmatization, and
infection,2 and HIV exacerbates TB clinically and in economic loss.3,6,7 In contrast, drug-susceptible TB
terms of social impact.3 In South Africa, the epicenter is typically treated over a period of 6 months, with far
of the drug-resistant TB-HIV syndemic, up to 80% of fewer and far less toxic medications, through largely
patients with extensively drug-resistant TB (XDR- decentralized channels of care. While recent innova-
TB) are HIV co-infected. Even in low HIV burden tions in TB diagnostics, such as the Xpertw MTB/RIF

Correspondence to: Max O’Donnell, Department of Epidemiology, Mailman School of Public Health, Columbia University,
Suite E101, 622 W 168th St, PH Building, New York, NY 10032, USA. e-mail: mo2130@columbia.edu
Article submitted 3 May 2015. Final version accepted 27 October 2015.
 Reinventing adherence for MDR-TB and HIV 431

assay (Cepheid, Sunnyvale, CA, USA), have enhanced patient’s perspective and build on patient-provider
MDR-TB case detection, cure rates remain appall- relationships to enhance the humaneness of care
ingly low.1 Poor treatment outcomes have a number through communication, shared decision-making and
of potential causes. Low levels of medication support for self-management. Patient-centered care
adherence are predicted to be an important cause of has been shown to have positive effects on patient
treatment failure,8,9 and are strongly associated with behavior, well-being, and treatment outcomes.28 For
failure to convert TB culture to negative during treatment of DR-TB and HIV, successful programs
treatment.8–10 have included important elements of patient-centered
Medication adherence in ART has been carefully care, including emphasizing patient preference; decen-
studied.11 Each medication has a defined adherence- tralized, community-based care;29 and intensive coun-
resistance relationship, which is a function of the seling, accompaniment, 30 and support; while
potency of the medication and replicative capacity of programs using mostly conventional models of care
drug-resistant organisms. Time on ART as well as have shown poor outcomes.31
patterns of treatment interruptions also influence We conceptualize patient-centered care as being
drug resistance-induced treatment failure.11–13 In oriented toward addressing patients’ priorities, not in
contrast to HIV, medication adherence in DR-TB- the sense of a menu of choices, but rather as a holistic
HIV is substantially understudied.14–18 Preliminary model of health care delivery that considers the
research from South Africa finds that XDR-TB/HIV patient as the central figure in the process or
co-infected patients report significantly lower adher- continuum of care. A patient-centered approach is
ence to TB medications than ART.10 High ART therefore not a one-size-fits-all solution to the
adherence with low TB medication adherence may multifactorial patient-related barriers to MDR/
improve patient survival without improving TB XDR-TB/HIV treatment adherence that have been
treatment outcomes,19 and contribute to ongoing identified, including high TB pill burden and adverse
transmission. drug effects, lack of patient education and counseling,
Although the WHO has endorsed more progressive provider supervision of anti-tuberculosis treatment,
approaches, such as the International Standards for inability to access care in the community, and the
Tuberculosis Care,20,21 the reality is that anti- stigma of public TB notification.3,7,10 Conversely, a
tuberculosis treatment programs around the world patient-centered approach is a flexible model of care
focus on directly observed therapy (DOT) as the that reacts to the specialized needs of individuals.
centerpiece of treatment delivery and adherence Studies of DR-TB/HIV co-infected patients have
support. As an isolated intervention, DOT lacks a identified HIV-specific services as facilitators of
rigorous evidence base and is often at odds with ART adherence, including treatment literacy coun-
patient needs and preferences.3,22–24 From the health seling, patient involvement in care, and simpler drug
systems perspective, DOT programs may integrate regimens.3,32
poorly into health systems, face technical challenges Patient-centered care depends on engaging each
and variability of access, and poorly address stig- individual patient with tailored education/counseling,
ma.24–26 To improve adherence in DR-TB/HIV, there understanding their motivations, and enhancing
is an urgent need to evaluate patient-centered care behavioral skills within the context of local social,
approaches that look beyond DOT, in particular its structural and cultural factors. A patient-centered
conventional facility-based form. Although HIV care approach is particularly critical in vulnerable and
delivery can inform future advances in TB manage- marginalized MDR-/XDR-TB patients. The current
ment, long-term HIV management itself requires model of care in much of the world, which relies on a
paradigm shifts from centralized to decentralized, clinician to examine the MDR-TB/HIV patient and
patient-focused approaches that address the waiting prescribe TB medications without input from coun-
times for ART refills, improved management of selors, social workers or mental health professionals,
medical complications, transportation barriers, and much less patients, addresses very little of this
burden on the strained health care workforce.25 vulnerability. A team-based approach that includes
A patient-centered approach to adherence in DR-TB mental health trained providers, social work trained
and HIV treatment that reflects the Institute of providers, and behavioral counselors who can engage
Medicine (Washington DC, USA) recommendation with patients more directly and holistically, and
for ‘partnership among practitioners, patients, and explicitly integrates HIV and DR-TB care, allows us
their families (when appropriate) to ensure that to think about and make treatment decisions that
decisions respect patients’ wants, needs, and prefer- encompass the full range of clinical, socio-economic
ences and that patients have the education and support and structural issues confronting patients.
they need to make decisions and participate in their Patient-centered approaches recognize that compre-
own care’ is imperative.26,27 In other words, not only hensive care must be provided along a locally
should we recognize the time, cost and quality of contextualized continuum of services. The continuum
health care services, we should also consider the or cascade of care for DR-TB/HIV describes the
432 The International Journal of Tuberculosis and Lung Disease

Figure The continuum of DR-TB/HIV care defines the processes and linkages that comprise
optimal care for MDR-/XDR-TB/HIV. The y-axis represents patients retained in care; the x-axis
represents the stages of the continuum; the arrows represent the linkages in the continuum. The
box below defines tasks and processes that occur at each stage. TB ¼ tuberculosis; HIV ¼ human
immunodeficiency virus; DR-TB ¼ drug-resistant TB; VL ¼ viral load; DST ¼ drug susceptibility
testing; MDR-TB ¼ multidrug-resistant TB; XDR-TB ¼ extensively drug-resistant TB. This image can
be viewed online in colour at http://www.ingentaconnect.com/content/iuatld/ijtld/2016/
00000020/00000004/art00004

complex, integrated steps from diagnosis to cure. In where patients live and work, and are connected to
DR-TB/HIV, this should incorporate early TB diagno- networks of social capital and social support.
sis and drug susceptibility testing, early HIV diagnosis, 2 Patient education and counseling—with the goals
comprehensive patient education and support, infec- of patient empowerment, treatment literacy, ac-
tion control, streamlined entry into co-treatment, countability, and reducing stigma—should be at the
unimpeded access to medications, adherence support, heart of adherence support for DR-TB/HIV. Core
and retention in dual care. For patients cured of DR- standards in counseling and education for DR-TB/
TB, the cascade should conclude with support for HIV need to be developed, as education and DOT
reintegration back into the community, family life, and may have different meanings and are implemented
employment. For patients with disease considered differently throughout the world.
incurable, it must include palliative care (Figure). The 3 Public health approaches to DR-TB/HIV should be
decline between steps in the continuum represents based on human rights and equity. Where public
patient attrition, and underscores the need to improve health and individual rights conflict—for example,
care and retention at each step. the forcible detention or isolation of people with
In March 2015, a meeting of clinicians, behavioral infectious XDR-TB to protect others from trans-
and social scientists, patients, and activists convened mission—a rights-based approach will use deliber-
at the Mailman School of Public Health, Columbia ation in accordance with the Siracusa Principles33
University, New York, NY, USA, to generate a call to to justify rights-limiting public health measures.
action for patient-centered care in the treatment of 4 Patient-centered care does not mean centering all
DR-TB/HIV. We commit to working with affected responsibility on the person with TB. Grounding
communities to improve medication adherence by re- patient-centered care in rights-based approaches
inventing models of care delivery that respect and recognizes that governments and health systems
address patients’ needs. This commitment is based on must bear the responsibility to respect, protect, and
the following principles that emerged from the 2015 fulfill the right to health along the cascade of care.
symposium: 5 There are critical research gaps in understanding
the cascade of care for DR-TB/HIV, including
1 Patient-centered care is team-based, decentralized biomedical, behavioral, and implementation sci-
care that requires substantial investment in human ence components. This research agenda must be
resources to provide high-quality care in settings urgently prioritized in parallel with operationaliz-
 Reinventing adherence for MDR-TB and HIV 433

ing patient-centered practices, and donors should drug-resistant tuberculosis and HIV in South Africa: a
commit to funding this research. prospective cohort study. J Acquir Immune Defic Syndr 2014;
67: 22–29.
The development of new TB diagnostics, drugs, 11 Genberg B L, Wilson I B, Bangsberg D R, et al. Patterns of
and treatment regimens presents exciting opportuni- antiretroviral therapy adherence and impact on HIV RNA
among patients in North America. AIDS 2012; 26: 1415–
ties to improve outcomes and reduce community 1423.
transmission of DR-TB. With innovative and effective 12 Oyugi J H, Byakika-Tusiime J, Ragland K, et al. Treatment
approaches to patient-centered care, the opportunity interruptions predict resistance in HIV-positive individuals
to impact the epidemic afforded by new diagnostics purchasing fixed-dose combination antiretroviral therapy in
and drugs may not be realized. It is time for clinicians, Kampala, Uganda. AIDS 2007; 21: 965–971.
13 Rosenblum M, Deeks S G, van der Laan M, Bangsberg D R.
researchers and TB practitioners to re-invent the The risk of virologic failure decreases with duration of HIV
understanding of adherence in DR-TB/HIV to elim- suppression, at greater than 50% adherence to antiretroviral
inate disease and stigma by focusing efforts and therapy. PLOS ONE 2009; 4: e7196.
attention on affected patients and communities. 14 van den Boogaard J, Boeree M J, Kibiki G S, Aarnoutse R E.
The complexity of the adherence-response relationship in
Acknowledgements tuberculosis treatment: why are we still in the dark and how can
we get out? Trop Med Int Health 2011; 16: 693–698.
On behalf of the attendees of ‘Re-inventing adherence: patient- 15 Gardner E M, Burman W J, Steiner J F, Anderson P L,
centered care for drug-resistant TB and HIV’, 19–20 March 2015, Bangsberg D R. Antiretroviral medication adherence and the
Columbia Mailman School of Public Health, Columbia University, development of class-specific antiretroviral resistance. AIDS
New York, NY, USA. The symposium was supported by the 2009; 23: 1035–1046.
Columbia Mailman School of Public Health (New York, NY), 16 Bangsberg D R, Acosta E P, Gupta R, et al. Adherence-
Centre for AIDS Programme of Research in South Africa (Durban, resistance relationships for protease and non-nucleoside reverse
South Africa), ICAP (New York, NY), Treatment Action Group transcriptase inhibitors explained by virological fitness. AIDS
(New York, NY), and the Stony Wold-Herbert Fund (New York, 2006; 20: 223–231.
NY, USA). 17 Hatano H, Lampiris H, Fransen S, et al. Evolution of integrase
Conflicts of interest: none declared. resistance during failure of integrase inhibitor-based
antiretroviral therapy. J Acquir Immune Defic Syndr 2010;
54: 389–393.
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 Reinventing adherence for MDR-TB and HIV i

RESUME
CONTEXTE : En dépit d’une attention renouvelée au soutien à l’adhésion. L’adhésion aux médicaments et la
diagnostic moléculaire de la tuberculose (TB) et de la prise en charge de la TB-VIH pharmacorésistante
disponibilité de nouveaux agents antimycobactériens, le pourraient cependant être améliorées par la mise en
résultat du traitement des patients co-infect és œuvre complète d’une prise en charge centrée sur le
par une TB pharmacorésistante et par le virus de patient par une équipe, autonomiser les patients grâce à
l’immunodéficience humaine (VIH) restent affligeants, des conseils et du soutien, maintenir une approche basée
en partie par manque d’attention vis-à-vis de l’adhésion sur les droits tout en reconnaissant la responsabilité du
aux médicaments dans le cadre d’une continuité des système de santé en ce qui concerne l’ensemble de la prise
soins centrée sur le patient. en charge et l’établissement des priorités en matière de
O B J E C T I F : Revoir les obstacles actuels au traitement de besoins cruciaux dans le domaine de la recherche.
la TB-VIH pharmacorésistante et proposer un modèle C O N C L U S I O N : Il est temps de r éinventer notre
alternatif aux approches conventionnelles du soutien au compréhension de l’adhésion au traitement de la TB-
traitement. VIH pharmacorésistante en concentrant notre attention
D I S C U S S I O N : Actuellement, les programmes sur les besoins complexes cliniques, comportementaux,
nationaux de lutte contre la TB s’appuient fortement sociaux et structurels des patients affectés et de leurs
sur le traitement sous observation directe (DOT) comme communautés.
pièce maı̂tresse de la prestation du traitement et comme

RESUMEN
M A R C O D E R E F E R E N C I A:Pese a un interés renovado en apoyo al cumplimiento terapéutico; es posible mejorar la
los métodos diagnósticos moleculares de la tuberculosis adhesión al tratamiento y la atención de la coinfección
(TB) y en los nuevos medicamentos antituberculosos, los por el VIH y la TB farmacorresistente con las siguientes
desenlaces terapéuticos de los pacientes coinfectados por medidas: la plena adopción de una atención prestada por
el virus de la inmunodeficiencia humana (VIH) y el equipos del personal de salud y centrada en el paciente,
bacilo de la TB farmacorresistente siguen siendo muy la promoci ón de la corresponsabilizaci ón de los
desfavorables, en parte debido a la falta de refuerzo del pacientes mediante el asesoramiento y el apoyo, el
cumplimiento terap éutico, como un componente mantenimiento de un enfoque basado en los derechos y
integral de la continuidad asistencial centrada en el al mismo tiempo el reconocimiento de la responsabilidad
paciente. de los sistemas de atención de salud en la prestación de
O B J E T I V O: Examinar los obstáculos actuales al una atención integral y la priorización de las principales
tratamiento de la coinfección por el VIH y la TB lagunas de la investigación.
farmacorresistente y proponer una nueva opción a las C O N C L U S I Ó N: Llegó el momento de reinventar nuestro
estrategias convencionales de apoyo al tratamiento. concepto del cumplimiento terapéutico en los casos de
D I S C U S I Ó N: En la actualidad, los programas nacionales infección por el VIH y la TB farmacorresistente,
contra la TB aplican el tratamiento breve directamente centrando la atención en las complejas necesidades
observado (DOT), como pilar central de la clı́nicas, comportamentales, sociales y estructurales de
administración del tratamiento antituberculoso y de los pacientes y las comunidades afectados.