In 2017, over 10 million people worldwide developed tuberculosis disease (TB), with 9% of
cases among people with HIV (PWH). In that same year, there were 1.6 million deaths from
TB, with 300,000 among PWH. The highest incidence of TB is in India, accounting for 27%
of all new cases globally, with approximately 86,000 among PWH. Unhealthy alcohol use
triples the risk of TB in the general population, increasing susceptibility to primary
infection and reactivation. Among PWH, unhealthy alcohol use is associated with decreased
use of and adherence to antiretroviral therapy (ART), lower viral suppression and
increased mortality. Treatment for TB presents a unique opportunity to address unhealthy
alcohol use among people with TB and TB/HIV coinfection and HIV given the frequent
contact participants have with healthcare providers and the deleterious effects of
unhealthy use on both HIV and TB clinical outcomes. Although combined cognitive
behavioral therapy (CBT) and motivational enhancement therapy (MET) can be effective in
reducing alcohol use, access to and implementation of such interventions is limited in
high-need, under-resourced low and middle income (LMIC) settings. Even in settings where
formal treatment is available, alcohol-related stigma and cost of treatment may prevent
individuals from seeking care. Integrating treatment for unhealthy alcohol use into TB
and TB/HIV and HIV care may overcome barriers to alcohol treatment for such individuals
at risk for poor health outcomes. HATHI (Hybrid trial for Alcohol reduction among people
with TB, TB/HIV and HIV in India), is a 2-arm hybrid type 1 effectiveness-implementation
randomized controlled trial (RCT) examining the effectiveness of a four-session combined
CBT/MET alcohol reduction intervention (HATHI), followed by three intervention boosters,
integrated into TB and TB/HIV and TB care, compared with usual care (provider advice,
referral to treatment as needed). There will be 3 phases. In Phase 1) investigators will
tailor the intervention based on results from a) focus groups (FG) with patients with TB
and HIV, medical and clinical staff, and the intervention counselors (IC) and b)
individual intervention testing with a subgroup of patients with TB and HIV. In Phase 2)
investigators will conduct an RCT in which participants will be randomized to HATHI
intervention or to usual care. Investigators will stratify persons with TB/HIV
coinfection by HIV status to ensure balance of HIV between the groups. Effectiveness
outcomes measured at 3, 6 and 12 months will include 1) phosphatidyl ethanol (PEth), an
alcohol biomarker (primary), and self reported alcohol use (secondary) 2) TB and HIV
clinical outcomes. In Phase 3, evaluating trial participants, counselors, clinical and
organizational staff, investigators will use the RE-AIM implementation framework using
mixed methods to assess barriers and facilitators to alcohol treatment integration in TB
and HIV clinical settings and to assess the incremental costs of this intervention
strategy.
Setting: All phases of the study will take place at two sites in India: the Byramjee
Jeejeebhoy Government Medical College (BJGMC) and Dr. DY Patil Medical College, Pune
(DYPMC).
Objectives/Aims:
Aim 1: In a randomized controlled trial (RCT), to examine the effectiveness of CBT/MET
integrated into TB, TB/HIV and HIV care compared to usual care on alcohol use.
Aim 2: In a RCT, to examine the effectiveness of CBT/MET integrated into TB, TB/HIV and
HIV care compared to usual care on TB and HIV treatment outcomes.
Aim 3: Guided by the RE-AIM implementation framework, and using mixed methods, to 3a)
evaluate patient, provider and organizational barriers and facilitators to integrated
alcohol treatment in TB and HIV settings, and 3b) measure incremental costs from health
system and societal perspectives.
Prior to RCT implementation investigators will tailor HATHI and make final modifications
to the HATHI manual. HATHI will be enhanced with content specific to Pune such as local
alcohol containing beverages and local or state drinking norms and alcohol impacts on TB
and HIV progression and clinical outcomes. Investigators will modify the manual and test
in focus groups.
Phase 2-Clinical Trial. This phase involves collection of routinely used research
assessments for individuals with TB and TB/HIV and HIV at baseline, 3, 6, and 12 months
and the launch of the RCT. The study will include adults individuals with 1) newly
diagnosed TB (with or without HIV), unhealthy alcohol use, initiating TB medication
treatment and 2) persons with HIV and unhealthy alcohol use. Individuals will be
recruited through both provider and self-referral. Up to half of the sample will have
both TB and HIV. Eligible individuals will undergo baseline assessment which includes a
medical history, clinical exam, questionnaires, and a blood spot for the alcohol
biomarker PEth.
Assignments of Participants to the Study Intervention: Eligible participants will be
randomized in a 1:1 ratio upon completion of the baseline evaluation. The study
biostatistician, independent of the trial will generate the randomization sequence in
permuted blocks and randomization of persons with TB will be stratified by the presence
of HIV infection. A sealed envelope with study assignment will be used to conceal the
study group assignment.
Study Conditions:
Control: Individuals in the control arm will receive standard of care TB and HIV
treatment and usual care from participants' provider, which includes advice to reduce
alcohol use and referral to alcohol treatment services at participants' provider's
discretion.
Intervention: HATHI is an up to 4-session manualized alcohol reduction treatment based on
Cognitive Behavioral and Motivational Enhancement Therapy. Each session lasts up to 45
minutes. The 4 HATHI sessions will be delivered by a counselor during an 8 week period,
closely aligned to regular TB treatment follow up visits. After the 4 intervention
sessions, individuals will receive 3 scripted booster sessions, one month apart,
corresponding to participants' follow up visits.
Research Data Ascertainment: Assessments will occur at baseline (prior to randomization),
3 months (end of 4 session intervention), 6, and 12 months post-baseline. Data collection
will include self-report questionnaires staff interviews, and biomarker and specimens and
will encompass demographics, a clinical assessment, measurement of alcohol use, its
severity and consequences; HIV measures including viral load, medication adherence and
HIV retention in care; TB measures, including TB clearance, TB treatment default, TB
medication adherence and TB retention in care. Other measures span mental health, tobacco
and other substance use, quality of life, diabetes mellitus, motivation to change and
self-efficacy.
Investigators' primary alcohol endpoint will occur at 6 months after baseline, with
investigators' secondary endpoint at 12 months. Sample size calculations are based on
data from behavioral alcohol reduction interventions in low and middle income countries.
Investigators' trial will enroll a total of 450 participants with TB or TB/HIV or HIV;
The study will be conducted at two sites and 2 counselors at each site will administer
the intervention. Power calculations assume a 10% loss to follow-up, and intra-class
correlation coefficient of 0.04 (based on Counseling on Alcohol Problems (CAP)/PREMIUM
RCT) to account for 2 counselors per site, 2 sites). Analyses will also account for
variation by counselor and by site.
Phase 3: The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM)
implementation framework will be used to collect quantitative and qualitative assessments
from 3 levels of stakeholders (Numbers approximate, pending thematic saturation).
Investigators will evaluate barriers and facilitators to intervention reach,
effectiveness, adoption, implementation and maintenance, focusing in implementation
outcomes of feasibility, acceptability, appropriateness, fidelity and sustainability.
Investigators will also calculate the incremental costs of the intervention.