HIV I Infection, Tuberculosis
Conditions
Keywords
Tuberculosis, TPT, 3HP, differentiated service delivery, multi-month dispensing
Brief summary
This study will compare community-delivered, multi-month dispensing of tuberculosis preventive therapy (TPT) to standard-of-care clinic-based TPT delivery in a population of South African adults who are recommended to receive TB preventive therapy. We hypothesize that persons receiving multi-month dispensing of TPT in the community will have a higher rate of TPT completion at 3 months than persons receiving TPT via standard of care with monthly clinic-based refills.
Detailed description
The research objective is to understand and overcome key barriers to tuberculosis preventive therapy (TPT) delivery and completion in South Africa in the setting of 3HP scale-up. (3HP: short-course TPT consisting of 3 months weekly isoniazid\[H\] plus rifapentine \[P\]). The study will investigate these factors through a trial comparing community-delivered TPT, to clinic-based TPT and qualitative research investigating barriers to TPT completion and exploring task-shifted TPT delivery. Aim 1: To determine the effect of community-based initiation and delivery of TPT on TPT completion. Hypothesis: Community-delivered TPT will be associated with higher initiation and completion of TPT than standard of care clinic-based TPT. Approach: Persons eligible for TPT will be identified through the Triage+ TB study and other community-based TB screening activities. Eligible persons will be randomized at the household level to 1) Immediate initiation of TPT & full 12 weeks delivery at once, or 2) Immediate initiation of TPT, 2-week supply, and referral to clinic for TPT completion. TPT adherence and completion will be measured by a combination of self-report, pill count, and serum drug level indicators. Aim 2: To determine factors associated with TPT initiation and completion in people eligible for TPT identified in community settings. Hypothesis: People with HIV (PWH) will have better rates of initiation and completion of TPT than people without HIV. Approach: Participant interviews and surveys at baseline and end-of-study will assess willingness to take TPT, barriers and facilitators for individuals, experience taking TPT, and experience of interactions in clinic settings. Focus groups will be purposively selected based on end-of-study survey responses to elicit factors determining patient experience. Aim 3: To determine feasibility and acceptability of differentiated service delivery (DSD) approaches, including task-shifting, for TPT delivery and scale-up. Hypothesis: DSD TPT will be feasible and acceptable. Approach: Participatory qualitative research, and implementation science approaches including workflow mapping will be used to assess clinician-level barriers and inefficiencies in providing clinic-based TPT. In-depth interviews and focus groups will be conducted with pharmacy assistants, nurses, clinic operational managers, and district program managers to assess acceptability. Clinic flow will be mapped to determine effect of task-shifted pharmacy assistant TPT delivery on workflow and patient experience in the clinic.
Interventions
OTHERCommunity-delivered TB preventive therapy (TPT) - 3 months weekly isoniazid plus rifapentine (3HP)
Participants randomized to this arm will receive the entire supply of TB preventive therapy (TPT) at enrollment.
OTHERClinic-link TPT
Participants receive 2-week supply of TPT at initiation, then continue to receive remainder of TPT course at clinic (including refills).
Sponsors
University of Washington
Human Sciences Research Council
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Intervention model description
Household-level randomization -- all individuals in a household will be randomized to the same study arm of medication delivery.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥18 years of age * Living in the study catchment area * Eligible for TPT according to South African National guidelines(5), i.e. are a) living with HIV or b) are a close contact of a person with TB disease (defined by a person that resides in the same house as a person with TB), c) and in either case * Have screened negative for TB disease in the last 6 months, through TB TRIAGE+ Trial, other household contact tracing, or other community TB screening * Negative TB screening at enrolment (if TB TRIAGE+ screening was more than 3 months ago) * Willing and able to provide written or verbal consent * Participants whom have not received TPT in the last 12 months; this was confirmed verbally with participants during the enrolment process.
Exclusion criteria
* Less than 18 years of age. * Pregnant or planning on pregnancy within next three months * Planning on moving or relocating from the area within the next three months * Positive for active TB * Currently on TB treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Completion of a Course of TB Preventive Therapy (TPT) | 3 months, extended to 16 weeks as needed | TPT completion defined as taking 11 doses of 3HP (3 months weekly isoniazid \[H\] plus rifapentine \[P\] ) within 16 weeks of 3HP initiation. The outcome is measured as a composite outcome including: self-report of doses taken, periodic pill counts, one-time serum drug level of isoniazid. (Eight participants with contraindication to 3HP received 6H TPT. Completion of 6H was defined as taking 24 weeks within 9 months) |
| Number of TPT Doses by Week 16 | Enrollment to week 16 | The number of TPT doses taken by week 16 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Adherence With TPT | 3 months, extended to 16 weeks as needed | Number of doses taken by 16 weeks (N= 8 participants received 6H TPT excluded from this analysis) |
| Participant Satisfaction With the Assigned TPT Delivery Method | 3 months, extended to 16 weeks as needed | Number of participants who answered "somewhat motivated" or "very motivated" to take TPT in exit questionnaire |
| Adverse Events | 3 months, extended to 16 weeks as needed | Assessed by adverse event reporting |
Countries
South Africa
Contacts
PRINCIPAL_INVESTIGATORAdrienne E Shapiro, MD, PhD
University of Washington
Participant flow
Recruitment details
Recruitment for the trial occurred in conjunction with the Triage+ TB Study, a study of TB screening based at the study site. TB Triage+ participants and other community TB screening participants who were potentially eligible for the ThiPhiSA RCT, were identified by study recruiters, at the time of delivery of TB screening results to the participants and through review of study records to identify persons who were found to be eligible for TPT but did not initiate TPT at the time of TB testing.
Pre-assignment details
268 households of 301 participants were enrolled in the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 10 Participants |
| Age, Categorical Between 18 and 65 years | 286 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 159 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 142 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 0 Participants |
| Sex: Female, Male Female | 100 Participants |
| Sex: Female, Male Male | 48 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 142 | 1 / 159 |
| other Total, other adverse events | 0 / 142 | 0 / 159 |
| serious Total, serious adverse events | 1 / 142 | 4 / 159 |
Outcome results
None listed