Community-based TB Preventive Therapy in the DO ART Study

Adrienne Shapiro, MD, PhD

Senior Fellow/Acting Instructor

International Clinical Research Center, University of Washington

28 March 2018

• 3-site (1 UG, 2 SA), 3-arm randomized controlled trial of ART delivery models

• Offered community-based HIV testing, point-of-care baseline labs, followed by randomization for ART initiation strategy for asymptomatic HIV+ adults not on ART.

• Compare 2 differentiated service approaches to standard-of-care for initiating and continuing ART for 12 months.• Arm 1: Community-based – initiate ART immediately in community, 1 wk sx call, 1m refill, then

quarterly refills at mobile van clinic/community pickup. All monitoring done in community. (6M VL, creatinine, etc)

• Arm 3: Standard-of-care (Clinic) – initiate ART in clinic, follow clinic schedule for refills (q1-2M), monitoring labwork. Quarterly symptom calls.

• Arm 2: Hybrid arm – initiate ART in clinic, then transfer to community for quarterly refills & monitoring.

• Co-primary endpoints: viral load suppression at 12 months; cost-effectiveness

• All delivery arms/approaches* include TB preventive therapy per national guidelines.

The CQUIN Learning Network 2

The DO ART Study: Delivery Optimization for ART

*South Africa sites only

The CQUIN Learning Network 3

DO ART Study Schema

Eligibility Screen• HIV+• Not on ART, not on TB treatment• Negative TB symptom screen• CD4>100, Normal Cr – Clinically stable

Arm 1: CommunityCommunity-based ART

Initiation & Follow-Up/Refill

Arm 2: HybridClinic-based ART Initiation Community-based Follow-

Up/Refill

Arm 3: ClinicSOC: Clinic-based ART

Initiation &Follow-Up/Refill

Randomization

• Guidelines: isoniazid preventive therapy (IPT) for all PLWH

• Symptom screen to exclude active TB at entry to care,→ 6/12/36M IPT if no active TB

• Surveyed local clinics in study areas to ensure DO ART IPT duration compatible with local practice/standard of care provided

• →6M IPT

• Standard of care (Clinics): after IPT initiation, monthly visit for symptom screen, IPT refill. Usually separate nurse/consultation from ART refill.

The CQUIN Learning Network 4

TB Preventive Therapy in South Africa (KZN)

• Screen all participants at baseline for eligibility (counselor)

• In community arms, re-screen at 1M visit (or 1st

study visit in community if later than 1M); if asymptomatic, offer IPT

• Brief education about purpose of IPT, side effects, warning signs

• Dispense supply to last until next ART refill visit (study nurse)

• 300mg po daily + 25mg po pyridoxine (B6)

• Next visit: screen for side effects/adverse events, adherence; if all ok, dispense next refill (3M supply) with 3M ART supply. The CQUIN Learning Network 5

DO ART Approach to Integrating TB Preventive Therapy

INH Supply:KZN DOH central pharmaciesKZN CHC Clinics

• Study enrollment in SA began 2/2017• Study enrollment ended 11/2018

The CQUIN Learning Network 6

DO ART Study Timeline

EnrollmentStart ART –1M supply

Month 12M supply ART

Month 3 3M supply ART

Month 63M supply ART

Month 12 Study Exit

(1M supply ARTto transfer)

Month 93M supply ART

TB Sx screenIPT education

Start IPT—2M supply

TB Sx screenAdherence Qs

Urine test3M supply IPT

TB Sx screenAdherence Qs

Urine test1M supply IPT

IPT eligibility Qs

EndIPT

Community Arm (Arm 1) protocol timeline:

• Eligibility: mobile phone app guides counselor through exclusion criteria (reviewed by nurse):• Known liver disease

• Heavy alcohol use (>21 drinks/week F; >28 drinks/week M)

• Severe existing peripheral neuropathy

• Prior MDR-TB

• Adverse events (counselor, nurse):• Counselor used app to ask about TB symptoms, side effects, discontinuation at

each visit

• No routine lab monitoring

• Nurse-managed criteria to address SEs or stop IPT, refer to clinic for evaluation

• Adherence (counselor):• Counselor asked (app-guided) adherence at each refill visit.

• Spot check at 3M, 6M (or other midpoint) visit using point-of care urine colorimetric test

The CQUIN Learning Network 7

Assessing Eligibility, Adherence & Adverse Events

The CQUIN Learning Network 8

Interim Results (Study Ongoing)

• Exclusion criteria require a lot of explanation to/by staff • Peripheral neuropathy

• Stock-outs (INH) at central pharmacy depot/clinics → deferred IPT initiation• Almost never interrupted ongoing treatment

• Pill burden: 100mg vs. 300mg tablets

• Discordant self-report and urine test results led to probing about adherence.

The CQUIN Learning Network 9

Challenges & Lessons Learned

• Community-based TPT (no facility contact) is safe

• Providing multi-month refills is feasible, safe, acceptable

• No incident TB cases detected

• Community-based TPT has better initiation, refill completion vs. facility-based TPT

• POC urine-based testing can complement adherence monitoring. The CQUIN Learning Network 10

Key Findings – Case Study

• Feedback to improve SOC TPT delivery

• Additional qualitative research to better understand reasons for adherence and non-adherence to IPT

• Finish data collection and analysis of• IPT uptake across all arms

• IPT completion across arms

• Incident TB

• Adapt strategy for 3HP? 1HP?

• Consider modifying (eliminating?) exclusion criteria

• Better screening questions/tools for interim visits – symptoms not sensitive or specific.

The CQUIN Learning Network 11

Next steps

The CQUIN Learning Network 12

Acknowledgments

The DO ART Study

Lutz Lab

Principal Investigator: Ruanne BarnabasProtocol co-chair: Connie Celum

Site PIs: Heidi van Rooyen, Alastair van Heerden

Site PIs: Deenan Pillay, Olivier Koole

Barry Lutz, Daniel Leon