Clinical trial NCT02929992: Delivery Optimization for Antiretroviral Therapy (The DO ART Study)
Official title: Delivery Optimization for Antiretrovial Therapy (The DO ART Study): A Prospective, Interventional, Randomized Study of Community-based ART Initiation, Delivery, and Monitoring in South Africa and Uganda
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV
ART
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Bill and Melinda Gates Foundation
First posted: 2016-10-11
Enrollment: 1539
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The investigators propose the Delivery Optimization for Antiretroviral Therapy Study - The DO ART Study - a prospective randomized study of strategies to optimize community-based ART initiation, monitoring and resupply among HIV-positive persons in South Africa and Uganda. The investigators will work closely with community members, stakeholders, local providers, and the local Department of Health (DoH) to integrate the community-based ART delivery with HIV clinics, pharmacies and labs. Following community sensitization, participants will be recruited through community-based HTC and HIV clinics. HIV-positive persons not engaged in care will receive point-of-care CD4 testing to determine ART eligibility. HIV-positive persons who are eligible for ART by national guidelines will be randomized to one of three ART delivery arms: (i) Home ART initiation and mobile van ART monitoring and resupply, (ii) Hybrid model with clinic ART initiation and mobile van ART monitoring and resupply, and (iii) Clinic ART initiation, monitoring and resupply - the current standard of care (SOC)

Detailed description: Antiretroviral therapy (ART) has tremendous potential to prevent HIV-associated morbidity, mortality and transmission. With reliable ART supply and monitoring, the life expectancy of HIV-positive persons in southern Africa is comparable to that of HIV-negative persons. However, HIV-associated mortality continues to be high among HIV-positive persons not diagnosed and not engaged in care. Of the 35 million persons worldwide who meet WHO (World Health Organization) guidelines for ART, only 15 million are on ART. For already burdened health care systems faced with more than doubling of persons on ART, effective and efficient ART initiation and monitoring strategies are needed. First line ART regimens are once daily oral regimens and well-tolerated, which increases the simplicity of ART delivery in general, including community-based ART delivery a feasible alternative to clinic-based delivery. A priority for optimization of ART delivery is to directly compare and evaluate the impact and cost of community-based ART initiation and resupply to clinic delivery of ART in high prevalence settings in Africa, in order to expand capacity to provide ART coverage.

The investigators have extensive experience with community-based strategies for HIV testing and linkage to care. In a series of studies, the investigators have demonstrated that community-based HIV testing and counseling (HTC) results in \>90% knowledge of serostatus and similarly high linkage rates for HIV-positive persons to HIV care. However, the investigators observed bottlenecks within HIV clinics that resulted in delays in ART initiation, particularly for those with higher CD4 counts; only 59% of HIV-positive ART eligible persons were virally suppressed at 12 months, far below the UNAIDS target of 80%. Those findings suggest that community-based strategies for ART initiation and maintenance could address clinic inefficiencies and patient opportunity costs and barriers to optimize ART delivery.

South Africa and Uganda plan to provide decentralized services, including community health workers, CHWs, (known as community health extension workers, CHEWs, in Uganda) conducting HTC and linkage to care and local pharmacy pick-up locations for medication, to meet the challenge of scaling up ART. The investigators proposed Delivery Optimization for Antiretroviral Therapy (The DO ART Study). A rigorous evaluation of an innovative, decentralized ART optimization strategy to safely and cost-effectively deliver ART and monitor viral suppression among HIV-positive persons in South Africa and Uganda. Using a prospective individually-randomized design, the investigators will compare home ART initiation and local mobile van ART resupply to clinic centered care among HIV-positive persons in South Africa and Uganda. Following community sensitization, participants will be recruited through community-based HTC and HIV clinics. HIV-positive persons who are eligible for ART by national guidelines will be randomized to one of three ART delivery arms: (i) Home ART initiation and mobile van ART monitoring and resupply, (ii) A hybrid model of clinic ART initiation with mobile van ART monitoring and resupply, and (iii) Clinic ART initiation, monitoring and resupply - the standard of care (SOC).

The co-primary outcomes are 1) the proportion of HIV-positive persons who initiate ART and achieve viral suppression and 2) cost per HIV-positive person with suppressed HIV viral load at 12 months. The secondary outcomes are safety, social harms, acceptability, the cost-effectiveness of community-based ART delivery, and understanding qualitatively the drivers of engagement in care.

The investigators hypothesize that community-based ART initiation will be acceptable, efficient and improve outcomes, specifically with prompter ART initiation and a higher proportion of HIV-positive persons achieving viral suppression, compared to the standard clinic ART delivery model. Decentralizing HIV care for asymptomatic individuals will expand the overall capacity of the health system to provide care for HIV-positive persons using the existing clinical infrastructure.

Eligibility criteria: Inclusion Criteria:

* Reside in the study community for the duration of follow-up
* Able and willing to provide informed consent
* HIV positive and eligible to start ART according to national guidelines
* Not pregnant
* Normal renal function
* Not receiving treatment for active tuberculosis or other opportunistic infections

Exclusion Criteria:

* No separate exclusion criteria

Primary outcomes:
measure: HIV viral suppression at 12 months
timeFrame: 12 Months
Secondary outcomes:
measure: Measurement of safety across study arms
timeFrame: 1 month, 3 months, 6 months, 9 months, 12 months
measure: Estimate cost-effectiveness of each arm
timeFrame: 12 months
measure: Qualitative review
timeFrame: 1 month, 3 months, 6 months, 9 months, 12 months
measure: Minimize the cost of achieving viral suppression
timeFrame: 12 months
measure: Measurement of social harms
timeFrame: 12 months
Other outcomes:
Locations:
city: Sweetwaters
country: South Africa
facility: HSRC Sweetwaters
state: Kwa-Zulu Natal
city: Kabwohe
country: Uganda
facility: ICOBI
state: Bushenyi
Study officials:
affiliation: Assistant Professor
name: Ruanne Barnabas, MBChB, DPhil
role: PRINCIPAL_INVESTIGATOR
References:
citation: Barnabas RV, Szpiro AA, van Rooyen H, Asiimwe S, Pillay D, Ware NC, Schaafsma TT, Krows ML, van Heerden A, Joseph P, Shahmanesh M, Wyatt MA, Sausi K, Turyamureeba B, Sithole N, Morrison S, Shapiro AE, Roberts DA, Thomas KK, Koole O, Bershteyn A, Ehrenkranz P, Baeten JM, Celum C; Delivery Optimization of Antiretroviral Therapy (DO ART) Study Team. Community-based antiretroviral therapy versus standard clinic-based services for HIV in South Africa and Uganda (DO ART): a randomised trial. Lancet Glob Health. 2020 Oct;8(10):e1305-e1315. doi: 10.1016/S2214-109X(20)30313-2.