Clinical trial NCT03757104: Home-based Intervention to Test and Start
Official title: Home-based Interventions to Test and Start (HITS): a Cluster-randomized Controlled Trial to Reduce Mortality and Incidence Through HIV Treatment
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: HIV
HIV Testing
Linkage to Care
Lead sponsor: Africa Health Research Institute
Sponsor class: OTHER
Collaborators: name: Heidelberg University
name: University College, London
name: London School of Hygiene and Tropical Medicine
name: University of Glasgow
name: University of Southampton
First posted: 2018-11-28
Enrollment: 4667
Sex: ALL
Minimum age (years): 15
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: This study aims to establish the causal impact of two interventions - micro-incentives and a male-sensitive HIV- specific decision support app - on population-level HIV viral load and HIV-related mortality in men, as well as on population-based HIV incidence in young women.

Detailed description: Research aim:

The primary aim of the home-based intervention to test and start (HITS) trial is to establish whether (i) the provision of two micro-incentives and (ii) a male-sensitive and HIV-specific decision support app will reduce population-level HIV viral load and HIV-related mortality in men, as well as population-level HIV incidence in young women.

Specific objectives

1. Establish the causal impact of two micro-incentives (aimed at increasing uptake of home-based HIV testing and linkage to care, respectively) on:

   1. Population-level HIV viral load in men
   2. Population-level HIV-related mortality in men
   3. Population-level HIV incidence in young women.
2. Establish the causal impact of a male-sensitive and HIV-specific decision- support app (called EPIC-HIV) on:

   1. Population-level HIV viral load in men
   2. Population-level HIV-related mortality in men
   3. Population-level HIV incidence in young women.
3. Establish the causal impact of the two conditional micro-incentives on:

   1. HIV status knowledge in men and women
   2. HIV knowledge in men and women
   3. HIV treatment knowledge in men and women
   4. HIV treatment utilization in men and women
   5. Sexual behavior in men and women
   6. Healthcare utilization in men and women
   7. Household healthcare expenditures
   8. Household wealth
   9. Retention in HIV care in men and women
4. Establish the causal impact of the male-sensitive HIV-specific decision support app on:

   1. HIV status knowledge in men and women
   2. HIV knowledge in men and women
   3. HIV treatment knowledge in men and women
   4. HIV treatment utilization in men and women
   5. Sexual behavior in men and women
   6. Healthcare utilization in men and women
   7. Household healthcare expenditures
   8. Household wealth
   9. Retention in HIV care in men and women

Hypothesis:

The investigators hypothesize that each of the two interventions - micro-incentives aimed at encouraging HIV testing and linkage to HIV care and a male-sensitive HIV-specific decision support app - will each increase HIV testing and HIV treatment uptake and via this mechanism lead to reduced population viral load and HIV-related mortality particularly in men. Reduced viral load among men, in turn, will reduce HIV incidence in young women.

Research design Following a formative phase to develop the design of the two HITS intervention the investigators will determine the causal impact of the interventions on our three primary endpoints in a 2x2 factorial cluster-randomized controlled trial with a baseline adjustment. A mixed- methods approach will be employed that combines the strengths of rapid formative social science research (that will inform the precise delivery of the HITS intervention) with a causally rigorous statistical methodology to evaluate the effectiveness of the HITS intervention.

The HITS intervention will be delivered through the Africa Health Research Institute's (AHRI) existing HIV surveillance operations. The investigators will randomize 45 communities to the four interventions. 8 communities each will receive one of the interventions (micro-incentives only, male-sensitive HIV-specific decision support app only); 8 communities will receive both interventions and 21 communities will receive standard-of-care. Communities will be stratified by incidence in young women (2004-2016) to derive a similar baseline incidence across intervention and standard-of-care communities prior to the implementation of the intervention. Both men and women will be eligible to receive the financial incentives to test and link to care, whilst only men will be eligible for the EPIC HIV-specific decision support application.

In the total of 3x8=24 communities in the intervention arms, an estimated total of 4,667 individuals will receive a HITS intervention. In the 21 communities, 4,900 individuals will receive the standard-of-care. Outcomes will be assessed in all eligible individuals living in the 45 communities, which together have an estimated population size of 30,000 adults.

Sample size calculation The study was powered using the outcome of HIV incidence in women aged 15-30. Using actual Africa Health Research Institute HIV incidence data, the investigators simulated the HITS intervention introduced in 2011 to 24 of the 45 communities in the study area. The investigators simulated an intervention that led to a 25% reduction in arm 1 (micro-incentives), 25% reduction in arm 2 (male-sensitive counselling) and a 32% reduction in the combined arm. Communities were stratified by baseline incidence (three strata) in young women (2004-2011) to allow for a similar baseline incidence in intervention and control communities and the investigators included a random effect in the simulations to adjust for clustering by community. The results show that the investigators would have been able to detect this reduction in incidence in \>80% of simulation replicates (p\<0.05). Therefore, if the investigators were to introduce the HITS intervention in 2018 and follow young women up for at least 3 years post intervention (ie utilize a total of 17 years of incidence data - 2004 to 2021) the investigators would be in excess of 90% powered to detect such a reduction in incidence in this critical age-group.

Research methodology Research site:

The trial will be managed from the Africa Health Research Institute, formerly Africa Centre that conducts a large longitudinal Demographic and Health surveillance. Participants will be enrolled during the routine HIV surveillance study (Population Intervention Program) - trained fieldworkers visit participants at home once a year to conduct household surveys using tablet computers and offer point of care HIV testing to all individuals aged 15+.

Study procedures:

In those arms of this cluster Randomized Controlled Trial (RCT) that include the once-off two-stage micro-incentive scheme, consenting men and women will be offered a first opportunity to earn a R50 food voucher (redeemable in a local supermarket) conditional on HIV testing. If a participant tests positive for HIV, he/she will have the opportunity to receive a second R50 food voucher conditional on linking within 6 weeks following the HIV test to one of the 11 local primary care clinics where HIV treatment and care are available.

In those arms of this cluster RCT that include the male-sensitive HIV-specific decision support app, men will be offered EPIC-HIV (a first version, so-called EPIC-HIV-1) prior HIV counseling and testing. EPIC-HIV-1 is aimed at increasing HIV testing uptake. Those participants who do not link to care within a month of the HIV test will be offered a second version of EPIC-HIV (so-called EPIC-HIV-2) at home to encourage linkage to care.

Follow up of participants:

Participants will be followed up routinely through the AHRI's ongoing population-based HIV surveillance. All participants will be followed up for at least 3 years.

Linkage to care will be routinely established via the AHRI's ongoing linkage of clinical records for all patients in the local public sector ART program in the demographic surveillance.

Data management: Data will be collected and managed by AHRI Research Data Management within PIP databases as per AHRI comprehensive study operating procedures (SOPs). The Population Intervention Platform (PIP) database has strictly restricted access via a data enclave on a secure server.

Data analysis:

All primary analyses (of both primary and secondary endpoints) will be intent-to-treat (ITT).

For the binary primary outcomes - HIV testing uptake, HIV treatment linkage, and population-level HIV viral suppression - the investigators will use generalized linear models with a Poisson distribution, log link function, and robust error terms to determine effect sizes (risk ratios).

For the two survival-analytical primary endpoints - population-level mortality among men and population-level HIV incidence among women - the investigators will use the Cox proportional hazards model to determine effect sizes (hazard ratios). If the proportional hazards assumption of the Cox model is violated, the investigators will use appropriate alternative survival analytical models.

In all primary analyses, the investigators will adjust for both baseline endpoints and clustering. For the survival analytical endpoints, the investigators will use data from the period 2004-2017 for baseline endpoint adjustment.

In addition, to the ITT analyses, the investigators will measure intervention effects adjusted for non-compliance using instrumental variable (IV) approaches

Eligibility criteria: Inclusion Criteria:

* 15 years old and above
* Resident members of households within the Population Intervention Platform
* Have consented to participate in Population Intervention Platform

additional eligibility criteria for EPIC-HIV

-Male

Exclusion Criteria:

* Refused to take part in Population Intervention Platform
* Participant reported to already be on ART

Primary outcomes:
measure: HIV testing uptake at point of test offer in men
timeFrame: Baseline
measure: HIV treatment linkage at 1 year in men
timeFrame: year 1
measure: Population-level HIV viral suppression in men
timeFrame: year 1
measure: Population-level HIV-related mortality in men
timeFrame: year 3
measure: Population-level HIV incidence in young women (15-30 years of age)
timeFrame: year 3
Secondary outcomes:
measure: HIV testing uptake at point of test offer in women
timeFrame: Baseline
measure: HIV treatment linkage at 1 year in women
timeFrame: year 1
measure: Population-level HIV viral suppression (both sexes)
timeFrame: year 1
measure: Population-level HIV viral suppression (both sexes)
timeFrame: year 3
measure: Population-level HIV viral suppression in women
timeFrame: year 1
measure: Population-level HIV viral suppression in women
timeFrame: year 3
measure: Population-level HIV viral suppression in men
timeFrame: year 3
measure: Population level HIV incidence (both sexes)
timeFrame: year 3
measure: Population-level HIV-related mortality (both sexes)
timeFrame: year 3
measure: Population-level all-cause mortality (both sexes)
timeFrame: year 3
measure: Population-level HIV-related mortality in women
timeFrame: year 3
measure: Population-level HIV incidence in men
timeFrame: year 3
measure: HIV status knowledge in men and women
timeFrame: year 1
measure: HIV prevention knowledge in men and women
timeFrame: year 1
measure: HIV treatment utilization in men and women
timeFrame: year 1
measure: Reported condom use in men and women
timeFrame: year 1
measure: Tuberculosis (TB) healthcare utilization in men and women
timeFrame: year 1
measure: Diabetes Healthcare utilization in men and women
timeFrame: year 1
measure: Hypertension healthcare utilization in men and women
timeFrame: year 1
measure: Household wealth (household assets)
timeFrame: year 3
measure: Household wealth (food security)
timeFrame: year 3
measure: Partnership patterns in men and women
timeFrame: year 1
measure: Retention in HIV care in men and women
timeFrame: year 1
measure: Retention in HIV care in men and women
timeFrame: year 3
measure: Patient viral suppression in men and women
timeFrame: year 1
measure: Patient viral suppression in men and women
timeFrame: year 3
Other outcomes:
Locations:
city: Mtubatuba
country: South Africa
facility: AHRI
state: KwaZulu Natal
Study officials:
affiliation: Africa Health Research Institute
name: Frank Tanser, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tanser FC, Kim HY, Mathenjwa T, Shahmanesh M, Seeley J, Matthews P, Wyke S, McGrath N, Adeagbo O, Sartorius B, Yapa HM, Zuma T, Zeitlin A, Blandford A, Dobra A, Barnighausen T. Home-Based Intervention to Test and Start (HITS): a community-randomized controlled trial to increase HIV testing uptake among men in rural South Africa. J Int AIDS Soc. 2021 Feb;24(2):e25665. doi: 10.1002/jia2.25665.