TB Reduction Through ART and TB Screening Project

NCT03739736 | Unknown

• 2 other identifiers: 14905RIA2016S-1632
• Study Type: observational
• Target: 4,200
• Locations: 1 country
• Sites: 1

Brief Summary

Tuberculosis (TB) has overtaken HIV as the leading infectious cause of death worldwide and requires a major policy shift for it to be controlled in line with the WHO Stop-TB goal to "end TB". However, how to control TB at population level in the context of HIV, is unknown. Some of the best evidence to date comes from the Southern African ZAMSTAR trial, where a household-level TB /HIV intervention including TB symptom screening, HIV counselling and testing with linkage to care and isoniazid preventive therapy (IPT) as indicated, was offered to all household members of TB patients. Despite only reaching \~6% of households in the intervention communities, the data showed a nearly 20% reduction in TB disease prevalence and 50% reduction in TB infection incidence at the population-level. Increasing the scope of the intervention to all households and thus all community members, may therefore significantly change the burden of TB and "end TB". The proposed TREATS project builds on the experience of ZAMSTAR and is nested within the ongoing HPTN 071 (PopART) trial (NCT01900977), the largest ever trial of a combination HIV/TB prevention intervention being conducted in Zambia and South Africa. The project consists of 4 linked studies that will provide definitive cluster-randomised evidence of the effect of a household-level combined HIV and TB prevention intervention on the burden of TB at population level. The project will produce two major outputs of global importance to public health policy. The first will provide definitive evidence of the effectiveness of scaled up combination TB/HIV prevention interventions on TB. The second output will improve understanding of the best ways to measure the impact of public health interventions on TB burden. This is a unique opportunity to assess the impact of combination HIV prevention, including universal HIV testing and treatment, combined with population screening for active TB on the burden of TB. The HPTN071(PopART) trial,a cluster randomised trial in 21 communities in Zambia and South Africa with a population size of approximately 1 million individuals, is unlikely ever to be repeated. The recently adopted WHO guidelines of a "universal treatment" strategy for HIV, will prompt policy-makers to seek strategies of case-finding for HIV offering an opportunity to conduct TB screening on a large scale. The results from the TREATS project will therefore provide unique and timely information of the additional costs and benefits of combined TB and HIV prevention strategies at population level. TREATS will also assess novel methods to measure the effect of interventions on burden of TB in the trial communities. The latest interferon gamma release assay QuantiFERON® Gold Plus will be assessed for measuring impact of TB interventions on incidence of infection. A combination of Xpert® MTB/RIF and computer aided digital X-ray (CAD4TB) will be assessed for measuring prevalence of active TB. These new methods will provide important information about the best way of measuring TB incidence and prevalence rates and allow triangulation of the different methods to inform global estimates of TB burden in the post MDG era. The TREATS consortium will stimulate synergy between leading African research groups (Zambart, HST); new European technology (Delft Diagnostic Imaging, Qiagen); international TB bodies (The Union) and European research centres (LSHTM, Imperial College, Sheffield University and KNCV), as well as with the US funders of the HPTN071/PopART trial.

Conditions

Tuberculosis; HIV/AIDS

Keywords

Combination TB/HIV prevention interventions; Incidence of Tuberculosis; Prevalence of Tuberculosis; Africa; Community-based

Outcome Measures

Primary Outcomes (2)

• The incidence rate of TB infection

  Incidence rate of infection with M. tuberculosis (number of new TB infections per person year at risk) in a randomly selected cohort of approximately 4200 adolescents and adults (15-24 years) who were not infected with M. tuberculosis (initially QFT-negative) on the date of study enrolment, and followed up for two years during the time period 2018-2021.

  Up to 24 months

• The prevalence of TB disease

  The prevalence of bacteriologically confirmed TB disease measured cross-sectionally in a random sample of individuals (15 years and above) at baseline, 1-2 years after the end of the PopART intervention, which was delivered in 2014-2017.

  One time point at baseline

Secondary Outcomes (2)

• Notified bacteriologically confirmed pulmonary TB incidence rate in the parent HPTN071 trial Population Cohort

  Up to 24 months

• Notified bacteriologically confirmed pulmonary TB incidence rate among adults in the community

  Up to 24 months

Study Arms (3)

Combination of TB/HIV prevention activities (A)

Communities in the intervention group (A) were exposed to a combination of TB/HIV prevention activities, including active case finding (ACF) for TB and Universal Testing and Treatment for HIV delivered in the community. In this arm, ART was initiated regardless of CD4 count

Other: Combination of TB/HIV prevention activities (arm A)

Standard of care (C)

The standard of care arm (C) communities have access to TB/HIV testing, care and treatment services (usually at the health facility) and according to national guidelines. TB case finding is "passive" i.e. relies on individuals to present with symptoms to the health facility.

Other: Standard of care (arm C)

Combination of TB/HIV prevention activities (B)

The intervention in arm B was the same as in arm A, consisting in a package of combination of TB/HIV prevention activities, including active case finding (ACF) for TB and Universal Testing and Treatment for HIV delivered in the community. Differently to arm A, in arm B national guidelines on CD4 count were used for ART initiation. During the trial the thresholds for commencement of ART changed from 500 CD count to 350 CD count and then, in 2016, to universal ART regardless of CD4 count.

Other: Combination of TB/HIV prevention activities (arm B)

Interventions

Combination of TB/HIV prevention activities (arm A) OTHER

The intervention consists in a package of combination TB/HIV prevention activities, including active case finding for TB and universal test and treat for HIV. In arm A ART was initiated regardless of CD4 count. The intervention was delivered over a period of four years (2014-2017) by community health workers within the The HPTN071(PopART) trial (NCT01900977)

Combination of TB/HIV prevention activities (A)

Combination of TB/HIV prevention activities (arm B) OTHER

The intervention consists in a package of combination TB/HIV prevention activities, including active case finding for TB and universal test and treat for HIV. In this arm B ART was initiated according to national guidelines. The intervention was delivered over a period of four years (2014-2017) by community health workers within the The HPTN071(PopART) trial (NCT01900977)

Combination of TB/HIV prevention activities (B)

Standard of care (arm C) OTHER

The standard of care arm C communities have access to HIV testing services (usually at the health facility), HIV care and ART provision according to national guidelines. TB case finding is "passive" i.e. relies on individuals to present with symptoms to the health facility. TB diagnostics are as per national guidelines including Xpert®TB/RIF for those who are HIV positive. All diagnosed cases of TB are treated as in the intervention arm. TB screening and prevention at HIV care clinics are as is in the intervention arm.

Standard of care (C)

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

TREATS will work in the communities randomized to arms A, B and C in the PopART trial. In Zambia the sites are in Lusaka, Ndola, Kitwe, Kabwe, Choma and Livingstone.In South Africa two sites are in the Cape Town Metropolitan and one in the Cape Winelands district. Selection criteria for communities included having a health facility that offered TB and HIV services, a high HIV prevalence, a TB notification rate of at least 400/100,000 per year and a total population of about 20,000 or more to minimize the effects of contamination. Additional considerations that informed selection of these sites included to be: geographically distinct, no other major HIV prevention studies planned or ongoing, willing to be involved. The communities were selected in conjunction with national and local health authorities

You may qualify if:

• Usually resident in the community (defined as spends at least 9 months of the year living there),
• Residing in the community for at least 2 years previously
• Intending to stay in the community for next 2 years (\* only in Incident Cohort)
• Aged 15-24 years (\* ≥15 years in Prevalence Survey)
• Able to give informed consent
• On TB treatment (\* only in Incident Cohort)

You may not qualify if:

• Non-resident visitor
• Age \<15 or \>25 years (\* \<15 years in Prevalence Survey)
• Participation in TB vaccine or other TB prevention trial.

Sponsors & Collaborators

• London School of Hygiene and Tropical Medicine: lead
• Zambart: collaborator
• Health Systems Trust: collaborator
• International Union Against Tuberculosis and Lung Diseases: collaborator
• KNCV Tuberculosis Foundation: collaborator
• Imperial College London: collaborator
• University of Sheffield: collaborator
• QIAGEN GmbH, Germany: collaborator
• Delft Imaging Systems BV (Delft), Netherlands: collaborator
• London School of Economics and Political Science: collaborator

Study Sites (2)

Health Systems Trust

Cape Town, Western Cape, 7700, South Africa

Location

Zambart

Lusaka, 50697, Zambia

Location

Related Publications (5)

• Ayles H, Muyoyeta M, Du Toit E, Schaap A, Floyd S, Simwinga M, Shanaube K, Chishinga N, Bond V, Dunbar R, De Haas P, James A, Gey van Pittius NC, Claassens M, Fielding K, Fenty J, Sismanidis C, Hayes RJ, Beyers N, Godfrey-Faussett P; ZAMSTAR team. Effect of household and community interventions on the burden of tuberculosis in southern Africa: the ZAMSTAR community-randomised trial. Lancet. 2013 Oct 5;382(9899):1183-94. doi: 10.1016/S0140-6736(13)61131-9. Epub 2013 Aug 1.

  PMID: 23915882 BACKGROUND

• Klinkenberg E, Floyd S, Shanaube K, Mureithi L, Gachie T, de Haas P, Kosloff B, Dodd PJ, Ruperez M, Wapamesa C, Burnett JM, Kalisvaart N, Kasese N, Vermaak R, Schaap A, Fidler S, Hayes R, Ayles H; TREATS study team. Tuberculosis prevalence after 4 years of population-wide systematic TB symptom screening and universal testing and treatment for HIV in the HPTN 071 (PopART) community-randomised trial in Zambia and South Africa: A cross-sectional survey (TREATS). PLoS Med. 2023 Sep 8;20(9):e1004278. doi: 10.1371/journal.pmed.1004278. eCollection 2023 Sep.

  PMID: 37682971 DERIVED

• Mainga T, Gondwe M, Mactaggart I, Stewart RC, Shanaube K, Ayles H, Bond V. Qualitative study of patient experiences of mental distress during TB investigation and treatment in Zambia. BMC Psychol. 2022 Jul 19;10(1):179. doi: 10.1186/s40359-022-00881-x.

  PMID: 35854324 DERIVED

• Mainga T, Gondwe M, Stewart RC, Mactaggart I, Shanaube K, Ayles H, Bond V. Conceptualization, detection, and management of psychological distress and mental health conditions among people with tuberculosis in Zambia: a qualitative study with stakeholders' and TB health workers. Int J Ment Health Syst. 2022 Jul 12;16(1):34. doi: 10.1186/s13033-022-00542-x.

  PMID: 35820917 DERIVED

• Floyd S, Klinkenberg E, de Haas P, Kosloff B, Gachie T, Dodd PJ, Ruperez M, Wapamesa C, Burnett MJ, Kalisvaart N, Vermaak R, Mainga T, Schaap A, Fidler S, Mureithi L, Shanaube K, Hayes R, Ayles H; TREATS study team. Optimising Xpert-Ultra and culture testing to reliably measure tuberculosis prevalence in the community: findings from surveys in Zambia and South Africa. BMJ Open. 2022 Jun 16;12(6):e058195. doi: 10.1136/bmjopen-2021-058195.

  PMID: 35710250 DERIVED

Related Links

• WHO Global Tuberculosis Report 2018

Biospecimen

Retention: SAMPLES WITH DNA

* Blood sample (Infection Cohort) * Sputum sample (Infection Cohort and TB Prevalence Survey) * Capillary sample (TB Prevalence Survey)

MeSH Terms

Conditions

Tuberculosis; Acquired Immunodeficiency Syndrome

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; HIV Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Helen Ayles, Professor

  London School of Hygiene and Tropical Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2018
• First Posted: November 14, 2018
• Study Start: June 12, 2018
• Primary Completion: April 30, 2021
• Study Completion: April 30, 2021
• Last Updated: February 25, 2021

Record last verified: 2020-05

Data Sharing

• IPD Sharing: Will share
• Time Frame: Study findings on co-primary outcomes and key secondary outcomes will be made available on publication of research findings (which may occur during the 1st and 2nd year). Anonymised data used for the analysis of the co-primary outcomes and key secondary outcomes will be made openly accessible at the latest two years after all study databases are locked.
• Access Criteria: Data will be made available in CSV format to enable the use of a wide range of tools including STATA, SPSS, SAS and others. This will be accompanied by documentation necessary to understand the content. No restrictions on data access are envisaged. However, in the event that constraints are necessary (e.g. for confidentiality reasons), data will be made available through an application process, whereby researchers must provide details on their intended use.

Locations

ZA (1)