TB Reduction Through ART and TB Screening Project

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

Interventions

OTHER

Combination of TB/HIV prevention activities (arm A)

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)

OTHER

Combination of TB/HIV prevention activities (arm B)

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)

OTHER

Standard of care (arm C)

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.

Sponsors & Collaborators

• Zambart

  collaborator OTHER

• Health Systems Trust

  collaborator OTHER

• International Union Against Tuberculosis and Lung Diseases

  collaborator OTHER

• KNCV Tuberculosis Foundation

  collaborator OTHER

• Imperial College London

  collaborator OTHER

• University of Sheffield

  collaborator OTHER

• QIAGEN GmbH, Germany

  collaborator UNKNOWN

• Delft Imaging Systems BV (Delft), Netherlands

  collaborator UNKNOWN

• London School of Economics and Political Science

  collaborator OTHER

• London School of Hygiene and Tropical Medicine

  lead OTHER

Principal Investigators

• Helen Ayles, Professor · London School of Hygiene and Tropical Medicine

Eligibility

Min Age

15 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2018-06-12

Primary Completion

2021-04-30

Completion

2021-04-30

Countries

• South Africa
• Zambia

Study Locations