ART for TB prevention (& HIV) Studies, Planned or Underway

One of the recent editions of HATIP published in November 2011 addressed the extent to antiretroviral therapy (ART) could be used to reduce the burden of TB. There is no doubt that after the first few months of treatment ART dramatically decreases the risk of active TB in people living with advanced HIV disease — the question is how much of an effect it has on the risk of TB in HIV-positive people with higher CD4 cell counts.

The issue concluded that we need more data on how much early or immediate ART for everyone diagnosed with HIV with ART may improve TB control. There are several studies ongoing or planned that investigating the question, so we should have a clearer answer in a few years. We thought that we’d list the studies we’ve heard about in this blog post, for activists, public health specialists, the HIV and TB communities who are monitoring the issue.

Scaling Up Treatment to Reduce Population Level Incidence of HIV/AIDS

Design: Step-wedge community level randomised trial

Focus: Impact of ART scale-up on HIV incidence

Principal Interventions: Increased access to ART, initiation criteria ART according to national guidelines (CD4 < 250)

Endpoints: HIV and TB incidence, HIV- and TB-related mortality

Where: Uganda, UBC, JCRC

Who: University of British Columbia, Joint Clinical Research Centre

Medecins Sans Frontieres TasP (Treatment as Prevention)

Design: Prospective cohort study

Focus: Feasibility and acceptability test, link, treat and retain strategy

Principle Interventions/ART Criteria: ART initiated at CD4 count < 500 cells, unless viral load is >10,000 copies, male circumcision, and test, link, treat and retain strategy

Endpoints: HIV and TB incidence, HIV- and TB-related morbidity and mortality

Where: KZN, South Africa

Who: Medecins Sans Frontieres (MSF)

The Sustainable East Africa Research for Community Health (SEARCH )

Design: Community cluster- randomised trial

Focus: Health, economic and education outcomes of community health campaign providing HIV testing and treatment services

Principle Interventions/ART criteria: Annual HIV testing, ART regardless of CD4 cell count, streamlined care

Endpoints: HIV incidence; TB, malaria, maternal, HIV and all-cause mortality; education and economic outcomes

Where: Tanzania, Uganda, Kenya

Who: University of California, San Francisco, USA, International Development Research Centre (IDRC), Kenya Medical Research Institute (KEMRI)

Ending New Infections in Swaziland: A Catalytic Model for Southern Africa

Design: Population-based observational study (entire country)

Focus: Universal ART following concept of Treatment 2.0 within 3 years

Principle Interventions/ART criteria: Delivering ART according to 2010 national guidelines (CD4 count < 350) with at least 90% coverage of eligible population

Endpoints: HIV incidence, TB incidence

Where: Swaziland

WHO: STOP AIDS NOW! and the Clinton Health Access Initiative (CHAI)

Early Antiretroviral Treatment and/or Early Isoniazid Prophylaxis against TB in HIV-infected Adults (TEMPRANO trial)

Design: Randomised controlled trial

Focus: Benefits and risks of early ART in HIV-infected people

Principle Interventions/ART criteria: Comparison of 1) standard of care (starting ART according to existing guidelines (CD4 cell count < 350), 2) standard of care plus six months of IPT beginning one month after joining study, 3) early ART, starting before CD4 cell count reaches 350 (between 350 and 800), and 4) early ART plus six months of IPT

Endpoints: Death (all-cause), AIDS-defining disease, non-AIDS-defining malignancy, or non-AIDS-defining invasive bacterial disease, TB or tuberculosis-related death, as well as CD4 cell decline, adherence, resistance, etc.

Where: Abidjan, Côte D’Ivoire

Who: Université Bordeaux, France, Treichville Université Hôpital, Abidjan, Côte d’Ivoire, ANRS Sponsor

Note that this study has been ongoing and may produce results as early as this year

HPTN 070: International HIV Testing and Linkage to Care and Treatment  (iTLCT) Study (this is in concept phase)

Design: Feasibility study for a community randomised trial (

Focus: Enhanced testing, treatment and linkage to care strategy versus standard of care in resource-limited settings

Principle Interventions/ART criteria: Home-based HIV testing, home-based TB screening, linkage to care, ART for people with high viral load for those not eligible under current guidelines

Endpoints: Feasibility, for now

Where: Multiple sites in Africa

Who: NIH, NIAID, HPTN

Treatment 2.0 Project in Vietnam

Design: Population-based observational study (selected provinces)

Focus: Optimal time for ART initiation and effects of alternate service delivery systems

Principle Interventions/ART criteria: simple service delivery system and early ART starting at CD4 cell counts  < 500 vs starting at CD4 cell counts < 350,

Endpoints: HIV incidence, TB incidence, AIDS-related mortality, cost and cost-effectiveness of simple service delivery system

Where: Vietnam

Who: The Vietnam ministry of Health

The final ART for TB prevention study we thought we’d mention here is dramatically different than the other in that it compares immediate ART to ART that has been slightly delayed to follow empiric TB treatment.

The Reducing Early Mortality and Early Morbidity by Empiric Tuberculosis Treatment Regimens (REMEMBER) study (ACTG 5274)

Design: Randomised controlled trial

Focus: Impact of ART and empiric treatment for TB in people with very low CD4 cell counts (<50)

Principle Interventions/ART criteria: Empiric TB treatment followed by ART within a week or two vs local standard of care TB management and immediate ART

Endpoints: Survival status six months after randomisation. Secondary: Time to mortality and/or AIDS progression; virologic and CD4+ cell response; HIV and TB drug resistance; safety and tolerability of and adherence to HIV and TB drugs; cost-effectiveness of the two strategies

Where: All of the 18 international ACTG sites are eligible to participate. (Haiti, Peru, Brazil, South Africa, Zimbabwe, Zambia, Tanzania, Kenya, Uganda, Botswana, Malawi, India and Thailand). 

Who: (ACTG/John Hopkins)

The rationale for the Remember study will be presented in a following post.

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