art for art prevention introduction of ongoing or … · hptn 065 – tnt-plus test and treat in...

ART FOR ART PREVENTION

Introduction of ongoing or planned trials

François Dabis, MD, PhD

for WHO Department of HIV/AIDS

Geneva - November 3, 2009

ART FOR ART PREVENTIONas of November 2009

Descriptive epidemiology of « who does what »

Except modelling

ART FOR ART PREVENTIONas of November 2009

Who does whatAcknowledgements

M. Cohen, C. Dieffenbach, W. El-Sadr, S. Fidler, R. Gray, M-L. Newell,

J. Montaner, S. Reynolds, M. Sweat, J. Weber, B. Williams

Phase I: Pilot projects

• Acceptability of testing• Acceptability of treatment• Compliance with treatment• Minimal side effects• Make sure that we do not create stigma• Check that we get viral load suppression• Measure residual transmission• Check for viral rebound• Monitor drug resistance• Consider cost and delivery

NIMH Project Accept HPTN 043Impact of Community-Based

Provision of VCTThailand, ruralTanzania, very ruralSoweto, Gauteng, South Africa, urbanVulindlela, Kwazulu Natal, South Africa, ruralZimbabwe, very rural

Comparing two VCT approaches during 2.5 years: standard (clinic-based) versus community-based (mobile with post-test support services)

Behavioral and biological assessment at community level

CTN0032: HIV rapid testing& counselling in drug abuse treatment programs in the USA

• A randomized controlled trial of the relative effectiveness of three HIV testing strategies on increasing receipt of test results and reducing HIV sexual risk behaviors

• An adaptation to STD clinics planned

Long-term follow-up of serodiscordant couples

in the ART era

•Rakai, Uganda: prospective cohort

•…

A step-by-step research programin Uganda (Masaka) and Zambia (ZAMBART)

PopART feasibility - 2010-2012- Acceptability, feasibility, cost-effectiveness and safety of the Universal Test and Treat strategy

Population effect of Anti-retroviral therapy to Reduce HIV Transmission

(PopART)

A step-by-step research programin South Africa

TasP « zero » - 2010-2011- How to provide universal testing- How to provide effective universal ART- Determining origin of new infections- Documenting ARV resistance patterns

Treatment as Prevention (TasP)

TasP

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Phase II: Randomized controlled trials or step-wise interventions

Monitor all outcomes investigated in phase I studies

And measure changes in incidence of HIV and TB at a population level

HPTN 052 –Selected Research Goals

• Discordant couples study randomized to immediate or deferred therapy to determine :– Impact of early ART on HIV disease

progression (between 250 and 550 CD4 cells)

– Efficacy of ART in preventing HIV transmission

HPTN 052 … an RCT

1,750 couples, 8 countries and 12 sites1,750 couples, 8 countries and 12 sitesBoston, Rio de Janeiro, Blantyre, Lilongwe,

Harare, Pune, Chennai, Chiang Mai

Immediate ARTImmediate ART350350--550 cells/550 cells/µµLL

Deferred ART Deferred ART CD4 <200CD4 <200--250250AZT+3TC+EFV/ATVAZT+3TC+EFV/ATV

Endpoints: i) Transmission events Endpoints: i) Transmission events ii) ii) OIs OIs and clinical eventsand clinical events--WHO 2, 3, 4 (Tb)WHO 2, 3, 4 (Tb)iii) ART toxicityiii) ART toxicity

Randomization

HPTN 065 – TNT-Plus Test and treat in the USA

• Evaluate the feasibility and effectiveness of four components of a community-focused enhanced HIV TNT-Plus strategy in the Bronx and in Washington DC:– Expand HIV testing– Strengthen the link with care for prompt ART

initiation (site randomization)– Promote adherence to maximize viral

suppression (site randomization)– Decrease high-risk sex behaviors (prevention

for positives) (individual randomization)

Seek, test and treat: addressing HIV in the criminal justice system in the USA

• National Institute of Drug Abuse (NIDA)

• RFA recently published

Study hypothesis:Treatment of all HIV-infected individuals

regardless of CD4 cell count or viral load in a population will lower HIV

incidence in this community(population effectiveness)

A cluster-randomized trial of the preventive effect of ART - TasP 1

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Outcomes of the TasP 1 trial• Primary outcome:

HIV incidence

• Other outcomes:HIV-related morbidity (importantly TB)Adherence/complianceAdverse eventsBehavioural patternsImpact on the community

A community cluster-randomized trial

in preparation

Population effect of Anti-retroviral therapy to Reduce HIV Transmission

(PopART)

Phase III: Just do it

With the best possible monitoring and evaluation of all biomedical, behavioural and psycho-social consequences

Prospectively Evaluate the Impact of HAART Expansion on AIDS Morbidity and Mortality and

HIV Incidence in British Columbia

Intervention Primary EndpointHAART Expansion HIV Incidence within medical guidelines at years 3 to 5

Secondary Endpoints:

Morbidity and mortality, CD4 counts, HIV-1-RNA

levels, viral resistance, adverse events, safety,

adherence, hospitalization, resource utilization

* Supported by the National Institute for Drug Abuse (NIDA) at the NIH

STOP HIV & AIDSSTOP HIV & AIDS: Seek and Treat to Optimally Prevent HIV & AIDS*

ART FOR ART PREVENTIONas of November 2009Concluding remarks

- A lot to be learnt from feasibility studies and pilot projects throughout the world

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- Randomized trials are unavoidable to obtain high-level evidence at population level

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- Combining skills in clinical and behavioral research-




- Combining skills in clinical and behavioral research- Combining agendas of research agencies, implementers, MOH and communities

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