ART FOR ART PREVENTION. Introduction of ongoing or planned trials

Transcription

1 ART FOR ART PREVENTION Introduction of ongoing or planned trials François Dabis, MD, PhD for WHO Department of HIV/AIDS Geneva - November 3, 2009

2 ART FOR ART PREVENTION as of November 2009 Descriptive epidemiology of «who does what» Except modelling

3 ART FOR ART PREVENTION as of November 2009 Who does what Acknowledgements M. Cohen, C. Dieffenbach, W. El-Sadr, S. Fidler, R. Gray, M-L. Newell, J. Montaner, S. Reynolds, M. Sweat, J. Weber, B. Williams

4 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

5 NIMH Project Accept HPTN 043 Impact of Community-Based Provision of VCT Thailand, rural Tanzania, very rural Soweto, Gauteng, South Africa, urban Vulindlela, Kwazulu Natal, South Africa, rural Zimbabwe, 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

6 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

7 Long-term follow-up of serodiscordant couples in the ART era Rakai, Uganda: prospective cohort

8 Population effect of Anti-retroviral therapy to Reduce HIV Transmission (PopART) A step-by-step research program in Uganda (Masaka) and Zambia (ZAMBART) PopART feasibility Acceptability, feasibility, cost-effectiveness and safety of the Universal Test and Treat strategy

9 Treatment as Prevention (TasP) A step-by-step research program in South Africa TasP «zero» How to provide universal testing - How to provide effective universal ART - Determining origin of new infections - Documenting ARV resistance patterns

10 TasP QuickTime et un décompresseur TIFF (non compressé) sont requis pour visionner cette image.

11 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

12 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

13 HPTN 052 an RCT 1,750 couples, 8 countries and 12 sites Boston, Rio de Janeiro, Blantyre, Lilongwe, Harare, Pune, Chennai, Chiang Mai Randomization Immediate ART cells/µl AZT+3TC+EFV/ATV Deferred ART CD4 < Endpoints: i) Transmission events ii) OIs and clinical events-who 2, 3, 4 (Tb) iii) ART toxicity

14 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)

15 Seek, test and treat: addressing HIV in the criminal justice system in the USA National Institute of Drug Abuse (NIDA) RFA recently published

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17 A cluster-randomized trial of the preventive effect of ART - TasP 1 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) QuickTime et un décompresseur TIFF (non compressé) sont requis pour visionner cette image.

18 Outcomes of the TasP 1 trial Primary outcome: HIV incidence Other outcomes: HIV-related morbidity (importantly TB) Adherence/compliance Adverse events Behavioural patterns Impact on the community

19 Population effect of Anti-retroviral therapy to Reduce HIV Transmission (PopART) A community cluster-randomized trial in preparation

20 Phase III: Just do it With the best possible monitoring and evaluation of all biomedical, behavioural and psycho-social consequences

21 STOP HIV & AIDS STOP HIV & AIDS: Seek and Treat to Optimally Prevent HIV & AIDS* Prospectively Evaluate the Impact of HAART Expansion on AIDS Morbidity and Mortality and HIV Incidence in British Columbia Intervention Primary Endpoint HAART 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

22 ART FOR ART PREVENTION as of November 2009 Concluding remarks - A lot to be learnt from feasibility studies and pilot projects throughout the world - - -

23 ART FOR ART PREVENTION as of November 2009 Concluding remarks - A lot to be learnt from feasibility studies and pilot projects throughout the world - Randomized trials are unavoidable to obtain high-level evidence at population level - -

24 ART FOR ART PREVENTION as of November 2009 Concluding remarks - A lot to be learnt from feasibility studies and pilot projects throughout the world - Randomized trials are unavoidable to obtain high-level evidence at population level - Combining skills in clinical and behavioral research -

25 ART FOR ART PREVENTION as of November 2009 Concluding remarks - A lot to be learnt from feasibility studies and pilot projects throughout the world - Randomized trials are unavoidable to obtain high-level evidence at population level - Combining skills in clinical and behavioral research - Combining agendas of research agencies, implementers, MOH and communities

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