1. Population effect of ART therapy to Reduce HIV Transmission - PopART A study to assess the feasibility of increased HIV voluntary counselling and testing (VCT) and universal access to antiretroviral therapy (ART) to reduce HIV incidence Dr Ade Fakoya, Senior Advisor: HIV and Health Services, International HIV/AIDS Alliance

2. PopART Membership United Kingdom Imperial College London – Geoffrey Garnett – Sarah Fidler – Christophe Fraser – Becky Baggaley – Jonathan Weber Institute of Global Health – Peter Piot LSHTM – Richard Hayes – David Ross – Debby Watson-Jones – Johanna Hanefeld MRC CTU – Adbel Babiker – Sheena McCormack UCL – Andrew Phillips International HIV/ AIDS Alliance – Ade Fakoya Africa: PIs Uganda ( MRC-UVRI) Zambia ( Zambart)

3. The Prevention- Treatment gap….. By the end 2007: 3 million were receiving ART --about 1 million people added 6.7 million in need 2.7 million new infections

4. PopART – The Goal A comprehensive feasibility study to address the key assumptions underpinning the Universal Testing and Treatment concept (UTT) To determine whether a larger randomised trial is possible

5. ‘Know your status’. ‘Take Lifelong treatment if you are positive’ ‘Grace’ 18 years old Both brother and mother are positive HIV positive ( 12 years ) CD4 – 61 Viral Load 110,000 Not on ARV treatment

6. PopART- four levels of exploration ‘Logistical feasibility’ – pilot studies in districts in Uganda and Zambia. ‘ Test the approach’ ‘acceptability’ – individual, community, population, government ‘wider implications’ – health economics human rights, drug issue ( resistance, toxicity, ) Mathematical modelling ( data to support assumptions,

7. Feasibility Study Design Engage with country stakeholders National stakeholder and community engagement and acceptability of interventions Compilation of data on HIV epidemiology, testing and treatment monitoring Development of HIV incidence measurement Field testing of novel point of care assays

8. Some key questions Key area Main issues Acceptance of Treatment as prevention At individual, community and country levels, What will be the uptake of ARV treatment for those who may not need it for clinical need Logistical Provision of treatment in health systems which are already over- stretched Is it logistically feasible, what coverage is actually possible, will it divert funding from other areas, will it increase waiting lists for those who need treatment to actually stay alive Starting and staying on treatmentDrop out rate, the survival, the residual HIV transmission Resistance to ARV drugsWhat is the optimum regimen for TAP, what will the strategy do to population levels of resistance at what level resistance will assumptions become how will resistance be monitored at a population level

9. Some key questions Key area Main issues Marginalised groupsIn a generalised epidemic, what will be the focus and special attention required for hard to reach groups including sex workers, men who have sex with men, drug users, people who move (including migrants ) Human rightsWill a focus on a public health approach further erode human rights, is it acceptable for individuals to take treatment when they don’t need it. What about other health needs? What about marginalised populations? AdherenceWhat level of adherence is important to ensure success?

10. PopART: Feasibility Mathematical modelling Undertake critical evaluation of current models Develop an HIV transmission model Inform the design of the Cluster randomised trial( CRT), Determine the predicted effect size; For a given effect size, the model will be used to estimate the minimum proportion of the HIV+ve population that will need to be identified and treated. Estimate the minimum threshold that needs to be reached to ensure a substantial public health impact.

11. PopART Modelling Led by IC What % HIV+ threshold of detection is required to demonstrate an effect What % uptake of ART is required to demonstrate an effect What is the risk of viral drug resistance and toxicity What is the cost benefit analysis ► Set parameters for RCT

12. Epidemiology led by LSHTM, MRC CTU two selected communities of approximately 25 000 people comprehensive VCT package ( house-to-house testing, mobile testing units, work place testing and village facilities. All individuals identified as HIV+ve will be immediately referred into local standard care health care facilities Random selected population (10% of the total) enrolled into a pilot RCT: either standard care (CD4 driven initiation of ART) or a UTT strategy where irrespective of CD4 T-cell count ART will be immediately offered.

13. PopART Pilot - Human Rights Human rights based approaches an explicit part of the feasibility and pilot study. Two broad elements: 1/to better understand the effect and interaction of PopART interventions on human rights, 2/develop best practice human rights approaches especially in community interventions but at all levels of rights based approaches for treatment as prevention.

14. PopART Pilot - Human Rights Specific objectives To explore the human right dimensions of the concept of treatment as prevention (TAP) and ensure that the pilot study adheres to human rights principles, including the right to information, participation, non-discrimination and equity. To explore areas of investigation relating to the acceptability and feasibility of treatment as prevention at individual, community and national level To understand the potential barriers to universal HIV testing and immediate uptake of HIV treatment. To develop individual and community based interventions that address the barriers to successful recruitment and participation in any future CRT of treatment as prevention, while ensuring human rights of the individual are fulfilled, protected and guaranteed.

15. PopART Pilot - Human Rights How will this work in practice? Human rights/social science working group consisting of staff from each of the implementing partners, including the MRC Uganda and Zambart who develop and implement a detailed methodology. Local Community advisory group in each country *Ethics reference/advisory group made up of key external experts/individuals who can advise on the human rights dimension of treatment as prevention and the issues which arise during the execution of the study.

16. PopART Pilot - Human Rights Possible Methods include* Ethnographies In-depth interviews over time (3 year study) Work with policymakers at national level and district level. The human rights part of the research will focus on the individual level, but also on how to achieve greater acceptability for the inclusion of rights based approaches with policymakers at all levels. * The HR working group will develop these in detail as part of the study and will be led by country context.

17. PopART Pilot - Human Rights Your thoughts? Specifically around the areas of study and investigation More detail and information – Ade Fakoya at the AIDS Alliance afakoya@aidsalliance.org afakoya@aidsalliance.org – Johanna Hanefeld at London School of Hygiene and Tropical Medicine johanna.hanefeld@lshtm.ac.ukjohanna.hanefeld@lshtm.ac.uk

18. Combination prevention- no magic bullets

19. Summary I There will be a population effect of ARV treatment roll out Despite the enormous assumptions in the mathematical modelling, UTT and Universal Access to HIV treatment care and prevention are closer together than it would appear Need community engagement to find out what affected communities and individuals think.