Pre-exposure Prophylaxis (PrEP) Policy, Practice and Politics Pre-exposure Prophylaxis (PrEP) Preparing for PrEP Yasmin Halima Consultant, AIDS Vaccine Advocacy Coalition (AVAC) AIDS 2008, Mexico City 3 August 2008

Highlight research, policy and political issues Clinical trials update Introduce framework for panel discussion

Public notices observed in India In a hotel You are invited to take advantage of the chambermaid. At Edwards Laundry Drop your trousers here for best results. Please leave your values at the front desk. On the office door of a gynaecologist Specialist in women and other diseases. 3

What is PrEP and why do we need it? Pre-exposure prophylaxis (PrEP) involves the use of antiretrovirals to prevent HIV infection. Unlike post-exposure prophylaxis (PEP), prescribed following potential exposure to HIV such as a needle-stick injury, or therapy to prevent mother-to-child transmission, PrEP is intended for use by those who may be at frequent risk for HIV. Global burden Over 4 million new infections occur every year To impact the epidemic we have to reduce transmission Vulnerability to HIV Prevention can protect those most vulnerable - feminisation of HIV - IDUs, MSM Biological plausibility Potential agents and technologies are promising Lessons learned from PMTCT, PEP

Caveats of current research PrEP trials Status of research Caveats of current research Investment in PrEP

Study of daily oral chemoprophylaxis to prevent HIV-1 infection Design Phase II/III placebo-controlled randomised trials to determine if daily oral tenofovir (TDF, 300 mg) or TDF and emitricitabine (TDF/FTC, 300 mg + 200 mg) prevents HIV-1 acquisition and has acceptable safety in HIV uninfected men and women. Primary and secondary objectives Study rates of adverse events in TDF or TDF/FTC arm compared to placebo Determine if daily PrEP reduces HIV-1 seroincidence Determine if HBV flares follow cessation of TDF or TDF/FTC Substudy of changes in bone mineral density or body fat distribution Evolution of drug resistance in seroconverters Determine if viral load set point and immune characteristics are affected in seroconverters Impact on risk behaviors and adherence

Caveats and issues related to current research Test only TDF-based regimens Test once-daily regimens Selecting risk groups If PrEP works, who will pay? The treatment and prevention dichotomy Increasing but limited investment in PrEP Industry commitment?

Investment in PrEP research in 2007 CDC $15.6m Gates $12.56m USAID $6.0m NIH $4.1m Gilead $1.25m

Anticipating PrEP ‘For the first time, research that is traditionally thought of by the public as some mystified and esoteric process has immediate relevance and significance to many millions - there is a demand for accountability and transparency for how public funds are being used; a demand to see what scientific priorities are set and how; what scientific progress is being made and at what pace; a demand for findings from studies to be translated into policy and practice. As scientists we would do well to pause and reflect on this.’ Quarraisha Abdool Karim, University of KwaZulu Natal, South Africa

Courage is what it takes to stand up and speak. Engaging with PrEP Courage is what it takes to stand up and speak. Courage is also what it takes to sit down and listen. Winston Churchill

Thank you

Assumptions for hypothetical scenarios Size n = 3,000 Trial designed to test efficacy of 70% Lower range of CI 30% SOC for prevention includes regular counselling, male/female condoms Toxicity monitoring includes HBV, bone-mineral density, renal, hepatic impairments Primary endpoints are efficacy and safety; protect against HIV; safe to use on daily basis Secondary endpoints are lower viral set point, higher CD4, viral resistance and behaviour changes HIV testing conducted monthly Resistance testing as follow-up for all seroconverters Post-trial care includes 1 yr provision of PrEP if proven effective for those who do not seroconvert

Results from a PrEP trial testing Truvada (TDF/FTC) Scenario 1 Results from a PrEP trial testing Truvada (TDF/FTC) shows that it is 70% effective at reducing acquisition of HIV in this group.

Results from a PrEP trial testing TDF show that it is Scenario 2 Results from a PrEP trial testing TDF show that it is 50% effective at reducing acquisition of HIV in injecting drug users (IDU) when tested as directly-observed therapy (DOT).

Results from a PrEP trial testing Truvada (TDF/FTC) Scenario 3 Results from a PrEP trial testing Truvada (TDF/FTC) show that it is 70% effective at reducing acquisition of HIV in a heterosexual group of young men and women. However, 2% of those who seroconverted in the trial demonstrated resistance with K65R mutation.