International Partnership for Microbicides Approach to HIV Treatment and Care in Future IPM Microbicide Trials Pam Norick, Chief of External Relations 19 June 2008

IPM Mission Established in 2002 as a non-profit product development partnership Offices in the US, Belgium and South Africa Mission to prevent HIV transmission by accelerating the development and availability of safe and effective microbicides for use by women in developing countries

IPM Donors Belgium Canada Denmark France Germany Ireland Netherlands Norway Sweden United Kingdom United States European Commission World Bank UNFPA Rockefeller Foundation Gates Foundation

CompoundLicenseType/StageDevelopment status DapivirineTibotec (2004) NNRTI (reverse transcription) In Phase I/II clinical trials (vaginal gel & ring) M167, M872, M882 (DS001, 004, 005) Merck (2005) CCR5 blockers (attachment) Preclinical (development on hold) BMS793 (DS003) BMS (2005) gp120 binder (attachment) Early preclinical TenofovirGilead (2006) NRTI (reverse transcription) Phase I PK (CONRAD/IPM) Phase IIB (CAPRISA, MTN) MaravirocPfizer (2008) CCR5 blocker (attachment) Preclinical L’644 peptide (DS007) Merck (2008) gp41 binder (fusion) Early preclinical Partnerships with Industry

IPM Clinical Studies of Dapivirine Safety/ Feasibility PK Safety PK/Feasibility Safety Male tolerance Studies in Africa, Europe, United States Phase III efficacy Seroconverter protocol PK Safety

IPM work in Africa Completed or ongoing studies and activities Possible activity

Ethical Guidelines for Clinical Trials  Community engagement  Monitoring of social harms  Informed consent process  Risk reduction counseling  Male/female condoms  Family planning  Management of pregnancy  STI screening and treatment  Testing positive at screening  Counseling and Rx referrals  Participants who seroconvert  Counseling and Rx referrals  Follow-up study protocol  Partnerships/dedicated financing  Treatment for physical harms  Services for study staff  Post-trial access to products

Ethical Guidelines Updates  First developed in  Review by ethicists, stakeholders  Revisions in  Consistent with latest UNAIDS, WHO and country guidelines  Document refers principally to clinical trials in developing world  Currently under external review  Expected publication July 2008

Seroconversions – IPM Trials None to date So far conducted Phase I/II safety trials Small sample size (N=130 in Africa) Short enrollment duration (max 6 weeks) Many trials in Belgium (low HIV incidence) Preparing for larger safety trials in Africa IPM 014 A & B (dapivirine gel, N=640, 6 weeks) IPM 015 (dapivirine ring, N=280, 12 weeks)

IPM Plans and Approach Participants who seroconvert during trials offered appropriate HIV-related care and ARV therapy Plan to implement in multiple ways: Follow-up study (seroconverter protocol – IPM 007) Guided referrals for HIV care, treatment, support Pre-established partnerships with national/local institutions Dedicated financing if national programs cannot sustain Pursuing additional support from global donors

n IPM research centres established in areas where capacity for HIV care & treatment exists Part of site selection and development process To assure sustainability, develop partnerships with national ministries of health, hospitals, universities, etc. n Dedicated IPM financing in the event national programs cannot assume ongoing responsibility Funds independent of IPM business/financial status Insurance company or other mechanisms Approaches to Funding and Delivery

Key Challenges Timeframe: participants may not need treatment until years after a trial Migration: how to ensure access for people who move out of the area or country Follow-up: how best to keep in touch with participants & inform them of choices Referral networks: how to ensure their strength over time Sustainability: what is the best approach? (IPM options paper 2007)

n PEPFAR n Global Fund n Clinton Foundation n Other microbicide donors n Host country governments  UNAIDS/WHO recommend that countries include HIV prevention trial participants in their priority list for access to ARV treatment Pursuing Additional Support Ethical Considerations in Biomedical HIV Prevention Trials, 2007