Antiretroviral Therapy Projects Institute for Family Health

1. Antiretroviral Therapy ProjectsInstitute for Family Health

2. Antiretroviral Projects – Institute for Family Health ART for Prevention Transmission – HPTN 052 Acquisition – Oral TDF, Topical TVF, Perinatal ( HPTN 046, HPTN 057) ART for Treatment HPTN 052/AACTG 0175 HPTN 046/PACTG Interaction with Contraception HC/HIV Workshops – domestic (NICHD), international (WHO) Costs and ethics of ART in US-sponsored research

3. HPTN 052 Objective – To determine whether antiretroviral therapy can prevent sexual transmission of HIV in HIV discordant couples Design – Multi-center, two-arm randomized trial Study Population – 1750 HIV discordant couples, HIV infected participants with CD4 = 300-500 Study Regimens – ART + primary care vs. primary care alone (ART Rx if CD4 < 200) Study Sites – Brazil, India (x2), Malawi (x2), Thailand, Zimbabwe, San Francisco, Boston Secondary Objective – Effect of immediate vs. delayed ART on HIV prognosis

4. HPTN 052 – Status 7/04 Drugs Obtained - GSK (ZDV, 3TC, Combivir) - Gilead (TDF) - BI (NVP) - BMS (EFV) Protocol Approved in May Pilot studies to begin September ‘04 - Local purchase of supplementary ART - 10 couples per site

5. Oral TDF Pre-Exposure Prophylaxis Objective – To evaluate the safety and effectiveness of oral tenofovir (TDF) in preventing acquisition of HIV in high-risk women and men Design – Multi-center, two-arm, placebo-controlled double-blind randomized trial Study Population – 1200 HIV-uninfected women and 400 HIV uninfected heterosexual men in settings of high exposure to HIV Study Regimen – 300 mg. TDF vs. placebo, daily Study Sites – Cameroon, Ghana, Nigeria, Malawi Secondary Objectives – Factors affecting adherence and access, TDF resistance, potential disinhibiting effect

6. Oral TDF – Status 7/04 Staff trained for 3 African sites Approval of Malawi government Formative work on community needs – 4 abstracts at Bangkok Collaboration with Cambodian/CDC teams Screening for RCT began May in Ghana and June in Cameroon/Nigeria

9. Topical TVF Pre-Exposure Prophylaxis Part of FHI’s microbicide portfolio HPTN 050 - - Phase I dose and frequency - 96 women, 24 men - HIV uninfected and infected Male Tolerance (USAID) Phase II (NIH, USAID) - 1 international – Makerere, Uganda - 1 domestic – Columbia, NYC - approximately 200 participants

10. HPTN 046 Objective – To evaluate the safety of nevirapine in breastfeeding infants of HIV-infected mothers and its effectiveness in preventing HIV acquisition Design – Multi-center, two-arm, randomized double-blind, placebo-controlled trial Study Population – 1576 HIV-infected women and their breastfeeding infants Study Regimen – Nevirapine suspension (10 mg/ml) vs. placebo Study Sites – Uganda, South Africa, Zimbabwe, Tanzania Secondary Objectives – NVP resistance, infant survival

11. ART/Contraception/HIV Update Hormonal contraception/HIV studies - NICHD funded – 3 countries - Main study – HIV acquisition - Ancillary study – Genital shedding in incident HIV infections ART provided Proposals developed on - ART/hormonal interactions - Contraceptive choices for HIV- infected women

12. Cost of Introducing ART Evaluate costs of FHI START program in Mombasa, Kenya Focus on change in resource use when an ART program is introduced Type and intensity of staff needed Changes to procedures within clinic Drugs – ART, other palliative care Lab tests for monitoring Identify constraints to ART provision within Provincial Health System

13. ART Research Ethics Provision of ART for study participants who become infected during the investigation Provision of ART for volunteers found to be infected during screening for a trial Provision of ART for families of participants Local standard of care and “coercive accrual”