The DART Trial Evaluates two strategies for delivering

The DART Trial Evaluates two strategies for delivering ART, comparing: • clinical monitoring only with routine laboratory + clinical monitoring • structured treatment interruptions with continuous ART

Trial features I • • • 5 year trial 3 sites: Harare, Kampala, Entebbe 3000 patients – 1000 at each site / 1 year • Primary endpoints : Efficacy -progression to a new WHO stage 4 or death Safety - new SAE which is not HIV related Other outcomes: Adherence , Virological including resistance, Socioeconomic & behavioural impact •

DART Entebbe • Collaboration with TASO and Entebbe Hospital • DART Clinic at Entebbe Hospital – MOH • Care services: Counseling Diagnosis of HIV related illness & OIs Treatment of HIV related illness & OIs Antiretroviral therapy & monitoring Psychosocial support

Funding Sources • Medical Research Council, UK • Rockefeller Foundation, USA • Department for International Development, UK • Rock House Foundation, UK

Drugs Anti-retroviral drugs donated by • Boehringer-Ingelheim - Nevirapine • Gilead - Tenofovir • Glaxo. Smith. Kline - Combivir

Trial Review Process 2 yrs + • • • Risk benefits fine Most attention to end of trial issues Concern about exclusion of pregnant women ? What happens after patient 1000 - community Very little discussion on ability of participants to decline

Trial Approval • UVRI Science & Ethics Committee • Uganda National Council for Science & Technology - granted research clearance • Ethics committees in Zimbabwe & UK • Support letter from MOH

Trial Monitoring • • • Trial Steering Committee International Co-ordinating Group Local Trial Management Committees Analysis & Data Management Committee Data & Safety Monitoring Committee Pharmaceutical companies - adverse events • End Point Review Committee

International Coordinating Group PI’s Site investigators Dr Peter Mugyenyi - Kampala Prof Jimmy Whittworth - Entebbe Prof Ahmed Latif - Zimbabwe Prof James Hakim - Zimbabwe Prof Janet Darbyshire - London Prof Charles Gilks - Geneva Dr Diana Gibb - London Dr Andrew Reid - Zimbabwe Dr Cissy Kityo - Kampala Dr Paula Munderi - Entebbe Plus Dr Dorothy Bray - Consultant Dr Alex Coutinho - TASO Uganda

Other ART Trials in Uganda 1992 JCRC Determining the lowest effective dose of AZT 16 weeks duration 1 yr therapy to participants post trial

Other Trials……………. 2002 Care project ( Pharmaccess, GSK, Roche ) Uganda, Kenya, Senegal, Cote d’Ivoire Response, Side effects, Education & adherence 200 participants total, 50 in each country Will provide ART to participants post trial

Other Trials……………. . 2003 JCRC - NIH Evaluation of short STI strategies ( 7 days on 7 days off / Weekend off ) 171 participants to date Clinical follow up and monitoring provided Patients pay for own ART but save on drug cost ( 50% 7 days ; 30% weekend)