The DART Trial

Evaluates two strategies for delivering ART, comparing:

• clinical monitoring onlywith routine laboratory + clinical monitoring

• structured treatment interruptionswith 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:

CounselingDiagnosis of HIV related illness & OIsTreatment of HIV related illness & OIsAntiretroviral therapy & monitoringPsychosocial 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

• GlaxoSmithKline - 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

Dr Peter Mugyenyi - Kampala

Prof Jimmy Whittworth - Entebbe

Prof Ahmed Latif - Zimbabwe

Prof James Hakim - Zimbabwe

Prof Janet Darbyshire - London

Prof Charles Gilks - Geneva

Site investigators

Dr Diana Gibb - London

Dr Andrew Reid - Zimbabwe

Dr Cissy Kityo - Kampala

Dr Paula Munderi - Entebbe

PlusDr Dorothy Bray - Consultant

Dr Alex Coutinho - TASO Uganda

Other ART Trials in Uganda

1992

JCRCDetermining the lowest effective dose of AZT16 weeks duration1 yr therapy to participants post trial

Other Trials…………….

2002

Care project ( Pharmaccess, GSK, Roche ) Uganda, Kenya, Senegal, Cote d’Ivoire

Response, Side effects, Education & adherence200 participants total, 50 in each countryWill provide ART to participants post trial

Other Trials……………..

2003

JCRC - NIHEvaluation of short STI strategies

( 7 days on 7 days off / Weekend off )

171 participants to dateClinical follow up and monitoring providedPatients pay for own ART but save on drug cost

( 50% 7 days ; 30% weekend)