1. Care and Prevention in HIV Vaccine Trials: a site perspective Guy de Bruyn Perinatal HIV Research Unit University of the Witwatersrand Chris Hani Baragwanath Hospital Johannesburg, South Africa

2. Access to care (modified from Grady) Care which is part of the scientific design Care needed to safely complete the trial Care for injuries and adverse events Post trial access Ancillary care –Care that some participants will predictably need

3. Dialogue? “a comprehensive care package should be agreed upon through a host/community/sponsor dialogue which reaches consensus prior to initiation of a trial” (UNAIDS 2000, #16)…

4. Protocol mandates Avoiding pregnancy during the vaccination period Assessing symptoms of illness Ensuring adequate standard of care to control participants –Counselling – pre/post-test, risk reduction, safer sex –Providing condoms

5. Care needed to safely complete the trial Resuscitation equipment Laboratory monitoring of haematologic parameters and other clinical laboratory values of potential interest –Anaemia –Leukopaenia –Alteration of hepatic enzyme tests

6. Ancillary care in HIV Vaccine trials Some questions –What kind of care is needed? –For how long? –By whom? –Whose responsibility?

7. Ancillary care – some examples Hypertension –May be diagnosed incidentally during the conduct of trial procedures –Treatment is lifelong –Management is multi-modal, i.e. requires attention to weight, nutrition, exercise, in addition to possible pharmacotherapy Facilitating access to services –TOP –Psychosocial support – rape/trauma/DV –Mental illness Dental care

8. What is “the standard of prevention”? HIV counseling and testing –Some protocols may not provide results in ‘real- time’, depending on the complexity of ruling out vaccine-induced seropositivity –Impact on testing outside of the trial setting Other VCTs, blood donation, organ donation, testing for insurance purposes –What about partners? Should we offer CHCT and who is able to do that?

9. More “Standard of Prevention” Risk reduction counselling –Efforts to standardize that intervention, such as pilot efforts within DAIDS networks Condom promotion vs. provision –Male / Female / both –What other means should be used to promote condom uptake

10. What about additional HIV prevention technologies? Male circumcision STI treatment –Diagnostics –Directed versus syndromic therapy Post-exposure prophylaxis Pre-exposure prophylaxis Other investigational agents

11. What is the Threshold of Evidence for New Prevention Tools?

12. Cochrane Review of HIV and Circumcision in High Risk Heterosexual Men Siegfried et al. Lancet Infect Dis 2005

13. Phambili timelines 17Mar06. MCC submission. GMO submission 8May06. HREC submission 12Sep06. IBC submission 13Oct06. MCC approval 19Oct06. HREC approval 24Jan07. First pt enrolled 19 Sep 2007 STEP trial interim results July 2005 Orange Farm MC trial results December 2006 Kenyan and Ugandan MC trial results 7March 2007 First Phambili participant provided MC 8Nov06. IBC approval 21Nov06. GMO approval

14. Location of Studies of Acceptability Thirteen studies from nine sub- Saharan African countries Bailey R IAS 2007

15. Public Sector Circumcisions CHB

16. Local Expertise

17. Implementing at the Trial Site / Facilities

18. Circumcision *129/441 were circumcised at baseline