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Ucsf ctsi ghs-ari-volberding_nov 2012

Dr. Paul Volderding at UCSF presents on the international state of HIV/AIDS and current advances.

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Ucsf ctsi ghs-ari-volberding_nov 2012

  1. 1. UCSF International Research and the Connection to the HIV Community October 4, 2012
  2. 2. AgendaI. Scale of the issuesII. What have we done?III. What more needs to be done? 2
  3. 3. AgendaScale of the Issues Size and scope of international research Potential for adverse outcomes Inefficiencies 3
  4. 4. Size and Scope of UCSF International Research• 199+ faculty with funded research or active CHR- approved project with an international component• Working in more than 100+ countries (primarily in resource constrained settings)• $77.67M+ extramural awards received since Feb 2012 include a component conducted aboard• More than 250 students and trainees 4
  5. 5. Size and Scope of UCSF InternationalResearch 5 5
  6. 6. Scale of the Issues:Potential for Adverse Outcomes• Natural and political disasters (Ebola outbreak in Uganda, post-election riots in Kenya)• Illness and trauma (medical care in resource limited settings, evacuation, notification of UCSF leadership, family, etc.)• Charges of research misconduct (ethics of research vs. standards here, informed consent challenges)• Violation of laws there or policies here (hiring foreign staff, banking and other funding transactions) 6
  7. 7. Scale of the Issues: Inefficiencies• Multiple UCSF Departments working in the same site without coordination (travel, staff, etc.)• Many sites used for similar projects, even in the same country• Multiple systems used for similar tasks (data collection, etc.)• Questions of faculty oversight of UCSF trainees. UCSF faculty privileges at other sites vs. UCSF status of local faculty members 7
  8. 8. AgendaWhat have we done? 8
  9. 9. Welcome to My World!• CFAR: Co-Director• ARI: Director• GHS: Research Director• CTSI-GHP: Director• CTSI: Board of Directors• DOM: Associate Chair for Global Health• VA: Clinician• NCIRE: Board Chair 9
  10. 10. HIV at UCSF• Research funding: Well over $100M annually from USG• Research conducted domestically and in numerous RLS » Uganda, Kenya, Tanzania, Zimbabwe, South Africa, India, Brazil• Care at SFGH, Parnassus, VA• Education focused at SFGH• Efforts coordinated by well established organizations 10
  11. 11. HIV Coordination at UCSF• AIDS Research Institute » “Umbrella” meant to connect every aspect of HIV research at all sites providing communication, development.• Center for AIDS Research » NIH P-30 center grant with $3M annual budget » Convenes, coordinates, sustains investigative community with cores, pilot grants, mentorship• Center for AIDS Prevention Studies » NIH center grant supporting large group of behavioral/prevention scientists in DOM Division of Prevention Sciences 11
  12. 12. Selected Larger HIV Research Groups• HIV/AIDS Division at SFGH (Havlir)• Division of Experimental Medicine at SFGH (McCune)• Gladstone Institute of Virology and Immunology at MB(Greene)• Blood Systems Research Institute at Blood Bank (Busch)• SF DPH AIDS Research Group (Buchbinder)• Institute of Global Health at Beale Street (Rutherford) 12
  13. 13. Selected Interlaced Research Groups• Bixby Center: Maternal and Child Health with large HIV effort in Kisumu Kenya (Craig Cohen)• Curry Center at SFGH: TB (Hopewell)• Public Health Group at GHS: Malaria (Feachem)• Proctor Foundation: Ophthalmology including onchocirciasis 13
  14. 14. Silo 14
  15. 15. What Have We Done? 1.• Research policy review for RAB• Risk management actively engaged in providing services (travel insurance, email alerts, post-exposure prevention management)• Convened the International Research Advisory Council (IRAC) across all schools and disciplines 15
  16. 16. What Have We Done? 2. The UCSF International Projects Database:Provides access to public information; facilitating collaboration, communication, expertise, and development ofnew proposals.Current awards of UCSF global researchers through July 2012Data feeds to Profiles, plans for automation of data capture with new central systems rollout in 2013 Example of search result: 16
  17. 17. What Have We Done? 3.Global Research Consulting: Launched July 2011. One hour of free consultation.Predominantly enquiries regarding international grants administration and policy. 17
  18. 18. What have We done? 4. GlobalResearch Forum: Launched April 2012 An online moderated forum for global health research interest groups. 18
  19. 19. AgendaWhat more needs to be done? 19
  20. 20. What More Needs to be Done? 1.• Follow-up on initial RAB policy analysis » Continue to identify relevant policies governing global health research and educational activities reviewing policies and policy gaps to facilitate work in medium and lower income countries including: » Finalizing policy on post-exposure prophylaxis for UCSF employees (and foreign staff members working on UCSF projects?) » Develop policies and procedures for UC foreign affiliate operations » Define banking/financial policies and guidelines for registered entities » Define policies re: shipping specimens to US vs. research performed in-country 20
  21. 21. What More Needs to be Done? 2.• Monitor OE pre-ward teams with extensive global research experience to evaluate efficiency, effectiveness compared to similar grants by other teams• Provide more effective training of research personnel here and abroad in support of active research projects• Improve tracking of grants, multiple PI’s and specific sites (city, hospital, etc., not just country)• Better integrate research and educational activities given similar policy applications 21
  22. 22. What More Needs to be Done? 3.• Provide a One Stop Shop for UCSF International Activities from pre-award to project close out – including project management• Experts here helping to facilitate the work there, including: » Maintaining accurate and current database of resources here and in-country available for research support » Compliance (both ethical and fiscal) » Data collection, sharing, and analysis » Capacity building (for research, education, and research administration and management) » Support for educational placement and supervision of UCSF students, residents, trainees 22
  23. 23. What More Needs to be Done? 4.The Global Resource HUB: Uses new and existing data as a central resource forresearchers, program staff working abroad and international visiting scholars.Goal is to provide tool set designed specifically for the elimination of barriers forthe global researcher. The future Global Resource HUB GHRS web portal: Working issues 23
  24. 24. What more needs to be done? 5.• Review and provide feedback on UCOP draft policy on International Activities UCSF has initiated registration of UC foreign affiliate offices in two PEPFAR countries and is now registered in Tanzania as “Global Programs.” Legal registration in country allows researchers to: – Open a local bank account – Lease space – Hire local staff – Apply for work visas for UCSF staff working locally Please review the enclosed: – Context sheet – UCOP Draft policy on International Activities – Summary of comments to the UCOP policy 24
  25. 25. Four Prevention Opportunities Cohen et al, JCI, 2008 Cohen IAS 2008 UNEXPOSED EXPOSED EXPOSED INFECTED (precoital/coital) (postcoital) Behavioral, Vaccines Vaccines Treatment Of HIV Structural ART PrEP ART PEP Reduced Infectivity Microbicides Circumcision Condoms ARV Therapy YEARS HOURS 72h YEARS
  26. 26. Prevention Phase 4
  27. 27. Treatment of the Infected Person to Reduce Transmission? Observational data & HPTN 052
  28. 28. Treatment to Decrease Transmission?• Many models in other infectious diseases: TB, HSV• Early evidence in HIV » AZT in pregnant women decreased MCT by 75% » AZT PEP immediately accepted even without definite evidence• Surprisingly vigorous debate » Combination ARV therapy decreased viremia below detection and in genital fluids to a level that lead to many arguments whether it could be detected or not » Intense reaction to Swiss recommendation re: no condoms needed if suppressed
  29. 29. Transmission Risk Strongly Related to Viral Load Quinn et al N Engl J Med 2000 29
  30. 30. “Research is urgently needed to develop and evaluate cost-effective methods such as effective and inexpensive antiretroviral therapy…” “could reduce infectivity of and susceptibility to HIV-1 and prevent further sexual transmission of the virus”Transmission Risk Strongly Related to Viral Load Quinn et al N Engl J Med 2000 30
  31. 31. Antiretroviral Therapy Reduces HIV Titer in Semen Fig. 1. Detection rate of HIV in semen. Detection rates of cell-free and cell-associated HIV in drug naive historical controls (white) and treated individuals (black) in seminal plasma (HIV-RNA) and seminal cells (HIV-DNA). Seminal cells were only analysed in a subgroup of men from one centre. Potent antiretroviral treatment of HIV-infection results in suppression of the seminal shedding of HIV. Vernazza, Pietro; Troiani, Luigi; Flepp, Markus; Cone, Richard; Schock, Jody; Roth, Felix; Boggian, Katia; Cohen, Myron; Fiscus, Susan; Eron, Joseph AIDS. 14(2):117-121, January 28, 2000. © 2000 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 31 2
  32. 32. HPTN 052: Impact of earlier ART on HIV transmissionand disease progression 1763 HIV discordant couples (HIV+ partner CD4 350-550) Immediate HAART HAART at 250 All receiving HIV prevention services 13 sites in 9 countries: Botswana, Brazil, India, Kenya, Malawi, South Africa, Follow couples for 5 yrs Thailand, United States, Zimbabwe 1° endpoint: HIV infection in HIV-negative partnerCo- 1° endpoint: HIV disease progression in HIV+ partner 32
  33. 33. HPTN 052: Impact of earlier ART on HIV transmissionand disease progression 1763 HIV discordant *96% reduction in HIV couples transmission to HIV- (HIV+ partner CD4 350-550) negative partner, median follow-up 2 years 886 immediate 877 delayed HAART HAART (CD4 250) All receiving HIV prevention services 1 transmission* & 3 cases of extrapulmonary 27 transmissions* TB & 17 cases of extrapulmonary TBUpdate at AIDS 2012 extends benefit in AIDS delay and cost effectiveness 33
  34. 34. Continued Debateabout Starting ARV Now Affected by Prevention Application
  35. 35. When to Start ARV TherapyMovement to Earlier Initiation Favors early therapy Current ARV more potent, convenient, Longer duration of safe ARV therapy adds Less transmitted cost, toxicity resistance Favors later therapy New drugs control Risk of additional resistant HIV generation of Recognition of end resistance organ damage of untreated infection
  36. 36. When to Start ART: IAS–USARecommendations 2012• Patient readiness should be considered when deciding to initiate ART• ART is recommended and should be offered regardless of CD4 cell count• The strength of the recommendation and quality of the evidence increases as CD4 count decreases and in the presence of certain conditions Thompson et al JAMA 2012
  37. 37. CD4 count at HAART Initiation, 2003–5Probably Improving but Far to Go Egger M, et al. 14th CROI, Los Angeles 2007, #62
  38. 38. Questions in Treatment as Prevention• Would starting ARV therapy at time of diagnosis reduce HIV incidence at the community level? » Can we find those infected but not engaged? » What is the cost/benefit/risk balance of additional time on ARV?• Is PREP cost-effective? Will it be paid by government, insurance?• Does PREP displace vaginal ARV microbicides as prevention modality?• Will biologic prevention alter commitment to behavioral prevention strategies? Cause of syphilis resurgence in MSM?
  39. 39. Thanks! 39