Ucsf ctsi ghs-ari-volberding_nov 2012
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Transcript of Ucsf ctsi ghs-ari-volberding_nov 2012
UCSF International Research and the Connection to the HIV Community
October 4, 2012
Agenda
I. Scale of the issues
II. What have we done?
III. What more needs to be done?
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Agenda
Scale of the IssuesSize and scope of international research
Potential for adverse outcomes
Inefficiencies
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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
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5
Size and Scope of UCSF International Research
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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)
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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
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Agenda
What have we done?
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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 Chair9
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
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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
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)
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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
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Silo
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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
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What Have We Done? 2.
The UCSF International Projects Database:Provides access to public information; facilitating collaboration, communication, expertise, and development of new proposals. Current awards of UCSF global researchers through July 2012 Data feeds to Profiles, plans for automation of data capture with new central systems rollout in 2013
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Example of search result:
What Have We Done? 3.
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Global Research Consulting: Launched July 2011. One hour of free consultation.
Predominantly enquiries regarding international grants administration and policy.
What have We done? 4.
GlobalResearch Forum: Launched April 2012An online moderated forum for global health research interest groups.
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Agenda
What more needs to be done?
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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
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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
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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
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What More Needs to be Done? 4.
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The Global Resource HUB: Uses new and existing data as a central resource for
researchers, program staff working abroad and international visiting scholars.
Goal is to provide tool set designed specifically for the elimination of barriers for
the global researcher.The future Global Resource HUB
GHRS web portal: Working issues
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
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Four Prevention Opportunities
YEARS
Treatment Of HIVReduced Infectivity
INFECTED
YEARS
UNEXPOSED
Behavioral,Structural
CircumcisionCondoms
ARV Therapy
Cohen et al, JCI, 2008Cohen IAS 2008
HOURS
VaccinesART PrEPMicrobicides
EXPOSED
(precoital/coital)
72h
VaccinesART PEP
EXPOSED
(postcoital)
Prevention Phase 4
Treatment of the Infected Person to Reduce
Transmission?
Observational data & HPTN 052
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
29Quinn et al N Engl J Med 2000
Transmission Risk Strongly Related to Viral Load
30Quinn et al N Engl J Med 2000
Transmission Risk Strongly Related to Viral Load
“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”
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© 2000 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc.
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Antiretroviral Therapy Reduces HIV Titer in Semen
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.
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.
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HPTN 052: Impact of earlier ART on HIV transmission and disease progression
1763 HIV discordant couples (HIV+ partner CD4 350-550)
HAART at 250
1° endpoint: HIV infection in HIV-negative partner
Co- 1° endpoint: HIV disease progression in HIV+ partner
Follow couples for 5 yrs
Immediate HAART
All receiving HIV prevention services
13 sites in 9 countries:
Botswana, Brazil, India,
Kenya, Malawi, South Africa,
Thailand, United States,
Zimbabwe
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HPTN 052: Impact of earlier ART on HIV transmission and disease progression
1763 HIV discordant
couples (HIV+ partner CD4 350-550)
877 delayed
HAART (CD4
250)
*96% reduction in HIV
transmission to HIV-
negative partner, median
follow-up 2 years
1 transmission*
& 3 cases of
extrapulmonary
TB
886 immediate
HAART
All receiving HIV prevention services
27 transmissions*
& 17 cases of
extrapulmonary TB
Update at AIDS 2012 extends benefit in AIDS delay and cost effectiveness
Continued Debate about Starting ARV
Now Affected by Prevention Application
When to Start ARV TherapyMovement to Earlier Initiation
Current ARV more potent, convenient, safe
Less transmitted resistance
New drugs control resistant HIV
Recognition of end organ damage of untreated infection
Longer duration of ARV therapy adds cost, toxicity
Risk of additional generation of resistance
Favo
rs e
arly
th
erap
y
Favors later th
erapy
When to Start ART: IAS–USA Recommendations 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
CD4 count at HAART Initiation, 2003–5Probably Improving but Far to Go
Egger M, et al. 14th CROI, Los Angeles 2007, #62
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?
Thanks!
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