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

1. UCSF International Research and the
Connection to the HIV Community
October 4, 2012

2. Agenda
I. Scale of the issues
II. What have we done?
III. What more needs to be done?
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3. Agenda
Scale of the Issues
Size and scope of international research
Potential for adverse outcomes
Inefficiencies
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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
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5. Size and Scope of UCSF International
Research
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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)
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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
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8. Agenda
What have we done?
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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
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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
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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. 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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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
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14. Silo
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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
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16. 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
Example of search result:
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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.
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18. What have We done? 4.
GlobalResearch Forum: Launched April 2012
An online moderated forum for global health research interest groups.
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19. Agenda
What more needs to be done?
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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
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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
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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
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23. What More Needs to be Done? 4.
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
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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
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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. Prevention Phase 4

27. Treatment of the Infected
Person to Reduce
Transmission?
Observational data &
HPTN 052

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. Transmission Risk Strongly Related to Viral Load
Quinn et al N Engl J Med 2000
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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. 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.
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32. HPTN 052: Impact of earlier ART on HIV transmission
and 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 partner
Co- 1° endpoint: HIV disease progression in HIV+ partner
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33. HPTN 052: Impact of earlier ART on HIV transmission
and 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 TB
Update at AIDS 2012 extends benefit in AIDS delay and cost effectiveness
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34. Continued Debate
about Starting ARV
Now Affected by
Prevention
Application

35. When to Start ARV Therapy
Movement 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. 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

37. CD4 count at HAART Initiation, 2003–5
Probably Improving but Far to Go
Egger M, et al. 14th CROI, Los Angeles 2007, #62

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. Thanks!
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