ias aids conference – washington dc – july 20-27, 2012 · lohse, ann int med 2007; hogg. lancet...
TRANSCRIPT
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IAS AIDS Conference – Washington DC – July 20-27, 2012
Robert Reinhard
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OUTLINE OF TALK
CURE BASICS
CURE WITHIN THE GLOBAL PROGRAM TO END AIDS
IAS CURE RESEARCH PLAN
CURE RESEARCH PRESENTED AT CONFERENCE
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WITHOUT A CURE ALMOST ALL HIV-INFECTED PATIENTS MUST ACCESS AND ADHERE TO
SAFE, EFFECTIVE cART EVERY DAY THROUGHOUT THEIR LIFETIME
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HIV
RN
A
CD
4 c
ou
nt
50
Rapid rebound in virus when cART stopped
Years on cART 0
off cART 1
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WHAT DO WE MEAN BY “CURE”?
• STERILIZING CURE: ALL HIV ELIMINATED FROM THE BODY – NO cART BECAUSE NO VIRUS IS PRESENT
• FUNCTIONAL CURE: HIV REMAINS IN SMALL AMOUNTS – cART MAY NOT BE NEEDED BECAUSE VIRUS DOES NOT MULTIPLY OR IS CONTROLLED
WHAT ABOUT REINFECTION OR TRANSMISSION?
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Sharon Lewin http://pag.aids2012.org/session.aspx?s=150
what are the major barriers
to cure?
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BARRIERS TO CURE
• HIV hides and “sleeps” for many years (latency) in resting cells where drugs do not operate.
• “Wake Up” factors are unknown.
• Viral replication continues on cART- ?
• Anatomical tissue as a location for HIV where drugs do not operate
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Anatomical reservoirs
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Why do we need to cure HIV?
Life expectancy remains reduced on cART
Ongoing morbidity on cART
Prevent HIV transmission
Substantial stigma and discrimination
Lifelong cART: adherence toxicity long term-cost
Lohse, Ann Int Med 2007; Hogg. Lancet 2008; Deeks & Phillips, BMJ 2009; May, BMJ 2011 Viral Eradication: The Cure AgendaJ. Martinez-Picado, Spain- http://pag.aids2012.org/session.aspx?s=679#2
Estimated 2015 AIDS investment for universal prevention, treatment, care and
support
22 billion USD
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CURRENT – OR EVEN HOPED FOR - GLOBAL SPENDING IS NOT ENOUGH TO END AIDS
: The Lancet 2011; 377:2031-2041
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WE HAVE A NEED BUT WHY IS CURE RESEARCH POSSIBLE
Françoise Barré-Sinoussi
says so
The Berlin Patient
Critical mass of scientific advances
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Seven key scientific priorities for HIV cure research
• Determine why HIV remains even with cART
• Determine the sources of hidden HIV
• Study immune activation effects
• Determine how HIV replication can be controlled by the body
• Study ways to measure persistent HIV infection and hidden HIV.
• Test therapeutic agents or immunological strategies
• Test strategies to enhance immune response. http://www.iasociety.org/Web/WebContent/File/HIV_Cure_Full_recommendations_J
uly_2012.pdf
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STERILIZING OR FUNCTIONAL CURE
GENE THERAPY
THERAPEUTIC VACCINATION
TREATMENT OPTIMIZATION/INTENSIFICATION
REVERSAL OF LATENCY
IMMUNE-BASED THERAPIES
? REDUCING INFLAMMATION
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CURE STUDIES THAT MADE NEWS HEADLINES
THE BERLIN PATIENT
TWO PATIENTS RECEIVING STEM CELL TRANSPLANT BUT STILL ON cART
“VISCONTI COHORT”
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BERLIN PATIENT Effects of Leukemia Treatment and Transplant from
CCR5 mutation Donor
1. BERLIN PATIENT IS FUNCTIONALLY CURED
• Has not used cART for 5 years
• Decline in HIV antibody levels
2. EXPERIMENTAL LAB TESTS ARE NEGATIVE FOR PRESENCE OF HIV
• BUT some labs suggest presence of HIV: error, sample contamination, validity of test also possible
• Further tissue testing to to be conducted
3. BERLIN PATIENT CELLS ALSO RESISTANT TO CXCR4 HIV STRAINS?
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• WE DON’T KNOW WHY BERLIN PATIENT IS CURED[CHEMOTHERAPY? TRANSPLANT ALONE? GRAFT/HOST DISEASE?]
• TWO LYMPHOMA PATIENTS GIVEN TRANSPLANT, NO RADIATION, BUT REMAIN ON cART
• HIDDEN/LATENT HIV CANNOT BE DETECTED IN BLOOD OF THESE PATIENTS; HIV ANTIBODY DECLINES
• MORE STUDY NEEDED BEFORE REMOVING cART
OTHER PATIENTS RECEIVING STEM CELL TRANSPLANT Timothy Henrich study
http://pag.aids2012.org/session.aspx?s=274
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VISCONTI COHORT “Virological and Immunological Studies in CONtrollers after Treatment Interruption”
Asier Saéz-Cirión
• 14 patients treated with cART w/in 10 weeks of infection • Treatment interruption after an average of 3 years on cART • Controlling VL to <50 copies/ml - median of 6.6 years, range 4-9.5 years • Other French studies have found controllers among very early treaters: “HIV-1 control after transient antiretroviral treatment initiated in primary infection: role of patient characteristics and effect of therapy” Antiviral Therapy journal- http://www.intmedpress.com/journals/avt/abstract.cfm?id=2273&pid=88
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CURES ARE FOR KIDS: WHY SHOULD WE STUDY PEDIATRIC POPULATIONS?
• Infants are more like people than mice or
monkeys
• Historically, 15% of new infections worldwide were in individuals <15 years old (most from MTCT); new infections still high
• Lessons from a developing immune system
• Identification during very early infection possible
• Ethics experience available from multiple studies
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TWO DEVELOPMENTS IN INFANTS
• Published: Amount of hidden/latent HIV is reduced in 17 infants who achieved viral control with cART more quickly compared to others
AIDS 2012, 26:000–000; IAS ABSTRACT 12206
• Off the record discussion: In the next year, results will be presented of functional cure in infants treated very early.
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STERILIZING OR FUNCTIONAL CURE FOR WHOM? KIDS, EARLY INFECTION, CHRONIC
GENE THERAPY
THERAPEUTIC VACCINATION
TREATMENT OPTIMIZATION/INTENSIFICATION
REVERSAL OF LATENCY
IMMUNE-BASED THERAPIES
? REDUCING INFLAMMATION
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OTHER CURE RESEARCH AT IAS
• SOURCES OF HIDDEN HIV – IAS studies in tissue, central nervous system, and a new class of Tcells
• TESTING THERAPEUTIC AGENTS – early research with drugs that can “wake up” sleeping HIV
• MEASURING HIDDEN HIV – Infected resting cells may be identified by their differences. Measurement tests improving.
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CURE: The point of view of people living
with HIV
Fred Verdult
Amsterdam, The Netherlands
Your logo
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RESOURCES
• IAS PRECONFERENCE SYMPOSIUM – includes detailed presentations
http://www.iasociety.org/Default.aspx?pageId=606
• TOWARDS AN HIV CURE: A GLOBAL SCIENTIFIC STRATEGY
http://www.nature.com/nri/journal/v12/n8/full/nri3262.html
• IAS SCIENTIFIC STRATEGY – FULL SET OF RECOMMENDATIONS
http://www.iasociety.org/Web/WebContent/File/HIV_Cure_Full_recommendations_July_2012.pdf
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ACKNOWLEDGEMENTS
Canada
Mario Ostrowski ICAD/Nicci Stein
Rupert Kaul
Colin Kovacs
Shariq Mujib
Sonya MacParland
Ron Rosenes
OHTN – Towards HIV Eradication
US
Richard Jefferys
Travel Funding
Treatment Action Group, NY
IAS