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IAS Members Meeting July 19th 2011. Achievements and learning over the past 30 years: what do we need next?. Françoise BARR É-SINOUSSI Regulation of Retroviral Infections Unit Department of Virology. 30 years of HIV/AIDS Science: Main milestones. 35. SIV. HIV-2 Identification. - PowerPoint PPT Presentation
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IAS Members MeetingJuly 19th 2011
Achievements and learning over the past 30 years:
what do we need next?
Françoise BARRÉ-SINOUSSI
Regulation of Retroviral Infections Unit
Department of Virology
30 years of HIV/AIDS Science: Main milestones
Understanding the biology and pathogenesis of HIV infection: First step toward prevention and treatment
strategies….
Nu
mb
er o
f p
eop
le l
ivin
g w
ith
HIV
(m
illi
on
)
AIDS
35
25
15
5
81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09
HIV-1 Identification
HIV-1 Sequence
HIV-1 Diversity
HIV-2 Identification
HIV-1 subtypes
HIV-1 O
Recombinants VIH-1
Origin of HIV
HIV-1 N
HIV-1 P
CD4 Receptor
Co-receptors
HIV Reservoirs
CD4 Depletion in gut
Immune activation
Innate response
HIV Restriction factors
HIV controllers
Microbial Translocation
SIV
10 11
30 years of HIV/AIDS translational science…6,6 million
Prophylactic and therapeutic vaccine research
Therapy and prevention research
Number of people under HAART in LMIC
4
3
2
1
AZT therapy
HIV Testing
Circumcision (60%)
1st phase I trial
ARV Resistance
HIV Quantification
PMTCTVaccine therapy
VaxGen Trial
STEP Trial
RV144 trial
ARV as prevention
(Caprisa, Iprex)
HPTN
052First RDT
Protease inhibitor
HAART
Integrase & CCR5 inhibitor
Fusion inhibitor
6
5 UNGASS
81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 00 01 02 03 04 05 06 07 08 09 10 1199
Number of people annually infected with HIV
Global Fund
2,5 millionNumber of AIDS related death in LMIC
1,7 million
IAS
AIDS
HIV
Dates
Clinical
efficacy
studies
Strategy Viral targetsImmune
responseEfficacy
1999-2003 AidsVaxProtein subunit
(AIDSVAX)
monomeric
rgp120
Type specific
binding AbNO
2005-2007Step
Phambili
Viral vector
(Ad5)
gag/pol/nefCD8+T (+++) NO
2003- 2009RV144 (Thai
trial)
Prime: ALVAC-
vCP152 +
Boost: AIDSVAX
gag/pol/env
+
Monomeric
rgp120 B/E
CD4+ T cell
(+/-)
+
Type specific
binding Ab
31%
reduction
Lessons from Vaccine trials
v
EDUCATION
CONDOMS
TREATMENT AS PREVENTION
DRUG ALCOHOL TREATMENT
TESTING COUNSELING
STI TREATMENT
MICROBICIDES
CIRCUMCISION
PrEP
HARM REDUCTION
HIV CURE
VACCINE
Evidence based Prevention
Implementation of combined tools
Highly active HIV prevention
tools
Early Events in HIV infection are critical
Early pathogenic events: Inflammation/activation & reservoirs
Critical for vaccine and cure research…
How HIV persist during therapy
Better knowledge of viral and host factors implicated in establishment of HIV reservoirs and in HIV persistence
- Ongoing viral replication occurs insubject on suppressive HAART (TW Chun JCI; N Tobin, J Virol 2005)
- HIV integrate in long lived resting memory T cells and persist despite suppressive HAART (TW Chun, Nat Med 1995; D Finzi, Science; TW Chun PNAS 1997)
- Reservoir cells, like other memory T cells, divide very slowly to maintain the memory of the immune system (A. Bosque and V. Planelles)
T cell survival
Proliferation
Viral replication
Courtesy of Nicolas Chomont
• A decrease in viral load is clearly associated with clinical benefit
• Proof of concept from the Berlin patient (bone marrow transplant of CCR532 stem cells)
• A small percentage (<0.3%) of HIV-1-infected subjects show no disease
progression and/or spontaneous control of viral replication (e.g. long-
term nonprogressors and “HIV Controllers”)
• African NHP infected by SIV are naturally protected against disease
progression
Why it should be possible to obtain at least functional cure for HIV/AIDS?
It is time to engage in research towards an HIV Cure
Definition: Permanent suppression of viral replication without eradicating the virus from the body => Long-term remission + Prevention
From C. Katlama
“Towards an HIV Cure”
Global Scientific Strategy
Sign-on the Rome Statement for an HIV Cure:
www.iasociety.org