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