Are we most likely to cure HIV with gene therapy?

Sharon R LewinDirector, Infectious Disease Unit, Alfred HospitalProfessor, Department of Medicine, Monash UniversityCo-head, Centre for Virology, Burnet Institute, Melbourne, Australia

Amfar-IAS Satellite Meeting, 5th IAS Conference, Rome

Gene therapy is scientifically flawed,high risk,will never get to the clinic

The problem: 1 in a million cells are latently infected

Nucleases chop up DNA – lets hope they get it 100% right!

Naldini et al., Nature Genetics 2011; 12:301

Pharmacotherapy is rational, short term,toxicities that are mild and reversible,available now to test, scalable

Licensed drugs that also …..eliminate latently infected cells

HDACi

Vorinostat YesRomidepsin YesPanabinostat Entinostat GivinostatBelinostat

2

5-azacytidine

Others (9)

1Disulfiram Yes 1

Minocycline ` Yes

Auranofin Yes

Phase I

PhaseII

PhaseIII

Licensed Latency trials

Methylation inhibitor

Cytokine

Anti-alcoholic

Antibiotic

Anti-rheumatic

Interleukin-7

* Total number of trials listed on http://clinicaltrials.gov (July 2011)

# Trials*

17632942028

7>26

52

20

Latent HIV activity

Latency activators

Immune modulators

MDX-1106 Anti PD-1

++++++

+++

-

+

++9

BryostatinPKC modulators

+22Others Yes (1) +

Combination strategies enhance potency

SAHA

+ Pro

Vira

l RN

A (c

opie

s/m

l)

50000

0

20000

30000

40000

10000

NI

VPA

SAHA

VPA

+ Pro

Pro

60000 WHS 22

Pro = prostratin; VPA = valproic acid; SAHA = vorinostat Reuse et al., Plos One 2009

Latency activators(combination)

Immune modulators+

New possibilities to enhance specificity

AIDS 2009; 23(14):1799-806

Plos One 2011; 6: e18270

We need a cure that is scalable, deliverable and cheap

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