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Interactive Workshop “HIV Cure 101”: Challenges in identifying and targeting the HIV reservoir Sarah Palmer Centre for Virus Research Westmead Millennium Institute for Medical Research University of Sydney. Definitions.

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Presentation Transcript
slide1

Interactive Workshop

“HIV Cure 101”:

Challenges in identifying and

targeting the HIV reservoir

Sarah Palmer

Centre for Virus Research

Westmead Millennium Institute for Medical Research

University of Sydney

slide2

Definitions

Residual Viremia: Persistent HIV RNA measured in plasma at levels below the limit of detection of the standard clinical assay (20-50 copies/ml).

Viral Reservoir: A viralreservoiris an anatomical site or cell type in which a replication-competent form of HIV persists, accumulating with more stable properties than the circulating pool of actively replicating virus. This HIV can persist even during effective therapy.

slide3

Viremia Persists after Suppression by Antiretroviral Therapy

Start Therapy (d4T/3TC/efavirenz)

Start Therapy (d4T/3TC/efavirenz)

4 ± 2 c/ml

22 ± 6 c/ml

bDNA

bDNA <75 copies/ml

Single-Copy Assay

Single-Copy Assay < 1 copy/ml

107

107

106

106

105

105

104

104

Plasma HIV-1 RNA (copies/ml)

103

103

102

102

101

101

100

100

10-1

10-1

0 200 400 600 800

0 200 400 600 800

Time (days)

Time (days)

Palmer et al. JCM 2003

Maldarelli et al. PLoSPath 2007

slide4

720 study

720 study assay limit

11.6 copies/ml

1.5 copies/ml

half-life=

half-life=39 weeks

Biphasic decline in persistent viremia

over 7 years of treatment

100

32

10

3.2

1

0.32

Palmer et al. PNAS 2008

slide5

Persistent HIV Infection

The IAS Scientific Working Group on HIV Cure: Nature Reviews Immunology 2012

Palmer et al. JIM 2011

measuring persistent hiv

CNS/CSF

Measuring Persistent HIV
  • Where to Measure
  • Persistent Virus?
  • Peripheral Blood
    • Plasma
    • Cells: RNA versus DNA
  • Tissue Compartments
    • T cells
    • Other cell types
    • RNA versus DNA
  • Role of Replication
    • Defective HIV
measuring persistent hiv1
Measuring Persistent HIV

Culture assay : IUPM

Lewin & Rouzioux, AIDS 2011

Rouzioux & Richman, 2012

persistent hiv infection in tissues
Persistent HIV Infection in Tissues

Svicher et al. Curr HIV/AIDs Rep. 2014

looking ahead
Looking Ahead

Does a “cure” require the total absence of HIV RNA and DNA?

If not, then new more sensitive assays will be needed to differentiate between replication competent and non-replicating virus.

Must all potential reservoirs be analyzed? If not, are we confident that certain reservoirs are determinative of cure/remission?

With advances in curative strategies, will our current sensitive assays provide sufficient confidence to stop HIV therapy in patients showing a near absence of HIV RNA and DNA?

Looking ahead, to determine the effectiveness of curative strategies, our field will need to develop a more standardized assay system which is sensitive, efficient, less costly, and adoptable in local settings.