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NM Archin 1 , J Anderson 1 , KS Keedy 1 , KM Barton 1 , M Cheema 1 , R Sackmann 1 , PowerPoint PPT Presentation


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Persistent low-level viremia despite clinically successful antiretroviral therapy appears correlated with more frequent resting CD4+ T cell Infection. NM Archin 1 , J Anderson 1 , KS Keedy 1 , KM Barton 1 , M Cheema 1 , R Sackmann 1 ,

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NM Archin 1 , J Anderson 1 , KS Keedy 1 , KM Barton 1 , M Cheema 1 , R Sackmann 1 ,

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Nm archin 1 j anderson 1 ks keedy 1 km barton 1 m cheema 1 r sackmann 1

Persistent low-level viremia despite clinically successful antiretroviral therapy appears correlated with more frequent resting CD4+ T cell Infection

NM Archin1, J Anderson1, KS Keedy1, KM Barton1, M Cheema1, R Sackmann1,

A Wiegand2, JD Kuruc1, JJ Eron1, MS Cohen1, JM Coffin2 , R Swanstrom1 and DM Margolis1

Department of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; 2NCI HIV Drug Resistance Program, Frederick, MD, USA.

Poster : WEPDA101


Background

Background

  • Persistent infection of resting CD4+ T cells (RCI)remains a barrier to HIV eradication despite antiretrovial therapy (ART).

  • In approximately 75% individuals, low-level viremia is detectable by sensitive PCR assays despite successful ART.

  • Is RCI a potential source of this viremia?


Nm archin 1 j anderson 1 ks keedy 1 km barton 1 m cheema 1 r sackmann 1

Correlation between low-level viremia and

resting cell infection

  • All patients with LLV of < 1 copy were assigned an arbitrary value of 0.5. Purple line indicates the single copy limit of detection of this assay


Nm archin 1 j anderson 1 ks keedy 1 km barton 1 m cheema 1 r sackmann 1

env plasma sequences

hypervariable V1-V2 loop plasma sequences

env sequences from resting cell outgrowth

hypervariable V1-V5 loop sequences from resting cell outgrowth (visit A)

hypervariable V1-V5 loop sequences from resting cell outgrowth (visit B)

Similarity of plasma and resting cell outgrowth virus sequences from patient M

Patient M


Conclusions

Conclusions

  • Our study supports the hypothesis that resting CD4 positive T cells are a major source of intermittent low-level viremia, and therapies that target RCI are essential in the effort to eradicate HIV Infection.

  • However, our findings do not exclude other potential cellular sources of low level viremia and explicit identification of these cells will be critical in the effort to purge persistent HIV infection


Nm archin 1 j anderson 1 ks keedy 1 km barton 1 m cheema 1 r sackmann 1

Acknowledgements

Sarah Palmer

University of North Carolina Chapel Hill

Clinical Coordinators:

Jenny Scepanski

JoAnnKuruc

Alyssa Sugarbaker

Linh Ngo

UNC Blood Bank and Staff

Our patients

Margolis lab:

Daniel Parker

Noelle Dahl

LiguoNiu

ShaileshChoudhary

Abigail Lees

Support from:

amfAR107168-44-RGRL, R00046,

U54RR024383, AI50410 (UNC CFAR),

NIH R01 AI045297, T32 AI07001 and AI07151


Nm archin 1 j anderson 1 ks keedy 1 km barton 1 m cheema 1 r sackmann 1

Similarity of plasma and resting cell outgrowth virus sequences from patient O:

up to 99.87% identity

env plasma sequences

env sequences from resting

cell outgrowth

Patient O


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