Integrated HIV DNA accumulates prior to treatment while episomal HIV DNA records ongoing transmission afterwards

Murray, John M., McBride, Kristin, Boesecke, Christoph, Bailey, Michelle, Amin, Janaki, Suzuki, Kazuo, Baker, David, Zaunders, John J., Emery, Sean, Cooper, David A., Koelsch, Kersten K. and Kelleher, Anthony D. (2012) Integrated HIV DNA accumulates prior to treatment while episomal HIV DNA records ongoing transmission afterwards. AIDS, 26 5: 543-550. doi:10.1097/QAD.0b013e328350fb3c


Author Murray, John M.
McBride, Kristin
Boesecke, Christoph
Bailey, Michelle
Amin, Janaki
Suzuki, Kazuo
Baker, David
Zaunders, John J.
Emery, Sean
Cooper, David A.
Koelsch, Kersten K.
Kelleher, Anthony D.
Title Integrated HIV DNA accumulates prior to treatment while episomal HIV DNA records ongoing transmission afterwards
Journal name AIDS   Check publisher's open access policy
ISSN 0269-9370
1473-5571
Publication date 2012-03-13
Sub-type Article (original research)
DOI 10.1097/QAD.0b013e328350fb3c
Open Access Status Not yet assessed
Volume 26
Issue 5
Start page 543
End page 550
Total pages 8
Place of publication Philadelphia, PA, United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted abstract
Objective: We investigated the dynamics of HIV RNA and HIV DNA levels after the commencement of raltegravir-based antiretroviral therapy (ART) in primary (PHI) and chronically HIV-infected (CHI) individuals (the PINT study).

Design: We recruited 8 PHI and 8 CHI ART-naive individuals who commenced a 1-year combination regimen of Truvada and the integrase inhibitor raltegravir.

Methods: Nonlinear mixed effects modelling was used to determine multiphasic decay of plasma HIV RNA levels (pVL), as well as dynamics of total, episomal [2-long terminal repeats (LTR)] and integrated HIV DNA in CD4+ T cells from peripheral blood.

Results: Although pVL decreased faster through first and second phase for PHI individuals there was no difference in the final level reaching a mean of 9 copies/ml by week 16 that was maintained thereafter. Total HIV DNA and integrated HIV DNA levels from CHI patients were significantly higher than from PHI patients. However, at no time did 2-LTR levels differ between groups. Of note, 2-LTR circles exhibited an initial increase peaking at week 3 followed by biphasic decay with a half-life of 29 days. Second phase integrated HIV DNA levels were significantly correlated with duration of infection and consistent with this form of infection occurring at approximately 100 000 integration events per day in the absence of ART, achieving its 50% level 2 years after infection.

Conclusions: Integrated HIV DNA levels accumulate with duration of untreated HIV infection. The relatively short half-life and high levels of 2-LTR circles after 1 year support continued HIV transmission during ART.
Keyword Episomal
HIV DNA
HIV RNA
Latency
Primary HIV infection
Raltegravir
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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