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.
aSchool of Mathematics and Statistics, University of New South Wales
bThe Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia
cDepartment of Internal Medicine I, University of Bonn, Bonn, Germany
dSt Vincent's Hospital, Sydney, Centre for Applied Medical Research
eEast Sydney Doctors, Darlinghurst, New South Wales, Australia.
*These authors contributed equally to this study.
Correspondence to Associate Professor John M. Murray, School of Mathematics and Statistics, University of New South Wales, Sydney 2052, NSW, Australia. Tel: +61 2 9385 7042; fax: +61 2 9385 7123; e-mail: J.Murray@unsw.edu.au
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com).
Received 20 September, 2011
Revised 15 December, 2011
Accepted 23 December, 2011