Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

OBJECTIVE:Interruption of antiretroviral therapy (ART) in chronic HIV disease is associated with increased mortality, predicted by elevations in interleukin-6 (IL-6) and D-dimer. The effect of ART interruption in primary HIV-1 infection on these biomarkers is unknown. METHODS:Plasma samples from 200 HIV seroconverters enrolled in the Short Pulse Anti-Retroviral Therapy At HIV Seroconversion trial of deferred ART (standard of care) - 12 or 48 week ART (ART12 or ART48, respectively) - were analysed for IL-6 and D-dimer at weeks 0, 12, 16, 48, 52, 60 and 108 after randomization. Changes in log10 levels from weeks 0 to 12 were analysed using linear regression, as were changes from baseline to 4 weeks after stopping ART. Areas under the biomarker-time curves (AUC) to week 108 were adjusted for baseline values, and compared across all arms. RESULTS:Median (inter-quartile range) baseline IL-6 and D-dimer were 1.45 (0.88, 2.41) pg/ml and 0.34 (0.20, 0.50) mg/l, respectively. At week 12, D-dimer levels were significantly lower among treated compared to untreated individuals (P < 0.001), whereas IL-6 levels were similar (P = 0.23). Within 4 weeks from stopping ART, IL-6 and D-dimer levels rose by 22 and 18%, reaching pre-ART levels. Over 108-week follow-up, there was no difference between arms in IL-6 AUC (P = 0.53), but D-dimer AUC was significantly lower for ART12 and ART48 compared to standard of care (overall P = 0.008). CONCLUSION:Stopping ART in primary HIV-1 infection leads to inflammatory biomarker rebound to pre-treatment levels. However, over 108-week follow-up, we found no evidence that biomarker levels were higher for those interrupting ART, compared to those remaining ART-naïve, and D-dimer levels were significantly lower.

Original publication

DOI

10.1097/qad.0000000000000675

Type

Journal article

Journal

AIDS (London, England)

Publication Date

07/2015

Volume

29

Pages

1355 - 1361

Addresses

aImperial College London bKings College Hospital NHS Foundation Trust cMedical Research Council Clinical Trials Unit at University College London, London, UK dKirby Institute, University of New South Wales, Sydney, Australia eBrighton and Sussex University Hospitals, Brighton, UK fOspedale San Raffaele, Milan, Italy gProjeto Praça Onze, Hospital Escola São Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil hHospital Clinic-Institut d'investigacions Biomèdiques August Pi I Sunyer, University of Barcelona, Barcelona, Spain iLondon School of Hygiene & Tropical Medicine, London, UK. *Kholoud Porter and Sarah Fidler contributed equally to the writing of this manuscript.

Keywords

SPARTAC Investigators, Humans, HIV-1, HIV Seropositivity, C-Reactive Protein, Fibrin Fibrinogen Degradation Products, Interleukin-6, Anti-HIV Agents, Linear Models, Adult, Middle Aged, Female, Male, Biomarkers