The effect of short-course antiretroviral therapy initiated in primary HIV-1 infection on interleukin-6 and D-dimer levels

被引:19
作者
Hamlyn, Elizabeth [1 ,2 ]
Stoehr, Wolfgang [3 ]
Cooper, David A. [4 ]
Fisher, Martin [5 ,6 ]
Tambussi, Giuseppe [7 ]
Schechter, Mauro [8 ]
Miro, Jose M. [9 ]
Vanobberghen, Fiona [3 ,10 ]
Babiker, Abdel [3 ]
Weber, Jonathan [1 ]
Mcclure, Myra [1 ]
Porter, Kholoud [3 ]
Fidler, Sarah [1 ]
机构
[1] Univ London Imperial Coll Sci Technol & Med, London, England
[2] Kings Coll Hosp NHS Fdn Trust, London, England
[3] UCL, Med Res Council, Clin Trials Unit, London, England
[4] Univ New S Wales, Kirby Inst, Sydney, NSW, Australia
[5] Brighton Univ Hosp, Brighton, E Sussex, England
[6] Sussex Univ Hosp, Brighton, E Sussex, England
[7] Univ Milan, Osped San Raffaele, I-20127 Milan, Italy
[8] Univ Fed Rio de Janeiro, Hosp Escola Sao Francisco de Assis, Projeto Praca Onze, Rio De Janeiro, Brazil
[9] Univ Barcelona, Hosp Clin, Inst Invest Biomed August Pi & Sunyer, Barcelona, Spain
[10] London Sch Hyg & Trop Med, London WC1, England
基金
英国惠康基金;
关键词
INTERRUPTION; COAGULATION;
D O I
10.1097/QAD.0000000000000675
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 log(10) 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-naive, and D-dimer levels were significantly lower.
引用
收藏
页码:1355 / 1361
页数:7
相关论文
共 17 条
[1]   Changes in Inflammatory and Coagulation Biomarkers: A Randomized Comparison of Immediate versus Deferred Antiretroviral Therapy in Patients With HIV Infection [J].
Baker, Jason V. ;
Neuhaus, Jacqueline ;
Duprez, Daniel ;
Kuller, Lewis H. ;
Tracy, Russell ;
Belloso, Waldo H. ;
De Wit, Stephane ;
Drummond, Fraser ;
Lane, H. Clifford ;
Ledergerber, Bruno ;
Lundgren, Jens ;
Nixon, Daniel E. ;
Paton, Nicholas I. ;
Neaton, James D. .
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2011, 56 (01) :36-43
[2]   Prevention of HIV-1 Infection with Early Antiretroviral Therapy [J].
Cohen, Myron S. ;
Chen, Ying Q. ;
McCauley, Marybeth ;
Gamble, Theresa ;
Hosseinipour, Mina C. ;
Kumarasamy, Nagalingeswaran ;
Hakim, James G. ;
Kumwenda, Johnstone ;
Grinsztejn, Beatriz ;
Pilotto, Jose H. S. ;
Godbole, Sheela V. ;
Mehendale, Sanjay ;
Chariyalertsak, Suwat ;
Santos, Breno R. ;
Mayer, Kenneth H. ;
Hoffman, Irving F. ;
Eshleman, Susan H. ;
Piwowar-Manning, Estelle ;
Wang, Lei ;
Makhema, Joseph ;
Mills, Lisa A. ;
de Bruyn, Guy ;
Sanne, Ian ;
Eron, Joseph ;
Gallant, Joel ;
Havlir, Diane ;
Swindells, Susan ;
Ribaudo, Heather ;
Elharrar, Vanessa ;
Burns, David ;
Taha, Taha E. ;
Nielsen-Saines, Karin ;
Celentano, David ;
Essex, Max ;
Fleming, Thomas R. .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 365 (06) :493-505
[3]  
El-Sadr WM, 2006, NEW ENGL J MED, V355, P2283, DOI 10.1056/NEJMoa062360
[4]   Short-Course Antiretroviral Therapy in Primary HIV Infection [J].
Fidler, Sarah ;
Porter, Kholoud ;
Ewings, Fiona ;
Frater, John ;
Ramjee, Gita ;
Cooper, David ;
Rees, Helen ;
Fisher, Martin ;
Schechter, Mauro ;
Kaleebu, Pontiano ;
Tambussi, Giuseppe ;
Kinloch, Sabine ;
Miro, Jose M. ;
Kelleher, Anthony ;
McClure, Myra ;
Kaye, Steve ;
Gabriel, Michelle ;
Phillips, Rodney ;
Weber, Jonathan .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 368 (03) :207-217
[5]   Interleukin-6 and D- dimer levels at seroconversion as predictors of HIV-1 disease progression [J].
Hamlyn, Elizabeth ;
Fidler, Sarah ;
Stoehr, Wolfgang ;
Cooper, David A. ;
Tambussi, Giuseppe ;
Schechter, Mauro ;
Miro, Jose M. ;
Mcclure, Myra ;
Weber, Jonathan ;
Babiker, Abdel ;
Porter, Kholoud .
AIDS, 2014, 28 (06) :869-874
[6]   Plasma HIV Viral Rebound following Protocol-Indicated Cessation of ART Commenced in Primary and Chronic HIV Infection [J].
Hamlyn, Elizabeth ;
Ewings, Fiona M. ;
Porter, Kholoud ;
Cooper, David A. ;
Tambussi, Giuseppe ;
Schechter, Mauro ;
Pedersen, Court ;
Okulicz, Jason F. ;
McClure, Myra ;
Babiker, Abdel ;
Weber, Jonathan ;
Fidler, Sarah .
PLOS ONE, 2012, 7 (08)
[7]   A multicenter observational study of the potential benefits of initiating combination antiretroviral therapy during acute HIV infection [J].
Hecht, Frederick M. ;
Wang, Lei ;
Collier, Ann ;
Little, Susan ;
Markowitz, Martin ;
Margolick, Joseph ;
Kilby, J. Michael ;
Daar, Eric ;
Conway, Brian ;
Holte, Sarah .
JOURNAL OF INFECTIOUS DISEASES, 2006, 194 (06) :725-733
[8]   Inflammatory and Coagulation Biomarkers and Mortality in Patients with HIV Infection [J].
Kuller, Lewis H. ;
Tracy, Russell ;
Belloso, Waldo ;
De Wit, Stephane ;
Drummond, Fraser ;
Lane, H. Clifford ;
Ledergerber, Bruno ;
Lundgren, Jens ;
Neuhaus, Jacqueline ;
Nixon, Daniel ;
Paton, Nicholas I. ;
Neaton, James D. .
PLOS MEDICINE, 2008, 5 (10) :1496-1508
[9]   Enhanced CD4+T-Cell Recovery with Earlier HIV-1 Antiretroviral Therapy [J].
Le, Tuan ;
Wright, Edwina J. ;
Smith, Davey M. ;
He, Weijing ;
Catano, Gabriel ;
Okulicz, Jason F. ;
Young, Jason A. ;
Clark, Robert A. ;
Richman, Douglas D. ;
Little, Susan J. ;
Ahuja, Sunil K. .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 368 (03) :218-230
[10]   Immunovirologic Control 24 Months After Interruption of Antiretroviral Therapy Initiated Close to HIV Seroconversion [J].
Lodi, Sara ;
Meyer, Laurence ;
Kelleher, Anthony D. ;
Rosinska, Magdalena ;
Ghosn, Jade ;
Sannes, Mette ;
Porter, Kholoud .
ARCHIVES OF INTERNAL MEDICINE, 2012, 172 (16) :1252-1255