BACKGROUND: The pathogenesis of and risk factors for hepatic flare (HF) after the initiation of hepatitis B virus (HBV)-active antiretroviral therapy (ART) in HIV/HBV-coinfected individuals is not well understood. METHODS: We studied HF in ART-naive HIV/HBV-coinfected individuals in Thailand (n = 36) who were beginning HBV-active ART as part of a prospective clinical trial. HF was defined as an alanine aminotransferase (ALT) level>5 times the upper limit of normal or >200 IU/L higher than that at baseline. Immune mediators (interleukin [IL]-18, IL-2, IL-6, IL-8, IL-10, soluble CD26 [sCD26], sCD30, sCD8, CXCL-10, CCL-2, tumor necrosis factor-alpha, interferon [IFN]-gamma, and IFN-alpha) and activated NK cells were quantified. RESULTS:HBV DNA and ALT levels at baseline were higher in patients with HF (n=8) than in patients without HF (n=28) (P=.01). After the initiation of ART, CXCL-10 levels remained elevated in patients with HF but decreased in patients without HF (P<.01). sCD30 levels increased and were significantly higher at week 8 in patients with HF (P<.05). There was a positive correlation between levels of ALT and levels of CXCL-10, sCD30, CCL-2, and IL-18 at week 8 (the time of peak ALT level) but not at other time points. CONCLUSION:Elevated HBV DNA and ALT levels before the initiation of HBV-active ART are risk factors for HF. The pathogenesis of HF after the initiation of HBV-active ART is probably consistent with immune restoration disease.
RCT Entities:
BACKGROUND: The pathogenesis of and risk factors for hepatic flare (HF) after the initiation of hepatitis B virus (HBV)-active antiretroviral therapy (ART) in HIV/HBV-coinfected individuals is not well understood. METHODS: We studied HF in ART-naive HIV/HBV-coinfected individuals in Thailand (n = 36) who were beginning HBV-active ART as part of a prospective clinical trial. HF was defined as an alanine aminotransferase (ALT) level>5 times the upper limit of normal or >200 IU/L higher than that at baseline. Immune mediators (interleukin [IL]-18, IL-2, IL-6, IL-8, IL-10, soluble CD26 [sCD26], sCD30, sCD8, CXCL-10, CCL-2, tumor necrosis factor-alpha, interferon [IFN]-gamma, and IFN-alpha) and activated NK cells were quantified. RESULTS:HBV DNA and ALT levels at baseline were higher in patients with HF (n=8) than in patients without HF (n=28) (P=.01). After the initiation of ART, CXCL-10 levels remained elevated in patients with HF but decreased in patients without HF (P<.01). sCD30 levels increased and were significantly higher at week 8 in patients with HF (P<.05). There was a positive correlation between levels of ALT and levels of CXCL-10, sCD30, CCL-2, and IL-18 at week 8 (the time of peak ALT level) but not at other time points. CONCLUSION: Elevated HBV DNA and ALT levels before the initiation of HBV-active ART are risk factors for HF. The pathogenesis of HF after the initiation of HBV-active ART is probably consistent with immune restoration disease.
Authors: Anchalee Avihingsanon; Gail V Matthews; Sharon R Lewin; Pip Marks; Jose Sasadeusz; David A Cooper; Scott Bowden; Stephen Locarnini; Greg J Dore; Kiat Ruxrungtham Journal: AIDS Res Ther Date: 2012-03-09 Impact factor: 2.250
Authors: Paul U Cameron; Suha Saleh; Georgina Sallmann; Ajantha Solomon; Fiona Wightman; Vanessa A Evans; Genevieve Boucher; Elias K Haddad; Rafick-Pierre Sekaly; Andrew N Harman; Jenny L Anderson; Kate L Jones; Johnson Mak; Anthony L Cunningham; Anthony Jaworowski; Sharon R Lewin Journal: Proc Natl Acad Sci U S A Date: 2010-09-13 Impact factor: 11.205
Authors: Quarraisha Abdool Karim; Salim S Abdool Karim; Janet A Frohlich; Anneke C Grobler; Cheryl Baxter; Leila E Mansoor; Ayesha B M Kharsany; Sengeziwe Sibeko; Koleka P Mlisana; Zaheen Omar; Tanuja N Gengiah; Silvia Maarschalk; Natasha Arulappan; Mukelisiwe Mlotshwa; Lynn Morris; Douglas Taylor Journal: Science Date: 2010-07-19 Impact factor: 47.728
Authors: Patricia Price; David M Murdoch; Upasna Agarwal; Sharon R Lewin; Julian H Elliott; Martyn A French Journal: Clin Microbiol Rev Date: 2009-10 Impact factor: 26.132
Authors: Rachel P Simmons; Eileen P Scully; Erin E Groden; Kelly B Arnold; J Judy Chang; Kim Lane; Jeff Lifson; Eric Rosenberg; Douglas A Lauffenburger; Marcus Altfeld Journal: AIDS Date: 2013-10-23 Impact factor: 4.177
Authors: Vincent Soriano; Pablo Labarga; Carmen de Mendoza; José M Peña; José V Fernández-Montero; Laura Benítez; Isabella Esposito; Pablo Barreiro Journal: Curr HIV/AIDS Rep Date: 2015-09 Impact factor: 5.071