Corrilynn O Hileman1,2, Nicholas T Funderburg3. 1. Case Western Reserve University School of Medicine, 10900 Euclid Ave, Cleveland, OH, 44106, USA. corrilynn.hileman@case.edu. 2. Department of Medicine, Division of Infectious Diseases, MetroHealth Medical Center, 2500 MetroHealth Drive, Cleveland, OH, 44109, USA. corrilynn.hileman@case.edu. 3. School of Health and Rehabilitation Sciences, Division of Medical Laboratory Science, Ohio State University, 535A Atwell Hall, 453 W. 10th Ave, Columbus, OH, 43210, USA.
Abstract
PURPOSE OF REVIEW: This review focuses on the differential effects of contemporary antiretrovirals on systemic inflammation as heightened immune activation is linked to important co-morbidities and mortality with HIV infection. RECENT FINDINGS: Antiretroviral therapy (ART) reduces dramatically systemic inflammation and immune activation, but not to levels synchronous with HIV-uninfected populations. In one ART initiation trial, integrase inhibitors appear to reduce inflammation to a greater degree than non-nucleoside reverse transcriptase inhibitors (NNRTIs); however, it is not clear that there are beneficial effects on inflammation resulting from treatment with integrase inhibitors compared to PIs, between PIs and NNRTIs, between specific nucleoside reverse transcriptase inhibitors, or with maraviroc in ART-naïve patients. In ART switch studies, changing to an integrase inhibitor from a PI-, NNRTI-, or enfuvirtide-containing regimen has resulted in improvement in several markers of inflammation. Additional research is needed to conclusively state whether there are clear differences in effects of specific antiretrovirals on inflammation and immune activation in HIV.
PURPOSE OF REVIEW: This review focuses on the differential effects of contemporary antiretrovirals on systemic inflammation as heightened immune activation is linked to important co-morbidities and mortality with HIV infection. RECENT FINDINGS: Antiretroviral therapy (ART) reduces dramatically systemic inflammation and immune activation, but not to levels synchronous with HIV-uninfected populations. In one ART initiation trial, integrase inhibitors appear to reduce inflammation to a greater degree than non-nucleoside reverse transcriptase inhibitors (NNRTIs); however, it is not clear that there are beneficial effects on inflammation resulting from treatment with integrase inhibitors compared to PIs, between PIs and NNRTIs, between specific nucleoside reverse transcriptase inhibitors, or with maraviroc in ART-naïve patients. In ART switch studies, changing to an integrase inhibitor from a PI-, NNRTI-, or enfuvirtide-containing regimen has resulted in improvement in several markers of inflammation. Additional research is needed to conclusively state whether there are clear differences in effects of specific antiretrovirals on inflammation and immune activation in HIV.
Entities:
Keywords:
Antiretroviral therapy; HIV infection; Immune activation; Inflammation
Authors: Michael M Lederman; Nicholas T Funderburg; Rafick P Sekaly; Nichole R Klatt; Peter W Hunt Journal: Adv Immunol Date: 2013 Impact factor: 3.543
Authors: Netanya G Sandler; Handan Wand; Annelys Roque; Matthew Law; Martha C Nason; Daniel E Nixon; Court Pedersen; Kiat Ruxrungtham; Sharon R Lewin; Sean Emery; James D Neaton; Jason M Brenchley; Steven G Deeks; Irini Sereti; Daniel C Douek Journal: J Infect Dis Date: 2011-01-20 Impact factor: 5.226
Authors: Corrilynn O Hileman; David A Wohl; Daniel J Tisch; Sara M Debanne; Grace A McComsey Journal: AIDS Res Hum Retroviruses Date: 2012-04-26 Impact factor: 2.205
Authors: Matthew S Freiberg; Chung-Chou H Chang; Lewis H Kuller; Melissa Skanderson; Elliott Lowy; Kevin L Kraemer; Adeel A Butt; Matthew Bidwell Goetz; David Leaf; Kris Ann Oursler; David Rimland; Maria Rodriguez Barradas; Sheldon Brown; Cynthia Gibert; Kathy McGinnis; Kristina Crothers; Jason Sico; Heidi Crane; Alberta Warner; Stephen Gottlieb; John Gottdiener; Russell P Tracy; Matthew Budoff; Courtney Watson; Kaku A Armah; Donna Doebler; Kendall Bryant; Amy C Justice Journal: JAMA Intern Med Date: 2013-04-22 Impact factor: 21.873
Authors: Jacob D Estes; Levelle D Harris; Nichole R Klatt; Brian Tabb; Stefania Pittaluga; Mirko Paiardini; G Robin Barclay; Jeremy Smedley; Rhonda Pung; Kenneth M Oliveira; Vanessa M Hirsch; Guido Silvestri; Daniel C Douek; Christopher J Miller; Ashley T Haase; Jeffrey Lifson; Jason M Brenchley Journal: PLoS Pathog Date: 2010-08-19 Impact factor: 6.823
Authors: Jeffrey L Lennox; Raphael J Landovitz; Heather J Ribaudo; Ighovwerha Ofotokun; Lumine H Na; Catherine Godfrey; Daniel R Kuritzkes; Manish Sagar; Todd T Brown; Susan E Cohn; Grace A McComsey; Francesca Aweeka; Carl J Fichtenbaum; Rachel M Presti; Susan L Koletar; David W Haas; Kristine B Patterson; Constance A Benson; Bryan P Baugh; Randi Y Leavitt; James F Rooney; Daniel Seekins; Judith S Currier Journal: Ann Intern Med Date: 2014-10-07 Impact factor: 25.391
Authors: Todd T Brown; Grace A McComsey; Martin S King; Roula B Qaqish; Barry M Bernstein; Barbara A da Silva Journal: J Acquir Immune Defic Syndr Date: 2009-08-15 Impact factor: 3.771
Authors: Stanzi M le Roux; Kirsten A Donald; Kirsty Brittain; Tamsin K Phillips; Allison Zerbe; Kelly K Nguyen; Andrea Strandvik; Max Kroon; Elaine J Abrams; Landon Myer Journal: AIDS Date: 2018-08-24 Impact factor: 4.177
Authors: Nathaniel D Bachtel; Greta A Beckerle; Talia M Mota; Miguel de Mulder Rougvie; Rui André Saraiva Raposo; R Brad Jones; Douglas F Nixon; Richard Apps Journal: AIDS Res Hum Retroviruses Date: 2018-10-16 Impact factor: 2.205
Authors: Vanessa El Kamari; Carlee Moser; Corrilynn O Hileman; Judith S Currier; Todd T Brown; Liz Johnston; Peter W Hunt; Grace A McComsey Journal: Clin Infect Dis Date: 2019-04-08 Impact factor: 9.079
Authors: Haidong Lu; Pamela J Surkan; Michael R Irwin; Glenn J Treisman; Elizabeth C Breen; Ned Sacktor; Ron Stall; Steven M Wolinsky; Lisa P Jacobson; Alison G Abraham Journal: Am J Epidemiol Date: 2019-11-01 Impact factor: 4.897
Authors: Bernard J C Macatangay; Edwin K Jackson; Kaleab Z Abebe; Diane Comer; Joshua Cyktor; Cynthia Klamar-Blain; Luann Borowski; Delbert G Gillespie; John W Mellors; Charles R Rinaldo; Sharon A Riddler Journal: J Infect Dis Date: 2020-04-27 Impact factor: 5.226