Inflammation, Immune Activation, and Antiretroviral Therapy in HIV

Overview

Journal Curr HIV/AIDS Rep

Publisher Current Science

Specialty Infectious Diseases

Date 2017 Apr 24

PMID 28434169

Citations 115

Authors

Corrilynn O Hileman

Nicholas T Funderburg

Affiliations

Soon will be listed here.

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.

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References

Yi T, Walmsley S, Szadkowski L, Raboud J, Rajwans N, Shannon B . A randomized controlled pilot trial of valacyclovir for attenuating inflammation and immune activation in HIV/herpes simplex virus 2-coinfected adults on suppressive antiretroviral therapy. Clin Infect Dis. 2013; 57(9):1331-8. DOI: 10.1093/cid/cit539. View

Estes J, Harris L, Klatt N, Tabb B, Pittaluga S, Paiardini M . Damaged intestinal epithelial integrity linked to microbial translocation in pathogenic simian immunodeficiency virus infections. PLoS Pathog. 2010; 6(8):e1001052. PMC: 2924359. DOI: 10.1371/journal.ppat.1001052. View

Sandler N, Wand H, Roque A, Law M, Nason M, Nixon D . Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis. 2011; 203(6):780-90. PMC: 3071127. DOI: 10.1093/infdis/jiq118. View

Lennox J, Landovitz R, Ribaudo H, Ofotokun I, Na L, Godfrey C . Efficacy and tolerability of 3 nonnucleoside reverse transcriptase inhibitor-sparing antiretroviral regimens for treatment-naive volunteers infected with HIV-1: a randomized, controlled equivalence trial. Ann Intern Med. 2014; 161(7):461-71. PMC: 4412467. DOI: 10.7326/M14-1084. View

Lederman M, Funderburg N, Sekaly R, Klatt N, Hunt P . Residual immune dysregulation syndrome in treated HIV infection. Adv Immunol. 2013; 119:51-83. PMC: 4126613. DOI: 10.1016/B978-0-12-407707-2.00002-3. View

Crane M, Avihingsanon A, Rajasuriar R, Velayudham P, Iser D, Solomon A . Lipopolysaccharide, immune activation, and liver abnormalities in HIV/hepatitis B virus (HBV)-coinfected individuals receiving HBV-active combination antiretroviral therapy. J Infect Dis. 2014; 210(5):745-51. DOI: 10.1093/infdis/jiu119. View

Brown T, McComsey G, King M, Qaqish R, Bernstein B, da Silva B . Loss of bone mineral density after antiretroviral therapy initiation, independent of antiretroviral regimen. J Acquir Immune Defic Syndr. 2009; 51(5):554-61. DOI: 10.1097/QAI.0b013e3181adce44. View

Freiberg M, Chang C, Kuller L, Skanderson M, Lowy E, Kraemer K . HIV infection and the risk of acute myocardial infarction. JAMA Intern Med. 2013; 173(8):614-22. PMC: 4766798. DOI: 10.1001/jamainternmed.2013.3728. View

Hileman C, Wohl D, Tisch D, Debanne S, McComsey G . Short communication: initiation of an abacavir-containing regimen in HIV-infected adults is associated with a smaller decrease in inflammation and endothelial activation markers compared to non-abacavir-containing regimens. AIDS Res Hum Retroviruses. 2012; 28(12):1561-4. PMC: 3505065. DOI: 10.1089/AID.2012.0034. View

10.

Gupta S, Dube M, Stein J, Clauss M, Liu Z . A pilot trial of pentoxifylline on endothelial function and inflammation in HIV-infected patients initiating antiretroviral therapy. AIDS. 2016; 30(13):2139-42. PMC: 4968583. DOI: 10.1097/QAD.0000000000001172. View

11.

Friis-Moller N, Reiss P, Sabin C, Weber R, Monforte A, El-Sadr W . Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med. 2007; 356(17):1723-35. DOI: 10.1056/NEJMoa062744. View

12.

McComsey G, Kitch D, Daar E, Tierney C, Jahed N, Melbourne K . Inflammation markers after randomization to abacavir/lamivudine or tenofovir/emtricitabine with efavirenz or atazanavir/ritonavir. AIDS. 2012; 26(11):1371-85. PMC: 3560932. DOI: 10.1097/QAD.0b013e328354f4fb. View

13.

Calza L, Magistrelli E, Danese I, Colangeli V, Borderi M, Bon I . Changes in Serum Markers of Inflammation and Endothelial Activation in HIV-Infected Antiretroviral Naive Patients Starting A Treatment with Abacavir-Lamivudine or Tenofovir-Emtricitabine Plus Efavirenz. Curr HIV Res. 2015; 14(1):61-70. DOI: 10.2174/1570162x1401151102143222. View

14.

Chun T, Nickle D, Justement J, Meyers J, Roby G, Hallahan C . Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy. J Infect Dis. 2008; 197(5):714-20. DOI: 10.1086/527324. View

15.

Funderburg N, Kalinowska M, Eason J, Goodrich J, Heera J, Mayer H . Effects of maraviroc and efavirenz on markers of immune activation and inflammation and associations with CD4+ cell rises in HIV-infected patients. PLoS One. 2010; 5(10):e13188. PMC: 2950842. DOI: 10.1371/journal.pone.0013188. View

16.

Funderburg N, McComsey G, Kulkarni M, Bannerman T, Mantini J, Thornton B . Equivalent Decline in Inflammation Markers with Tenofovir Disoproxil Fumarate vs. Tenofovir Alafenamide. EBioMedicine. 2016; 13:321-327. PMC: 5264242. DOI: 10.1016/j.ebiom.2016.10.009. View

17.

Meier A, Alter G, Frahm N, Sidhu H, Li B, Bagchi A . MyD88-dependent immune activation mediated by human immunodeficiency virus type 1-encoded Toll-like receptor ligands. J Virol. 2007; 81(15):8180-91. PMC: 1951290. DOI: 10.1128/JVI.00421-07. View

18.

Martinez E, Larrousse M, Llibre J, Gutierrez F, Saumoy M, Antela A . Substitution of raltegravir for ritonavir-boosted protease inhibitors in HIV-infected patients: the SPIRAL study. AIDS. 2010; 24(11):1697-707. DOI: 10.1097/QAD.0b013e32833a608a. View

19.

Obel N, Farkas D, Kronborg G, Larsen C, Pedersen G, Riis A . Abacavir and risk of myocardial infarction in HIV-infected patients on highly active antiretroviral therapy: a population-based nationwide cohort study. HIV Med. 2009; 11(2):130-6. DOI: 10.1111/j.1468-1293.2009.00751.x. View

20.

Lederman M, Calabrese L, Funderburg N, Clagett B, Medvik K, Bonilla H . Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells. J Infect Dis. 2011; 204(8):1217-26. PMC: 3218674. DOI: 10.1093/infdis/jir507. View