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Erschienen in: Current HIV/AIDS Reports 2/2012

01.06.2012 | Antiretroviral Therapies (A Pozniak, Section Editor)

HIV and Inflammation: Mechanisms and Consequences

verfasst von: Peter W. Hunt

Erschienen in: Current HIV/AIDS Reports | Ausgabe 2/2012

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Abstract

Persistent immune activation and inflammation despite sustained antiretroviral therapy (ART)-mediated viral suppression has emerged as a major challenge of the modern HIV treatment era. While immune activation, inflammatory, and coagulation markers typically decline during suppressive ART, they remain abnormally elevated in many HIV-infected individuals and predict subsequent mortality and non-AIDS morbidities including cardiovascular disease. The goal of this review is to summarize the current state of our knowledge regarding the underlying causes of persistent immune activation during ART-mediated viral suppression as well as the link between persistent immune activation and morbidity and mortality in this setting. Several recent studies have linked surrogate markers of this persistent inflammatory state to clinical outcomes, validating persistent immune activation as a viable therapeutic target. Other recent studies have helped clarify the roles of persistent HIV expression and/or replication, microbial translocation, and co-infections in driving this persistent inflammatory state, identifying targets for novel interventions.
Literatur
1.
Zurück zum Zitat Gottlieb MS, Schroff R, Schanker HM, et al. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med. 1981;305(24):1425–31.PubMedCrossRef Gottlieb MS, Schroff R, Schanker HM, et al. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med. 1981;305(24):1425–31.PubMedCrossRef
2.
Zurück zum Zitat Fahey JL, Taylor JM, Manna B, et al. Prognostic significance of plasma markers of immune activation, HIV viral load and CD4 T-cell measurements. AIDS. 1998;12(13):1581–90.PubMedCrossRef Fahey JL, Taylor JM, Manna B, et al. Prognostic significance of plasma markers of immune activation, HIV viral load and CD4 T-cell measurements. AIDS. 1998;12(13):1581–90.PubMedCrossRef
3.
Zurück zum Zitat Giorgi JV, Ho HN, Hirji K, et al. CD8+ lymphocyte activation at human immunodeficiency virus type 1 seroconversion: development of HLA-DR + CD38- CD8+ cells is associated with subsequent stable CD4+ cell levels. The Multicenter AIDS Cohort Study Group. J Infect Dis. 1994;170(4):775–81.PubMedCrossRef Giorgi JV, Ho HN, Hirji K, et al. CD8+ lymphocyte activation at human immunodeficiency virus type 1 seroconversion: development of HLA-DR + CD38- CD8+ cells is associated with subsequent stable CD4+ cell levels. The Multicenter AIDS Cohort Study Group. J Infect Dis. 1994;170(4):775–81.PubMedCrossRef
4.
Zurück zum Zitat Giorgi JV, Hultin LE, McKeating JA, et al. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis. 1999;179(4):859–70.PubMedCrossRef Giorgi JV, Hultin LE, McKeating JA, et al. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis. 1999;179(4):859–70.PubMedCrossRef
5.
Zurück zum Zitat Giorgi JV, Liu Z, Hultin LE, et al. Elevated levels of CD38+ CD8+ T cells in HIV infection add to the prognostic value of low CD4+ T cell levels: results of 6 years of follow-up. The Los Angeles Center, Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr 1993;6(8):904–12. Giorgi JV, Liu Z, Hultin LE, et al. Elevated levels of CD38+ CD8+ T cells in HIV infection add to the prognostic value of low CD4+ T cell levels: results of 6 years of follow-up. The Los Angeles Center, Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr 1993;6(8):904–12.
6.
Zurück zum Zitat Giorgi JV, Lyles RH, Matud JL, et al. Predictive value of immunologic and virologic markers after long or short duration of HIV-1 infection. J Acquir Immune Defic Syndr. 2002;29(4):346–55.PubMed Giorgi JV, Lyles RH, Matud JL, et al. Predictive value of immunologic and virologic markers after long or short duration of HIV-1 infection. J Acquir Immune Defic Syndr. 2002;29(4):346–55.PubMed
7.
Zurück zum Zitat Liu Z, Cumberland WG, Hultin LE, et al. Elevated CD38 antigen expression on CD8+ T cells is a stronger marker for the risk of chronic HIV disease progression to AIDS and death in the Multicenter AIDS Cohort Study than CD4+ cell count, soluble immune activation markers, or combinations of HLA-DR and CD38 expression. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;16(2):83–92.PubMedCrossRef Liu Z, Cumberland WG, Hultin LE, et al. Elevated CD38 antigen expression on CD8+ T cells is a stronger marker for the risk of chronic HIV disease progression to AIDS and death in the Multicenter AIDS Cohort Study than CD4+ cell count, soluble immune activation markers, or combinations of HLA-DR and CD38 expression. J Acquir Immune Defic Syndr Hum Retrovirol. 1997;16(2):83–92.PubMedCrossRef
8.
Zurück zum Zitat Deeks SG, Kitchen CM, Liu L, et al. Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load. Blood. 2004;104(4):942–7.PubMedCrossRef Deeks SG, Kitchen CM, Liu L, et al. Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load. Blood. 2004;104(4):942–7.PubMedCrossRef
9.
Zurück zum Zitat Papagno L, Spina CA, Marchant A, et al. Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1 infection. PLoS Biol. 2004;2(2):E20.PubMedCrossRef Papagno L, Spina CA, Marchant A, et al. Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1 infection. PLoS Biol. 2004;2(2):E20.PubMedCrossRef
10.
Zurück zum Zitat Doisne JM, Urrutia A, Lacabaratz-Porret C, et al. CD8+ T cells specific for EBV, cytomegalovirus, and influenza virus are activated during primary HIV infection. J Immunol. 2004;173(4):2410–8.PubMed Doisne JM, Urrutia A, Lacabaratz-Porret C, et al. CD8+ T cells specific for EBV, cytomegalovirus, and influenza virus are activated during primary HIV infection. J Immunol. 2004;173(4):2410–8.PubMed
11.
Zurück zum Zitat •• Burdo TH, Lentz MR, Autissier P, et al. Soluble CD163 made by monocyte/macrophages is a novel marker of HIV activity in early and chronic infection prior to and after anti-retroviral therapy. J Infect Dis 2011, 204(1): p. 154–63. This study demonstrated that abnormal monocyte/macrophage activation persists in most HIV-infected individuals despite ART, but can potentially be reversed if ART is started during acute HIV infection. •• Burdo TH, Lentz MR, Autissier P, et al. Soluble CD163 made by monocyte/macrophages is a novel marker of HIV activity in early and chronic infection prior to and after anti-retroviral therapy. J Infect Dis 2011, 204(1): p. 154–63. This study demonstrated that abnormal monocyte/macrophage activation persists in most HIV-infected individuals despite ART, but can potentially be reversed if ART is started during acute HIV infection.
12.
Zurück zum Zitat Brenchley JM, Price DA, Schacker TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12(12):1365–71.PubMedCrossRef Brenchley JM, Price DA, Schacker TW, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006;12(12):1365–71.PubMedCrossRef
13.
Zurück zum Zitat Brenchley JM, Silvestri G, Douek DC. Nonprogressive and progressive primate immunodeficiency lentivirus infections. Immunity. 2010;32(6):737–42.PubMedCrossRef Brenchley JM, Silvestri G, Douek DC. Nonprogressive and progressive primate immunodeficiency lentivirus infections. Immunity. 2010;32(6):737–42.PubMedCrossRef
14.
Zurück zum Zitat Silvestri G, Sodora DL, Koup RA, et al. Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity. 2003;18(3):441–52.PubMedCrossRef Silvestri G, Sodora DL, Koup RA, et al. Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. Immunity. 2003;18(3):441–52.PubMedCrossRef
15.
Zurück zum Zitat Hasegawa A, Liu H, Ling B, et al. The level of monocyte turnover predicts disease progression in the macaque model of AIDS. Blood. 2009;114(14):2917–25.PubMedCrossRef Hasegawa A, Liu H, Ling B, et al. The level of monocyte turnover predicts disease progression in the macaque model of AIDS. Blood. 2009;114(14):2917–25.PubMedCrossRef
16.
Zurück zum Zitat Mandl JN, Barry AP, Vanderford TH, et al. Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections. Nat Med. 2008;14(10):1077–87.PubMedCrossRef Mandl JN, Barry AP, Vanderford TH, et al. Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections. Nat Med. 2008;14(10):1077–87.PubMedCrossRef
17.
Zurück zum Zitat Bosinger SE, Li Q, Gordon SN, et al. Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys. J Clin Invest. 2009;119(12):3556–72.PubMed Bosinger SE, Li Q, Gordon SN, et al. Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys. J Clin Invest. 2009;119(12):3556–72.PubMed
18.
Zurück zum Zitat Brenchley JM, Paiardini M, Knox KS, et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood. 2008;112(7):2826–35.PubMedCrossRef Brenchley JM, Paiardini M, Knox KS, et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood. 2008;112(7):2826–35.PubMedCrossRef
19.
Zurück zum Zitat Favre D, Lederer S, Kanwar B, et al. Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. PLoS Pathog. 2009;5(2):e1000295.PubMedCrossRef Favre D, Lederer S, Kanwar B, et al. Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. PLoS Pathog. 2009;5(2):e1000295.PubMedCrossRef
20.
Zurück zum Zitat Raffatellu M, Santos RL, Verhoeven DE, et al. Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med. 2008;14(4):421–8.PubMedCrossRef Raffatellu M, Santos RL, Verhoeven DE, et al. Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med. 2008;14(4):421–8.PubMedCrossRef
21.
Zurück zum Zitat •• Favre D, Mold J, Hunt PW, et al. Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease. Sci Transl Med 2010;2(32):32ra36. This study identified indoleamine 2,3-dioxygenase 1 as a major determinant of Th17 depletion and potentially microbial translocation in HIV infection, highlighting it as a potential target for interventions. •• Favre D, Mold J, Hunt PW, et al. Tryptophan catabolism by indoleamine 2,3-dioxygenase 1 alters the balance of TH17 to regulatory T cells in HIV disease. Sci Transl Med 2010;2(32):32ra36. This study identified indoleamine 2,3-dioxygenase 1 as a major determinant of Th17 depletion and potentially microbial translocation in HIV infection, highlighting it as a potential target for interventions.
22.
Zurück zum Zitat Valdez H, Connick E, Smith KY, et al. Limited immune restoration after 3 years' suppression of HIV-1 replication in patients with moderately advanced disease. AIDS. 2002;16(14):1859–66.PubMedCrossRef Valdez H, Connick E, Smith KY, et al. Limited immune restoration after 3 years' suppression of HIV-1 replication in patients with moderately advanced disease. AIDS. 2002;16(14):1859–66.PubMedCrossRef
23.
Zurück zum Zitat Hunt PW, Martin JN, Sinclair E, et al. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis. 2003;187(10):1534–43.PubMedCrossRef Hunt PW, Martin JN, Sinclair E, et al. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis. 2003;187(10):1534–43.PubMedCrossRef
24.
Zurück zum Zitat Goicoechea M, Smith DM, Liu L, et al. Determinants of CD4+ T cell recovery during suppressive antiretroviral therapy: association of immune activation, T cell maturation markers, and cellular HIV-1 DNA. J Infect Dis. 2006;194(1):29–37.PubMedCrossRef Goicoechea M, Smith DM, Liu L, et al. Determinants of CD4+ T cell recovery during suppressive antiretroviral therapy: association of immune activation, T cell maturation markers, and cellular HIV-1 DNA. J Infect Dis. 2006;194(1):29–37.PubMedCrossRef
25.
Zurück zum Zitat Gandhi RT, Spritzler J, Chan E, et al. Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: results from ACTG 384. J Acquir Immune Defic Syndr. 2006;42(4):426–34.PubMedCrossRef Gandhi RT, Spritzler J, Chan E, et al. Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: results from ACTG 384. J Acquir Immune Defic Syndr. 2006;42(4):426–34.PubMedCrossRef
26.
Zurück zum Zitat • Hunt PW, Cao H, Muzoora C, et al. Impact of CD8+ T Cell Activation on CD4+ T Cell Recovery and Mortality in HIV-infected Ugandans Initiating Antiretroviral Therapy. AIDS, 2011;25(17):2123–31. This study was the first to demonstrate that T cell activation markers predict subsequent mortality during ART-mediated viral suppression. • Hunt PW, Cao H, Muzoora C, et al. Impact of CD8+ T Cell Activation on CD4+ T Cell Recovery and Mortality in HIV-infected Ugandans Initiating Antiretroviral Therapy. AIDS, 2011;25(17):2123–31. This study was the first to demonstrate that T cell activation markers predict subsequent mortality during ART-mediated viral suppression.
27.
Zurück zum Zitat Massanella M, Negredo E, Perez-Alvarez N, et al. CD4 T-cell hyperactivation and susceptibility to cell death determine poor CD4 T-cell recovery during suppressive HAART. AIDS. 2010;24(7):959–68.PubMedCrossRef Massanella M, Negredo E, Perez-Alvarez N, et al. CD4 T-cell hyperactivation and susceptibility to cell death determine poor CD4 T-cell recovery during suppressive HAART. AIDS. 2010;24(7):959–68.PubMedCrossRef
28.
Zurück zum Zitat Negredo E, Massanella M, Puig J, et al. Nadir CD4 T cell count as predictor and high CD4 T cell intrinsic apoptosis as final mechanism of poor CD4 T cell recovery in virologically suppressed HIV-infected patients: clinical implications. Clin Infect Dis. 2010;50(9):1300–8.PubMedCrossRef Negredo E, Massanella M, Puig J, et al. Nadir CD4 T cell count as predictor and high CD4 T cell intrinsic apoptosis as final mechanism of poor CD4 T cell recovery in virologically suppressed HIV-infected patients: clinical implications. Clin Infect Dis. 2010;50(9):1300–8.PubMedCrossRef
29.
Zurück zum Zitat Lederman MM, Calabrese L, Funderburg NT, et al. Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells. J Infect Dis. 2011;204(8):1217–26.PubMedCrossRef Lederman MM, Calabrese L, Funderburg NT, et al. Immunologic failure despite suppressive antiretroviral therapy is related to activation and turnover of memory CD4 cells. J Infect Dis. 2011;204(8):1217–26.PubMedCrossRef
30.
Zurück zum Zitat French MA, King MS, Tschampa JM, et al. Serum immune activation markers are persistently increased in patients with HIV infection after 6 years of antiretroviral therapy despite suppression of viral replication and reconstitution of CD4+ T cells. J Infect Dis. 2009;200(8):1212–5.PubMedCrossRef French MA, King MS, Tschampa JM, et al. Serum immune activation markers are persistently increased in patients with HIV infection after 6 years of antiretroviral therapy despite suppression of viral replication and reconstitution of CD4+ T cells. J Infect Dis. 2009;200(8):1212–5.PubMedCrossRef
31.
Zurück zum Zitat • Neuhaus J, Jacobs DR Jr., Baker JV, et al. Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection. J Infect Dis 2010;201(12):1788–95. This study demonstrated that soluble inflammatory biomarkers remain abnormally elevated during treated HIV infection. • Neuhaus J, Jacobs DR Jr., Baker JV, et al. Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection. J Infect Dis 2010;201(12):1788–95. This study demonstrated that soluble inflammatory biomarkers remain abnormally elevated during treated HIV infection.
32.
Zurück zum Zitat Jain V, Hartogensis W, Bacchetti P, et al. Antiretroviral Therapy Initiation during Acute/Early HIV Infection vs. Later ART Initiation is Associated with Improved Immunologic and Virologic Parameters during Suppressive ART. in In the Program and Abstracts of the 18th Conference on Retroviruses and Opportunistic Infections, Boston, MA, Abstract #517. 2011. Jain V, Hartogensis W, Bacchetti P, et al. Antiretroviral Therapy Initiation during Acute/Early HIV Infection vs. Later ART Initiation is Associated with Improved Immunologic and Virologic Parameters during Suppressive ART. in In the Program and Abstracts of the 18th Conference on Retroviruses and Opportunistic Infections, Boston, MA, Abstract #517. 2011.
33.
Zurück zum Zitat Vinikoor M, Cope A, Gay C, et al. ART Started During Acute HIV Infection Failed to Prevent Persistent Immune Activation. In the Program and Abstracts of the 19th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, Abstract # 554. 2012. Vinikoor M, Cope A, Gay C, et al. ART Started During Acute HIV Infection Failed to Prevent Persistent Immune Activation. In the Program and Abstracts of the 19th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, Abstract # 554. 2012.
34.
Zurück zum Zitat Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365(6):493–505.PubMedCrossRef Cohen MS, Chen YQ, McCauley M, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365(6):493–505.PubMedCrossRef
35.
Zurück zum Zitat Emery S, Neuhaus JA, Phillips AN, et al. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis. 2008;197(8):1133–44.PubMedCrossRef Emery S, Neuhaus JA, Phillips AN, et al. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis. 2008;197(8):1133–44.PubMedCrossRef
36.
Zurück zum Zitat van Sighem AI, Gras LA, Reiss P, et al. Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individuals. AIDS. 2010;24(10):1527–35.PubMedCrossRef van Sighem AI, Gras LA, Reiss P, et al. Life expectancy of recently diagnosed asymptomatic HIV-infected patients approaches that of uninfected individuals. AIDS. 2010;24(10):1527–35.PubMedCrossRef
37.
Zurück zum Zitat The Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet. 2008;372(9635):293–9.CrossRef The Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet. 2008;372(9635):293–9.CrossRef
38.
Zurück zum Zitat Marchetti G, Bellistri GM, Borghi E, et al. Microbial translocation is associated with sustained failure in CD4+ T-cell reconstitution in HIV-infected patients on long-term highly active antiretroviral therapy. AIDS. 2008;22(15):2035–8.PubMedCrossRef Marchetti G, Bellistri GM, Borghi E, et al. Microbial translocation is associated with sustained failure in CD4+ T-cell reconstitution in HIV-infected patients on long-term highly active antiretroviral therapy. AIDS. 2008;22(15):2035–8.PubMedCrossRef
39.
Zurück zum Zitat • Jiang W, Lederman MM, Hunt P, et al. Plasma Levels of Bacterial DNA Correlate with Immune Activation and the Magnitude of Immune Restoration in Persons with Antiretroviral-Treated HIV Infection. J Infect Dis 2009;199(8):1177–1185. This study demonstrated that microbial translocation persists during suppressive ART and is associated with persistent immune activation. • Jiang W, Lederman MM, Hunt P, et al. Plasma Levels of Bacterial DNA Correlate with Immune Activation and the Magnitude of Immune Restoration in Persons with Antiretroviral-Treated HIV Infection. J Infect Dis 2009;199(8):1177–1185. This study demonstrated that microbial translocation persists during suppressive ART and is associated with persistent immune activation.
40.
Zurück zum Zitat Baker JV, Peng G, Rapkin J, et al. CD4+ count and risk of non-AIDS diseases following initial treatment for HIV infection. AIDS. 2008;22(7):841–8.PubMedCrossRef Baker JV, Peng G, Rapkin J, et al. CD4+ count and risk of non-AIDS diseases following initial treatment for HIV infection. AIDS. 2008;22(7):841–8.PubMedCrossRef
41.
Zurück zum Zitat Maldarelli F, Palmer S, King MS, et al. ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog. 2007;3(4):e46.PubMedCrossRef Maldarelli F, Palmer S, King MS, et al. ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog. 2007;3(4):e46.PubMedCrossRef
42.
Zurück zum Zitat Anton PA, Mitsuyasu RT, Deeks SG, et al. Multiple measures of HIV burden in blood and tissue are correlated with each other but not with clinical parameters in aviremic subjects. AIDS. 2003;17(1):53–63.PubMedCrossRef Anton PA, Mitsuyasu RT, Deeks SG, et al. Multiple measures of HIV burden in blood and tissue are correlated with each other but not with clinical parameters in aviremic subjects. AIDS. 2003;17(1):53–63.PubMedCrossRef
43.
Zurück zum Zitat Dinoso JB, Kim SY, Wiegand AM, et al. Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc Natl Acad Sci U S A. 2009;106(23):9403–8.PubMedCrossRef Dinoso JB, Kim SY, Wiegand AM, et al. Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc Natl Acad Sci U S A. 2009;106(23):9403–8.PubMedCrossRef
44.
Zurück zum Zitat Gandhi RT, Zheng L, Bosch RJ, et al. The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: a randomized controlled trial. PLoS Med 2010, 7(8):e1000321. Gandhi RT, Zheng L, Bosch RJ, et al. The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: a randomized controlled trial. PLoS Med 2010, 7(8):e1000321.
45.
Zurück zum Zitat Hatano H, Hayes TL, Dahl V, et al. A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response. J Infect Dis. 2011;203(7):960–8.PubMedCrossRef Hatano H, Hayes TL, Dahl V, et al. A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response. J Infect Dis. 2011;203(7):960–8.PubMedCrossRef
46.
Zurück zum Zitat Buzon MJ, Massanella M, Llibre JM, et al. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med. 2010;16(4):460–5.PubMedCrossRef Buzon MJ, Massanella M, Llibre JM, et al. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med. 2010;16(4):460–5.PubMedCrossRef
47.
Zurück zum Zitat • Llibre JM, Buzon MJ, Massanella M, et al. Treatment intensification with raltegravir in subjects with sustained HIV-1 viraemia suppression: a randomized 48-week study. Antivir Ther 2012;17(2):355–64. This is the only modern ART intensification study to demonstrate a benefit on T cell activation markers, potentially suggesting that productive HIV replication may contribute to immune activation in the setting of ART, but it needs to be confirmed in other studies given negative findings from shorter trials. • Llibre JM, Buzon MJ, Massanella M, et al. Treatment intensification with raltegravir in subjects with sustained HIV-1 viraemia suppression: a randomized 48-week study. Antivir Ther 2012;17(2):355–64. This is the only modern ART intensification study to demonstrate a benefit on T cell activation markers, potentially suggesting that productive HIV replication may contribute to immune activation in the setting of ART, but it needs to be confirmed in other studies given negative findings from shorter trials.
48.
Zurück zum Zitat Brenchley JM, Schacker TW, Ruff LE, et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med. 2004;200(6):749–59.PubMedCrossRef Brenchley JM, Schacker TW, Ruff LE, et al. CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med. 2004;200(6):749–59.PubMedCrossRef
49.
Zurück zum Zitat Mehandru S, Poles MA, Tenner-Racz K, et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med. 2004;200(6):761–70.PubMedCrossRef Mehandru S, Poles MA, Tenner-Racz K, et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med. 2004;200(6):761–70.PubMedCrossRef
50.
Zurück zum Zitat Guadalupe M, Reay E, Sankaran S, et al. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol. 2003;77(21):11708–17.PubMedCrossRef Guadalupe M, Reay E, Sankaran S, et al. Severe CD4+ T-cell depletion in gut lymphoid tissue during primary human immunodeficiency virus type 1 infection and substantial delay in restoration following highly active antiretroviral therapy. J Virol. 2003;77(21):11708–17.PubMedCrossRef
51.
Zurück zum Zitat Veazey RS, DeMaria M, Chalifoux LV, et al. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science. 1998;280(5362):427–31.PubMedCrossRef Veazey RS, DeMaria M, Chalifoux LV, et al. Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection. Science. 1998;280(5362):427–31.PubMedCrossRef
52.
Zurück zum Zitat Sankaran S, George MD, Reay E, et al. Rapid onset of intestinal epithelial barrier dysfunction in primary human immunodeficiency virus infection is driven by an imbalance between immune response and mucosal repair and regeneration. J Virol. 2008;82(1):538–45.PubMedCrossRef Sankaran S, George MD, Reay E, et al. Rapid onset of intestinal epithelial barrier dysfunction in primary human immunodeficiency virus infection is driven by an imbalance between immune response and mucosal repair and regeneration. J Virol. 2008;82(1):538–45.PubMedCrossRef
53.
Zurück zum Zitat Sankaran S, Guadalupe M, Reay E, et al. Gut mucosal T cell responses and gene expression correlate with protection against disease in long-term HIV-1-infected nonprogressors. Proc Natl Acad Sci U S A. 2005;102(28):9860–5.PubMedCrossRef Sankaran S, Guadalupe M, Reay E, et al. Gut mucosal T cell responses and gene expression correlate with protection against disease in long-term HIV-1-infected nonprogressors. Proc Natl Acad Sci U S A. 2005;102(28):9860–5.PubMedCrossRef
54.
Zurück zum Zitat Epple HJ, Schneider T, Troeger H, et al. Impairment of the intestinal barrier is evident in untreated but absent in suppressively treated HIV-infected patients. Gut. 2009;58(2):220–7.PubMedCrossRef Epple HJ, Schneider T, Troeger H, et al. Impairment of the intestinal barrier is evident in untreated but absent in suppressively treated HIV-infected patients. Gut. 2009;58(2):220–7.PubMedCrossRef
55.
Zurück zum Zitat Li Q, Estes JD, Duan L, et al. Simian immunodeficiency virus-induced intestinal cell apoptosis is the underlying mechanism of the regenerative enteropathy of early infection. J Infect Dis. 2008;197(3):420–9.PubMedCrossRef Li Q, Estes JD, Duan L, et al. Simian immunodeficiency virus-induced intestinal cell apoptosis is the underlying mechanism of the regenerative enteropathy of early infection. J Infect Dis. 2008;197(3):420–9.PubMedCrossRef
56.
Zurück zum Zitat Cassol E, Malfeld S, Mahasha P, et al. Persistent Microbial Translocation and Immune Activation in HIV-1-Infected South Africans Receiving Combination Antiretroviral Therapy. J Infect Dis. 2010;202(5):723–33.PubMedCrossRef Cassol E, Malfeld S, Mahasha P, et al. Persistent Microbial Translocation and Immune Activation in HIV-1-Infected South Africans Receiving Combination Antiretroviral Therapy. J Infect Dis. 2010;202(5):723–33.PubMedCrossRef
57.
Zurück zum Zitat •• Funderburg NT, Mayne E, Sieg SF, et al. Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation. Blood 2010;115(2):161–7. This study provides a mechanistic link between microbial translocation, monocyte activation, and activation of the coagulation cascade, potentially explaining the increased risk of thromboembolic and cardiovascular disease in HIV infection. •• Funderburg NT, Mayne E, Sieg SF, et al. Increased tissue factor expression on circulating monocytes in chronic HIV infection: relationship to in vivo coagulation and immune activation. Blood 2010;115(2):161–7. This study provides a mechanistic link between microbial translocation, monocyte activation, and activation of the coagulation cascade, potentially explaining the increased risk of thromboembolic and cardiovascular disease in HIV infection.
58.
Zurück zum Zitat Byakwaga H, Kelly M, Purcell DF, et al. Intensification of antiretroviral therapy with raltegravir or addition of hyperimmune bovine colostrum in HIV-infected patients with suboptimal CD4+ T-cell response: A randomized controlled trial. J Infect Dis 2011;204(10):1532–40 . Byakwaga H, Kelly M, Purcell DF, et al. Intensification of antiretroviral therapy with raltegravir or addition of hyperimmune bovine colostrum in HIV-infected patients with suboptimal CD4+ T-cell response: A randomized controlled trial. J Infect Dis 2011;204(10):1532–40 .
59.
Zurück zum Zitat • Gori A, Rizzardini G, Van't Land B, et al. Specific prebiotics modulate gut microbiota and immune activation in HAART-naive HIV-infected adults: results of the "COPA" pilot randomized trial. Mucosal Immunol 2011;4(5):554–63. This study suggested potentially favorable effects of probiotics on indices of microbial translocation. • Gori A, Rizzardini G, Van't Land B, et al. Specific prebiotics modulate gut microbiota and immune activation in HAART-naive HIV-infected adults: results of the "COPA" pilot randomized trial. Mucosal Immunol 2011;4(5):554–63. This study suggested potentially favorable effects of probiotics on indices of microbial translocation.
60.
Zurück zum Zitat Murray SM, Down CM, Boulware DR, et al. Reduction of immune activation during chronic hiv infection with chloroquine therapy. J Virol 2010;84(22):12082–6. Murray SM, Down CM, Boulware DR, et al. Reduction of immune activation during chronic hiv infection with chloroquine therapy. J Virol 2010;84(22):12082–6.
61.
Zurück zum Zitat • Piconi S, Parisotto S, Rizzardini G, et al. Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders. Blood 2011;118(12):3263–72. This study suggested that blockade of toll-like receptors might decrease immune activation in treated HIV infection. • Piconi S, Parisotto S, Rizzardini G, et al. Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders. Blood 2011;118(12):3263–72. This study suggested that blockade of toll-like receptors might decrease immune activation in treated HIV infection.
62.
Zurück zum Zitat Sylwester AW, Mitchell BL, Edgar JB, et al. Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J Exp Med. 2005;202(5):673–85.PubMedCrossRef Sylwester AW, Mitchell BL, Edgar JB, et al. Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J Exp Med. 2005;202(5):673–85.PubMedCrossRef
63.
Zurück zum Zitat Naeger DM, Martin JN, Sinclair E, et al. Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease. PLoS One. 2010;5(1):e8886.PubMedCrossRef Naeger DM, Martin JN, Sinclair E, et al. Cytomegalovirus-specific T cells persist at very high levels during long-term antiretroviral treatment of HIV disease. PLoS One. 2010;5(1):e8886.PubMedCrossRef
64.
Zurück zum Zitat Hsue PY, Hunt PW, Sinclair E, et al. Increased carotid intima-media thickness in HIV patients is associated with increased cytomegalovirus-specific T-cell responses. AIDS. 2006;20(18):2275–83.PubMedCrossRef Hsue PY, Hunt PW, Sinclair E, et al. Increased carotid intima-media thickness in HIV patients is associated with increased cytomegalovirus-specific T-cell responses. AIDS. 2006;20(18):2275–83.PubMedCrossRef
65.
Zurück zum Zitat •• Hunt PW, Martin JN, Sinclair E, et al. Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+ T cell recovery on antiretroviral therapy. J Infect Dis 2011;203(10):1474–83. This is the first study to demonstrate that suppressing a root cause of systemic immune activation in the setting of treated HIV infection—in this case CMV replication—can decrease immune activation in this setting. •• Hunt PW, Martin JN, Sinclair E, et al. Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+ T cell recovery on antiretroviral therapy. J Infect Dis 2011;203(10):1474–83. This is the first study to demonstrate that suppressing a root cause of systemic immune activation in the setting of treated HIV infection—in this case CMV replication—can decrease immune activation in this setting.
66.
Zurück zum Zitat Franceschi C, Bonafe M, Valensin S, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.PubMedCrossRef Franceschi C, Bonafe M, Valensin S, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.PubMedCrossRef
67.
Zurück zum Zitat Wikby A, Nilsson BO, Forsey R, et al. The immune risk phenotype is associated with IL-6 in the terminal decline stage: findings from the Swedish NONA immune longitudinal study of very late life functioning. Mech Ageing Dev. 2006;127(8):695–704.PubMedCrossRef Wikby A, Nilsson BO, Forsey R, et al. The immune risk phenotype is associated with IL-6 in the terminal decline stage: findings from the Swedish NONA immune longitudinal study of very late life functioning. Mech Ageing Dev. 2006;127(8):695–704.PubMedCrossRef
68.
Zurück zum Zitat Reuben DB, Cheh AI, Harris TB, et al. Peripheral blood markers of inflammation predict mortality and functional decline in high-functioning community-dwelling older persons. J Am Geriatr Soc. 2002;50(4):638–44.PubMedCrossRef Reuben DB, Cheh AI, Harris TB, et al. Peripheral blood markers of inflammation predict mortality and functional decline in high-functioning community-dwelling older persons. J Am Geriatr Soc. 2002;50(4):638–44.PubMedCrossRef
69.
Zurück zum Zitat Volpato S, Guralnik JM, Ferrucci L, et al. Cardiovascular disease, interleukin-6, and risk of mortality in older women: the women's health and aging study. Circulation. 2001;103(7):947–53.PubMed Volpato S, Guralnik JM, Ferrucci L, et al. Cardiovascular disease, interleukin-6, and risk of mortality in older women: the women's health and aging study. Circulation. 2001;103(7):947–53.PubMed
70.
Zurück zum Zitat Harris TB, Ferrucci L, Tracy RP, et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med. 1999;106(5):506–12.PubMedCrossRef Harris TB, Ferrucci L, Tracy RP, et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med. 1999;106(5):506–12.PubMedCrossRef
71.
Zurück zum Zitat El-Sadr WM, Lundgren JD, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355(22):2283–96.PubMedCrossRef El-Sadr WM, Lundgren JD, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355(22):2283–96.PubMedCrossRef
72.
Zurück zum Zitat Kuller LH, Tracy R, Belloso W, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Medicine. 2008;5(10):e203.PubMedCrossRef Kuller LH, Tracy R, Belloso W, et al. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Medicine. 2008;5(10):e203.PubMedCrossRef
73.
Zurück zum Zitat • Tien PC, Choi AI, Zolopa AR, et al. Inflammation and mortality in HIV-infected adults: analysis of the FRAM study cohort. JAIDS Journal of Acquired Immune Deficiency Syndromes 2010;55(3):316. This study demonstrated that inflammation is a potential contributor to mortality risk even in patients with optimal CD4+ T cell recovery. • Tien PC, Choi AI, Zolopa AR, et al. Inflammation and mortality in HIV-infected adults: analysis of the FRAM study cohort. JAIDS Journal of Acquired Immune Deficiency Syndromes 2010;55(3):316. This study demonstrated that inflammation is a potential contributor to mortality risk even in patients with optimal CD4+ T cell recovery.
74.
Zurück zum Zitat Kalayjian RC, Machekano RN, Rizk N, et al. Pretreatment levels of soluble cellular receptors and interleukin-6 are associated with HIV disease progression in subjects treated with highly active antiretroviral therapy. J Infect Dis. 2010;201(12):1796–805.PubMedCrossRef Kalayjian RC, Machekano RN, Rizk N, et al. Pretreatment levels of soluble cellular receptors and interleukin-6 are associated with HIV disease progression in subjects treated with highly active antiretroviral therapy. J Infect Dis. 2010;201(12):1796–805.PubMedCrossRef
75.
Zurück zum Zitat • Boulware DR, Hullsiek KH, Puronen CE, et al. Higher levels of CRP, D-dimer, IL-6, and hyaluronic acid before initiation of antiretroviral therapy (ART) are associated with increased risk of AIDS or death. J Infect Dis 2011;203(11):1637–46. This study demonstrated that in addition to markers of inflammation, markers of tissue fibrosis may also predict AIDS or death. • Boulware DR, Hullsiek KH, Puronen CE, et al. Higher levels of CRP, D-dimer, IL-6, and hyaluronic acid before initiation of antiretroviral therapy (ART) are associated with increased risk of AIDS or death. J Infect Dis 2011;203(11):1637–46. This study demonstrated that in addition to markers of inflammation, markers of tissue fibrosis may also predict AIDS or death.
76.
Zurück zum Zitat •• Sandler NG, Wand H, Roque A, et al. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis 2011;203(6):780–90. This is the first study to demonstrate a link between potential indices of microbial translocation and mortality in treated HIV infection. •• Sandler NG, Wand H, Roque A, et al. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis 2011;203(6):780–90. This is the first study to demonstrate a link between potential indices of microbial translocation and mortality in treated HIV infection.
77.
Zurück zum Zitat Hunt P, Rodriguez B, Shive C, et al. Gut Epithelial Barrier Dysfunction, Inflammation, and Coagulation Predict Higher Mortality during Treated HIV/AIDS. in in the Program and Abstracts from the 19th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, Abstract #278. 2012. Hunt P, Rodriguez B, Shive C, et al. Gut Epithelial Barrier Dysfunction, Inflammation, and Coagulation Predict Higher Mortality during Treated HIV/AIDS. in in the Program and Abstracts from the 19th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, Abstract #278. 2012.
78.
Zurück zum Zitat Hsue PY, Deeks SG, Hunt PW. Immunologic Basis of Cardiovascular Disease in HIV-Infected Adults. J Infect Dis 2012, in press. Hsue PY, Deeks SG, Hunt PW. Immunologic Basis of Cardiovascular Disease in HIV-Infected Adults. J Infect Dis 2012, in press.
79.
Zurück zum Zitat Triant VA, Meigs JB, Grinspoon SK. Association of C-reactive protein and HIV infection with acute myocardial infarction. Journal of Acquired Immune Deficiency Syndromes (1999) 2009;51(3):268. Triant VA, Meigs JB, Grinspoon SK. Association of C-reactive protein and HIV infection with acute myocardial infarction. Journal of Acquired Immune Deficiency Syndromes (1999) 2009;51(3):268.
80.
Zurück zum Zitat Baker JV, Neuhaus J, Duprez D, et al. Inflammation predicts changes in high-density lipoprotein particles and apolipoprotein A1 following initiation of antiretroviral therapy. AIDS. 2011;25(17):2133–42.PubMedCrossRef Baker JV, Neuhaus J, Duprez D, et al. Inflammation predicts changes in high-density lipoprotein particles and apolipoprotein A1 following initiation of antiretroviral therapy. AIDS. 2011;25(17):2133–42.PubMedCrossRef
81.
Zurück zum Zitat Baker JV, Neuhaus J, Duprez D, et al. Changes in inflammatory and coagulation biomarkers: a randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection. J Acquir Immune Defic Syndr. 2011;56(1):36–43.PubMedCrossRef Baker JV, Neuhaus J, Duprez D, et al. Changes in inflammatory and coagulation biomarkers: a randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection. J Acquir Immune Defic Syndr. 2011;56(1):36–43.PubMedCrossRef
82.
Zurück zum Zitat Musselwhite LW, Sheikh V, Norton TD, et al. Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV. AIDS. 2011;25(6):787–95.PubMedCrossRef Musselwhite LW, Sheikh V, Norton TD, et al. Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV. AIDS. 2011;25(6):787–95.PubMedCrossRef
83.
Zurück zum Zitat • Brown TT, Tassiopoulos K, Bosch RJ, et al. Association between systemic inflammation and incident diabetes in HIV-infected patients after initiation of antiretroviral therapy. Diabetes Care 2010;33(10):2244–9. This study was the first to demonstrate that inflammation predicts subsequent type II diabetes in the context of HIV infection. • Brown TT, Tassiopoulos K, Bosch RJ, et al. Association between systemic inflammation and incident diabetes in HIV-infected patients after initiation of antiretroviral therapy. Diabetes Care 2010;33(10):2244–9. This study was the first to demonstrate that inflammation predicts subsequent type II diabetes in the context of HIV infection.
84.
Zurück zum Zitat • Breen EC, Hussain SK, Magpantay L, et al. B-cell stimulatory cytokines and markers of immune activation are elevated several years prior to the diagnosis of systemic AIDS-associated non-Hodgkin B-cell lymphoma. Cancer Epidemiol Biomarkers Prev 2011;20(7):1303–14. This study was the first to link soluble inflammatory markers to the risk of lymphoma in the setting of suppressive ART. • Breen EC, Hussain SK, Magpantay L, et al. B-cell stimulatory cytokines and markers of immune activation are elevated several years prior to the diagnosis of systemic AIDS-associated non-Hodgkin B-cell lymphoma. Cancer Epidemiol Biomarkers Prev 2011;20(7):1303–14. This study was the first to link soluble inflammatory markers to the risk of lymphoma in the setting of suppressive ART.
85.
Zurück zum Zitat Burdo T, Weiffenbach A, Woods S, et al. Elevated sCD163 Is a Marker of Neurocognitive Impairment in HIV-infected Individuals on Effective ART. in in the Program and Abstracts from the 19th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, Abstract #81. 2012. Burdo T, Weiffenbach A, Woods S, et al. Elevated sCD163 Is a Marker of Neurocognitive Impairment in HIV-infected Individuals on Effective ART. in in the Program and Abstracts from the 19th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, Abstract #81. 2012.
86.
Zurück zum Zitat Letendre S, Marcotte T, Deutsch R, et al. In the Program and Abstracts from the 19th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, Abstract #82. 2012. Letendre S, Marcotte T, Deutsch R, et al. In the Program and Abstracts from the 19th Conference on Retroviruses and Opportunistic Infections, Seattle, WA, Abstract #82. 2012.
87.
Zurück zum Zitat Justice AC, McGinnis KA, Skanderson M, et al. Towards a combined prognostic index for survival in HIV infection: the role of 'non-HIV' biomarkers. HIV Med. 2010;11(2):143–51.PubMedCrossRef Justice AC, McGinnis KA, Skanderson M, et al. Towards a combined prognostic index for survival in HIV infection: the role of 'non-HIV' biomarkers. HIV Med. 2010;11(2):143–51.PubMedCrossRef
88.
Zurück zum Zitat •• Justice AC, Freiberg MS, Tracy R, et al. Does an index composed of clinical data reflect effects of inflammation, coagulation, and monocyte activation on mortality among those aging with HIV? Clin Infect Dis 2012;54(7):984–994. This study links the inflammatory state to several indices of end-organ disease that contribute to mortality risk. •• Justice AC, Freiberg MS, Tracy R, et al. Does an index composed of clinical data reflect effects of inflammation, coagulation, and monocyte activation on mortality among those aging with HIV? Clin Infect Dis 2012;54(7):984–994. This study links the inflammatory state to several indices of end-organ disease that contribute to mortality risk.
89.
Zurück zum Zitat Erlandson K, Allshouse A, MaWhinney S, et al. Frailty in HIV-1 infected individuals is associated with immune activation and inflammation but not immune senescence. in in the Program and Abstracts from the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Rome, Italy, Abstract #TULBPE029. 2011. Erlandson K, Allshouse A, MaWhinney S, et al. Frailty in HIV-1 infected individuals is associated with immune activation and inflammation but not immune senescence. in in the Program and Abstracts from the 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Rome, Italy, Abstract #TULBPE029. 2011.
90.
Zurück zum Zitat Desquilbet L, Margolick JB, Fried LP, et al. Relationship between a frailty-related phenotype and progressive deterioration of the immune system in HIV-infected men. J Acquir Immune Defic Syndr. 2009;50(3):299–306.PubMedCrossRef Desquilbet L, Margolick JB, Fried LP, et al. Relationship between a frailty-related phenotype and progressive deterioration of the immune system in HIV-infected men. J Acquir Immune Defic Syndr. 2009;50(3):299–306.PubMedCrossRef
91.
Zurück zum Zitat Desquilbet L, Jacobson LP, Fried LP, et al. HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty. J Gerontol A Biol Sci Med Sci. 2007;62(11):1279–86.PubMedCrossRef Desquilbet L, Jacobson LP, Fried LP, et al. HIV-1 infection is associated with an earlier occurrence of a phenotype related to frailty. J Gerontol A Biol Sci Med Sci. 2007;62(11):1279–86.PubMedCrossRef
92.
Zurück zum Zitat Payne BA, Wilson IJ, Hateley CA, et al. Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations. Nat Genet. 2011;43(8):806–10.PubMedCrossRef Payne BA, Wilson IJ, Hateley CA, et al. Mitochondrial aging is accelerated by anti-retroviral therapy through the clonal expansion of mtDNA mutations. Nat Genet. 2011;43(8):806–10.PubMedCrossRef
93.
Zurück zum Zitat Lichtenstein KA, Armon C, Baron A, et al. Modification of the incidence of drug-associated symmetrical peripheral neuropathy by host and disease factors in the HIV outpatient study cohort. Clin Infect Dis. 2005;40(1):148–57.PubMedCrossRef Lichtenstein KA, Armon C, Baron A, et al. Modification of the incidence of drug-associated symmetrical peripheral neuropathy by host and disease factors in the HIV outpatient study cohort. Clin Infect Dis. 2005;40(1):148–57.PubMedCrossRef
94.
Zurück zum Zitat •• Ganesan A, Crum-Cianflone N, Higgins J, et al. High dose atorvastatin decreases cellular markers of immune activation without affecting HIV-1 RNA levels: results of a double-blind randomized placebo controlled clinical trial. J Infect Dis. 2011;203(6):756–64. This study showed that statins can decrease immune activation in untreated HIV disease. Ongoing trials will assess whether these agents are also beneficial in the setting of ART. •• Ganesan A, Crum-Cianflone N, Higgins J, et al. High dose atorvastatin decreases cellular markers of immune activation without affecting HIV-1 RNA levels: results of a double-blind randomized placebo controlled clinical trial. J Infect Dis. 2011;203(6):756–64. This study showed that statins can decrease immune activation in untreated HIV disease. Ongoing trials will assess whether these agents are also beneficial in the setting of ART.
95.
Zurück zum Zitat Pettersen FO, Torheim EA, Dahm AE, et al. An exploratory trial of cyclooxygenase type 2 inhibitor in HIV-1 infection: downregulated immune activation and improved T Cell-dependent vaccine responses. J Virol. 2011;85(13):6557–66.PubMedCrossRef Pettersen FO, Torheim EA, Dahm AE, et al. An exploratory trial of cyclooxygenase type 2 inhibitor in HIV-1 infection: downregulated immune activation and improved T Cell-dependent vaccine responses. J Virol. 2011;85(13):6557–66.PubMedCrossRef
Metadaten
Titel
HIV and Inflammation: Mechanisms and Consequences
verfasst von
Peter W. Hunt
Publikationsdatum
01.06.2012
Verlag
Current Science Inc.
Erschienen in
Current HIV/AIDS Reports / Ausgabe 2/2012
Print ISSN: 1548-3568
Elektronische ISSN: 1548-3576
DOI
https://doi.org/10.1007/s11904-012-0118-8

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