321
Views
7
CrossRef citations to date
0
Altmetric
Review

Impact of HIV infection on aging and immune status

, , &
Pages 719-731 | Received 04 Sep 2020, Accepted 06 Nov 2020, Published online: 26 Nov 2020

References

  • Wandeler G, Johnson LF, Egger M. Trends in life expectancy of HIV-positive adults on antiretroviral therapy across the globe: comparisons with general population. Current Opinion HIV AIDS. 2016 Sep;;11(5):492–500.
  • Deeks SG. HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med. 2011;62:141–155.
  • Guaraldi G, Orlando G, Zona S, et al. Premature age-related comorbidities among HIV-infected persons compared with the general population. Clin Infect Dis. 2011 Dec;;53(11):1120–1126. .
  • Appay V, Kelleher AD. Immune activation and immune aging in HIV infection. Current Opinion HIV AIDS. 2016 Mar;11(2):242–249.
  • de Armas LR, Pallikkuth S, George V, et al. Reevaluation of immune activation in the era of cART and an aging HIV-infected population. JCI Insight. 2017 Oct 19 2;(20)20.
  • UNAIDS. Get on the fast-track, the life-cycle approach to HIV. 2016; Available at: http://www.unaids.org/sites/default/files/media_asset/Get-on-the-Fast-Track_en.pdf.
  • High KP, Brennan-Ing M, Clifford DB, et al. HIV and aging: state of knowledge and areas of critical need for research. A Report to the NIH Office of AIDS Research by the HIV and Aging Working Group. Journal of Acquired Immune Deficiency Syndromes. 2012 Jul 1;60(Suppl 1):S1–18.
  • Cardoso SW, Torres TS, Santini-Oliveira M, et al. Aging with HIV: a practical review. Braz J Infect Dis. 2013;17(4):464–479. . Jul-Aug;
  • Group ISS, Lundgren JD, Babiker AG, et al. Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. N Engl J Med. 2015 Aug 27;373(9):795–807.
  • KM E, MY K. HIV and aging: reconsidering the approach to management of comorbidities. Infect Dis Clin North Am. 2019 Sep;33(3):769–786.
  • Kanters S, Vitoria M, Doherty M, et al. Comparative efficacy and safety of first-line antiretroviral therapy for the treatment of HIV infection: a systematic review and network meta-analysis. Lancet HIV. 2016 Nov;3(11):e510–e520. .
  • De Francesco D, Wit FW, Burkle A, et al. Do people living with HIV experience greater age advancement than their HIV-negative counterparts? Aids. 2019 Feb 1;33(2):259–268.
  • d’Arminio Monforte A, Diaz-Cuervo H, De LA, et al. Evolution of major non-HIV-related comorbidities in HIV-infected patients in the Italian Cohort of Individuals. Naive for Antiretrovirals (ICONA) Foundation Study Cohort in the Period 2004-2014. HIV Medicine. 2019 Feb;20(2):99–109.
  • Bagkeris E, Burgess L, Mallon PW, et al. Cohort profile: the Pharmacokinetic and clinical Observations in PeoPle over fiftY (POPPY) study. Int J Epidemiol. 2018 Oct 1;47(5):1391–1392e.
  • De Francesco D, Underwood J, Bagkeris E, et al. Risk factors and impact of patterns of co-occurring comorbidities in people living with HIV. Aids. 2019 Oct 1;33(12):1871–1880.
  • Schouten J, FW W, IG S, et al. Cross-sectional comparison of the prevalence of age-associated comorbidities and their risk factors between HIV-infected and uninfected individuals: the AGEhIV cohort study. Clin Infect Dis. 2014 Dec 15;59(12):1787–1797.
  • Wong C, Gange SJ, Moore RD, et al. Multimorbidity among persons living with human immunodeficiency virus in the United States. Clin Infect Dis. 2018 Apr 3 66;(8)1230–1238.
  • Guaraldi G, Malagoli A, Calcagno A, et al. The increasing burden and complexity of multi-morbidity and polypharmacy in geriatric HIV patients: a cross sectional study of people aged 65-74 years and more than 75 years. BMC Geriatr. 2018 Apr 20;18(1):99.
  • Smit M, Brinkman K, Geerlings S, et al. Future challenges for clinical care of an ageing population infected with HIV: a modelling study. Lancet Infect Dis. 2015 Jul;15(7):810–818. .
  • Nasi M, De BS, Gibellini L, et al. Ageing and inflammation in patients with HIV infection. Clin Exp Immunol. 2017 Jan;;187(1):44–52. .
  • Lopez-Otin C, Blasco MA, Partridge L, et al. The hallmarks of aging. Cell. 2013 Jun 6;153(6):1194–1217.
  • Torres RA, Aging LW. HIV/AIDS: pathogenetic role of therapeutic side effects. Lab Invest. 2014 Feb;94(2):120–128.
  • Leng SX, Margolick JB. Aging, sex, inflammation, frailty, and CMV and HIV infections. Cell Immunol. 2020 Feb;348:104024.
  • Gruver AL, Hudson LL, Sempowski GD. Immunosenescence of ageing. J Pathol. 2007 Jan;211(2):144–156.
  • Negredo E, Back D, Blanco JR, et al. Aging in HIV-infected subjects: a new scenario and a new view. Biomed Res Int. 2017;2017:5897298.
  • Tiraboschi J, Ray S, Patel K, et al. Short communication: lack of effect of maraviroc intensification on blood and gut reservoir. AIDS Res Human Retroviruses. 2017 Feb;33(2):143–146. .
  • van Lelyveld SF, Drylewicz J, Krikke M, et al. Maraviroc intensification of cart in patients with suboptimal immunological recovery: a 48-week, placebo-controlled randomized trial. PloS One. 2015;10(7):e0132430. .
  • 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 Aug 10;7(8):8.
  • 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 Apr 1;203(7):960–968.
  • Hunt PWHI. V and inflammation: mechanisms and consequences. Current HIV/AIDS Reports. 2012 Jun;9(2):139–147.
  • Sokoya T, Steel HC, Nieuwoudt M, et al. HIV as a cause of immune activation and immunosenescence. Mediators Inflammation. 2017;2017:6825493.
  • Appay V, Fastenackels S, Katlama C, et al. Old age and anti-cytomegalovirus immunity are associated with altered T-cell reconstitution in HIV-1-infected patients. Aids. 2011 Sep 24;25(15):1813–1822. .
  • 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 Nov 28;20(18):2275–2283.
  • Petrara MR, Cattelan AM, Zanchetta M, et al. Epstein-Barr virus load and immune activation in human immunodeficiency virus type 1-infected patients. J Clin Virol. 2012 Mar;53(3):195–200.
  • Sandler NG, Douek DC. Microbial translocation in HIV infection: causes, consequences and treatment opportunities. Nat Rev Microbiol. 2012 Sep;10(9):655–666.
  • Ancuta P, Kamat A, Kunstman KJ, et al. Microbial translocation is associated with increased monocyte activation and dementia in AIDS patients. PloS One. 2008 Jun 25;3(6):e2516.
  • Massanella M, Negredo E, Puig J, et al. Raltegravir intensification shows differing effects on CD8 and CD4 T cells in HIV-infected HAART-suppressed individuals with poor CD4 T-cell recovery. Aids. 2012 Nov 28;26(18):2285–2293.
  • Massanella M, Gomez-Mora E, Carrillo J, et al. Increased ex vivo cell death of central memory CD4 T cells in treated HIV infected individuals with unsatisfactory immune recovery. J Transl Med. 2015 Jul 17;13:230.
  • Hoffmann M, Pantazis N, Martin GE, et al. Exhaustion of activated CD8 T cells predicts disease progression in primary HIV-1 infection. PLoS Pathog. 2016 Jul;12(7):e1005661.
  • Massanella M, Fromentin R, Chomont N. Residual inflammation and viral reservoirs: alliance against an HIV cure. Current Opinion HIV AIDS. 2016 Mar;11(2):234–241.
  • Gomez-Mora E, Massanella M, Garcia E, et al. Elevated humoral response to cytomegalovirus in HIV-infected individuals with poor CD4+ T-cell immune recovery. PloS One. 2017;12(9):e0184433. .
  • JM B, DA P, TW S, et al. Microbial translocation is a cause of systemic immune activation in chronic HIV infection. Nat Med. 2006 Dec;;12(12):1365–1371.
  • 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 Sep 20;200(6):749–759.
  • Brenchley JM, Paiardini M, Knox KS, et al. Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood. 2008 Oct 1;112(7):2826–2835.
  • Voigt RM, Keshavarzian A, Losurdo J, et al. HIV-associated mucosal gene expression: region-specific alterations. Aids. 2015 Mar 13;29(5):537–546.
  • Epple HJ, Allers K, Troger H, et al. Acute HIV infection induces mucosal infiltration with CD4+ and CD8+ T cells, epithelial apoptosis, and a mucosal barrier defect. Gastroenterology. 2010 Oct;139(4):1289–1300.
  • Suy A, Castro P, Nomdedeu M, et al. Immunological profile of heterosexual highly HIV-exposed uninfected individuals: predominant role of CD4 and CD8 T-cell activation. J Infect Dis. 2007 Oct 15;196(8):1191–1201.
  • Hayashi F, Smith KD, Ozinsky A, et al. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature. 2001 Apr 26;410(6832):1099–1103.
  • Hearps AC, Martin GE, Angelovich TA, et al. Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell. 2012 Oct;11(5):867–875. .
  • Hearps AC, Maisa A, Cheng WJ, et al. HIV infection induces age-related changes to monocytes and innate immune activation in young men that persist despite combination antiretroviral therapy. Aids. 2012 Apr 24;26(7):843–853.
  • Nakanjako D, Ssewanyana I, Mayanja-Kizza H, et al. High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort. BMC Infect Dis. 2011 Feb 8;11(1):43.
  • Merlini E, Tincati C, Biasin M, et al. Stimulation of PBMC and monocyte-derived macrophages via Toll-Like Receptor activates innate immune pathways in HIV-infected patients on virally suppressive combination antiretroviral therapy. Front Immunol. 2016;7:614.
  • Sandler NG, Wand H, Roque A, et al. Plasma levels of soluble CD14 independently predict mortality in HIV infection. J Infect Dis. 2011 Mar 15;203(6):780–790.
  • Massanella M, Ouchi D, Marfil S, et al. Different plasma markers of inflammation are influenced by immune recovery and cART composition or intensification in treated HIV infected individuals. PloS One. 2014;9(12):e114142. .
  • 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 Jan 14;115(2):161–167.
  • Marchetti G, Tincati C, Silvestri G. Microbial translocation in the pathogenesis of HIV infection and AIDS. Clin Microbiol Rev. 2013 Jan;26(1):2–18.
  • Ferrando-Martinez S, De Pablo-Bernal RS, De Luna-Romero M, et al. Thymic function failure is associated with human immunodeficiency virus disease progression. Clin Infect Dis. 2017 May 1;64(9):1191–1197. .
  • 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 May 1;50(9):1300–1308. .
  • Massanella M, Negredo E, Clotet B, et al. Immunodiscordant responses to HAART–mechanisms and consequences. Expert Rev Clin Immunol. 2013 Nov;9(11):1135–1149.
  • 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 Apr 24;24(7):959–968.
  • Pacheco YM, Jarrin I, Rosado I, et al. Increased risk of non-AIDS-related events in HIV subjects with persistent low CD4 counts despite cART in the CoRIS cohort. Antiviral Res. 2015 May;117:69–74.
  • Epidemiological Research in Europe (COHERE) in EuroCoord, Young J, Psichogiou M, et al. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE. PLoS Med. 2012; 9(3):e1001194.
  • Gallant J, Hsue PY, Shreay S, et al. Comorbidities among US patients with prevalent HIV infection. A Trend Analysis. The Journal of Infectious Diseases. 2017 Dec 19;216(12):1525–1533.
  • Christensen S, Wolf E, Altevers J, et al. Comorbidities and costs in HIV patients: A retrospective claims database analysis in Germany. PloS One. 2019;14(11):e0224279. .
  • Adih WK, Selik RM, Hu X. Trends in diseases reported on us death certificates that mentioned HIV infection, 1996-2006. J Int Assoc Phys AIDS Care (Chicago, Ill: 2002). 2011;10(1):5–11. . Jan-Feb
  • Shah ASV, Stelzle D, Lee KK, et al. Global burden of atherosclerotic cardiovascular disease in people living with HIV: systematic review and meta-analysis. Circulation. 2018 Sep 11;138(11):1100–1112.
  • McGettrick P, Mallon PWG, Sabin CA. Cardiovascular disease in HIV patients: recent advances in predicting and managing risk. Exp Rev Anti-Infective Ther. 2020 Jul;18(7):677–688. .
  • Kaplan RC, Sinclair E, Landay AL, et al. T cell activation and senescence predict subclinical carotid artery disease in HIV-infected women. J Infect Dis. 2011 Feb 15;203(4):452–463.
  • Calza L, Pocaterra D, Pavoni M, et al. Plasma levels of VCAM-1, ICAM-1, E-Selectin, and P-Selectin in 99 HIV-positive patients versus 51 HIV-negative healthy controls. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2009 Apr 1;50(4):430–432.
  • Karpatkin S, Nardi M, Green D. Platelet and coagulation defects associated with HIV-1-infection. Thromb Haemost. 2002 Sep;88(9):389–401.
  • Jacobson MC, Dezube BJ, Aboulafia DM. Thrombotic complications in patients infected with HIV in the era of highly active antiretroviral therapy: a case series. Clin Infect Dis. 2004 Oct 15;39(8):1214–1222.
  • Zidar DA, Juchnowski S, Ferrari B, et al. Oxidized LDL levels are increased in HIV infection and may drive monocyte activation. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2015 Jun 1;69(2):154–160.
  • Butt AA, Chang CC, Kuller L, et al. Risk of heart failure with human immunodeficiency virus in the absence of prior diagnosis of coronary heart disease. Arch Intern Med. 2011 Apr 25;171(8):737–743.
  • Freiberg MS, Chang CC, Kuller LH, et al. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med. 2013 Apr 22;173(8):614–622.
  • Wyatt CM, Winston JA, Malvestutto CD, et al. Chronic kidney disease in HIV infection: an urban epidemic. Aids. 2007 Oct 1;21(15):2101–2103.
  • Alfano G, Cappelli G, Fontana F, et al. Kidney Disease in HIV Infection. J Clin Med. 2019 Aug 19;8:8. .
  • Achhra AC, Mocroft A, Ross MJ, et al. Kidney disease in antiretroviral-naive HIV-positive adults with high CD4 counts: prevalence and predictors of kidney disease at enrolment in the INSIGHT strategic timing of antiretroviral treatment (START) trial. HIV Med. 2015 Apr;16(Suppl 1):55–63. .
  • Kalayjian RC, Lau B, Mechekano RN, et al. Risk factors for chronic kidney disease in a large cohort of HIV-1 infected individuals initiating antiretroviral therapy in routine care. Aids. 2012 Sep 24;26(15):1907–1915.
  • Abraham AG, Darilay A, McKay H, et al. Kidney dysfunction and markers of inflammation in the Multicenter AIDS Cohort Study. J Infect Dis. 2015 Oct 1;212(7):1100–1110.
  • Chen P, Chen BK, Mosoian A, et al. Virological synapses allow HIV-1 uptake and gene expression in renal tubular epithelial cells. J Am Soc Nephrol. 2011 Mar;22(3):496–507. .
  • Blasi M, Balakumaran B, Chen P, et al. Renal epithelial cells produce and spread HIV-1 via T-cell contact. Aids. 2014 Oct 23;28(16):2345–2353.
  • Segerer S, Nelson PJ, Schlondorff D. Chemokines, chemokine receptors, and renal disease: from basic science to pathophysiologic and therapeutic studies. J Am Soc Nephrol. 2000 Jan;11(1):152–176.
  • McGinty T, Mirmonsef P, Mallon PW, et al. Does systemic inflammation and immune activation contribute to fracture risk in HIV? Curr Opin HIV AIDS. 2016 May;11(3):253–260. .
  • Triant VA, Brown TT, Lee H, et al. Fracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large U.S. healthcare system. J Clin Endocrinol Metab. 2008 Sep;93(9):3499–3504. .
  • Fakruddin JM, Laurence J. HIV envelope gp120-mediated regulation of osteoclastogenesis via receptor activator of nuclear factor kappa B ligand (RANKL) secretion and its modulation by certain HIV protease inhibitors through interferon-gamma/RANKL cross-talk. J Biol Chem. 2003 Nov 28;278(48):48251–48258.
  • Ginaldi L, Di Benedetto MC, De Martinis M. Osteoporosis, inflammation and ageing. Immun Ageing. 2005 Nov;4(2):14.
  • Grund B, Peng G, Gibert CL, et al. Continuous antiretroviral therapy decreases bone mineral density. Aids. 2009 Jul 31;23(12):1519–1529.
  • Glidden DV, Mulligan K, McMahan V, et al. Brief report: recovery of bone mineral density after discontinuation of tenofovir-based HIV pre-exposure prophylaxis. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2017 Oct 1;76(2):177–182.
  • Kaspar MB, Sterling RK. Mechanisms of liver disease in patients infected with HIV. BMJ Open Gastroenterol. 2017;4(1):e000166.
  • Marquez M, Romero-Cores P, Montes-Oca M, et al. Immune activation response in chronic HIV-infected patients: influence of Hepatitis C virus coinfection. PloS One. 2015;10(3):e0119568. .
  • Mastroianni CM, Lichtner M, Mascia C, et al. Molecular mechanisms of liver fibrosis in HIV/HCV coinfection. Int J Mol Sci. 2014 May 26;15(6):9184–9208.
  • Medrano LM, Garcia-Broncano P, Berenguer J, et al. Elevated liver stiffness is linked to increased biomarkers of inflammation and immune activation in HIV/hepatitis C virus-coinfected patients. Aids. 2018 Jun 1;32(9):1095–1105.
  • Patel SV, Jayaweera DT, Althoff KN, et al. Real-world efficacy of direct acting antiviral therapies in patients with HIV/HCV. PloS One. 2020;15(2):e0228847. .
  • Parisi SG, Andreis S, Mengoli C, et al. Soluble CD163 and soluble CD14 plasma levels but not cellular HIV-DNA decrease during successful interferon-free anti-HCV therapy in HIV-1-HCV co-infected patients on effective combined anti-HIV treatment. Med Microbiol Immunol. 2018 Aug;207(3–4):183–194. .
  • Leone S, Prosperi M, Costarelli S, et al. Incidence and predictors of cardiovascular disease, chronic kidney disease, and diabetes in HIV/HCV-coinfected patients who achieved sustained virological response. Eur J Clin Microbiol Infect Dis. 2016 Sep;35(9):1511–1520.
  • Cervo A, Milic J, Mazzola G, et al. Prevalence, predictors and severity of lean non-alcoholic fatty liver disease in HIV-infected patients. Clin Inf Dis. 2020 Apr;13.
  • Guaraldi G, Lonardo A, Maia L, et al. Metabolic concerns in aging HIV-infected persons: from serum lipid phenotype to fatty liver. Aids. 2017 Jun 1;31(Suppl 2):S147–S156.
  • Franzetti M, Ricci E, Bonfanti P. The pattern of non-AIDS-defining cancers in the HIV population: epidemiology, risk factors and prognosis. A Review Curr HIV Res. 2019;17(1):1–12.
  • Mitsuyasu RT. Non-AIDS-defining cancers. Topics Anti Med. 2014;22(3):660–665. Jun-Jul
  • Yarchoan R, Uldrick TS, Longo DL. HIV-associated cancers and related diseases. N Engl J Med. 2018 May 31;378(22):2145.
  • Mahale P, Engels EA, Coghill AE, et al. Cancer risk in older persons living with human immunodeficiency virus infection in the United States. Clin Infect Dis. 2018 Jun 18;67(1):50–57.
  • Colon-Lopez V, Shiels MS, Machin M, et al. Anal cancer risk among people with HIV infection in the United States. J Clin Oncol. 2018 Jan 1;36(1):68–75.
  • Franzetti M, Adorni F, Parravicini C, et al. Trends and predictors of non-AIDS-defining cancers in men and women with HIV infection: a single-institution retrospective study before and after the introduction of HAART. J Acquired Immune Deficiency Syndromes. 2013 Apr 1;62(4):414–420.
  • Shiels MS, Pfeiffer RM, Gail MH, et al. Cancer burden in the HIV-infected population in the United States. J Natl Cancer Inst. 2011 May 4;103(9):753–762.
  • Lowy DR, Schiller JT. Prophylactic human papillomavirus vaccines. J Clin Invest. 2006 May;116(5):1167–1173.
  • Valdez AN, Rubin LH, Neigh GN. Untangling the Gordian knot of HIV, stress, and cognitive impairment. Neurobiol Stress. 2016 Oct;4:44–54.
  • Ivey NS, MacLean AG, Lackner AA. Acquired immunodeficiency syndrome and the blood-brain barrier. J Neurovirol. 2009 Apr;15(2):111–122.
  • Sartori AC, Vance DE, Slater LZ, et al. The impact of inflammation on cognitive function in older adults: implications for healthcare practice and research. J Neurosci Nurs. 2012 Aug;44(4):206–217. .
  • Chen NC, Partridge AT, Sell C, et al. Fate of microglia during HIV-1 infection: from activation to senescence? Glia. 2017 Mar;65(3):431–446. .
  • Garvey LJ, Pavese N, Politis M, et al. Increased microglia activation in neurologically asymptomatic HIV-infected patients receiving effective ART. Aids. 2014 Jan 2;28(1):67–72.
  • Carroll A, Brew B. HIV-associated neurocognitive disorders: recent advances in pathogenesis, biomarkers, and treatment. F1000Res. 2017;6:312.
  • Neri S, Leung J, Besutti G, et al. Chronic lung disease in HIV patients. AIDS Rev. 2018;20(3):150–157. .
  • Lassiter C, Fan X, Joshi PC, et al. HIV-1 transgene expression in rats causes oxidant stress and alveolar epithelial barrier dysfunction. AIDS Res Ther. 2009 Feb 4;6:1. .
  • Gundavarapu S, Mishra NC, Singh SP, et al. HIV gp120 induces mucus formation in human bronchial epithelial cells through CXCR4/alpha7-nicotinic acetylcholine receptors. PloS One. 2013;8(10):e77160. .
  • Beck JM, Schloss PD, Venkataraman A, et al. Multicenter comparison of lung and oral microbiomes of HIV-infected and HIV-uninfected individuals. Am J Respir Crit Care Med. 2015 Dec 1;192(11):1335–1344.
  • Reddy KP, Parker RA, Losina E, et al. Impact of cigarette smoking and smoking cessation on life expectancy among people with HIV: a US-based modeling study. J Infect Dis. 2016 Dec 1;214(11):1672–1681.
  • Clegg A, Young J, Iliffe S, et al. Frailty in elderly people. Lancet. 2013 Mar 2;381(9868):752–762.
  • Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146–56. .
  • Schmaltz HN, Fried LP, Xue QL, et al. Chronic cytomegalovirus infection and inflammation are associated with prevalent frailty in community-dwelling older women. J Am Geriatr Soc. 2005 May;53(5):747–754. .
  • Blanco JR, Barrio I, Ramalle-Gomara E, et al. Gender differences for frailty in HIV-infected patients on stable antiretroviral therapy and with an undetectable viral load. PloS One. 2019;14(5):e0215764. .
  • Gandhi RT, McMahon DK, Bosch RJ, et al. Levels of HIV-1 persistence on antiretroviral therapy are not associated with markers of inflammation or activation. PLoS Pathog. 2017 Apr;13(4):e1006285. .
  • Falasca F, Di Carlo D, De Vito C, et al. Evaluation of HIV-DNA and inflammatory markers in HIV-infected individuals with different viral load patterns. BMC Infect Dis. 2017 Aug 22;17(1):581.
  • Mavigner M, Delobel P, Cazabat M, et al. HIV-1 residual viremia correlates with persistent T-cell activation in poor immunological responders to combination antiretroviral therapy. PloS One. 2009 Oct 30;4(10):e7658. .
  • Elvstam O, Marrone G, Medstrand P, et al. All-cause mortality and serious non-AIDS events in adults with low-level HIV viremia during combination antiretroviral therapy: results from a swedish nationwide observational study. Clin Inf Dis. 2020 Apr;9.
  • Rusconi S, Vitiello P, Adorni F, et al. Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: an Italian randomized clinical trial. PloS One. 2013;8(11):e80157.
  • Cillo AR, Hilldorfer BB, Lalama CM, et al. Virologic and immunologic effects of adding maraviroc to suppressive antiretroviral therapy in individuals with suboptimal CD4+ T-cell recovery. Aids. 2015 Oct 23;29(16):2121–2129.
  • 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):355–364. .
  • Yadav A, Kossenkov AV, Knecht VR, et al., Evidence for persistent monocyte and immune dysregulation after prolonged viral suppression despite normalization of monocyte subsets, scd14 and scd163 in HIV-infected individuals. Pathog Immun. 4(2): 324–362. 2019. .
  • Kelesidis T, Tran TT, Stein JH, et al. Changes in inflammation and immune activation with atazanavir-, raltegravir-, darunavir-based initial antiviral therapy: ACTG 5260s. Clin Infect Dis. 2015 Aug 15;61(4):651–660.
  • Castillo-Mancilla JR, Brown TT, Palella FJ Jr., et al. Partial normalization of biomarkers of inflammation and immune activation among virally suppressed men with HIV infection and high ART adherence. Open Forum Infect Dis. 2020 Apr;7(4):ofaa099. .
  • Boulougoura A, Sereti I. HIV infection and immune activation: the role of coinfections. Current Opinion HIV AIDS. 2016 Mar;11(2):191–200.
  • Lopez-Cortes LF, Trujillo-Rodriguez M, Baez-Palomo A, et al. Eradication of hepatitis C virus (HCV) reduces immune activation, microbial translocation, and the HIV DNA level in HIV/HCV-coinfected patients. J Infect Dis. 2018 Jul 13;218(4):624–632.
  • 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 May 15;203(10):1474–1483. .
  • De Wit S, Delforge M, Necsoi CV, et al. Downregulation of CD38 activation markers by atorvastatin in HIV patients with undetectable viral load. Aids. 2011 Jun 19;25(10):1332–1333.
  • 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 Mar 15;203(6):756–764. .
  • Funderburg NT, Jiang Y, Debanne SM, et al. Rosuvastatin reduces vascular inflammation and T-cell and monocyte activation in HIV-infected subjects on antiretroviral therapy. J Acquired Immune Deficiency Syndromes. 2015 Apr 1;68(4):396–404.
  • Toribio M, Fitch KV, Sanchez L, et al. Effects of pitavastatin and pravastatin on markers of immune activation and arterial inflammation in HIV. Aids. 2017 Mar 27;31(6):797–806.
  • Nixon DE, Bosch RJ, Chan ES, et al. Effects of atorvastatin on biomarkers of immune activation, inflammation, and lipids in virologically suppressed, human immunodeficiency virus-1-infected individuals with low-density lipoprotein cholesterol <30 mg/dl (aids clinical trials group study a5275). J Clin Lipidol. 2017 Jan - Feb;11(1):61–69.
  • O’Brien M, Montenont E, Hu L, et al. Aspirin attenuates platelet activation and immune activation in HIV-1-infected subjects on antiretroviral therapy: a pilot study. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2013 Jul 1;63(3):280–288.
  • O’Brien MK, Kitch D, Hunt PW, et al. Aspirin fails to impact immune activation or endothelial function in treated HIV. Presented at: CROI 2016; February 22–25, 2016; Boston, Massachusetts.
  • Macatangay BJC, Jackson EK, Abebe KZ, et al. A randomized.pilot clinical trial of dipyridamole to decrease HIV-associated chronic inflammation. The Journal of infectious diseases: placebo-controlled; 2019 Jul 6.
  • Jacobson JM, Bosinger SE, Kang M, et al. The effect of chloroquine on immune activation and interferon signatures associated with HIV-1. AIDS Res Hum Retroviruses. 2016 Jul;32(7):636–647.
  • Hsue PY, Ribaudo HJ, Deeks SG, et al. Safety and impact of low-dose methotrexate on endothelial function and inflammation in individuals with treated human immunodeficiency virus: AIDS clinical trials group study A5314. Clin Infect Dis. 2019 May 17;68(11):1877–1886.
  • Katlama C, Lambert-Niclot S, Assoumou L, et al. Treatment intensification followed by interleukin-7 reactivates HIV without reducing total HIV DNA: a randomized trial. Aids. 2016 Jan;30(2):221–230. .
  • Hsue PY, Li D, Ma Y, et al. IL-1beta inhibition reduces atherosclerotic inflammation in HIV infection. J Am Coll Cardiol. 2018 Dec 4;72(22):2809–2811.
  • Ruiz-Ortega M, Ruperez M, Esteban V, et al. Angiotensin II: a key factor in the inflammatory and fibrotic response in kidney diseases. Nephrol Dial Transplant. 2006 Jan;21(1):16–20. .
  • Cockerham LR, Yukl SA, Harvill K, et al. A randomized controlled trial of lisinopril to decrease lymphoid fibrosis in antiretroviral-treated, HIV-infected individuals. Pathog Immun. 2017;2(3):310–334. .
  • Baker JV, Wolfson J, Collins G, et al. Losartan to reduce inflammation and fibrosis endpoints in HIV disease (LIFE-HIV). Presented at: CROI 2020; March 8–11, 2020; Boston, MA.
  • Zevin AS, McKinnon L, Burgener A, et al. Microbial translocation and microbiome dysbiosis in HIV-associated immune activation. Curr Opin HIV AIDS. 2016 Mar;11(2):182–190. .
  • Vazquez-Castellanos JF, Serrano-Villar S, Latorre A, et al. Altered metabolism of gut microbiota contributes to chronic immune activation in HIV-infected individuals. Mucosal Immunol. 2015 Jul;8(4):760–772. .
  • Dillon SM, Frank DN, Wilson CC. The gut microbiome and HIV-1 pathogenesis: a two-way street. Aids. 2016 Nov 28;30(18):2737–2751.
  • Roberfroid M. Prebiotics: the concept revisited. J Nutr. 2007 Mar;137(3):830S-837S. 137(3 Suppl 2):830S–7S
  • Sanders ME  Probiotics: definition, sources, selection, and uses. Clin Infect Dis. 2008 Feb; 1; 46 Suppl 2:S58-61; discussion S144–51.
  • 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 Sep;4(5):554–563. .
  • Meyer-Myklestad MH, Kummen M, Stiksrud B, et al. Altered gut immunity in immunological non-responders is partly restored by probiotics. Presented at: CROI 2019; March 4–7, 2019; Seattle, Washington.
  • Villar-Garcia J, Guerri-Fernandez R, Moya A, et al. Impact of probiotic Saccharomyces boulardii on the gut microbiome composition in HIV-treated patients: A double-blind, randomised, placebo-controlled trial. PloS One. 2017;12(4):e0173802. .
  • Serrano-Villar S, de Lagarde M, Vazquez-Castellanos J, et al. Effects of immunonutrition in advanced human immunodeficiency virus disease: a randomized placebo-controlled clinical trial (promaltia study). Clin Infect Dis. 2019 Jan 1;68(1):120–130.
  • Hensley-McBain T, Zevin AS, Manuzak J, et al. Effects of fecal microbial transplantation on microbiome and immunity in simian immunodeficiency virus-infected Macaques. J Virol. 2016 May 15;90(10):4981–4989.
  • Wang S, Xu M, Wang W, et al. Systematic review: adverse events of fecal microbiota transplantation. PloS One. 2016;11(8):e0161174. .
  • Tenorio AR, Chan ES, Bosch RJ, et al. Rifaximin has a marginal impact on microbial translocation, T-cell activation and inflammation in HIV-positive immune non-responders to antiretroviral therapy - ACTG A5286. J Infect Dis. 2015 Mar 1;211(5):780–790.
  • Williams BB, Green SJ, Bosch RJ, et al. Four weeks of treatment with rifaximin fails to significantly alter microbial diversity in rectal samples of HIV-infected immune non-responders (actg a5286) which may be attributed to rectal swab use. Pathog Immun. 2019;4(2):235–250. .
  • Somsouk M, Dunham RM, Cohen M, et al. The immunologic effects of mesalamine in treated HIV-infected individuals with incomplete CD4+ T cell recovery: a randomized crossover trial. PloS One. 2014;9(12):e116306. .
  • Kristoff J, Haret-Richter G, Ma D, et al. Early microbial translocation blockade reduces SIV-mediated inflammation and viral replication. J Clin Invest. 2014 Jun;124(6):2802–2806. .
  • Sandler NG, Zhang X, Bosch RJ, et al. Sevelamer does not decrease lipopolysaccharide or soluble CD14 levels but decreases soluble tissue factor, low-density lipoprotein (LDL) cholesterol, and oxidized LDL cholesterol levels in individuals with untreated HIV infection. J Infect Dis. 2014 Nov 15;210(10):1549–1554.
  • Robinson-Papp J, Nmashie A, Pedowitz E, et al. The effect of pyridostigmine on small intestinal bacterial overgrowth (SIBO) and plasma inflammatory biomarkers in HIV-associated autonomic neuropathies. J Neurovirol. 2019 Aug;25(4):551–559. .
  • Bonato M, Galli L, Passeri L, et al. A pilot study of brisk walking in sedentary combination antiretroviral treatement (cART)- treated patients: benefit on soluble and cell inflammatory markers. BMC Infect Dis. 2017 Jan 11;17(1):61.
  • Ceccarelli G, Pinacchio C, Santinelli L, et al. Physical activity and HIV: effects on fitness status, metabolism, inflammation and immune-activation. AIDS Behav. 2020 Apr;24(4):1042–1050. .
  • He T, Xu C, Krampe N, et al. High-fat diet exacerbates SIV pathogenesis and accelerates disease progression. J Clin Invest. 2019 Dec 2;129(12):5474–5488. .
  • Cioe PA, Baker J, Kojic EM, et al. Elevated soluble CD14 and lower D-Dimer are associated with cigarette smoking and heavy episodic alcohol use in persons living with HIV. JAIDS Journal of Acquired Immune Deficiency Syndromes. 2015 Dec 1;70(4):400–405.
  • Steel HC, Venter WDF, Theron AJ, et al. Effects of tobacco usage and antiretroviral therapy on biomarkers of systemic immune activation in HIV-infected participants. Mediators Inflammation. 2018;2018:8357109.
  • Song P, An J, Zou MH. Immune clearance of senescent cells to combat ageing and chronic diseases. Cells. 2020 Mar 10;9(3). 10.3390/cells9030671.
  • Szaniawski MA, Spivak AM. Senotherapeutics for HIV and aging. Current Opinion HIV AIDS. 2020 Mar;15(2):83–93.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.