CDC. HIV in the United States and Dependent Areas. 2020 [cited 2020 May 10]. Available from: https://www.cdc.gov/hiv/statistics/overview/ataglance.html
•• Martin-Iguacel R, Negredo E, Peck R, Friis-Møller N. Hypertension Is a Key Feature of the Metabolic Syndrome in Subjects Aging with HIV. Curr Hypertens Rep. 2016;18:46 This review elucidates components of metabolic syndrome in HIV in a comprehensive manner and highlights the role of hypertension in metabolic syndrome.
•• Zicari S, Sessa L, Cotugno N, Ruggiero A, Morrocchi E, Concato C, et al. Immune Activation, Inflammation, and Non-AIDS Co-Morbidities in HIV-Infected Patients under Long-Term ART. Viruses. 2019 [cited 2020 Mar 11];11. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466530/. This review highlights some of the underlying mechanisms the predispose HIV-infected adults to non-communicable disease and some aspects of metabolic syndrome.
Rogalska-Płońska M, Grzeszczuk A, Rogalski P, Łucejko M, Flisiak R. Metabolic syndrome in HIV infected adults in Poland. Kardiol Pol. 2018;76:548–53.
Kiama CN, Wamicwe JN, Oyugi EO, Obonyo MO, Mungai JG, Roka ZG, et al. Prevalence and factors associated with metabolic syndrome in an urban population of adults living with HIV in Nairobi, Kenya. Pan Afr Med J. 2018 [cited 2020 Mar 11];29. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5987082/
Osoti A, Temu TM, Kirui N, Ngetich EK, Kamano JH, Page S, et al. Metabolic syndrome among antiretroviral therapy-naive versus experienced HIV-infected patients without preexisting cardiometabolic disorders in Western Kenya. AIDS Patient Care STDs. 2018;32:215–22.
•• Kolgiri V, Nagar V, Patil V. Association of Metabolic Syndrome and Oxidative DNA Damage in HIV/AIDS Patients. Indian J Clin Biochem. 2018;33:273–81 This study reports novel information that extrapolates a molecular mechanism for metabolic syndrome in HIV. The study highlights the effect of ART on cellular DNA.
• Phalane E, Fourie CMT, Schutte AE. The metabolic syndrome and renal function in an African cohort infected with human immunodeficiency virus. South Afr J HIV Med. 2018 [cited 2020 Mar 11];19. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191676/. This study reports a unique finding where metabolic syndrome was more prevalent in non-HIV infected population when compared with HIV positive group on ART and ART-naïve.
• Neves JS, Guerreiro V, Carvalho D, Serrão R, Sarmento A, Freitas P. Metabolically Healthy or Metabolically Unhealthy Obese HIV-Infected Patients: Mostly a Matter of Age? Front Endocrinol (Lausanne). 2018 [cited 2020 Mar 11];9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250744/. This study highlights important phenotypes of obesity and implications on CVD and metabolic syndrome.
Msoka TF, Van Guilder GP, Smulders YM, van Furth M, Bartlett JA, van Agtmael MA. Association of HIV-infection, antiretroviral treatment and metabolic syndrome with large artery stiffness: a cross-sectional study. BMC Infect Dis. 2018 [cited 2020 Mar 11];18. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6311066/.
•• Todowede OO, Sartorius B. Prevalence of metabolic syndrome, discrete or comorbid diabetes and hypertension in sub-Saharan Africa among people living with HIV versus HIV-negative populations: a systematic review and meta-analysis protocol. BMJ Open. 2017;7:e016602 This study highlights some current information on the epidemiology of metabolic syndrome in sub-Saharan Africa with differences unique to the HIV-infected population.
Agu CE, Uchendu IK, Nsonwu AC, Okwuosa CN, Achukwu PU. Prevalence and associated risk factors of peripheral artery disease in virologically suppressed HIV-infected individuals on antiretroviral therapy in Kwara state, Nigeria: a cross sectional study. BMC Public Health. 2019; [cited 2020 Mar 11];19. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6700806/.
Sears S, Buendia JR, Odem S, Qobadi M, Wortley P, Mgbere O, et al. Metabolic syndrome among people living with HIV receiving medical Care in Southern United States: prevalence and risk factors. AIDS Behav. 2019;23:2916–25.
• Paula AA, Falcão MC, Pacheco AG. Metabolic syndrome in HIV-infected individuals: underlying mechanisms and epidemiological aspects. AIDS Res Ther. 2013;10:32 This study highlights important mechanisms for the development of metabolic syndrome and some of the effects of specific ART combinations in inducing metabolic syndrome.
Hirigo AT, Tesfaye DY. Influences of gender in metabolic syndrome and its components among people living with HIV virus using antiretroviral treatment in Hawassa, southern Ethiopia. BMC Res Notes. 2016; [cited 2020 Apr 1];9. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4779577/.
Solomon IH, De Girolami U, Chettimada S, Misra V, Singer EJ, Gabuzda D. Brain and liver pathology, amyloid deposition, and interferon responses among older HIV-positive patients in the late HAART era. BMC Infect Dis. 2017;17:151.
•• Vona R, Gambardella L, Straface E. Gender-associated biomarkers in metabolic syndrome. Carotid artery - gender and health. IntechOpen; 2018 [cited 2020 Apr 1]; Available from: https://www.intechopen.com/books/carotid-artery-gender-and-health/gender-associated-biomarkers-in-metabolic-syndrome. Gender differences have huge implications on the pathophysiology of metabolic syndrome and his study highlights some of these.
Nauli AM, Matin S. Why do men accumulate abdominal visceral fat? Front Physiol. 2019; [cited 2020 May 20];10. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906176/.
Palmer BF, Clegg DJ. The sexual dimorphism of obesity. Mol Cell Endocrinol. 2015;402:113–9.
Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech. 2009;2:231–7.
•• Koethe JR. Adipose Tissue in HIV Infection. Compr Physiol. 2017;7:1339–57 This study details mechanisms and changes in adipose tissue health that have huge implications on our understanding of dyslipidemia in HIV.
Agarwal N, Iyer D, Patel SG, Sekhar RV, Phillips TM, Schubert U, et al. HIV-1 Vpr induces adipose dysfunction in vivo through reciprocal effects on PPAR/GR co-regulation. Sci Transl Med. 2013;5:213ra164.
Bourgi K, Jenkins CA, Rebeiro PF, Palella F, Moore RD, Altoff KN, et al. Weight gain among treatment-naïve persons with HIV starting integrase inhibitors compared to non-nucleoside reverse transcriptase inhibitors or protease inhibitors in a large observational cohort in the United States and Canada. J Int AIDS Soc. 2020;23:e25484.
Gorwood J, Bourgeois C, Pourcher V, Pourcher G, Charlotte F, Mantecon M, et al. The integrase inhibitors dolutegravir and raltegravir exert pro-adipogenic and profibrotic effects and induce insulin resistance in human/simian adipose tissue and human adipocytes. Clin Infect Dis. 2020.
Calza L, Colangeli V, Magistrelli E, Rossi N, Turco ERD, Bussini L, et al. Prevalence of metabolic syndrome in HIV-infected patients naive to antiretroviral therapy or receiving a first-line treatment. HIV Clinical Trials. Taylor & Francis. 2017;18:110–7.
Krishnan S, Schouten J, Atkinson B, Brown T, Wohl D, McComsey G, et al. Changes in metabolic syndrome status after initiation of antiretroviral therapy. J Acquir Immune Defic Syndr. 2015;68:73–80.
Damouche A, Lazure T, Avettand-Fènoël V, Huot N, Dejucq-Rainsford N, Satie A-P, et al. Adipose tissue is a neglected viral reservoir and an inflammatory site during chronic HIV and SIV infection. PLoS Pathog. 2015; [cited 2020 May 10];11. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581628/.
Han S-J, Glatman Zaretsky A, Andrade-Oliveira V, Collins N, Dzutsev A, Shaik J, et al. White adipose tissue is a reservoir for memory T cells and promotes protective memory responses to infection. Immunity. 2017;47:1154–1168.e6.
Gorwood J, Bourgeois C, Mantecon M, Atlan M, Pourcher V, Pourcher G, et al. Impact of HIV/simian immunodeficiency virus infection and viral proteins on adipose tissue fibrosis and adipogenesis. AIDS. 2019;33:953–64.
Maurin T, Saillan-Barreau C, Cousin B, Casteilla L, Doglio A, Pénicaud L. Tumor necrosis factor-alpha stimulates HIV-1 production in primary culture of human adipocytes. Exp Cell Res. 2005;304:544–51.
Munier S, Borjabad A, Lemaire M, Mariot V, Hazan U. In vitro infection of human primary adipose cells with HIV-1: a reassessment. AIDS. 2003;17:2537–9.
Surmi BK, Hasty AH. Macrophage infiltration into adipose tissue: initiation, propagation and remodeling. Future Lipidol. 2008;3:545–56.
Couturier J, Winchester LC, Suliburk JW, Wilkerson GK, Podany AT, Agarwal N, et al. Adipocytes impair efficacy of antiretroviral therapy. Antivir Res. 2018;154:140–8.
• Masenga SK, Hamooya BM, Nzala S, Kwenda G, Heimburger DC, Mutale W, et al. Patho-immune mechanisms of hypertension in HIV: a systematic and thematic review. Curr Hypertens Rep. 2019;21:56 This study explains underlying factors associated with HIV-related hypertension.
De Socio GV, Ricci E, Maggi P, Parruti G, Pucci G, Di Biagio A, et al. Prevalence, awareness, treatment, and control rate of hypertension in HIV-infected patients: the HIV-HY study. Am J Hypertens. 2014;27:222–8.
Bigna JJR, Nansseu JRN, Um LN, Noumegni SRN, Simé PSD, Aminde LN, et al. Prevalence and incidence of pulmonary hypertension among HIV-infected people in Africa: a systematic review and meta-analysis. BMJ Open. 2016;6:e011921.
Bigna JJ, Tankeu AT, Kaze AD, Noubiap JJ, Nansseu JR. Prevalence and incidence of hypertension in the global HIV-infected population: a systematic review and meta-analysis protocol. BMJ Open. 2017;7:e016531.
Bigna JJ, Noubiap JJ, Nansseu JR, Aminde LN. Prevalence and etiologies of pulmonary hypertension in Africa: a systematic review and meta-analysis. BMC Pulm Med. 2017;17:183.
•• Masenga SK, Elijovich F, Hamooya BM, Nzala S, Kwenda G, Heimburger DC, et al. Elevated eosinophils as a feature of inflammation associated with hypertension in virally suppressed people living with HIV. J Am Heart Assoc. 2020;9:e011450 This study reports novel findings that link development of hypertension, a component of metabolic syndrome, to inflammatory cytokines and eosinophilia suggesting a novel pathway linking hypertension and eosinophils in both HIV positive and HIV negative populations.
Mayanja BN, Kasamba I, Levin J, Namakoola I, Kazooba P, Were J, et al. COHORT PROFILE: the complications of long-term antiretroviral therapy study in Uganda (CoLTART), a prospective clinical cohort. AIDS Res Ther. 2017;14:26.
•• Chandel N, Ayasolla K, Lan X, Rai P, Mikulak J, Husain M, et al. Renin modulates HIV replication in T cells. J Leukoc Biol. 2014;96:601–9 This study demonstrates a direct effect of renin enhancing HIV viral replication in T-cells, linking RAAS hyperactivation and immunity in HIV disease.
Tzoupis H, Leonis G, Megariotis G, Supuran CT, Mavromoustakos T, Papadopoulos MG. Dual inhibitors for aspartic proteases HIV-1 PR and renin: advancements in AIDS-hypertension-diabetes linkage via molecular dynamics, inhibition assays, and binding free energy calculations. J Med Chem. 2012;55:5784–96.
Ouellette DR, Kelly JW, Anders GT. Serum angiotensin-converting enzyme level is elevated in patients with human immunodeficiency virus infection. Arch Intern Med. 1992;152:321–4.
Srinivasa S, Burdo TH, Williams KC, Mitten EK, Wong K, Fitch KV, et al. Effects of sodium restriction on activation of the renin-angiotensin-aldosterone system and immune indices during HIV infection. J Infect Dis. 2016;214:1336–40.
Utay NS, Kitch DW, Yeh E, Fichtenbaum CJ, Lederman MM, Estes JD, et al. Telmisartan therapy does not improve lymph node or adipose tissue fibrosis more than continued antiretroviral therapy alone. J Infect Dis. 2018;217:1770–81.
•• Chandel N, Ayasolla KS, Lan X, Sultana-Syed M, Chawla A, Lederman R, et al. Epigenetic modulation of human podocyte vitamin d receptor in HIV milieu. J Mol Biol. 2015;427:3201–15 This study describes the mechanisms involved in HIV-induced renal damage and activation of the RAAS via local downregulation of the vitamin D receptor.
Rai P, Singh T, Lederman R, Chawla A, Kumar D, Cheng K, et al. Hyperglycemia enhances kidney cell injury in HIVAN through down-regulation of vitamin D receptors. Cell Signal. 2015;27:460–9.
Salhan D, Husain M, Subrati A, Goyal R, Singh T, Rai P, et al. HIV-induced kidney cell injury: role of ROS-induced downregulated vitamin D receptor. Am J Physiol Renal Physiol. 2012;303:F503–14.
Shimizu A, Zhong J, Miyazaki Y, Hosoya T, Ichikawa I, Matsusaka T. ARB protects podocytes from HIV-1 nephropathy independently of podocyte AT1. Nephrol Dial Transplant. 2012;27:3169–75.
Rai P, Lederman R, Haque S, Rehman S, Kumar V, Sataranatrajan K, et al. Renin angiotensin system modulates mTOR pathway through AT2R in HIVAN. Exp Mol Pathol. 2014;96:431–7.
Burns GC, Paul SK, Toth IR, Sivak SL. Effect of angiotensin-converting enzyme inhibition in HIV-associated nephropathy. J Am Soc Nephrol. 1997;8:1140–6.
Ucciferri C, Falasca K, Mancino P, Di Iorio A, Vecchiet J. Microalbuminuria and hypertension in HIV-infected patients: a preliminary study of telmisartan. Eur Rev Med Pharmacol Sci. 2012;16:491–8.
Cabandugama PK, Gardner MJ, Sowers JR. The renin angiotensin aldosterone system in obesity and hypertension: roles in the cardiorenal metabolic syndrome. Med Clin North Am. 2017;101:129–37.
Srinivasa S, Fitch KV, Wong K, Torriani M, Mayhew C, Stanley T, et al. RAAS activation is associated with visceral adiposity and insulin resistance among HIV-infected patients. J Clin Endocrinol Metab. 2015;100:2873–82.
Murphy CA, Fitch KV, Feldpausch M, Maehler P, Wong K, Torriani M, et al. Excessive adiposity and metabolic dysfunction relate to reduced natriuretic peptide during RAAS activation in HIV. J Clin Endocrinol Metab. 2018;103:1558–65.
Sutinen J, Kannisto K, Korsheninnikova E, Nyman T, Ehrenborg E, Andrew R, et al. In the lipodystrophy associated with highly active antiretroviral therapy, pseudo-Cushing’s syndrome is associated with increased regeneration of cortisol by 11β-hydroxysteroid dehydrogenase type 1 in adipose tissue. Diabetologia. 2004;47:1668–71.
Srinivasa S, Fitch KV, Wong K, O’Malley TK, Maehler P, Branch KL, et al. Randomized, placebo-controlled trial to evaluate effects of Eplerenone on metabolic and inflammatory indices in HIV. J Clin Endocrinol Metab. 2018;103:2376–84.