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Review

Current pharmacotherapy for the treatment of dyslipidemia associated with HIV infection

& ORCID Icon
Pages 1719-1729 | Received 22 Apr 2019, Accepted 21 Jun 2019, Published online: 28 Jun 2019

References

  • Feingold KR, Krauss RM, Pang M, et al. The hypertriglyceridemia of acquired immunodeficiency syndrome is associated with an increased prevalence of low density lipoprotein subclass pattern B. J Clin Endocrinol Metab. 1993;76:1423–1427.
  • Shor-Posner G, Basit A, Lu Y, et al. Hypercholesterolemia is associated with immune dysfunction in early human immunodeficiency virus-1 infection. Am J Med. 1993;94:515–519.
  • Buchacz K, Baker RK, Palella FJ Jr, et al. HIV outpatient study investigators. Disparities in prevalence of key chronic diseases by gender and race/ethnicity among antiretroviral-treated HIV-infected adults in the US. Antivir Ther. 2013;18(1):65–75.
  • Tóth PP, Potter D, Ming EE. Prevalence of lipid abnormalities in the United States: the national health and nutrition examination survey 2003–2006. J Clin Lipidol. 2012;6(4):325–330.
  • Gili S, Grosso Marra W, D’Ascenzo F, et al. Comparative safety and efficacy of statins for primary prevention in human immunodeficiency virus-positive patients: a systematic review and meta-analysis. Eur Heart J. 2016;37(48):3600–3609.
  • Khovidhunkit W, Memon RA, Feingold KR, et al. Infection and Inflammation-Induced Proatherogenic Changes of Lipoproteins. J Infect Dis. 2000;181(Suppl 3):S462–72.
  • Riddler SA, Smit E, Cole SR, et al. Impact of HIV infection and HAART on serum lipids in men. JAMA. 2003;289:2978–2982.
  • Mujawar Z, Rose H, Morrow MP, et al. Human immunodeficiency virus impairs reverse cholesterol transport from macrophages. PLoS Biol. 2006;4(11):e365.
  • Sekhar RV, Jahoor F, White AC, et al. Metabolic basis of HIV-lipodystrophy syndrome. Am J Physiol Endocrinol Metab. 2002;283:E332–E337.
  • Grunfeld C, Pang M, Doerrler W, et al. Lipids, lipoproteins, triglyceride clearance, and cytokines in human immunodeficiency virus infection and the acquired immunodeficiency syndrome. J Clin Endocrinol Metab. 1992;74:1045–1052.
  • Reeds DN, Mittendorfer B, Patterson BW, et al. Alterations in lipid kinetics in men with HIV-dyslipidemia. Am J Physiol Endocrinol Metab. 2003;285:E490–E497.
  • Dron JS, Hegele RA. Polygenic influences on dyslipidemias. Curr Opin Lipidol. 2018;29:133–143.
  • Egaña-Gorroño L, Martínez E, Cormand B, et al. Impact of genetic factors on dyslipidemia in HIV-infected patients starting antiretroviral therapy. AIDS. 2013;27:529–538.
  • Enkhmaa B, Anuurad E, Zhang W, et al. HIV disease activity as a modulator of lipoprotein(a) and allele-specific apolipoprotein(a) levels. Arterioscler Thromb Vasc Biol. 2013;33:387–392.
  • MacInnes A, Lazzarin A, Di Perri G, et al. Maraviroc can improve lipid profiles in dyslipidemic patients with HIV: results from the MERIT trial. HIV Clin Trials. 2011;12(1):24–36.
  • Fung HB, Guo Y. Enfuvirtide: a fusion inhibitor for the treatment of HIV infection. Clin Ther. 2004;26(3):352–378.
  • Quercia R, Roberts J, Martin-Carpenter L, et al. Comparative changes of lipid levels in treatment-naive, HIV-1-infected adults treated with dolutegravir vs. efavirenz, raltegravir, and ritonavir-boosted darunavir-based regimens over 48 weeks. Clin Drug Investig. 2015;35(3):211–219.
  • Anastos K, Lu D, Shi Q, et al. Association of serum lipid levels with HIV serostatus. Specific antiretroviral agents, and treatment Regimens. J Acquir Immune Defic Syndr. 2007;45:34–42.
  • Ofotokun I, Na LH, Landovitz RJ, et al. Comparison of the metabolic effects of ritonavir-boosted darunavir or atazanavir versus raltegravir, and the impact of ritonavir plasma exposure: ACTG 5257. Clin Infect Dis. 2015;60(12):1842–1851.
  • Sax PE, Pozniak A, Montes ML, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomized, double-blind, multicentre, phase 3, non-inferiority trial. Lancet. 2017;390(10107):2073–2082. (Supplemental Appendix).
  • Sax PE, Wohl D, Yin MT, et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomized, double-blind, phase 3, non-inferiority trials. Lancet. 2015;385(9987):2606–2615.
  • Tebas P, Sension M, Arribas J, et al. Lipid levels and changes in body fat distribution in treatment-naive, HIV-1-Infected adults treated with rilpivirine or Efavirenz for 96 weeks in the ECHO and THRIVE trials. Clin Infect Dis. 2014;59(3):425–434.
  • Orkin C, Squires KE, Molina JM, et al. Doravirine/Lamivudine/Tenofovir disoproxil fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir disoproxil fumarate in treatment-naive adults with human immunodeficiency virus-1 infection: week 48 results of the DRIVE-AHEAD trial. Clin Infect Dis. 2019;68(4):535–544.
  • Molina JM, Andrade-Villanueva J, Echevarria J, et al. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet. 2008;372(9639):646–655.
  • Tungsiripat M, Kitch D, Glesby MJ, et al. A pilot study to determine the impact on dyslipidemia of adding tenofovir to stable background antiretroviral therapy: ACTG 5206. AIDS. 2010;24:1781–1784.
  • Wohl D, Arnoczy G, Fichtenbaum CJ, et al. Cardiovascular disease (CVD) risk markers in patients receiving abacavir, tenofovir, and zidovudine: the nucleoside inflammation, coagulation and endothelial function (NICE) study. Antivir Ther. 2014;19(2):141–147.
  • Molina JM, Cahn P, Grinsztejn B, et al. Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomized double-blind active-controlled trial. Lancet. 2011;378:238–246.
  • Cohen CJ, Andrade-Villanueva J, Clotet B, et al. Rilpivirine versus efavirenz with two background nucleoside or nucleotide reverse transcriptase inhibitors in treatment-naive adults infected with HIV-1 (THRIVE): a phase 3, randomized, non-inferiority trial. Lancet. 2011;378:229–237.
  • Periard D, Telenti A, Sudre P, et al. Atherogenic dyslipidemia in HIV-infected individuals treated with protease inhibitors. Circulation. 1999;100:700–705.
  • Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Department of Health and Human Services. [cited 2019 Jun 25]. Available from: http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
  • Landovitz RJ, Zangeneh SZ, Chau G, et al. Cabotegravir is not associated with weight gain in HIV-negative individuals: HPTN 077. Conference on Retroviruses and Opportunistic Infections (CROI); 2019 Mar 4–7; Seattle, WA. Abstract 34.
  • Bourgi K, Jenkins C, Rebeiro PF, et al. Greater weight gain among treatment-naïve persons starting integrase inhibitors. Conference on Retroviruses and Opportunistic Infections (CROI); 2019 Mar 4–7; Seattle, WA. Abstract 670.
  • Triant VA, Lee H, Hadigan C, et al. Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab. 2007;92:2506–2512.
  • Freiberg MS, Chang CH, Kuller LH, et al. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med. 2013;173(8):614–622.
  • Anoop SV, Shah ASV, Stelzle D, et al. Global burden of atherosclerotic cardiovascular disease in people living with HIV. Circulation. 2018;138:1100–1112.
  • Lo J, Abbara S, Shturman L, et al. Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed tomography angiography in HIV-infected men. AIDS. 2010;24:243–253.
  • Post WS, Budoff M, Kingsley L, et al. Associations between HIV infection and subclinical coronary atherosclerosis. Ann Intern Med. 2014;160(7):458–467.
  • Martin-Iguacel R, Llibre JM, Friis-Moller N. Risk of cardiovascular disease in an aging HIV population: where are we now? Curr HIV/AIDS Rep. 2015;12(4):375–387.
  • Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. Circulation. 2018 Nov 10:CIR0000000000000625. [Epub ahead of print]. DOI: 10.1161/CIR.0000000000000625.
  • Feinstein MJ, Nance RM, Drozd DR, et al. Assessing and refining myocardial infarction risk estimation among patients with human immunodeficiency virus: a study by the centers for AIDS research network of integrated clinical systems. JAMA Cardiol. 2017;2(2):155–162.
  • Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388:2532–2561.
  • Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713–1722.
  • Ridker PM, Revkin J, Amarenco P, et al. Cardiovascular efficacy and safety of bococizumab in high-risk patients. N Engl J Med. 2017;376(16):1527–1539.
  • Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomized trials. Lancet. 2010;376(9753):1670–1681.
  • Oesterle A, Laufs U, Liao JK. Pleiotropic effects of statins on the cardiovascular system. Circ Res. 2017;120(1):229–243.
  • Aberg JA, Zackin RA, Brobst SW, et al. A randomized trial of the efficacy and safety of fenofibrate versus pravastatin in HIV-infected subjects with lipid abnormalities: AIDS clinical trials group study 5087. AIDS Res Hum Retroviruses. 2005;21(9):757–767.
  • Singh S, Willig JH, Mugavero MJ, et al. Comparative effectiveness and toxicity of statins among HIV-infected patients. Clin Infect Dis. 2011;52(3):387–395.
  • Eckard AR, Jiang Y, Debanne SM, et al. Effect of 24 weeks of statin therapy on systemic and vascular inflammation in HIV-infected subjects receiving antiretroviral therapy. J Infect Dis. 2014;209(8):1156–1164.
  • 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 Aquir Immune Defic Syndr. 2015;68:396–404.
  • Aberg JA, Sponseller CA, Ward DJ, et al. Pitavastatin versus pravastatin in adults with HIV-1 infection and dyslipidaemia (INTREPID): 12 week and 52 week results of a phase 4, multicentre, randomized, double-blind, superiority trial. Lancet HIV. 2017;4(7):e284–e294.
  • Calza L, Colangeli V, Manfredi R, et al. Rosuvastatin for the treatment of hyperlipidaemia in HIV-infected patients receiving protease inhibitors: a pilot study. AIDS. 2005;19:1103–1108.
  • Calza L, Manfredi R, Colangeli V, et al. Substitution of nevirapine or efavirenz for protease inhibitor versus lipid-lowering therapy for the management of dyslipidaemia. AIDS. 2005;19(10):1051–1058.
  • Palacios R, Santos J, González M, et al. Efficacy and safety of atorvastatin in the treatment of hypercholesterolemia associated with antiretroviral therapy. J Acquir Immune Defic Syndr. 2002;30(5):536–537.
  • 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 <130 mg/dL. J Clin Lipidol. 2017;11(1):61–69.
  • Lo J, Lu MT, Ihenachor EJ, et al. Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomized, double-blind, placebo-controlled trial. Lancet HIV. 2015;2(2):e52–e63.
  • Longenecker CT, Sattar A, Gilkeson R, et al. Rosuvastatin slows progression of subclinical atherosclerosis in patients with treated HIV infection. AIDS. 2016;30(14):2195–2203.
  • Hileman CO, Turner R, Funderburg NT, et al. Changes in oxidized lipids drive the improvement in monocyte activation and vascular disease after statin therapy in HIV. AIDS. 2016;30(1):65–73.
  • Nou E, Lu MT, Looby SE, et al. Serum oxidized low-density lipoprotein decreases in response to statin therapy and relates independently to reductions in coronary plaque in patients with HIV. AIDS. 2016;30(4):583–590.
  • Longenecker CT, Eckard AR, McComsey GA. Statins to improve cardiovascular outcomes in treated HIV infection. Curr Opin Infect Dis. 2016;29(1):1–9.
  • 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;31(6):797–806.
  • Calza L, Colangeli V, Magistrelli E, et al. Significant decrease in plasma levels of D-Dimer, Interleukin-8, and Interleukin-12 after a 12-month treatment with rosuvastatin in HIV-infected patients under antiretroviral therapy. AIDS Res Hum Retroviruses. 2017;33(2):126–132.
  • Grinspoon SK, Fitch KV, Overton ET, et al. Rationale and design of the randomized trial to prevent cardiovascular events in HIV (REPRIEVE). Am Heart J. 2019;212:23–35.
  • Hoffmann U, Lu MT, Olalere D, et al. Rationale and design of the mechanistic substudy of REPRIEVE: effects of pitavastatin on coronary artery disease and inflammatory biomarkers. Am Heart J. 2019;212:1–12.
  • Hsu A, Granneman GR, Bertz RJ. Ritonavir. Clinical pharmacokinetics and interactions with other anti-HIV agents. Clin Pharmacokinet. 1998;35(4):275–291.
  • Dube MP, Stein JH, Aberg JA, et al. Guidelines for the evaluation and management of dyslipidemia in HIV-infected adults receiving antiretroviral therapy. Updated recommendations of the Adult AIDS Clinical Trials Group Cardiovascular Subcommittee. Clin Infect Dis. 2003;37:613–627.
  • Calza L, Manfredi R, Colangeli V, et al. Two-year treatment with rosuvastatin reduces carotid intima-media thickness in HIV type 1-infected patients receiving highly active antiretroviral therapy with asymptomatic atherosclerosis and moderate cardiovascular risk. AIDS Res Hum Retroviruses. 2013;29(3):547–556.
  • Stein JH, Merwood MA, Bellehumeur JL, et al. Effects of pravastatin on lipoproteins and endothelial function in patients receiving human immunodeficiency virus protease inhibitors. Am Heart J. 2004;147(4):E18.
  • Hürlimann D, Chenevard R, Ruschitzka F, et al. Effects of statins on endothelial function and lipid profile in HIV infected persons receiving protease inhibitor-containing anti-retroviral combination therapy: a randomized double blind crossover trial. Heart. 2006;92(1):110–112.
  • 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):756–764.
  • Shah BM, Schafer JJ, Priano J, et al. Cobicistat: a new boost for the treatment of human immunodeficiency virus infection. Pharmacotherapy. 2013;33(10):1107–1116.
  • Fichtenbaum CJ, Gerber JG, Rosenkranz SL, et al. Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG study A5047. AIDS. 2002;16(4):569–577.
  • Gerber JG, Rosenkranz SL, Fichtenbaum CJ, et al. Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin: results of AIDS clinical trials group 5108 study. J Acquir Immune Defic Syndr. 2005;39(3):307–312.
  • Sameneni DY, Sallans L, Desai PB, et al. Steady state pharmacokinetic interactions of Darunavir/ritonavir with lipid lowering agent rosuvastatin. J Clin Pharmacol. 2012;52(6):922–931.
  • Kiser JJ, Gerber JG, Predhomme JA, et al. Drug/Drug interaction between lopinavir/ritonavir and rosuvastatin in healthy volunteers. J Acquir Immune Defic Syndr. 2008;47(5):570–578.
  • Elsby R, Martin P, Surry D, et al. Solitary inhibition of the breast cancer resistance protein efflux transporter results in a clinically significant drug-drug interaction with rosuvastatin by causing up to a 2-fold increase in statin exposure. Drug Metab Dispos. 2016;44:398–408.
  • Fujimoto H, Higuchi M, Watanabe H, et al. P-glycoprotein mediates efflux transport of darunavir in human intestinal Caco-2 and ABCB1 gene-transfected renal LLC-PK1 cell lines. Biol Pharm Bull. 2009;32(9):1588–1593.
  • Wiggins BS, Lamprecht DG Jr, Page RL 2nd, et al. Recommendations for managing drug-drug interactions with statins and HIV medications. Am J Cardiovasc Drugs. 2017 Oct;17(5):375–389.
  • Kashani A, Phillips CO, Foody JM, et al. Risks associated with statin therapy: a systematic overview of randomized clinical trials. Circulation. 2006;114(25):2788–2797.
  • Chou R, Dana T, Blazina I, et al. Statins for prevention of cardiovascular disease in adults evidence report and systematic review for the US preventive services task force. JAMA. 2016;316(19):2008–2024.
  • Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomized statin trials. Lancet. 2010;375:735–742.
  • GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto miocardico. Lancet. 1999;354:447–455.
  • Simons LA, Hickie JB, Balasubramaniam S. On the effects of dietary n-3 fatty acids (Maxepa) on plasma lipids and lipoproteins in patients with hyperlipidaemia. Atherosclerosis. 1985;54:75–88.
  • The REDUCE-IT trial analyzed the effects of high dose icosapent ethyl on HIV negative patients (Bhatt). The study focused on patients who had elevated TG levels despite receiving statin treatment. The study indicated that patients receiving two doses of 2 g icosapent ethyl daily had significantly lower TG levels than the placebo.
  • Muñoz MA, Liu W, Delaney JAC, et al. Comparative effectiveness of fish oil versus fenofibrate, gemfibrozil, and atorvastatin on lowering triglyceride levels among HIV-infected patients in routine clinical care. J Acquir Immune Defic Syndr. 2013;64:254–260.
  • Wohl DA, Tien HC, Busby M, et al. Randomized study of the safety and efficacy of fish oil (omega-3 fatty acid) supplementation with dietary and exercise counseling for the treatment of antiretroviral therapy-associated hypertriglyceridemia. Clin Infect Dis. 2005 15;41(10):1498–1504.
  • De Truchis P, Kirstetter M, Perier A, et al. Reduction in triglyceride level with N-3 polyunsaturated fatty acids in HIV-infected patients taking potent antiretroviral therapy: a randomized prospective study. J Acquir Immune Defic Syndr. 2007;44(3):278–285.
  • Gerber JG, Kitch DW, Fichtenbaum CJ, et al. Fish oil and fenofibrate for the treatment of hypertriglyceridemia in HIV-infected subjects on antiretroviral therapy: results of ACTG A5186 protocol. J Acquir Immune Defic Syndr. 2008;47:459–466.
  • Sameneni D, Fichtenbaum CJ. Fenofibrate in the treatment of dyslipidemia associated with HIV infection. Expert Opin Drug Metab Toxicol. 2010;6:995–1004.
  • Miller J, Brown D, Amin J, et al. A randomized, double-blind study of gemfibrozil for the treatment of protease inhibitor-associated hypertriglyceridemia. AIDS. 2002;16(16):2195–2200.
  • Fruchart J-C. Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor alpha modulator for management of atherogenic dyslipidaemia. Cardiovasc Diabetol. 2017;16(1). DOI:10.1186/s12933-017-0602-y
  • Arai H, Yamashita S, Yokote K, et al. Efficacy and safety of pemafibrate versus fenofibrate in patients with high triglyceride and low HDL cholesterol levels: a multicenter, placebo-controlled, double-blind, randomized trial. J Atheroscler Thromb. 2018;25(6):521–538.
  • Schandelmaier S, Briel M, Saccilotto R, et al. Niacin for primary and secondary prevention of cardiovascular events. Cochrane Database Syst Rev. 2017;6:CD009744. Review. .
  • Dubé MP, Wu JW, Aberg JA, et al. Safety and efficacy of extended-release niacin for the treatment of dyslipidaemia in patients with HIV infection: AIDS clinical trials group study A5148. Antivir Ther. 2006;11(8):1081–1089.
  • Balasubramanyam A, Coraza I, Smith EO, et al. Combination of niacin and fenofibrate with lifestyle changes improves dyslipidemia and hypoadiponectinemia in HIV patients on antiretroviral therapy: results of “heart positive,” a randomized, controlled trial. J Clin Endocrinol Metab. 2011;96(7):2236–2247.
  • Dubé MP, Komarow L, Fichtenbaum CJ, et al. Extended-release niacin versus fenofibrate in HIV-infected participants with low high-density lipoprotein cholesterol: effects on endothelial function, lipoproteins, and inflammation. Clin Infect Dis. 2015;61(5):840–849.
  • Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–2397.
  • Wohl DA, Waters D, Simpson RJ Jr, et al. Ezetimibe alone reduces low-density lipoprotein cholesterol in HIV-infected patients receiving combination antiretroviral therapy. Clin Infect Dis. 2008;47(8):1105–1108.
  • Chow D, Chen H, Glesby MJ, et al. Short-term ezetimibe is well tolerated and effective in combination with statin therapy to treat elevated LDL cholesterol in HIV-infected patients. AIDS. 2009;23(16):2133–2141.
  • Grandi AM, Nicolini E, Rizzi L, et al. Dyslipidemia in HIV-positive patients: a randomized, controlled, prospective study on ezetimibe+fenofibrate versus pravastatin monotherapy. J Int AIDS Soc. 2014;17:19004. eCollection 2014. .
  • Saeedi R, Johns K, Frohlich J, et al. Lipid lowering efficacy and safety of ezetimibe combined with rosuvastatin compared with titrating rosuvastatin monotherapy in HIV-positive patients. Lipids Health Dis. 2015;14:57.
  • Della Badia LA, Elshourbagy NA, Mousa SA. Targeting PCSK9 as a promising new mechanism for lowering low-density lipoprotein cholesterol. Pharmacol Ther. 2016;164:183–194.
  • O’Keefe JH, DiNicolantonio JJ, Lavie CJ. Statins, ezetimibe, and proprotein convertase subtilisin-kexin type 9 inhibitors to reduce low-density lipoprotein cholesterol and cardiovascular events. Am J Cardiol. 2017;119(4):565–571.
  • Ference BA, Cannon CP, Landmesser U, et al. Reduction of low density lipoprotein-cholesterol and cardiovascular events with proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors and statins: an analysis of FOURIER, SPIRE, and the cholesterol treatment trialists collaboration. Eur Heart J. 2018;39(27):2540–2545.
  • Kohli M, Patel K, MacMahon Z, et al. Pro- protein subtilisin kexin- 9 (PCSK9) inhibition in practice: lipid clinic experience in 2 contrasting UK centres. Int J Clin Pract. 2017 Nov;71(11):e13032.
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29. Identifier NCT02833844, safety, tolerability & efficacy on LDL-C of evolocumab in subjects with HIV & hyperlipidemia/mixed dyslipidemia. 2016 Jul 14. [cited 2019 Jun 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT02833844?term=NCT02833844&rank=1
  • ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000 Feb 29. Identifier NCT03207945, effect of PCSK9 inhibition on cardiovascular risk in treated HIV infection (EPIC-HIV Study) (EPIC-HIV). 2017 Jul 5. [cited 2019 Jun 25]. Available from: https://clinicaltrials.gov/ct2/show/NCT03207945?term=NCT03207945&rank=1

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