Impact of Lopinavir/Ritonavir and Efavirenz-Based Antiretroviral Therapy on the Lipid Profile of Chinese HIV/AIDS Treatment-Naïve Patients in Beijing: A Retrospective Study

Author(s): Lili Dai*, An Liu, Hongwei Zhang, Hao Wu, Tong Zhang, Bin Su, Ying Shao, Jianwei Li, Jiangzhu Ye, Sarah Robbins Scott, Supriya D. Mahajan*, Stanley A Schwartz, Hongwei Yu, Lijun Sun

Journal Name: Current HIV Research

Volume 17 , Issue 5 , 2019

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Graphical Abstract:


Background: Antiretroviral therapy (ART) is associated with lipid abnormalities that contribute to increased risk of cardiovascular (CV) events among patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). Although disorders of lipid metabolism associated with ART have been described before in developed countries, data on lipid profile disorders associated with ART use in China are limited. This study aimed to examine the changes in lipid profile among patients with HIV/AIDS who initiated lopinavir/ritonavir LPV/r or efavirenz (EFV)-based antiretroviral treatment regimens, which continue to be widely used China and other developing countries.

Methods: This is a retrospective, matched case-control study of HIV-positive patients initiating either LPV/r or EFV regimens at the Beijing You’an Hospital, Capital Medical University between July 2012 and January 2017. Generalized estimating equations were used to compare the differences in total cholesterol [TC], triglycerides [TG], low-density lipoprotein-cholesterol [LDL-C], and highdensity lipoprotein-cholesterol [HDL-C] at baseline and up to 24-months after ART initiation between the two treatment arms.

Results: Baseline characteristics, including age, sex, CD4 cell count, viral load, and serum lipids, which were comparable between the two groups. The LPV/r-based regimen group had increased TC, TG, HDL-C, and LDL-C after 24-months of treatment. In the EFV-regimen group, TC, HDL-C, and LDL-C were increased compared to baseline, while the TC/HDL-C ratio decreased, and TG did not change significantly. After 24-months of treatment, the percentage of patients with dyslipidemia in the LPV/r group was much higher than in the EFV group (84.0% vs. 52.6%, P<0.001), and 17(10%) patients on LPV/r-based regimens had severe dyslipidemia. Patients on LPV/r-based regimens were at increased odds of hypercholesterolemia (odds ratio [OR]=1.709, P=0.038), hypertriglyceridemia (OR=4.315, P<0.001), and high TC/HDL-C ratio (OR=1.951, P=0.003). However, no significant difference was found in HDL-C (OR=1.246, P=0.186) or LDL-C (OR=1.253, P=0.410) between the treatment groups.

Conclusion: Both LPV/r or EFV treatment regimens impacted patients’ lipid profiles. Compared to EFV-based regimens, patients on LPV/r-based regimens had increased odds of dyslipidemia, such as hypercholesterolemia, hypertriglyceridemia, or high TC/HDL-C ratio; however, there was no obvious effect on LDL-C, which is more relevant to the development of the cardiovascular disease.

Keywords: Human immunodeficiency virus, acquired immunodeficiency syndrome, lipid profile, anti-retroviral therapy, lopinavir/ ritonavir, cardiovascular disease.

Maggi P, Di Biagio A, Rusconi S, et al. Cardiovascular risk and dyslipidemia among persons living with HIV: A review. BMC Infect Dis 2017; 17(1): 551.
[] [PMID: 28793863]
Bowman E, Funderburg NT. Lipidome Abnormalities and Cardiovascular Disease Risk in HIV Infection. Curr HIV/AIDS Rep 2019; 16(3): 214-23.
[] [PMID: 30993515]
Jain A, Kolvekar T, Nair DR. HIV infection and lipids. Curr Opin Cardiol 2018; 33(4): 429-35.
[] [PMID: 29601329]
Prabhu S, Harwell JI, Kumarasamy N. Advanced HIV: diagnosis, treatment, and prevention. Lancet HIV 2019; 6(8): e540-51.
[] [PMID: 31285181]
Farel CE, Dennis AM. why everyone (almost) with HIV needs to be on treatment: A review of the critical data. Infect Dis Clin North Am 2019; 33(3): 663-79.
[] [PMID: 31248703]
Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV department of health and human services. http://wwwaidsinfonihgov/ ContentFiles/Adultand AdolescentGL. pdf [May 24, 2018]
Saag MS, Benson CA, Gandhi RT, et al. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2018 Recommendations of the International Antiviral Society-USA Panel. JAMA 2018; 320(4): 379-96.
[] [PMID: 30043070]
European AIDS Clinical Society. Guidelines for treatment of HIVpositive adults in Europe. Available at: http://wwweacsocietyorg/ guidelines/eacs-guidelines/eacs-guidelineshtml.pdf [Accessed October, 2018]
Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: Recommendations for a public health approach. Geneva 2016.
Zanetti HR, Roever L, Gonçalves A, Resende ES. Human Immunodeficiency Virus Infection, Antiretroviral Therapy, and Statin: a Clinical Update. Curr Atheroscler Rep 2018; 20(2): 9.
[] [PMID: 29423787]
He Q, Du X, Xu H, et al. Intention to initiate antiretroviral therapy (ART) among people living with HIV in China under the scaling-up of ART: the role of healthcare workers’ recommendations. BMC Health Serv Res 2019; 19(1): 314.
[] [PMID: 31096967]
Liu P, Tang Z, Lan G, et al. Early antiretroviral therapy on reducing HIV transmission in China: strengths, weaknesses and next focus of the program. Sci Rep 2018; 8(1): 3431.
[] [PMID: 29467460]
Zicari S, Sessa L, Cotugno N, et al. Immune activation, inflammation, and non-AIDS co-morbidities in HIV-infected patients under long-term ART. Viruses 2019; 11(3): 11.
[] [PMID: 30818749]
Stone L, Looby SE, Zanni MV. Cardiovascular disease risk among women living with HIV in North America and Europe. Curr Opin HIV AIDS 2017; 12(6): 585-93.
[] [PMID: 28832367]
Chawla A, Wang C, Patton C, et al. A review of long-term toxicity of antiretroviral treatment regimens and implications for an aging population. Infect Dis Ther 2018; 7(2): 183-95.
[] [PMID: 29761330]
Ghosh AK, Osswald HL, Prato G. Recent progress in the development of HIV-1 protease inhibitors for the treatment of HIV/AIDS. J Med Chem 2016; 59(11): 5172-208.
[] [PMID: 26799988]
Dou Z, Zhang F, Zhao Y, et al. Progress on China’ s national free antiretroviral therapy strategy in 2002-2014. Zhonghua Liu Xing Bing Xue Za Zhi 2015; 36(12): 1345-50.
[PMID: 26850386]
Randell P, Jackson A, Milinkovic A, Boffito M, Moyle G. An open-label, randomized study of the impact on insulin sensitivity, lipid profile and vascular inflammation by treatment with lopinavir/ritonavir or raltegravir in HIV-negative male volunteers. Antivir Ther (Lond) 2017; 22(2): 145-51.
[] [PMID: 27708251]
Waters DD, Hsue PY. Lipid abnormalities in persons living with HIV infection. Can J Cardiol 2019; 35(3): 249-59.
[] [PMID: 30704819]
Magenta L, Dell-Kuster S, Richter WO, et al. Lipid and lipoprotein profile in HIV-infected patients treated with lopinavir/ritonavir as a component of the first combination antiretroviral therapy. AIDS Res Hum Retroviruses 2011; 27(5): 525-33.
[] [PMID: 20854107]
Montes ML, Pulido F, Barros C, et al. Lipid disorders in antiretroviral-naive patients treated with lopinavir/ritonavir-based HAART: frequency, characterization and risk factors. J Antimicrob Chemother 2005; 55(5): 800-4.
[] [PMID: 15761071]
Rhew DC, Bernal M, Aguilar D, Iloeje U, Goetz MB. Association between protease inhibitor use and increased cardiovascular risk in patients infected with human immunodeficiency virus: a systematic review. Clin Infect Dis 2003; 37(7): 959-72.
[] [PMID: 13130409]
Worm SW, Sabin C, Weber R, et al. Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: the data collection on adverse events of anti-HIV drugs (D:A:D) study. J Infect Dis 2010; 201(3): 318-30.
[] [PMID: 20039804]
Sierra-Madero J, Villasis-Keever A, Méndez P, et al. Prospective, randomized, open label trial of Efavirenz vs Lopinavir/Ritonavir in HIV+ treatment-naive subjects with CD4+<200 cell/mm3 in Mexico. J Acquir Immune Defic Syndr 2010; 53(5): 582-8.
[] [PMID: 20090545]
Rojas J, Lonca M, Imaz A, et al. Improvement of lipoatrophy by switching from efavirenz to lopinavir/ritonavir. HIV Med 2016; 17(5): 340-9.
[] [PMID: 27089862]
De Luca A, Cozzi-Lepri A, Antinori A, et al. Lopinavir/ritonavir or efavirenz plus two nucleoside analogues as first-line antiretroviral therapy: a non-randomized comparison. Antivir Ther (Lond) 2006; 11(5): 609-18.
[PMID: 16964829]
Limsreng S, Marcy O, Ly S, et al. Dyslipidemias and elevated cardiovascular risk on lopinavir-based antiretroviral therapy in cambodia. PLoS One 2016; 11(8)e0160306
[] [PMID: 27579612]
Pacheco AG, Tuboi SH, Faulhaber JC, Harrison LH, Schechter M. Increase in non-AIDS related conditions as causes of death among HIV-infected individuals in the HAART era in Brazil. PLoS One 2008; 3(1)e1531
[] [PMID: 18231611]
Chen WT, Shiu CS, Yang JP, et al. Antiretroviral therapy (ART) side effect impacted on quality of life, and depressive symptomatology: A mixed-method study. J AIDS Clin Res 2013; 4: 218.
[] [PMID: 24083060]
Ministry of Health Working Group on Clinical AIDS Treatment. China free antiretroviral therapy manual. Beijing: People’s Medical Publishing House 2016.
Gomo ZA, Hakim JG, Walker SA, et al. Impact of second-line antiretroviral regimens on lipid profiles in an African setting: the DART trial sub-study. AIDS Res Ther 2014; 11(1): 32.
[] [PMID: 25320632]
Friis-Møller N, Reiss P, Sabin CA, et al. Class of antiretroviral drugs and the risk of myocardial infarction. N Engl J Med 2007; 356(17): 1723-35.
[] [PMID: 17460226]
Grunfeld C. Dyslipidemia and its treatment in HIV infection. Top HIV Med 2010; 18(3): 112-8.
[PMID: 20921577]
Currier JS, Havlir DV. CROI 2018: Complications of HIV Infection and Antiretroviral Therapy. Top Antivir Med 2018; 26(1): 22-9.
[PMID: 29727294]
Zhang F, Dou Z, Ma Y, et al. Effect of earlier initiation of antiretroviral treatment and increased treatment coverage on HIV-related mortality in China: a national observational cohort study. Lancet Infect Dis 2011; 11(7): 516-24.
[] [PMID: 21600849]
Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014; 63(25 Pt B): 2889-934.
[] [PMID: 24239923]
Bekolo CE, Nguena MB, Ewane L, Bekoule PS, Kollo B. The lipid profile of HIV-infected patients receiving antiretroviral therapy in a rural Cameroonian population. BMC Public Health 2014; 14: 236.
[] [PMID: 24606888]
Silva BF, Peixoto G, da Luz SR, de Moraes S, Peres SB. Adverse effects of chronic treatment with the Main subclasses of highly active antiretroviral therapy: a systematic review. HIV Med 2019; 20(7): 429-38.
[] [PMID: 31006976]
Trevillyan JM, Wong G, Puls R, et al. Changes in plasma lipidome following initiation of antiretroviral therapy. PLoS One 2018; 13(8)e0202944
[] [PMID: 30157268]
Guo F, Hsieh E, Lv W, et al. Cardiovascular disease risk among Chinese antiretroviral-naïve adults with advanced HIV disease. BMC Infect Dis 2017; 17(1): 287.
[] [PMID: 28427339]
Hsue PY. Mechanisms of Cardiovascular Disease in the Setting of HIV Infection. Can J Cardiol 2019; 35(3): 238-48.
[] [PMID: 30825947]
Laurence J, Elhadad S, Ahamed J. HIV-associated cardiovascular disease: importance of platelet activation and cardiac fibrosis in the setting of specific antiretroviral therapies. Open Heart 2018; 5(2)e000823
[] [PMID: 30018781]
Bourgi K, Wanjalla C, Koethe JR. Inflammation and metabolic complications in HIV. Curr HIV/AIDS Rep 2018; 15(5): 371-81.
[] [PMID: 30058057]
Funderburg NT, Mehta NN. Lipid Abnormalities and Inflammation in HIV Inflection. Curr HIV/AIDS Rep 2016; 13(4): 218-25.
[] [PMID: 27245605]
Lake JE, Currier JS. Metabolic disease in HIV infection. Lancet Infect Dis 2013; 13(11): 964-75.
[] [PMID: 24156897]
Taramasso L, Tatarelli P, Ricci E, et al. Improvement of lipid profile after switching from efavirenz or ritonavir-boosted protease inhibitors to rilpivirine or once-daily integrase inhibitors: results from a large observational cohort study (SCOLTA). BMC Infect Dis 2018; 18(1): 357.
[] [PMID: 30064371]
Strehlau R, Coovadia A, Abrams EJ, et al. Lipid profiles in young HIV-infected children initiating and changing antiretroviral therapy. J Acquir Immune Defic Syndr 2012; 60(4): 369-76.
[] [PMID: 22134152]
Ballocca F, Gili S, D’Ascenzo F, et al. HIV infection and primary prevention of cardiovascular disease: Lights and shadows in the HAART Era. Prog Cardiovasc Dis 2016; 58(5): 565-76.
[] [PMID: 26943980]
Adal M, Howe R, Kassa D, Aseffa A, Petros B. Associations of gender and serum total cholesterol with CD4+ T cell count and HIV RNA load in antiretroviral-naïve individuals in Addis Ababa. BMC Public Health 2018; 18(1): 943.
[] [PMID: 30064395]
Krikke M, Tesselaar K, van den Berk GEL, et al. The effect of switching protease inhibitors to raltegravir on endothelial function, in HIV-infected patients. HIV Clin Trials 2018; 19(2): 75-83.
[] [PMID: 29770748]
Lagathu C, Béréziat V, Gorwood J, et al. Metabolic complications affecting adipose tissue, lipid and glucose metabolism associated with HIV antiretroviral treatment. Expert Opin Drug Saf 2019; 18(9): 829-40.
[] [PMID: 31304808]
Apostolova N, Blas-Garcia A, Galindo MJ, Esplugues JV. Efavirenz: What is known about the cellular mechanisms responsible for its adverse effects. Eur J Pharmacol 2017; 812: 163-73.
[] [PMID: 28690189]
Li H, Marley G, Ma W, et al. The role of ARV associated adverse drug reactions in influencing adherence among HIV-infected individuals: A systematic review and qualitative meta-synthesis. AIDS Behav 2017; 21(2): 341-51.
[] [PMID: 27613645]
Matoga MM, Hosseinipour MC, Aga E, et al. Hyperlipidaemia in HIV-infected patients on lopinavir/ritonavir monotherapy in resource-limited settings. Antivir Ther (Lond) 2017; 22(3): 205-13.
[] [PMID: 27740537]
Pefura Yone EW, Kengne AP, Ashuntantang G, Betyoumin AF, Ngogang J. Dyslipidaemia in HIV-1-infected patients receiving protease inhibitors after initial treatment with first-line-based non-nucleoside reverse transcriptase inhibitors: a cross-sectional study. BMJ Open 2012; 2(4): 2.
[] [PMID: 22874631]
Oh J, Hegele RA. HIV-associated dyslipidaemia: pathogenesis and treatment. Lancet Infect Dis 2007; 7(12): 787-96.
[] [PMID: 18045561]
Burkholder GA, Muntner P, Zhao H, et al. Low-density lipoprotein cholesterol response after statin initiation among persons living with human immunodeficiency virus. J Clin Lipidol 2018; 12(988- 998): e985.
Grinspoon S. Novel Mechanisms and Anti-Inflammatory Strategies to Reduce Cardiovascular Risk in Human Immunodeficiency Virus. Trans Am Clin Climatol Assoc 2018; 129: 140-54.
[PMID: 30166708]
Loelius SG, Lannan KL, Blumberg N, Phipps RP, Spinelli SL. The HIV protease inhibitor, ritonavir, dysregulates human platelet function in vitro. Thromb Res 2018; 169: 96-104.
[] [PMID: 30031293]
So-Armah K, Freiberg MS. HIV and cardiovascular disease: Update on clinical events, special populations, and novel biomarkers. Curr HIV/AIDS Rep 2018; 15(3): 233-44.
[] [PMID: 29752699]
McCrary AW, Nduka CU, Stranges S, Bloomfield GS. Features of cardiovascular disease in low-income and middle-income countries in adults and children living with HIV. Curr Opin HIV AIDS 2017; 12(6): 579-84.
[] [PMID: 28799999]
Sinha A, Feinstein MJ. Coronary artery disease manifestations in HIV: What, how, and why. Can J Cardiol 2019; 35(3): 270-9.
[] [PMID: 30825949]
Ahmed D, Roy D, Cassol E. Examining relationships between metabolism and persistent inflammation in HIV patients on antiretroviral therapy. Mediators Inflamm 2018; 20186238978
[] [PMID: 30363715]
Feingold KR, Grunfeld C. The Effect of Inflammation and Infection on Lipids and Lipoproteins. In: Endotext. Edited by Feingold KR, Anawalt B, Boyce A, et al. South Dartmouth (MA); 2000.
Phan BAP, Weigel B, Ma Y, et al. Utility of 2013 american college of cardiology/American heart association cholesterol guidelines in HIV-infected adults with carotid atherosclerosis. Circ Cardiovasc Imaging 2017; 10(7): 10.
[] [PMID: 28674084]
Boccara F. Cardiovascular health in an aging HIV population. AIDS 2017; 31(Suppl. 2): S157-63.
[] [PMID: 28471946]
Glesby MJ. Cardiovascular complications of HIV infection. Top Antivir Med 2017; 24(4): 127-31.
[PMID: 28208120]
Uthman OA, Nduka C, Watson SI, et al. Statin use and all-cause mortality in people living with HIV: a systematic review and meta-analysis. BMC Infect Dis 2018; 18(1): 258.
[] [PMID: 29866059]
Roever L, Resende ES, Diniz ALD, et al. Statins in adult patients with HIV: Protocol for a systematic review and network meta-analysis. Medicine (Baltimore) 2018; 97(15)e0116
[] [PMID: 29642140]
Lundgren J, Mocroft A, Ryom L. Contemporary protease inhibitors and cardiovascular risk. Curr Opin Infect Dis 2018; 31(1): 8-13.
[] [PMID: 29232276]
Hyle EP, Mayosi BM, Middelkoop K, et al. The association between HIV and atherosclerotic cardiovascular disease in sub-Saharan Africa: a systematic review. BMC Public Health 2017; 17(1): 954.
[] [PMID: 29246206]
Pinto DSM, da Silva MJLV. Cardiovascular Disease in the Setting of Human Immunodeficiency Virus Infection. Curr Cardiol Rev 2018; 14(1): 25-41.
[] [PMID: 29189172]
Levy ME, Greenberg AE, Magnus M, Younes N, Castel A. Evaluation of statin eligibility, prescribing practices, and therapeutic responses using ATP III, ACC/AHA, and NLA dyslipidemia treatment guidelines in a large urban cohort of HIV-infected outpatients. AIDS Patient Care STDS 2018; 32(2): 58-69.
[] [PMID: 29561173]
Dekkers CC, Westerink J, Hoepelman AIM, Arends JE. Overcoming obstacles in lipid-lowering therapy in patients with HIV - A systematic review of current evidence. AIDS Rev 2018; 20(4): 205-19.
[PMID: 30548018]
Dimala CA, Blencowe H, Choukem SP. The association between antiretroviral therapy and selected cardiovascular disease risk factors in sub-Saharan Africa: A systematic review and meta-analysis. PLoS One 2018; 13(7)e0201404
[] [PMID: 30059546]

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Year: 2019
Published on: 04 December, 2019
Page: [324 - 334]
Pages: 11
DOI: 10.2174/1570162X17666191025115508
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