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ORIGINAL ARTICLE
Year : 2021  |  Volume : 14  |  Issue : 2  |  Page : 162-165  

A Follow-up Study to Evaluate Lipids as Cost-Effective Markers in HIV-Infected Patients on Antiretroviral Therapy


Department of Biochemistry, Armed Forces Medical College, Pune, Maharashtra, India

Date of Submission24-Feb-2020
Date of Decision14-Jul-2020
Date of Acceptance27-Jul-2020
Date of Web Publication3-Mar-2021

Correspondence Address:
Pratibha Misra
Department of Biochemistry, Armed Forces Medical College, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_60_20

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  Abstract 


Background: Human immunodeficiency virus (HIV) infection per se and antiretroviral therapy (ART) both are associated with dyslipidemias, one of the important risk factors in the development of premature atherosclerosis and coronary artery disease. Certain classes of highly active antiretroviral therapy (HAART), especially protease inhibitors, are more frequently associated with dyslipidemia. The objectives of this study were to evaluate and compare lipid profile – total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglyceride in HIV patients before and after starting ART and also to correlate lipid profile and CD4 counts in HIV infection, thus evaluating the feasibility of using lipid profile to monitor the progression of infection in HIV-infected patients as an adjunct to CD4 counts in resource-limited settings. Methods: Paired samples of 100 newly diagnosed HIV patients were taken before and after treatment with HAART. CD4 cell counts and lipid parameters measured and compared using paired 't'-test. Each of the lipid parameter correlated with CD4 cell count. Results: Significant increase was seen in the levels of TC and HDL-C (P < 0.05) with treatment. CD4 cell count also showed a significant increase (P < 0.05) with therapy. HDL-C levels correlated significantly with CD4 cell counts in pretreatment group (r = 0.23, P = 0.020, 95% C.I.). Conclusion: Combination of zidovudine, lamivudine, and nevirapine is associated with significant increase in HDL-C. HDL-C levels are a good indicator of disease severity in HIV-infected patients before starting the therapy.

Keywords: Cardiovascular diseases, highly active antiretroviral therapy, human immunodeficiency virus-infected patients, lipid profile


How to cite this article:
Parmar A, Saha TK, Somani BL, Misra P. A Follow-up Study to Evaluate Lipids as Cost-Effective Markers in HIV-Infected Patients on Antiretroviral Therapy. Med J DY Patil Vidyapeeth 2021;14:162-5

How to cite this URL:
Parmar A, Saha TK, Somani BL, Misra P. A Follow-up Study to Evaluate Lipids as Cost-Effective Markers in HIV-Infected Patients on Antiretroviral Therapy. Med J DY Patil Vidyapeeth [serial online] 2021 [cited 2021 Nov 28];14:162-5. Available from: https://www.mjdrdypv.org/text.asp?2021/14/2/162/310713




  Introduction Top


Highly active antiretroviral therapy (HAART) has miraculously increased the life expectancy of human immunodeficiency virus (HIV)-infected patients.[1] CD4 cell count and viral loads are used to monitor the infection.[2] The lifelong therapy has led to the emergence of metabolic abnormalities, the most common being dyslipidemias, an important risk factor in the development of coronary artery disease (CAD). Certain classes of antiretroviral drugs are more commonly associated with dyslipidemias, especially protease inhibitors, as compared to others.[3] Recently, the data collection of adverse events of anti-HIV drugs study, conducted in 11 cohorts in Europe, Australia, and the United States, reported a 32% increase in the relative risk of CAD over a period of 5 years following initiation of HAART.[4] Several cross-sectional studies have also shown increased carotid intima–media thickness (IMT).[4],[5] In a case–control study by Lorenz et al., IMT values were found to be 24% greater at carotid bifurcation in HIV patients on HAART.[6] The primary objective of this study was to evaluate and compare the lipid profile in HIV patients before and after starting ART. The specific objective was to correlate lipid profile and CD4 counts in HIV infection. The secondary objective was to evaluate the feasibility of using lipid profile to monitor the progression of infection in HIV-infected patients as an adjunct to CD4 counts as this could prove to be more cost-effective in countries with poor resources.


  Materials and Methods Top


The study was carried out in the department of biochemistry of a medical college between December 2011 and July 2013. The therapy was started by following the WHO 2010 criteria.[7] Patients were treated with a combination of zidovudine, lamivudine, and nevirapine (2 NRTIs + 1 NNRTI). All 100 newly diagnosed consecutive HIV-infected consecutive patients, who reported at the ART center during 1½ years of the study period, were enrolled in the study from the ART center of the institution after complete history taking and detailed clinical examination. These patients were subjected to following exclusion criteria: patients on lipid-lowering drugs, body mass index (BMI) >30 kg/m2, diabetes mellitus, preexisting renal or liver disease, and any active opportunistic infection. The complete workup of the patient is being done at the ART center. Both history and investigations (C-reactive protein, hemoglobin, total Leukocyte Count, differential Leucocyte Count, and biochemical profile) were taken into account for exclusion criteria. Informed consent was obtained before their recruitment. Baseline blood samples were collected through a clean venepuncture after 12 h. Overnight fast for the estimation of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), and CD4 cell counts after which the treatment was started. Six months after treatment, samples were taken for repeat measurements of the above parameters.

The study was approved by the institutional ethical committee (IEC No is 2248/MRU/IEC/2011-NA).

Biochemical investigations

Enzymatic methods were used to measure the three lipid parameters on fully automated analyzer ERBA XL-600. TC was estimated by cholesterol oxidase-peroxidase method. HDL-C was measured by cholesterol oxidase and cholesterol esterase method (based on modified polyvinyl sulfonic acid and polyethylene glycol methyl ether coupled classic precipitation methods). TG estimation was done by glycerol phosphate oxidase-peroxidase methods. CD4 cell count was estimated by flow cytometry using BD FACS COUNTER.

Statistical analysis

Data were entered in Microsoft Excel and analyzed using SPSS Statistics for Windows, Version;17.0.Chicago: SPSS;Inc. Descriptive statistics were expressed as mean ± standard deviation (SD). Paired t-test was used to find the statistical significance between pre-HAART and post-HAART groups. Spearman rank correlation coefficient was used to correlate the three lipid parameters with CD4 cell count.


  Results Top


Of a total of 100 subjects enrolled in the study, 52 were males and 48 were females. The mean age (±SD in years) was 33.3 (±8.4) and mean BMI (±SD in kg/m2) was 20.46 (±4.432).

When the pre- and post-treatment parameters were compared [Table 1], it was observed that there was a significant increase in TC and HDL-C (P < 0.05). Although the TG levels were higher in 65 out of 100 subjects in the post-HAART group, the difference was not statistically significant (P > 0.05). There was also a significant increase in CD4 cell count (P < 0.05) in the post-HAART group.
Table 1: Comparison of total cholesterol, triglyceride, high-density lipoprotein-cholesterol, and CD4 cell counts in pre- and post-treatment human immunodeficiency virus-infected individuals on antiretroviral therapy

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The three lipid parameters studied were also correlated with the CD4 cell counts, the gold standard for monitoring HIV infection.[2] The HDL-C levels correlated weakly with the CD4 cell counts (r = 0.232, P = 0.020, 95% of C.I.) in the pretreatment group [Table 2].
Table 2: Correlation of lipid parameters with CD4 cell counts by Spearman correlation test

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  Discussion Top


The present study found predominant changes in lipid profile associated with three-drug regimen (2 NRTIs + 1NNRTI) in HIV patients. A statistically significant increase in CD4 cell counts (P < 0.05) was found after treatment, which shows an adequate response to therapy.[2] There was a significant increase in TC and HDL-C levels [Figure 1] following the treatment, which is in accordance with many of the previous studies.[8],[9],[10],[11] The rise in TC can be attributed to the rise in HDL-C fraction, as the mean rise in both TC and HDL-C after therapy was approximately 35 mg/dL. The increase in the level of HDL-C can be explained by the stimulation of ApoA-I production by nevirapine.[12],[13] The increased levels of HDL-C may be protective against HIV infection as Apo A-I of HDL inhibits the formation of syncytium between the virus and CD4 T-lymphocytes, thereby preventing the cytopathic effects of the virus.[14] Experiments in animal models have shown that the treatment with Apo A-I results in a decrease in monocyte chemotactic protein-1 (MCP-1) which is required for the interaction of monocyte with endothelial cell.[15] This is one of the earliest processes in the pathogenesis of atherosclerosis.[16],[17] HDL-C has also been shown to exert an antioxidant effect through enzyme paraoxonase-1, which is primarily responsible for retarding the oxidation of LDL.[18] This leads to a reduced stimulation of MCP-1 production by endothelial cells, which is mediated by oxidized LDL.[19] Thus, an increase in HDL-C in HIV patients treated with the HAART regimen (zidovudine + lamivudine + nevirapine) provides a protective response against dyslipidemia.
Figure 1: Comparison of total cholesterol, triglyceride, high-density lipoprotein cholesterol, and CD4 cell counts in pre- and post-treatment HIV-infected individuals on antiretroviral therapy

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In our study, the rise in TG levels after therapy was not found to be statistically significant (P > 0.05). This may be due to a reduction in cytokine activation as a result of therapy.[20] This finding is supported by an earlier study, in which HIV patients on nevirapine had a smaller increase in TG levels as compared to a larger increase in HDL-C levels.[9] Another Swiss HIV Cohort study also demonstrated a decrease in TG in those treated with nevirapine.[21] Mildvan et al. had reported decreased TG levels in HIV patients on treatment with zidovudine.[20] Another study reported that a high proportion of HIV-infected patients had a low HDL-C level after 1 year of NVP-based ART.[22] This finding is in contrast to the findings of our present study.

Furthermore, weak but significant correlation was found for HDL-C levels with the CD4 cell counts in the pretreatment group. This is in accordance with the earlier studies where HDL-C has been found to be a good marker of disease progression in HIV-infected individuals.[13],[23]


  Conclusion Top


We conclude that the use of zidovudine and nevirapine does not lead to dyslipidemias in the HIV-infected patients who are treated with this combination ART. This helps to reduce cardiovascular comorbidity associated with long-term ART in these patients, thus improving their quality of life. The study has also shown altered levels of the HDL-C in response to therapy. However, its role as a cost-effective potential marker for prediction of severity of HIV infection, especially in developing countries with limited resources, needs further evaluation. More studies with larger sample size and longer follow-up are required to support these findings.

Acknowledgments

We would like to acknowledge the contribution of the health workers of ART center of our institution for their help at each and every step during the study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Katz IT, Maughan-Brown B. Improved life expectancy of people living with HIV: who is left behind? Lancet HIV 2017;4:e324-6.  Back to cited text no. 1
    
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Fauci AS, Clifford H. Human immunodeficiency virus disease: AIDS and related disorders. In: Harrison's Principles of Internal Medicine. 20th ed.. USA: McGraw-Hill Publishing; 2018. p. 1393-463.  Back to cited text no. 2
    
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Friis-Møller N, Thiébaut R, Reiss P, et al. Predicting the risk of cardiovascular disease in HIV-infected patients: The data collection on adverse effects of anti-HIV drugs study. Eur J Cardiovasc Prev Rehabil 2010;17:491-501.  Back to cited text no. 3
    
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Currier JS, Kendall MA, Henry WK, Alston-Smith B, Torriani FJ, Tebas P, et al. Progression of carotid artery intima–media thickening in HIV-infected and uninfected adults. AIDS 2007;21:1137-45.  Back to cited text no. 4
    
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Lebech AM, Wiinberg N, Kristoffersen US, Hesse B, Petersen CL, Gerstoft J, et al. Carotid intima–media thickness in HIV patients treated with antiretroviral therapy. Clin Physiol Funct Imaging 2007;27:173-9.  Back to cited text no. 5
    
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Lorenz M W, Stephan C, et al. Both long-term HIV infection and highly active antiretroviral therapy are independent risk factors for early carotid atherosclerosis. Atherosclerosis. 2008;196(2):720-26. Doi:10.1016/j.atherosclerosis.2006.12.022.  Back to cited text no. 6
    
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Tohyama J, Billheimer JT, Fuki IV, Rothblat GH, Rader DJ, Millar JS. Effects of nevirapine and efavirenz on HDL cholesterol levels and reverse cholesterol transport in mice. Atherosclerosis 2009;204:418-23.  Back to cited text no. 8
    
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Van Leth F, Phanuphak P, Stroes E, Gazzard B, Cahn P, Raffi F, et al. Nevirapine and efavirenz elicit different changes in lipid profiles in antiretroviral-therapy-naive patients infected with HIV-1. PLoS Med 2004;1:e19.  Back to cited text no. 9
    
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Van der Valk M, Kastelein JJ, Murphy RL, van Leth F, Katlama C, Horban A, et al. Nevirapine-containing antiretroviral therapy in HIV-1 infected patients results in an anti-atherogenic lipid profile. AIDS 2001;15:2407-14.  Back to cited text no. 10
    
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Fontas E, Van Leth F, Sabin CA, Friis-Møller N, Rickenbach M, d'Arminio Monforte A, et al. Lipid profiles in HIV-infected patients receiving combination antiretroviral therapy: are different antiretroviral drugs associated with different lipid profiles? J Infect 2004;189:1056-74.  Back to cited text no. 11
    
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Franssen R, Sankatsing RR, Hassink E, Hutten B, Ackermans MT, Brinkman K, et al. Nevirapine increases high-density lipoprotein cholesterol concentration by stimulation of apolipoprotein AI production. Arterioscler Thromb Vasc Biol 2009;29:1336-41.  Back to cited text no. 12
    
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Devanath A, Ray S, Kumar R, Prarthana BS. A study to evaluate lipid profile in treatment naïve HIV positive patients. Indian J Clin Biochem 2014;29:45-50.  Back to cited text no. 13
    
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Owens BJ, Anantharamaiah GM, Kahlon JB, Srinivas RV, Compans RW, Segrest JP. Apolipoprotein AI and its amphipathic helix peptide analogues inhibit human immunodeficiency virus-induced syncytium formation. J Clin Invest 1990;86:1142-50.  Back to cited text no. 14
    
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Wang L, Chen WZ, Wu MP. Apolipoprotein AI inhibits chemotaxis, adhesion, activation of THP-1 cells and improves the plasma HDL inflammatory index. J Interferon Cytokine Res 2010;49:194-200.  Back to cited text no. 15
    
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Navab M, Imes SS, Hama SY, Hough GP, Ross LA, Bork RW, et al. Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein. J Clin Invest 1991;88:2039-46.  Back to cited text no. 16
    
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Mackness B, Hine D, Liu Y, Mastorikou M, Mackness M. Paraoxonase-1 inhibits oxidised LDL-induced MCP-1 production by endothelial cells. Biochem Biophys Res Commun 2004;318:680-3.  Back to cited text no. 17
    
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Litvinov D, Mahini H, Garelnabi M. Antioxidant and anti-inflammatory role of paraoxonase 1: implication in arteriosclerosis diseases. North Am J Med Sci 2012;4:523.  Back to cited text no. 18
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Pirillo A, Norata GD, Catapano AL. LOX-1, OxLDL, and atherosclerosis. Mediators Inflamm. 2013;2013:152786.  Back to cited text no. 19
    
20.
Mildvan D, Wilets I, Machado SG, Grossberg SE. Endogenous interferon and triglyceride concentrations to assess response to zidovudine in AIDS and advanced AIDS-related complex. Lancet 1992;339:453-6.  Back to cited text no. 20
    
21.
Young J, Weber R, Rickenbach M, Furrer H, Bernasconi E, Hirschel B, et al. Research article Lipid profiles for antiretroviral-naive patients starting PI-and NNRTI-based therapy in the Swiss HIV Cohort Study. Antivir Ther 2005;10:585-91.  Back to cited text no. 21
    
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Padmapriyadarsini C, Ramesh K, Sekar L, Ramachandran G, Reddy D, Narendran G, et al. Factors affecting high-density lipoprotein cholesterol in HIV-infected patients on nevirapine-based antiretroviral therapy. Ind J Med Res 2017;145:641.  Back to cited text no. 22
    
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Zangerle R, Sarcletti M, Gallati H, Reibnegger G, Wachter H, Fuchs D. Decreased plasma concentrations of HDL cholesterol in HIV-infected individuals are associated with immune activation. J Acquir Immune Defic Syndr 1994;7:1149-56.  Back to cited text no. 23
    


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