|Year : 2019 | Volume
| Issue : 1 | Page : 20-25
Dyslipidemia in HIV infected and AIDS patients: Association of serum lipids with HIV status, a cross-sectional study
Abhishek Singh Nayyar
Department of Oral Medicine and Radiology, Saraswati-Dhanwantari Dental College and Hospital and Post-Graduate Research Institute, Parbhani, Maharashtra, India
|Date of Web Publication||31-Jul-2019|
Dr. Abhishek Singh Nayyar
Reader cum PG Guide, Department of Oral Medicine and Radiology, Saraswati-Dhanwantari Dental College and Hospital and Post-Graduate Research Institute, Parbhani, Maharashtra
Source of Support: None, Conflict of Interest: None
Clinical trial registration Ref no: ABUTH/PGO/COMM/9
Context and Aim: Hematological abnormalities are among the most common complications of infection with human immunodeficiency virus (HIV). There have been quite a few studies on the alterations in lipid profile, too, although the results have largely been inconclusive. The present study was carried out to assess CD4 cell counts and lipid profile in the HIV-infected and AIDS patients in the Indian population and correlate them with the seronegative controls. Materials and Methods: The present study was designed as a cross-sectional, hospital-based study conducted between January 2017 to September 2017 to assess CD4 cell counts and lipid profile in the HIV-infected and AIDS patients in the Indian population and correlate them with the seronegative controls. Evaluation of lipid profile was done using Erba EM 360, an automated analyzer powered by a diffraction grating photometer, whereas CD4 cell counts were evaluated using Partec Cyflow Counter. Statistical Analysis: The data was analyzed using SPSS version 15.0 (SPSS Inc., Chicago, IL, USA). Comparison of the said parameters was done using analysis of variance and post hoc Games-Howell test. P value of <0.05 was considered statistically significant. Results: The levels of total cholesterol and low-density lipoproteins (LDLs) were significantly decreased whereas triglycerides and very LDLs were significantly increased in the HIV-infected and AIDS patients when compared with the seronegative controls. Conclusion: Total cholesterol, LDLs, triglycerides, and very LDLs were significantly altered in the HIV-infected and AIDS patients when compared with the seronegative controls.
Keywords: AIDS, AIDS patients, CD4 cell counts, dyslipidemia, HIV, HIV infected, HIV status, lipid profile, serum lipids
|How to cite this article:|
Nayyar AS. Dyslipidemia in HIV infected and AIDS patients: Association of serum lipids with HIV status, a cross-sectional study. J Med Trop 2019;21:20-5
|How to cite this URL:|
Nayyar AS. Dyslipidemia in HIV infected and AIDS patients: Association of serum lipids with HIV status, a cross-sectional study. J Med Trop [serial online] 2019 [cited 2019 Dec 14];21:20-5. Available from: http://www.jmedtropics.org/text.asp?2019/21/1/20/263742
| Introduction|| |
AIDS is an acronym for acquired immune deficiency syndrome caused by a retrovirus known as human immunodeficiency virus (HIV) that breaks down the body’s immune system leaving the patient vulnerable to a host of life-threatening opportunistic infections, neurological disorders, or unusual malignancies. The two known types of this virus include the HIV-1 and HIV-2 that belong to a family of primate lentiviruses., The pathogenesis of HIV infection is largely attributed to the decrease in the number of T cells (a specific type of lymphocytes) that bear the cluster of differentiation-4+ (CD4+) cell surface receptors. The immune status of an individual infected with HIV/AIDS can be assessed by measuring the absolute number (per mm3) or percentage of CD4+ cells and this is considered as the standard way to assess and characterize the severity of HIV-related immunodeficiency.,, According to estimates by World Health Organization and the Joint United Nations Program on HIV/AIDS, 35 million people were living with HIV globally at the end of the year 2013. The first case of AIDS in India was detected in the year 1986. HIV is transmitted by both homosexual and heterosexual contact, by blood and blood products, by infected mothers to infants via intrapartum or perinatal routes or breast milk, and by occupational transmission. Hematological abnormalities are among the most common complications of infection with HIV., There have been quite a few studies on the alterations in lipid profile, too, although the results have largely been inconclusive as well as the reasons behind such alterations also have remained debatable. A plethora of studies have been conducted correlating CD4 cell counts and hematologic parameters with the lipid profile in the HIV-infected and AIDS patients across different parts of the world; however, very few studies have been reported from India. The present study was carried out with the same intent to assess CD4 cell counts and lipid profile in the HIV-infected and AIDS patients in the Indian population and correlate them with the seronegative controls.
| Materials and methods|| |
The present study was designed as a cross-sectional, hospital-based study conducted between January 2017 to September 2017 to assess CD4 cell counts and lipid profile in the HIV-infected and AIDS patients and correlate them with the seronegative controls. The study population included 1500 patients reporting to the outpatient department divided into three groups based on their CD4 cell counts as follows:
- Control group: consisting of 500 individuals who were healthy controls without any systemic illness.
- HIV group: consisting of 500 patients who were diagnosed as HIV infected.
- AIDS group: consisting of 500 patients diagnosed as AIDS patients.
A written, informed consent was obtained from the patients forming the study sample to participate in the study. Also, the study was sent for approval to the Ethical Committee of the Institution and permission was obtained before the start of the study. The patients who were obese and were on statins, had any kind of obesity-related disorders including diabetes, alcoholics, those on chemotherapy, and pregnant females were excluded from the study because of their possibly weakened immune status as well as in the probability of disturbed lipid profile as a part of their condition or treatment. The patients who did not agree to give consent and were not willing to participate in the study were also excluded from the study. A detailed history was taken for each patient followed by clinical examination performed as per the protocol of Universal Precautions with the help of diagnostic instruments under artificial illumination. The findings were recorded in a specialized proforma and then all the patients were subjected to the phlebotomy procedure in the early morning hours to assess their CD4 cell counts and lipid profile after fasting for 8 h postlast meal.
Evaluation of CD4 cell counts
Fifty microliter of ethylenediaminetetraacetic acid anticoagulated blood was added to 10 μL of monoclonal antibody; after 15 min of incubation, 1 mL of No Lyse dilution buffer was added and the sample tube was attached to the Partec Cyflow Counter (Sysmex Partec GmbH, Am Flugplatz, Goerlitz, Germany) [Figure 1] for an automated evaluation of CD4 cell counts in the collected samples.
Evaluation of lipid profile, total cholesterol, triglycerides, HDLs, LDLs, and VLDLs
Evaluation of lipid profile was done using Erba EM 360 (ERBA Diagnostics Mannheim GmbH, Mallaustrasse, Mannheim, Germany) [Figure 2], an automated chemistry analyzer powered by a diffraction grating photometer.
The data was analyzed using SPSS version 15.0 (SPSS Inc., Chicago, IL, USA). Comparison of the said parameters was done using analysis of variance and post hoc Games-Howell test. P value of <0.05 was considered statistically significant.
| Results|| |
The present study was designed as a cross-sectional, hospital-based study to assess CD4 cell counts and lipid profile in the HIV-infected and AIDS patients and correlate them with the seronegative controls. The distribution of patients based on age and gender as well as the distribution of male and female patients based on age is shown in [Table 1]. In the present study, the mean CD4 cell count in the control group was found to be 1125.38 whereas in the HIV group, it was seen to be 501.35 and in the AIDS group was 256.41, dropping down significantly with the P value being <0.001 as the HIV infection progressed to full-blown AIDS [Table 2] and [Graph 1]. Furthermore, on analyzing the lipid profile in patients, a mean cholesterol level of 219.49 was observed in the control group with a mean of 219.29 in the HIV and 200.18 in the AIDS groups. The results were found to be statistically significant in this case too with the P value being <0.001 [Table 3]. In case of triglycerides also, the results came out to be statistically significant with a mean triglycerides level of 158.23 in the control group against a mean value of 140.88 in the HIV and 167.43 in the AIDS groups [Table 3]. For low-density lipoproteins (LDLs), a mean LDL level of 144.09 was observed in the control group with a mean of 138.47 in the HIV and 119.28 in the AIDS groups; again, the results were significant with a P value of <0.001 [Table 3]. In case of very low-density lipoproteins (VLDLs), a mean VLDL level of 32.55 was observed in the control group with a mean of 32.08 in the HIV and 37.27 in the AIDS groups; the results were again found to be significant with the P value being <0.001 [Table 3]. The P value in case of high-density lipoproteins (HDLs), though, was not found to be statistically significant [Table 3]. To summarize, the levels of total cholesterol and LDLs were significantly decreased whereas triglycerides and VLDLs significantly increased in the HIV-infected and AIDS patients when compared with the seronegative controls.
|Table 3: Evaluation of lipid profile and their mean comparison between the groups|
Click here to view
| Discussion|| |
The mean CD4 cell count in the control group in the present study was found to be 1125.38 whereas it was 501.35 in the HIV group and 256.41 in the AIDS group dropping down significantly with the P value being <0.001 as the HIV infection progressed to full-blown AIDS. The gradual decrease in the CD4 cell counts observed in the HIV-infected and AIDS patients in the present study when compared to the controls were still higher than the mean values observed in the studies conducted by Pasupathi et al.,, who, in their two studies, recorded a mean CD4 cell count of 394 in the HIV-infected and 191 in the AIDS groups and 375 in the HIV-infected and 150 in the AIDS groups, respectively, although the results obtained were found to be in accordance with the results of the study conducted by Tiwari et al. who recorded a mean value of 281 cells/mm3 in the HIV patients. The reason for the higher values obtained in the present study as compared to most of the studies might be due to the difference in the classification of the patients into HIV-infected and AIDS patients based on the CD4 cell counts. In the present study, the HIV-infected and AIDS patients were categorized based on their CD4 cell counts with 10 to 350 and 350 to 500 cells/mm3 of blood. Tiwari et al. hypothesized that the fall in CD4 cell counts seen in HIV infection could be due to disruption of the cell membranes of the said cells brought out by the budding of the infecting virus from the surface of the cells as well as the intracellular accumulation of the heterodisperse RNAs and unintegrated DNAs with the progression of the disease process. Furthermore, it has also been proposed that an intracellular complexing of CD4 cells with the viral envelope products results in cell killing. Similarly, Tiwari et al. also proposed untimely induction of a programmed cell death (apoptosis) as an additional mechanism for CD4 cell loss in HIV infection.
Pertaining to the lipid profile in the HIV-infected and AIDS patients, the results of the present study showed that the levels of total cholesterol and LDLs significantly decreased whereas triglycerides and VLDLs significantly increased in the HIV-infected and AIDS patients when compared with the seronegative controls. Hypertriglyceridemia and a decrease in total cholesterol and HDL cholesterol occurring in advanced phases of HIV infection are considered as markers of a chronic inflammatory process as proposed by Grunfeld and Shor-Posner et al. However, it has also been proposed that highly active antiretroviral therapy leads to lipid changes with increases in both triglycerides and total cholesterol. Various studies have shown an association between the use of protease inhibitors (PIs) and dyslipidemia. Young et al. concluded that HDL cholesterol levels increase whereas triglycerides levels decrease with increasing exposure to nonnuclear reverse transcriptase inhibitors-based therapy. Similarly, triglycerides levels increase with increasing exposure to PI-based therapy. This might be one of the possible reasons for the patients in the present study to have increased triglycerides levels as the patients in the present study were on PIs.
Infections have also been proposed to increase plasma triglycerides levels by decreasing the clearance of circulating lipoproteins, a process considered to be the result of reduced lipoprotein lipase, or by stimulating hepatic lipid synthesis through increases in either hepatic fatty acid synthesis or reesterification of fatty acids derived from lipolysis. Other factors that might contribute to dyslipidemia in HIV infection are altered cytokine profile, decreased lipid clearance, and an increased hepatic synthesis of VLDLs. Cytokines such as tumor necrosis factor alpha and interleukin-6 appear to promote lipid peroxidation besides endothelial and platelet cell activation and the production of reactive oxygen species. An increase in serum triglycerides levels is observed in HIV-infected patients as the disease progresses, particularly in the presence of opportunistic infections that might be possibly due to an increase in the levels of inflammatory cytokines (tumor necrosis factor alpha, interleukins, and interferon alpha) and steroid hormones. The lower the CD4+ lymphocyte levels in peripheral blood are seen, the higher are the levels of triglycerides and the lower are the levels of total cholesterol and LDL cholesterol. In contrast, lower levels of LDL cholesterol are found in HIV-infected patients regardless of their CD4+ T-lymphocyte counts. A study by Crook also showed that HIV infection is normally associated with hypocholesterolemia, hypertriglyceridemia, and low plasma HDL cholesterol levels. Another study by Pynka et al., however, showed that there was no significant difference in total cholesterol and LDL levels between HIV-infected and healthy controls.
The results of the present study were also in accordance with the results of the study conducted by Iffen et al. who concluded from their study an increase in the triglycerides and VLDL cholesterol in HIV-infected patients compared to the controls. The probable reason given by Iffen et al. for the increase in triglycerides and VLDL cholesterol levels in their study was that increased tumor necrosis factor and other cytokines that occur during the said infection increase lypolysis and insulin resistance. Insulin regulates the uptake of glucose into the skeletal muscle tissue and other cells in the body. As insulin sensitivity decreases in HIV-infected patient with reduction in CD4 cell counts and uptake of glucose into the skeletal muscle tissue, and other cells is reduced leading to increased free fatty acids in the circulation and reduced storage of triglycerides in the adipose tissues. These free fatty acids return to the liver where they are sent back into circulation as triglycerides. Thus, significantly higher triglyceride levels are seen among HIV seropositives compared to the seronegative controls. VLDLs are composed predominantly of triglycerides. That is the reason for VLDL to be elevated when the levels of triglycerides are increased.
According to El- Sadir, patients with lower CD4 cell counts of below 200 cells/mm3 of blood were associated with the elevation in VLDL cholesterol and triglycerides levels (P < 0.05). This observation was found to be in agreement with the findings from the present study. VLDL cholesterol carries fats around the body and elevation can increase the risk of heart disease. Similarly, Grunfeld also observed decreased total cholesterol levels in both HIV-infected and AIDS patients.
The results of the present study were also found to be in agreement with the results of the study conducted by Pasupathi et al. who observed decrease in serum levels of total cholesterol and LDL cholesterol and increase in levels of triglycerides and VLDL cholesterol in HIV-infected and AIDS patients when compared to the controls against the results obtained in the study conducted by Akpa et al., who found increased mean total cholesterol and LDL but decreased triglycerides and HDL levels, and Adewole et al., who observed increased total cholesterol, triglycerides, and HDL levels in HIV-positive patients when compared with HIV-negative patients. The probable reason for lack of association might be related to the close similarity in the CD4 cell counts as most patients were in the CD4 cell count range of 50 to 220 cells/mm3 of blood.
Likewise, Rogowska-Szadkowska and Borzuchowska and Ducobu and Payen, who determined the levels of plasma triglycerides, total cholesterol, and HDL cholesterol levels in HIV-infected patients by the level of immunological deficiency according to the CD4 cell counts, also concluded that with an increase in the immunological deficiency and clinical development of HIV infection, lipid profile disorders indicated by an increase in triglycerides levels and decreased concentrations of HDL cholesterol levels intensified. The results of the present study, too, in the same line showed that HIV infection induced an early decrease of cholesterol and a late increase of triglycerides levels with a reduction of HDL levels. Ducobu and Payen and Crook and Mir, however, reported that patients with AIDS had increased levels of LDL cholesterol contradicting the findings obtained in the present study. Contrary to this, Shor-Posner et al. reported significantly low levels of total cholesterol, HDL, and LDL in HIV-infected patients in agreement with the results of the present study.
Limitations of the present study
One of the major limitations of the present study included the duration of the disease process that was not considered, whereas the present study did not take into consideration the pre-ART and antiretroviral therapy (ART) patients distinguishing between the patients as this was not a longitudinal study where a patient follow-up could be done. Any coexisting disease processes that could have been significant in affecting the lipid profile in the patients can also be considered in the future studies, which could be another possible limitation of the present study.
| Conclusion|| |
Within the constraints of the limitations, the present study concluded that total cholesterol, LDLs, triglycerides, and VLDLs were significantly altered in the HIV-infected and AIDS patients when compared with the seronegative controls. Further studies are, thus, mandated from across the country with correlation analyses to come to valid conclusions and manage this deadly, infectious disease process.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Khiangte L, Vidyabati RK, Singh MK, Devi SB, Singh TR, Singh WG. A study of serum lipid profile in human immunodeficiency virus (HIV) infected patients. J Indian Acad Clin Med 2007;8:307-11.
Ananthanarayan R, Paniker CKJ. Human immunodeficiency virus: AIDS. Textbook of Microbiology. 7th ed. New Delhi: Universities Press 2005.
Abbas AK. Diseases of immunity. Robbins and Cotran Pathologic Basis of Disease. 7th ed. Philadelphia: Elsevier Saunders 2005.
Coyle TE. Hematologic complications of human immunodeficiency virus infection and the acquired immunodeficiency syndrome. Med Clin North Am 1997;81:449-70.
Pasupathi P, Manivannan P, Manivannan U, Mathiyalagan D. Thyroid function, cardiac risk assessment profile and hematological changes during HIV infection and AIDS patients. J Med 2010;11:131-6.
Pranitha SS, Kulkarni MH. Hematological changes in HIV infection with correlation to CD4 cell count. Aust Med J 2012;5:157-62.
HIV sentinels surveillance: 2010-11. National AIDS Control Organization, 2012, New Delhi, India.
Fauci AS, Lane HC. Human immunodeficiency disease (HIV): AIDS and related disorders. In: Braunwald E, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors. Harrison’s Principles of Internal Medicine. 14th ed. New York, NY: McGraw-Hill 1998.
Pasupathi P, Bakthavathsalam G, Saravanan G, Devaraj A. Changes in CD4 cell count, lipid profile and liver enzymes in HIV infection and AIDS patients. J Appl Biomed 2008;6:139-45.
Tiwari BR, Ghimire P, Malla S. Study on CD4 cell responses in HIV. Nepal Med Coll J 2008;10:45-7.
Grunfeld C. Dyslipidemia and Its treatment in HIV infection. Topics HIV Med 2010;18:112-8.
Shor-Posner G, Basit A, Lu Y, Cabrejos C, Chang J, Fletcher M et al.
Hypocholesterolemia is associated with immune dysfunction in early human immunodeficiency virus-1 infection. Am J Med 1993;94:515–9.
Pasupathi P, Ramachandran T, Sindhu P, Saravanan G, Bakthavathsalam G. Enhanced oxidative stress markers and antioxidant imbalance in HIV infection and AIDS patients. J Sci Res 2009;1:370-80.
Young J, Weber R, Rickenbach M, Furrer H, Bernasconi E, Hirschel B et al.
Lipid profiles for anti-retroviral naive patients starting PI- and NN-RTI based therapy in the Swiss HIV cohort study. Antivir Ther 2005;10:585-91.
Souza SJ, Luzia LA, Santos SS, Helen P. Lipid profile of HIV infected patients in relation to anti-retroviral therapy: a review. Rev Assoc Med Bras 2013;59:186-98.
Crook M. The basis and management of metabolic abnormalities associated with cardiovascular risk in human immunodeficiency virus infection and its treatment. Ann Clin Biochem 2007;44:219-31.
Pynka ML, Bauder D, Pynka S, Boron-Kaizmarsk A. HIV/AIDS. HIV/AIDS Rev 2004;2:35-8.
Iffen TS, Efobi H, Usoro CAO, Udonwa NE. Lipid profile of HIV positive patients attending University of Calabar Teaching Hospital, Nigeria. World J Med Sci 2010;5:89-93.
El- Sadir WM. Effects of HIV disease on lipid, glucose and insulin levels: results from a large anti-retroviral naive cohort. HIV Med 2005;6:114-21.
Akpa MR, Agomouh DI, Alasia DD. Lipid profile of healthy adult Nigerians in Port Harcourt, Nigeria. Niger J Med 2006;15:137-40.
Adewole OO, Eze S, Betiku Y, Anteyi E, Wada I, Ajuwon Z et al.
Lipid profile in HIV/AIDS patients in Nigeria. J Afr Health Sci 2010;10:144-9.
Rogowska-Szadkowska D, Borzuchowska A. The levels of triglycerides, total cholesterol and HDL cholesterol in various stages of human immunodeficiency virus (HIV) infection. Pol Arch Med Wewn 1999;101:145-50.
Ducobu J, Payen MC. Lipids and AIDS. Rev Med Brux 2000;21:11-7.
Crook MA, Mir N. Abnormal lipids and the acquired immune deficiency syndrome: is there a problem and what should we do about it. Int J STD AIDS 1999;10:353-6.
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3]