A Study of Lipid Abnormalities in Human Immunodeficiency Virus Infected Individuals
- K.G. Suresha , Senior Specialisthod Dept Of Medicine K. C. General Hospital Malleshwaram. Bengaluru
- Rekha.S , Assistant Professor Dept Of Medicine. Senior Specialist DNB PG Teaching Faculty. Mandya Institute Of Medical Science Mandya Karnataka
- Ausali. Ranadheer , Resident Dept of General Medicine K. C. General Hospital Malleshwaram Bengaluru
- Kavyashree C.V. , Senior Specialist Dept Of Microbiology Dnb Institute K.C.General Hospital Malleshwaram Bengaluru
Article Information:
Abstract:
Introduction HIV is a lentivirus (a subgroup of retrovirus) that causes AIDS, a condition in humans which causes a progressive failure of the immune system that leads to life threatening opportunistic infection and cancers. Without treatment the average survival time after infection with HIV is estimated to be 9 – 11 years. Dyslipidemias, or disorders of lipoprotein and lipid metabolism, are metabolic abnormalities that cause a chronic rise in cholesterol and triglyceride (TG) levels in the blood. Raised total cholesterol (TC), high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), and increased TG are all involved. Methods And Materials: 90 HIV diagnosed patients in K C General hospital were selected and the study was conducted during the year 2022-2024 which includes 45 patients started on HAART at least for 18 months and 45 HAART naïve patients, i.e, patients who are newly diagnosed but not yet started on HAART. Results: Marital status data shows that most individuals are unmarried in both groups, with no significant difference (p=0.839), suggesting marital status may not play a role in HIV exposure or management. Conclusion: Our study showed a high prevalence of dyslipidemia in HIV patients undergoing HAART therapy. Elevated levels of total cholesterol, triglycerides, and LDL, along with reduced HDL, contribute to the characterization of dyslipidemia. Significant differences in lipid parameters between baseline and follow-up periods (6 and 12 months) were evident, indicating the impact of HAART therapy on lipid metabolism.
Keywords:
Article :
Introduction:
HIV is a lentivirus (a subgroup of retrovirus) that causes AIDS, a condition in humans which causes a progressive failure of the immune system that leads to life threatening opportunistic infection and cancers. Without treatment the average survival time after infection with HIV is estimated to be 9 – 11 years.
Dyslipidemias, or disorders of lipoprotein and lipid metabolism, are metabolic abnormalities that cause a chronic rise in cholesterol and triglyceride (TG) levels in the blood. Raised total cholesterol (TC), high low-density lipoprotein cholesterol (LDL-C), low high-density lipoprotein cholesterol (HDL-C), and increased TG are all involved.1–3
Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is a chronic infection associated with dyslipidemia and insulin resistance.4 Highly Active Antiretroviral Therapy (HAART) is the mainstay of treatment for people living with HIV/AIDS (PLWHA).5 The goal of HAART is to suppress viral replication so that the patient’s immune system can recover and protect against the development of AIDS and death.6 Treatment of HIV/AIDS with HAART is complex because of its interaction with lipid-lowering medications in PLWHA.7
In HIV patients, dyslipidemia is a common comorbidity and can occur due to multiple factors. These factors include the virus itself, antiretroviral therapy medications, lifestyle factors, and genetic predisposition. Certain antiretroviral medications used in the treatment of HIV, particularly protease inhibitors and certain nucleoside reverse transcriptase inhibitors, have been shown to increase lipid levels in some patients. This predisposition to dyslipidemia in HIV patients can lead to complications such as atherosclerosis and cardiovascular disease.8
Dyslipidemia occur in up to 70%–80% of HIV-infected subjects who are receiving combined ART and is mainly associated with specific antiretroviral agents of the nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitor (PI) classes.9,10 Dyslipidemia associated with combination ART use is characterized by increased levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c) and triglycerides (TG) and a decreased high-density lipoprotein-cholesterol (HDL-c) level.11,12 Furthermore, the prevalence of dyslipidemia in HIV patients has been associated with other metabolic abnormalities, such as insulin resistance and diabetes.
In patients receiving combination ART, changes in lipid profiles have been also shown to be an independent risk factor for adverse outcomes, including cardiovascular-related events, reduced life expectancy and increased use of medical resources, which can greatly increase healthcare costs of the disease and reduce quality of life of patients with HIV.13,14
Methods And Materials:
In- patients and out-patients of Department of Medicine, K.C general Hospital, Malleshwaram.
STUDY DESIGN: An observational study.
PATIENT SELECTION: 90 HIV diagnosed patients in K C General hospital were selected and the study was conducted during the year 2022-2024 which includes 45 patients started on HAART at least for 18 months and 45 HAART naïve patients, i.e, patients who are newly diagnosed but not yet started on HAART.
STUDY DURATION: The study duration was for 18 months, from 15th august 2022 to 14th Feburary 2024
INCLUSION CRITERIA:
· HIV patients who visited the ART centre in KC General Hospital, Malleshwaram during the study period who give consent for the study.
· Age group of both sexes 18 to 60 years.
· Patients with good adherence to HAART.
EXCLUSION CRITERA:
· Patients with Diabetes Mellitus, known renal, liver disorders , thyroid and Autoimmune Diseases.
· Patients on long term steroid therapy
· Obese patients with (BMI >30)
· Known case of dyslipidaemia who is on medication of lipid abnormalities and with long standing cholestasis.
· Patients on drugs like Beta Blockers, Diuretics, Cyclosporine, estrogen, Growth hormone, Retinoids, etc.
· Patients who are pregnant and breastfeeding.
Methods:
HIV infected or incidentally detected individuals admitted in the wards and OPD of Internal Medicine department and ART Centre at K C General Hospital was be chosen for the study. Patients who fulfilled the inclusion and the exclusion criteria was subjected to a detailed history and clinical evaluation, after getting an informed consent from them.
RESULTS:
Table 1. Distribution Of Study Population According To Age
|
AGE |
HIV NAIVE |
P VALUE |
|
|
YES |
NO |
||
|
MEAN + SD |
39.6 + 8.622 |
43.93 + 9.411 |
0.025 |
Figure 1. Bar Diagram Showing Distribution Of Study Population According To Age
Table 2. Distribution Of Study Population According To Sex
|
SEX |
HIV NAIVE |
Total |
P VALUE |
||
|
YES |
NO |
||||
|
F |
Count |
21 |
25 |
46 |
0.399 |
|
% |
46.7% |
55.6% |
51.1% |
||
|
M |
Count |
24 |
20 |
44 |
|
|
% |
53.3% |
44.4% |
48.9% |
||
|
Total |
Count |
45 |
45 |
90 |
|
|
% |
100% |
100% |
100% |
||
Figure 2. Bar Diagram Showing Distribution Of Study Population According To Sex
In terms of gender distribution, there is no significant difference between the groups; both feature a nearly even split between males and females, indicating gender does not influence HIV naive status in this cohort (p=0.399).
Table 3. Distribution Of Study Population According To Marital Status
|
MARITAL STATUS |
HIV NAIVE |
Total |
P VALUE |
||
|
YES |
NO |
||||
|
YES |
Count |
30 |
30 |
60 |
0.839 |
|
% |
66.6% |
66.6% |
66.6% |
||
|
NO |
Count |
15 |
15 |
30 |
|
|
% |
33.3% |
33.3% |
33.3% |
||
|
Total |
Count |
45 |
45 |
90 |
|
|
% |
100% |
100% |
100% |
||
Figure 3. Bar Diagram Showing Distribution Of Study Population According To Marital Status
Marital status data shows that most individuals are unmarried in both groups, with no significant difference (p=0.839), suggesting marital status may not play a role in HIV exposure or management.
Table 4. Distribution Of Study Population According To Smoker
|
SMOKER |
HIV NAIVE |
Total |
P VALUE |
||
|
YES |
NO |
||||
|
YES |
Count |
21 |
16 |
37 |
0.284 |
|
% |
46.7% |
35.6% |
41.1% |
||
|
NO |
Count |
24 |
29 |
53 |
|
|
% |
53.3% |
64.4% |
58.9% |
||
|
Total |
Count |
45 |
45 |
90 |
|
|
% |
100% |
100% |
100% |
||
Figure 4. Bar Diagram Showing Distribution Of Study Population According To Smoker
Smoking habits do not differ significantly between groups, with roughly half of each group being smokers (p=0.284)
Table 5. Distribution Of Study Population According To Alcoholic
|
ALCOHOLIC |
HIV NAIVE |
Total |
P VALUE |
||
|
YES |
NO |
||||
|
YES |
Count |
21 |
22 |
43 |
0.833 |
|
% |
46.7% |
48.9% |
47.8% |
||
|
NO |
Count |
24 |
23 |
47 |
|
|
% |
53.3% |
51.1% |
52.2% |
||
|
Total |
Count |
45 |
45 |
90 |
|
|
% |
100% |
100% |
100% |
||
Figure 5. Bar Diagram Showing Distribution Of Study Population According To Alcoholic
Discussion:
This observational study was conducted to study the lipid abnormalities in human immunodeficiency virus infected individuals on Highly active antiretroviral therapy (HAART) in our hospital. A total of 90 HIV diagnosed patients were studied in our research, which included 45 patients on HAART at least for 18 months and 45 HAART naïve patients, i.e., patients who are newly diagnosed but not yet started on HAART.
Given the high prevalence of age-related metabolic diseases and the complex etiology of these comorbidities in inflammation and immune activation, dyslipidemia in PLHIV continues to be a challenge today, with HIV viremia and antiretroviral therapy representing two sides of the same coin.
Lipid abnormalities are common in HIV-positive individuals and are significant for a number of reasons. Clinically speaking, HIV raises the risk of cardiovascular (CV) events by the same amount as more conventional risk factors like diabetes or high blood pressure. Antiretroviral therapy (ART) has also decreased mortality and made HIV infection a chronic illness; however, ART—especially the earlier medications, including the early protease inhibitors (PIs)—is linked to lipodystrophy and lipid abnormalities. HIV has evolved into a chronic illness with patients living longer and into ages where co-morbidities like cardiovascular disease (CVD) are common since the discovery and development of antiretroviral therapy (ART). The identification and treatment of CVD risk factors, especially dyslipidemia, have grown to be critical components of HIV infection treatment plans.
In an investigation that compared HIV-positive individuals with uninfected controls who were matched for age, gender, and body mass index, the HIV patients showed increased levels of triglycerides, C-reactive protein (CRP), and interleukin (IL)-6, but decreased levels of HDL-C and LDL-C.113 Even when viral replication is inhibited by antiretroviral therapy (ART), HIV infection is frequently associated with prolonged inflammation and immunological activation, which further complicates alterations in lipid profiles in HIV positive individuals. Combination antiretroviral therapy (ART) significantly extends the projected life expectancy of HIV-positive individuals, but it also raises their risk of cardiovascular disease.
The available HAART drug combinations in our hospital were Tenofovir disoproxil fumerate (TDF) + Lamuvidine(3TC) + Doltugravir (DTG); Zidovudine (ZDV) + Lamivudine(3TC) + Doltugravir (DTG); Abacavir (ABC) + Lamuvidine(3TC) + Doltugravir (DTG); and Atazanavir (ATV) + Retonavir (RTV)+ Doltugravir (DTG).
In our study, age differences were notable, with the HIV-naive group averaging younger at 39.6±8.622 years compared to 43.93±9.411 years for non-naives, which was statistically significant (p=0.025). Comparatively, in the Indumati V et al study.113 the average age of the ART group was 36±8.99 years, while the ART-naïve group was 35.75±9.05 years. Also, Singh et al.111 observed a mean age of the controls as 39.23±4.5 years, while the patients' mean age was 36.43±9.62 years in their research. In another study by Aseefa et al.124 the authors found a mean age of 43.5±11.27 years in their study.
Abnormalities in lipid metabolism linked to HAART have been documented, mostly in individuals receiving PIs and d-4T therapy regimens, but also NVP and EFV treatment regimens. The participants' overall cardiovascular risk was not evaluated in our study. However, the substantial lipid disturbance is known to be linked to an increased risk of cardiovascular disorders, which implies that HAART may potentially be detrimental to the cardiovascular system.
Conclusion:
Our study showed a high prevalence of dyslipidemia in HIV patients undergoing HAART therapy. Elevated levels of total cholesterol, triglycerides, and LDL, along with reduced HDL, contribute to the characterization of dyslipidemia. Significant differences in lipid parameters between baseline and follow-up periods (6 and 12 months) were evident, indicating the impact of HAART therapy on lipid metabolism.
Our study aimed to analyze lipid abnormalities in adult HIV patients on HAART therapy, determine the prevalence of dyslipidemia, and compare the lipid profiles of patients on HAART for at least 12 months with HAART-naïve patients. The findings revealed that HAART therapy is associated with significant lipid abnormalities, including increased levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), and decreased high-density lipoprotein cholesterol (HDL-C). The prevalence of dyslipidemia was notably higher in HIV patients on HAART therapy compared to HAART-naïve patients, highlighting the impact of antiretroviral therapy on lipid metabolism.
Reference :
1. Jeppesen J, Hein HO, Suadicani P, Gyntelberg F. Relation of high TG–low HDL cholesterol and LDL cholesterol to the incidence of ischemic heart disease. Arterioscler Thromb Vasc Biol. 1997;17(6):1114–20. doi: 10.1161/01.ATV.17.6.1114.
2. Mach F. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(44):4255.
3. Pirillo A, Casula M, Olmastroni E, Norata GD, Catapano AL. Global epidemiology of dyslipidaemias. Nat Rev Cardiol. 2021;18(10):689–700. doi: 10.1038/s41569-021-00541-4.
4. Husain NEO, Ahmed MH. Managing dyslipidemia in HIV/AIDS patients: challenges and solutions. HIV AIDS (Auckl). 2015;7:1.
5. Miners A, Sabin C, Trueman P, et al. Assessing the cost-effectiveness of HAART for adults with HIV in England: the cost-effectiveness of HAART. HIV Med. 2001;2(1):52–8. doi: 10.1046/j.1468-1293.2001.00048.x.
6. Eggleton JS, Nagalli S. Highly active antiretroviral therapy (HAART). In: StatPearls. StatPearls Publishing; 2022. Available from: http://www.ncbi.nlm.nih.gov/books/NBK554533/. Accessed March 17, 2022.
7. Calza L, Manfredi R, Chiodo F. Dyslipidaemia associated with antiretroviral therapy in HIV-infected patients. J Antimicrob Chemother. 2004;53(1):10–4. doi: 10.1093/jac/dkh013.
8. Ojong E, Iya B, Djeufouata J, et al. Metabolic syndrome and its components among HIV/AIDS patients on antiretroviral therapy and ART-naïve patients at the University of Calabar Teaching Hospital, Calabar, Nigeria. Afr Health Sci. 2022;22(1):410–7. doi: 10.4314/ahs.v22i1.50.
9. Tilahun A, Chekol E, Teklemaryam AB, et al. Prevalence and predictors of dyslipidemia among HAART treated and HAART naive HIV positive clients attending Debre Tabor Hospital, Debre Tabor, Ethiopia. Heliyon. 2022;8(11). doi: 10.1016/j.heliyon.2022.e11342.
10. Calza L, Colangeli V, Manfredi R, Bon I, Re MC, Viale P. Clinical management of dyslipidaemia associated with combination antiretroviral therapy in HIV-infected patients. J Antimicrob Chemother. 2016;71:1451–65. https://doi.org/10.1093/jac/dkv494.
11. Estrada V, Portilla J. Dyslipidemia related to antiretroviral therapy. AIDS Rev. 2011;13:49–56.
12. Souza SJ, Luzia LA, Santos SS, Rondó PHC. Lipid profile of HIV-infected patients in relation to antiretroviral therapy: a review. Rev Assoc Med Bras (1992). 2013;59:186–98. https://doi.org/10.1016/j.ramb.2012.11.003.
13. da Cunha J, Maselli LMF, Stern ACB, Spada C, Bydlowski SP. Impact of antiretroviral therapy on lipid metabolism of human immunodeficiency virus-infected patients: Old and new drugs. World J Virol. 2015;4:56–77. https://doi.org/10.5501/wjv.v4.i2.56.
14. Riddler SA, Li X, Chu H, Kingsley LA, Dobs A, Evans R, et al. Longitudinal changes in serum lipids among HIV-infected men on highly active antiretroviral therapy. HIV Med. 2007;8:280–7. https://doi.org/10.1111/j.1468-1293.2007.00470.x.
15. Grover SA, Coupal L, Gilmore N, Mukherjee J. Impact of dyslipidemia associated with Highly Active Antiretroviral Therapy (HAART) on cardiovascular risk and life expectancy. Am J Cardiol. 2005;95:586–91. https://doi.org/10.1016/j.amjcard.2004.11.004.
16. World Health Organization. Global Health Sector Strategy on HIV 2016-2021. Towards Ending AIDS; World Health Organization: Geneva, Switzerland, 2016.
17. Thaker HK, Snow MH. HIV viral suppression in the era of antiretroviral therapy. Postgrad Med J. 2003;79:36–42.
18. Kaufmann GR, Zaunders J, Cooper DA. Immune reconstitution in HIV-1 infected subjects treated with potent antiretroviral therapy. Sex Transm Infect. 1999;75:218–24.
19. Nunan E, Wright CL, Semola OA, Subramanian M, Balasubramanian P, Lovern PC, et al. Obesity as a premature aging phenotype-implications for sarcopenic obesity. Geroscience. 2022;44:1393–405.
20. Enanoria WT, Ng C, Saha SR, Colford JM Jr. Treatment outcomes after highly active antiretroviral therapy: A meta-analysis of randomised controlled trials. Lancet Infect Dis. 2004;4:414–25.
21. Porter K, Babiker A, Bhaskaran K, Darbyshire J, Pezzotti P, Porter K, et al. Determinants of survival following HIV-1 seroconversion after the introduction of HAART. Lancet. 2003;362:1267–74.
22. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA. 2001;285:2486–97.
23. Koethe JR. Adipose Tissue in HIV Infection. Compr Physiol. 2017;7:1339–57.
24. Smit M, Brinkman K, Geerlings S, Smit C, Thyagarajan K, Sighem A, et al. Future challenges for clinical care of an ageing population infected with HIV: A modelling study. Lancet Infect Dis. 2015;15:810–8.