M.A Kuti1, O.T Bamidele2, N.S Nduka3, O. Olaniyi4, O.A Ogundeji5, K.S Adedapo1, O.A Awolude6

  1. Department of Chemical Pathology, College of Medicine, University of Ibadan/University College Hospital.
  2. Department of Chemical Pathology, Babcock University, Ilishan Remo, Ogun State.
  3. Department of Chemical Pathology, College of Medicine, University of Ibadan, Ibadan.
  4. Infectious Diseases Institute, College of Medicine, University of Ibadan, Ibadan
  5. Department of Chemical Pathology, University College Hospital, Ibadan
  6. Department of Obstetrics and Gynaecology/Infectious Diseases Institute, College of Medicine, University of Ibadan/University College Hospital, Ibadan.


Background and Objective: A major modifiable risk factor for atherosclerotic cardiovascular disease is abnormalities in lipid and lipoprotein metabolism which are frequently seen in HIV as well as its treatment. Apo-E is a protein that is important in plasma lipid homeostasis and its genetic alleles have been shown to contribute to lipid abnormalities. We examined for the effect of Apo-E gene polymorphisms on plasma lipid levels in PLHIV on protease inhibitor therapy.

Methods: This was a cross-sectional study conducted among adult persons living with HIV. Lipid profile, Apo-B and Apo-A were measured in fasting plasma. Amplification and analysis of Apo-E genotypes were determined using the Seeplex Apo-E ACE genotyping kit. Differences in quantitative values were compared with non-parametric analysis methods.

Results: Eighty-four persons were recruited into the study, 75% of whom were virally suppressed. The 3 homozygous genotypes had significantly different levels of low-density lipoprotein cholesterol (LDL-C), Apolipoprotein B (Apo-B) and Apolipoprotein A1 (Apo-A1). Persons with apo 2/2 had higher LDL-C compared to those with apo 3/3 (3.26 (3.61) mmol/L vs. 2.76 (1.28) mmol/L, p = 0.010). Those with apo 4/4 had lower Apo-A1 compared to those with apo 3/3 (0.84 (0.48) g/dL vs. 1.27 (0.70) g/dL, p =0.009). Compared with the same group, the heterozygous genotype, apo 2/3 had lower triglyceride levels :1.33 (0.65) mmol/ L vs. 1.86 (1.11) mmol/L, p = 0.045.

Conclusion: Polymorphisms in the Apo-E gene may have significant influences on plasma lipid and apolipoprotein levels in PLHIV on PI therapy. This may have implications for the assessment of risk for cardiovascular disease.

Keywords: Polymorphisms, Genotypes, Dyslipidaemia, Protease Inhibitor, HIV


Dr. M.A Kuti
Department of Chemical Pathology,
College of Medicine,
University of Ibadan,
Email: modupekuti@gmail.com
Submission Date: 1st Jan., 2023
Date of Acceptance: 1st April, 2024
Publication Date: 30th April, 2024


Persons living with HIV (PLHIV) have an increased risk of atherosclerotic cardiovascular disease (ASCVD). The relative risk of Cardiovascular Disease (CVD) in this population is at least 50% higher than observed in the general population.1,2 This is a consequence of an increased prevalence of traditional risk factors for CVD in PLHIV as well HIV specific factors which include the chronic inflammation and immune activation caused by the disease as well as side effects of some antiretroviral drugs. An effective risk management response requires primary prevention efforts at the level of the individual. At the heart of efforts is the identification of individuals at high risk who may then be offered appropriate intervention.3

Interventional options aimed at primary prevention focus on the modification of the traditional risk factors. A major modifiable risk factor for CVD is abnormalities in lipid and lipoprotein metabolism. HIV as well as its treatment are associated with dyslipidemia. HIV is characterized by low levels of Total Cholesterol (TC), High-Density Lipoprotein–Cholesterol (HDLC) and Low-Density Lipoprotein-Cholesterol (LDLC) and in more advanced disease with increased Triglycerides (TG). All classes of antiretroviral therapy (ART) induce dyslipidemia but regimens which include protease inhibitors (PI), second line ART agents in Nigeria, have been reported to have greater than a 3-fold risk of dyslipidemia compared to patients on regimens that did not include this class of drug.4 Hypercholesterolemia and hypertriglyceridemia have been noted to be present in over 50% of PLHIV after 2 years of PI based therapy.5 Other factors may, however, be involved in the metabolic and lipid alterations observed in PLHIV on ART because not all of the patients exposed to the same regimen are similarly affected6. Such factors may include virologic, individual immunologic features as well as genetic factors.

Apo-E is a polymorphic protein that is central to the regulation of plasma lipid levels. The major way it serves this role is by mediating the binding of remnant lipoproteins in the plasma to specific cell-surface receptors which internalize Apo-E-containing lipoprotein particles.7 It has three major isoforms ApoE2, Apo-E3, and Apo-E4 which are the gene products of three alleles, 2, 3 and 4, of a single gene locus located on chromosome 19.8 The 3 isoforms of ApoE have differential effect on lipid metabolism due to their affinity for the receptors in the clearing of the remnant lipoproteins with Apo-E2 having reduced and Apo-E4 having increased binding ability to the receptor compared to Apo-E3, the wild type.7 The presence of Apo-E alleles have been shown to contribute significantly to the variability of lipid and apolipoprotein concentrations.9

The manifestation of the dyslipidemia associated genetic alterations in the Apo-E gene has however been shown to frequently require an additional factor to precipitate the occurrence of dyslipidemia. The additional effect of diseases like diabetes, hypothyroidism and chronic kidney disease have been associated with the development of dyslipidemia in persons homozygous for a variant Apo-E gene.10,11 Given the effects of HIV and PI therapy on lipid metabolism we aimed to examine for the effect of polymorphisms of the Apo-E gene on the plasma lipid and apolipoprotein levels among a group PLHIV on protease inhibitor therapy.