|Year : 2013 | Volume
| Issue : 1 | Page : 24-28
Prevalence of dyslipidemia among human immunodeficiency virus infected Nigerians
Sanusi Muhammad1, Mahmoud U Sani2, Basil N Okeahialam3
1 Department of Medicine, Federal Medical Centre Azare, Bauchi State, Nigeria
2 Department of Medicine, Bayero University/Aminu Kano Teaching Hospital, Kano, Kano State, Nigeria
3 Department of Medicine, Jos University Teaching Hospital, Jos, Plateau State, Nigeria
|Date of Web Publication||7-Mar-2013|
Department of Medicine, Federal Medical Centre Azare, Bauchi State
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Dyslipidemia is a significant risk factor for premature cardiovascular disease. People infected with human immunodeficiency virus (HIV) have been shown to develop alterations in body composition, lipid and glucose metabolism, which predisposes them to cardiovascular disease. Human immunodeficiency virus (HIV) infection and its therapies may contribute to these changes. These metabolic changes in addition to the other traditional risk factors may contribute to the excess cardiovascular disease (CVD) morbidity and mortality observed in HIV-infected individuals. We, therefore set out to describe the prevalence of dyslipidemia among HIV infected Nigerians.
Materials and Methods : This is a cross sectional study, was conducted in HIV specialty clinic of Aminu Kano Teaching Hospital (AKTH) between May and August 2009. HIV infected patients were recruited. Half of them were on HAART for 6 months and above while the other half were HAART naïve. Patients who satisfied inclusion criteria were recruited consecutively until the required sample size was obtained. Data were collected using the pre-tested interviewer administered questionnaire. Socio-demographic information, anthropometric measurements and blood pressure were obtained from the subjects in a standardized manner. Venous samples were collected for necessary investigations and analyzed at the hospital central laboratory.
Results: Two hundred subjects were studied, the mean age for all the participants was 32.5 ± 7.55 years. The age ranged from 20 to 50 years, 64% of the respondents (128) were aged between 20 and 34 years. Forty three (21.5%) of them were above the age of 40 years. Fifty percent were on HAART and the other 50% were HAART naïve. The duration of HAART treatment ranged from 6-84 months. The mean CD4 cell counts was higher for subjects on HAART compared to HAART naive 376.33±215.66 and 261.09 ±195.64, respectively (P < 0.001). High TC (31% vs. 7%, P ≤ 0.001), low HDL-C (61% vs. 76%, P = 0.022), high LDL (36% vs. 26%, P = 0.126), high TG (19% vs. 13%, P = 0.247).
Conclusion: HIV infected patients on HAART demonstrated higher prevalence of high TC while HAART naïve subject showed higher prevalence of low HDL.
| Abstract in French|| |
Contexte: Dyslipidémie est un facteur de risque important de maladies cardiovasculaires prématurées.Personnes infectées par le virus de l'immunodéficience humaine (VIH) ont démontré que développer des altérations dans le métabolisme de composition, de lipides et de glucose corps, qui prédispose aux maladies cardiovasculaires. Infection à virus de l'immunodéficience humaine (VIH) et ses traitements peuvent contribuer à ces changements. Ces changements métaboliques en plus des autres facteurs de risque traditionnels peuvent contribuer à la morbidité de l'excès des maladies cardiovasculaires (MCV) et de la mortalité observée chez les personnes infectées par le VIH. Nous, donc entrepris de décrire la prévalence de la dyslipidémie chez les VIH infectées nigérians.
Matériel et méthodes: C'est une étude transversale croisée, a été menée dans une clinique spécialisée de VIH de Aminu Kano Teaching Hospital (AKTH) entre mai et août 2009. Les patients infectés par le VIH ont été recrutés. La moitié d'entre eux étaient sous MULTITHÉRAPIE pendant 6 mois et plus haut tandis que l'autre moitié n'avaient jamais reçu HAART. Les patients qui satisfaisaient les critères d'inclusion ont été recrutés consécutivement jusqu'à ce que la taille de l'échantillon requis a été obtenue. Données ont été recueillies au moyen du questionnaire de l'intervieweur pré-testées administré. Informations sociodémographiques, des mesures anthropométriques et la pression artérielle proviennent de sujets d'une manière standardisée. Échantillons veineux ont été prélevés pour les investigations nécessaires et analysés au laboratoire central hospital.
Résultats: Deux cents sujets ont été étudiés, l'âge moyen pour tous les participants était de 32,5 ± années 7.55. L'âge varie de 20 à 50 ans, 64% des personnes interrogées (128) étaient âgés de 20 à 34 ans. Quarante-trois (21,5%) d'entre eux étaient au-dessus de l'âge de 40 ans. Cinquante pour cent étaient sous MULTITHÉRAPIE et l'autre 50% n'avaient jamais reçu HAART. La durée du traitement HAART varie entre 6-84 mois. La moyenne les numérations de CD4 était plus élevé chez les sujets sous MULTITHÉRAPIE contre HAART naïf 376.33±215.66 et ±195.64 261.09, respectivement (P < 0,001). TC élevé (31% vs 7%, P ≤ 0,001), faible HDL-C (61% contre 76%, P = 0,022), LDL élevé (36% contre 26%, P = 0,126), TG élevé (19% contre 13%, P = 0,247).
Conclusion: Les patients infectés par le VIH sous MULTITHÉRAPIE a démontré une prévalence plus élevée de haute TC sujet naïf HAART ont montré une prévalence plus élevée de HDL bas.
Mots clés: Dyslipidémie, virus de l'immunodéfi cience humaine HAART, syndrome métabolique, Nigeria
Keywords: Dyslipidemia, human immunodeficiency virus highly active antiretroviral therapy, metabolic syndrome, Nigeria
|How to cite this article:|
Muhammad S, Sani MU, Okeahialam BN. Prevalence of dyslipidemia among human immunodeficiency virus infected Nigerians. Ann Afr Med 2013;12:24-8
| Introduction|| |
The global estimates of human immunodeficiency virus (HIV) prevalence in 2007 showed that the Sub-Saharan Africa housed more than two third (68%) of all people living with HIV.  The increasing accessibility of antiretroviral drugs in poor resource countries like ours has led to a significant reduction in morbidity and mortality from HIV/AIDS. People infected with HIV have been shown to develop alterations in body composition, lipid and glucose metabolism which predisposes them cardiovascular disease. Human immunodeficiency virus infection and its therapies may contribute to these changes.
Dyslipidemia is a significant risk factor for premature cardiovascular disease. Altered lipid metabolism is known to occur in association with HIV disease, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels are reduced, while triglycerides (TG) levels are increased in HIV positive patients. , Since the emergence of highly active antiretroviral therapy (HAART), it has been shown to have significant effect on lipids profile. ,,, Protease inhibitors (PI) in particular have been associated with moderate to severe elevation in total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG).  The non nucleoside reverse transcriptase inhibitor (NNRTI), especially stavudine have been associated with lipodystrophy and dyslipidemia.
The precise pathogenesis of cardiovascular complications on HAART is incompletely characterized. It appears to be multifactorial and to involve metabolic derangements leading to some or all of the components of the metabolic syndrome, atherogenic, and proinflammatory condition. ,,, Within the general population, people with the metabolic syndrome have a markedly higher risk of developing diabetes and cardiovascular disease than those without this syndrome.  It is assumed that persons on HAART with the metabolic syndrome are at similar cardiovascular risk to seronegatives with the metabolic syndrome
The proposed mechanism for HAART induced dyslipidemia is multifactorial and includes insulin resistance which is associated with PI, NNRTI, and NRTI use.  Protease inhibitors suppress the degradation of sterol receptor expression- binding proteins (SREBP) 1 and 2, resulting in their accumulation in the nucleus and consequent fatty acid synthesis by up regulation of fatty acid synthase (FAS) expression.  In addition, the similarity between the catalytic region of HIV1 protease and two homologous human protein involved in lipid metabolism cytoplasmic retinoic acid binding protein type 1 (CRABP-1) and LDL- receptor- related protein (LRP) also contribute lipid abnormality. 
The objective of the study is to describe the prevalence dyslipidemia among HIV positive patience attending HIV specialty clinic in Aminu Kano Teaching Hospital in North-Western Nigeria.
| Materials and Methods|| |
The study was a cross sectional carried out at the HIV specialty clinic of Aminu Kano Teaching Hospital, between May and August 2009. We studied HIV positive subjects attending HIV specialty clinic. Half of them were on HAART for 6 months and above while the other half were HAART naïve. We excluded patients less than 18-years old, pregnant and lactating women. Patients with documented hypertension, diabetes and dyslipidemia before commencing HAART were also excluded.
Patients that certified the inclusion criteria and signed consent were recruited consecutively. Recruitment was done during the routine follow-up and also during initial visits. Data were collected using a pretested interviewer administered questionnaire. History was obtained and thorough physical examination was also done, including measurement of blood pressure, weight, height, and body mass index (BMI) was calculated. Waist circumference and waist-hip ratio were done in a standard pattern. Venous blood was taken on their subsequent scheduled visit after (10 h) overnight fast for the purpose of doing Lipid profile, fasting blood sugar (FBS) and Uric acid levels.
HAART was defined as a combination of at least three classes of antiretroviral drugs, protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and nucleoside reverse transcriptase inhibitors (NRTIs), one of which was a PI or an NNRTI or a triple combination of (NRTIs). Dyslipidemia was defined using the national cholesterol education program (NCEP) adult treatment panel (ATP) III guidelines.  Total cholesterol was considered to be high if it was >200 mg/dl (5.17 mmol/l). LDLc was considered to be raised if it was >130 mg/dl (3.34 mmol/l), triglycerides was considered to be high if it was >150 mg/dl (1.7 mmol/l) and HDLc was considered to be low if it was <40 mg/dl (1.03 mmol/l) and <50 mg/dl (1.3 mmol/l) in men and women, respectively.
Data analysis was done using the Statistical Package for the Social Sciences (SPSS), version 16.0. The analysis of continuous variables was carried out using the procedures of descriptive statistics and later, to identify any differences we used Student's t-test. Categorical variables were analyzed using contingency tables involving Chi-square (X 2 ) tests to identify statistical differences between the groups. The relationship between HAART and dyslipidemia was determined using logistic regression analysis. P-value (≤0.05) was considered significant.
| Results|| |
Two hundred subjects were studied, 100 were on HAART and the other 100 were HAART naïve. The mean age for all the participants was 32.5 ± 7.55 years. The age ranged from 20 to 50 years, 64% of the respondents (128) were aged between 20 and 34 years. Forty three (21.5%) of them were above the age of 40 years. Females constituted 53% of the participants. The duration of HIV diagnosis ranged from less than one month to 12 years.
All the subjects on HAART were on either lamivudine (3TC), or emtricitabine (FTC). Fifty-four percent were on zidovudine (AZT), while 46% were on stavudine (D4T) or tenofovir (TDF). Ninety percent of them were on nevirapine (NVP) as the third agent, 9% on efavirenz (EFV), only a single participant was on lopinavir (LPVr). The duration of treatment ranged from 6-84 months. The mean CD4 cell counts was higher for subjects on HAART compared to HAART naive 376.33 ± 215.66 and 261.09 ± 195.64, respectively (P < 0.001). Subjects on HAART had higher BMI, Waist circumference and waist-hip ratio were also higher among subjects on HAART compared HAART naïve subjects. [Table 1] shows means of the clinical and laboratory parameters.
|Table 1: Baseline clinical and laboratory parameters of the study subjects|
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Dyslipidemia: High TC was found among 31% subjects on HAART compared to 7% among HAART naïve (P < 0.001). HDL was significantly higher among HAART naïve 76% compared to 61% among subjects on HAART (P = 0.022). The prevalence of high LDL among subjects on HAART did not differ from HAART naïve subjects, 36% vs. 26% respectively (P = 0.126). Hypertriglyceridemia was 19% among HAART and 13% among HAART naïve subjects (P = 0.247). Female sex was associated with 3 times likelihood of having low HDL compared to males (OR 3.33, P = <0.005 CI 1.71-6.45) while the duration of HAART did not have effect on dyslipidemia. [Figure 1] shows the distribution of dyslipidemia among the groups and [Table 2], below shows distribution of dyslipidemia based on HAART regimens.
|Figure 1: Prevalence of dyslipidemia among the study groups. TC = total cholesterol, HDL = high density lipoprotein, LDL = low density lipoprotein, TG = triglyceride, group 1 = HAART +ve, group 2 = HAART -ve|
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|Table 2: Distribution of dyslipidaemia among group 1 based on the HAART regimen they are on|
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| Discussion|| |
Changes in lipid profiles associated with increased cardiovascular risk that have been observed with some HAART regimens have been a cause for concern among clinicians who treat HIV-infected patients. The relationship between elevated level of cholesterol and increased cardiovascular disease has been clearly demonstrated.
This study showed a higher prevalence of high TC among subjects treated with HAART compared to HAART naïve subjects 31% vs. 7% (P < 0.001), this support the finding of other investigators. In one study, the prevalence of high TC was 39.2% and 10% among HAART and HAART naïve, respectively.  Similarly workers from the Data collection on Adverse events of anti-HIV Drugs (DAD) study reported high TC ≥6.2 mmol/l among 22% of subjects on NNRTI. 
Kumar, et al., found that PI sparing regimen raised TC and TG least in comparison with regimens containing a PI or stavudine and a PI.  Only a single participants was on PI based regimen. The workers reported prevalence of high TG of 25.6% and 22.2% among subjects on HAART and not on HAART, respectively (CI 0.688-2.037). DAD study reported higher TG particularly among subjects on protease inhibitor based regimens. 
Low HDL was the most common dyslipidemia found in this study and was more common among HAART naïve 76% compared to 61% among subjects on HAART treatment (P = 0.022). This is consistent with other workers were prevalence of low HDL was 14.6% among HAART treated and 51.2% among HAART treatment naïve subjects (P < 0.0001).  Sani, et al., reported low HDL as the most common dyslipidemia among healthy HIV negative subjects in North- Western Nigeria, the workers reported prevalence of 59.3%, and the prevalence was much higher among women compared to men.  This finding of high prevalence of low HDL-C among subjects not on HAART may be as a result altered lipid metabolism, which is known to occur in association with HIV disease. Riddler, et al., reported in an analysis of serum samples collected between 1984 and 2002 from HIV seroconverters indicated that HIV seroconversion resulted in reductions in total cholesterol, LDL-C, and HDL-C levels and that initiation of HAART increased both TC and LDL-C levels, but not HDL-C.  Some studies suggest that efavirenz is associated with the development of increased TC levels, largely due to beneficial increases in HDL levels. ,,, We reported that 99% of the subjects on HAART arm in this study were on NNRTI. This class of Anti retroviral drugs (ARV) was shown to raise HDL-C level substantially as immunological status improves, which may provide a potential long term beneficial effect on cardiovascular risk profile.  This finding suggests that the reduction in viral replication, improved immunological status by NNRTI could have beneficial effects on lipids profile. Although, NNRTIs increase HDL cholesterol, most other antiretroviral therapies do not.
We have not found significant difference in the prevalence of high LDL-C among the HAART treated compared to HAART naïve subjects. This is consistent with results of other workers.  Low density lipoprotein cholesterol increases modestly with initiation of most forms of HAART, this increase may not be due to direct effects of specific antiretroviral drugs but whether it relates to immune effects or restoration of health remains unclear. Significant increases in LDL cholesterol among HIV-infected patients are more likely to be due to genetic and dietary causes.
HAART has been shown to reduce morbidity and mortality among HIV infected patients, however, other risk factors such as dyslipidemia and other cardiovascular risk factors that are becoming more prevalent in this group of people, if not properly evaluated and monitored during treatment with HAART may predispose to further cardiovascular morbidity and mortality.
This study is limited by the small sample size, having only few patients on protease inhibitors. The results can however still be generalized to low resource settings where PIs are rarely part of HAART because of cost. Our findings showed that exposure to HAART predisposes to development of dyslipidemia and metabolic syndrome. It is therefore recommended that dyslipidemia is assessed before initiation of HAART and monitored periodically.
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[Table 1], [Table 2]