An observational study on the prevalence of dyslipidemia and dysglycemia in human immunodeficiency virus patients

Context: Dyslipidemia and dysglycemia are prevalent among patients with human immunodeficiency virus (HIV) infection. Besides antiretroviral therapy, other factors like opportunistic infections may contribute to the development of these disorders. Aims: The objective of this study was to determine the prevalence and pattern of dysglycemia and dyslipidemia in HIV patients. Settings and Design: An observational cross-sectional study was done over a period of six months at the Gandhi Memorial and Associated Hospital, Lucknow, India (a tertiary care centre in north India). Materials and Methods: A total of 85 consecutive HIV patients, >15 years of age attending the outdoor clinic were enrolled. A single fasting blood sample was taken to estimate the sugar and lipid parameters. Acutely ill and previously diagnosed patients of diabetes mellitus were excluded. Statistical Analysis Used: Data were presented in percentage and mean values. Statistical analysis was done by using software “Stata Version 11 Texas”. Results: The mean (SD) age of the studied patients was 34.34 (8.3) years. The prevalence of dysglycemia was 30.9%; 10.9% patients were diagnosed to have frank diabetes mellitus while 20% patients had their blood sugars in the range of glucose intolerance. Prevalence rates of low high density lipoprotein (HDL), hypertriglyceridemia, raised low density lipoprotein (LDL) and total cholesterol were 69.41%, 29.41%, 10.58%, and 9.41% respectively. Conclusions: Dysglycemia and dyslipidemia are more prevalent among HIV patients. Advanced disease and antiretroviral therapy (ART)-naïve patients have higher rates of dysglycemia and dyslipidemia. High prevalence of low HDL, hypertriglyceridemia and impaired glucose intolerance comprising three components of metabolic syndrome are found in HIV patients. Hence, HIV disease “itself” is a major risk factor for cardiovascular disease.

Keywords: Antiretroviral therapy, dyslipidemia, dysglycemia, human immunodeficiency virus, world health organization stage of human immunodeficiency virus disease

HIV infection is now become a pandemic. In 2008, approximately 33.4 million people worldwide were living with HIV/AIDS. It is now thought that around 2.3 million people in India are living with HIV. ^[1] The incidence of various metabolic disorders has also been reported to be high in patients affected by HIV. ^[2],[3] With the use of antiretroviral therapy (ART), the incidence of opportunistic infections (OIs) has come down, but this has brought other systemic disorders including metabolic disorders to the forefront. Antiretroviral medications can directly or indirectly increase the risk of metabolic abnormalities such as insulin resistance and dyslipidemia. Now since most patients with HIV/AIDS have a potentially long life, attention is now being focused on how to prevent or reduce long-term complications in patients with HIV/AIDS. Some of these complications are induced by ART, OIs, while others are presumed to be result of the HIV infection. A number of metabolic complications which occur in HIV/AIDS patients include dyslipidemia, changes in body composition, insulin resistance, and glucose intolerance, mineral bone disease, and lactic acidosis. ^[4],[5] The prevalence of such abnormalities depends on the stage of disease, duration, OIs, ART, and type of ART. The prevalence and type of metabolic abnormalities may also depend on the race and ethnicity of the population. Hence, these may be different in different population groups. A number of studies are available from the Western world; however, the data from India is meager. It is imperative to know the extent and the nature of the problem in order to make preventive strategies. Hence, we undertook the present study to understand the prevalence pattern and manifestations encountered with metabolic disorders in the Indian population suffering from HIV disease. It may have great importance in the diagnosis and management of non-AIDS-related morbidity and mortality in HIV-infected patients.

Ours was a hospital-based observational cross-sectional study. HIV patients attending the outdoor clinic over a period of six months, at the Gandhi Memorial and Associated Hospital, Lucknow (a tertiary care centre in UP, India) were enrolled. Total patients enrolled were 85 including 66 (77.6%) males and 19 (22.4%) females. HIV patients > 15 years of age and who gave consent for the study were included. Previously diagnosed diabetic HIV patients and acutely ill patients were excluded from the study to avoid confounding factors. A single-time overnight fasting blood sample was taken to estimate sugar and lipid parameters. Fasting blood sugar (FBS) and lipid parameters were determined. All patients underwent thorough clinical assessment, and history specifically asked for dysglycemic symptoms. Patients were categorized into early (WHO Stage I and II) and advanced disease (WHO clinical Stage III and IV). Similarly, all patients were categorized on the basis of their ART status into ART and non-ART group. Dysglycemia was defined as FBS >100 mg/dl and diagnosis of diabetes was established when FBS >125 mg/dl. ^[6] Normolipidemic subjects were judged by the following criteria: Total cholesterol (TCH) <200 mg/dl triglycerides (TG) <170 mg/dl, HDL ≥ 35 mg/dl, LDL <130 mg/dl. ^[7] Blood samples for FBS and lipid parameters were collected after overnight fasting. Plasma glucose was estimated by enzymatic method using glucose oxidase and peroxidase as enzyme. Fasting lipid measurement was done by commercially available enzymatic method. Plasma TCH, TG and HDL were measured directly, whereas LDL was estimated indirectly by Friedewald equation i.e. LDL cholesterol = Total cholesterol – [HDL Cholesterol + TG/5]. Mann-Whitney U test, the Wilcoxon matched-pairs signed-ranks test, and the chi square test was applied when they required analyzing the data. A P value <0.05 for a two-sided test was considered statistically significant.

A total of 85 HIV-positive patients were enrolled. The mean (SD) age of patients was 34.34 (8.3) years with male to female ratio of 3.4:1. Most of the patients were in the age group of 30 to 39 years. Seventy patients (82.35%) were in advanced disease (WHO Stage III and IV) and the rest belonged to early stages (WHO Stage I and II). Thirty-one patients (36.47%) were on ART. Those who were not on ART were either newly diagnosed cases or were those who did not fulfill the NACO criteria for initiation of ART based on WHO clinical staging and CD4 counts. The median duration of antiretroviral therapy was three months with minimum of 15 days to maximum of 36 months. Four types of ART regimen were used with different combinations of zidovudine (AZT) or stavudine (d4T) with non-nucleoside reverse transcriptase inhibitors (NNRTIs) i.e. either NVP or EFV. Lamivudine (3TC) was common in each regimen. The most common regimen used was AZT with 3TC and NVP. We could identify opportunistic pathogens in 58 (68.2%) subjects. The most common organism was found to be M. tuberculosis (in 62.85% patients of advanced stages) followed by Candida, Cryptococcus, Pneumocystis, Toxoplasma in decreasing order. Hepatitis B co-infection was present in four (4.7%) patients of HIV.

Fasting blood sugar (FBS) was estimated in 55 (64.7%) patients. FBS levels were not determined in 30 (35.3%) patients because they were either taking corticosteroids for an illness like tuberculous meningitis (19 patients), Pneumocystis carinii pneumonia (3 patients), and acute inflammatory demyelinating polyneuropathy (1patient) or were suffering from liver disease (5 patients). In two patients the sample for blood sugar was lost. The prevalence of dysglycemia in this study was 30.9% and out of them 10.9% patients were diagnosed to have frank diabetes mellitus while 20% patients had their blood sugar in the range of pre-diabetes. Thirst and polyuria were present in 15 (27.2%) patients, but these symptoms were present in 4 (23%) patients who had dysglycemia. However, these symptoms were also reported in 11 (28.94%) euglycemic patients. Prevalence rates of low HDL, hypertriglyceridemia, raised LDL and total cholesterol were 69.41%, 29.41%, 10.58%, and 9.41%, respectively. Prevalence of hypercholesterolemia, hypertriglyceridemia, and low HDL was higher in advanced stages as compared to early stages; however, P values were not significant. In ART-naïve patients, the prevalence rates of hypercholesterolemia and low HDL were high in comparison to those who were on ART [Table 1]. Furthermore, ART-naïve patients had a lower prevalence of TCH and lower prevalence of elevated LDL compared to patients taking ART and there was no statistically significant difference in TG between ART-naïve patients and those taking ART. Significant difference was not observed when the mean values of TCH, TG and LDL were compared between early stages and advanced stages of HIV disease. Only the mean HDL values were significantly low in ART-naïve patients compared to ART-taking patients [Table 2]. There was no significant difference noticed in all parameters of lipid profile when compared among NNRTIs and NRTIs [Table 3].

India leads the world with the largest number of diabetic subjects with a prevalence of 11.7% in northern India. Studies have also suggested that there is a large pool of subjects with impaired glucose tolerance (IGT), 14% with a high risk of conversion to diabetes. ^[8] “Asian Indian phenotype” is considered to be one of the major factors contributing to the increased predilection towards diabetes. ^[9] In a cohort of HIV-infected patients receiving combination antiretroviral therapy ^[10] 35% had impaired glucose tolerance. While in another cross-sectional study of patients taking protease inhibitors (PIs), the prevalence of diabetes mellitus and impaired glucose tolerance was reported to be 7% and 16%, respectively. ^[11] Additionally, current evidence suggests that patients on ART are at risk of cardiovascular disease (CVD), and recent studies reported a higher prevalence of traditional risk factors for CVD in HIV-infected patients than in non-infected controls, such as arterial hypertension, dyslipidemia, and diabetes mellitus. ^{[5],[12],[13]}

In our study, the prevalence of dysglycemia and dyslipidemia was found to be more in HIV patients as compared to that reported for the general population. ^{[8],[10],[11],[14],[15]} Dysglycemia was found in 30.9% patients. However, the prevalence of diabetes mellitus in HIV patients (10.9%) was approximately similar to that reported for the general population (10.2%) in the age group of 30-39 years. ^[16] While 11 (20%) patients had their blood sugar in the range of impaired glucose tolerance, this number was more than that reported for the general population. ^[8] The most common dyslipidemia was found in the form of low HDL (69.41%). The mean LDL and HDL levels were markedly lower in comparison to those reported for healthy individuals of the same age group. ^[16] Hypercatabolic state and poor nutritional status associated with ongoing chronic inflammation in HIV patients of advanced stages would be one of the pathological conditions to have low LDL and HDL. ^[17] In different studies the prevalence of diabetes in HIV patients and impaired glucose tolerance has been reported with varying rates. ^{[11],[18],[19]} However, in our study higher rates of dysglycemia were more commonly seen in ART-naïve patients as compared to those on ART [Table 2]. Similarly, HDL level was found to be significantly more in patients on ART as compared to ART-naïve patients. Here we noticed that ART was not associated with low HDL cholesterol and had no significant effect on dysglycemia. These findings have already reported by Manuthu EM et.al. ^[20] Explanation for these contradictory findings could be the use of non-PIs-based ART that does not cause dysglycemia and dyslipidemia to such an extent as reported by PIs-based ART or requires long-term use. In prospective reports the prevalence of diabetes mellitus was 10% in HIV patients receiving ART as compared to 3% in ART-naïve patients. ^[21] Dysglycemia was found to be more prevalent in patients of advanced stages of HIV as compared to those in early stages. Although, the symptoms of dysglycemia were present in 27.2% patients, these were also reported in euglycemic patients with the same frequency as in dysglycemic patients. Therefore, on the basis of the absence of these classical symptoms, dysglycemia in HIV patients cannot be ruled out. However, if these symptoms are present in HIV patients, they must be screened for presence of dysglycemia. HDL in patients of advanced stages was found to be low as compared to early stages (by 1.9 mg/dl). HDL level was significantly more reduced in the non-ART group as compared to patients in the ART group. In this study HDL was determined to be reduced by 6.3 mg/dl in patients not receiving ART as compared to those on ART and these results were also supported by the Multicentre AIDS Cohort Study. ^[22] Triglyceride levels were found to be on the higher side in 28.2% patients. In other studies higher prevalence rates have been reported. ^[22] TG levels were found to be on the higher side in the ART group as compared to those who were not on ART. There were no significant differences found in the mean values of HDL and TG among NNRTIs and NRTIs. However, it would not be prudent to comment on the prevalence of dyslipidemia in patients of different categories of ART regimens because the study was limited by small sample size in each category, and the interval for which ART was received was widely varied. In India and most developing countries where the prevalence of HIV/AIDS is high, especially in young people, screening for dysglycemia and dyslipidemia should be recommended in all patients regardless of their clinical staging and ART status. HIV patients with dysglycemia and/or dyslipidemia should be managed rigorously. It is therefore imperative that due cognizance of the risk of cardiovascular disease with ART, be taken and accordingly addressed.

To conclude, we foundthat the prevalence of dysglycemia is higher in HIV patients as compared to that reported for the general population. However, frank diabetes is not more commonly seen among HIV patients as compared to the general population. Therefore, HIV patients had more propensities to develop IGT rather than to have frank diabetes. Low HDL was the most common form of lipid abnormality seen and it was followed by hypertriglyceridemia. HIV patients in advanced stages are more likely to have dyslipidemia. Patients taking ART have less prevalence of dyslipidemia compared to ART-naïve patients. Therefore, ART may have a beneficial effect on the lipid profile. However, further prospective studies are needed to foresee the long-term effect of dyslipidemia and dysglycemia occurring in HIV disease as a risk factor for cardiovascular diseases.

The authors wish to express their deepest gratitude and warmest appreciation to all the HIV patients enrolled in this study, who, in any way have contributed and inspired the authors to the overall success of the undertaking.

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1755-6783.115202

[Table 1], [Table 2], [Table 3]