Lipids are heterogenous group of water insoluble (hydrophobic) organic particles that can be extracted from tissues by non polar solvents. Lipids constitute 15-20% of body weight in humans [1].

Cholesterol and triglycerides are water insoluble lipids that are carried in blood by particles called lipoproteins. Diet, genetics and acquired factors may affect the circulating levels of one or more lipoproteins, thereby affecting the levels of cholesterol, triglycerides or both. Three main classes of lipoproteins can be measured in blood.

• Very low density lipoprotein (VLDL)

• Low density lipoprotein (LDL)

• High density lipoprotein (HDL)

LDL and HDL mainly transport cholesterol and VLDL is the major carrier of triglycerides. Triglycerides are the storage or carrier form of fatty acids in tissue and plasma [2].

Type 2 Diabetes is associated with an increased risk of cardiovascular disease (CVD). A major abnormal lipid profile is known as dyslipidemia, which is characterized by low HDL-cholesterol (HDL-C), raised serum triglycerides (TG’s) and a predominance of small dense LDL-Cholesterol (LDL-C) particles [3].

Insulin resistance and Hyperinsulinemia are associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very low-density lipoprotein cholesterol (VLDL-C) synthesis, leading to Hypertriglyceridemia. Progressive elimination of lipids and apolipoprotein from the very low-density lipoprotein cholesterol (VLDL-C) particle leads to an increased formation of intermediate density and low density lipoprotein cholesterol, both of which are atherogenic. Insulin enhances cholesterol transport into arteriolar smooth muscle cells and increases endogenous lipid synthesis by these cells [4].

Individuals with metabolic syndrome are associated with dyslipidemia. Dyslipidemia is characterized by hypertriglyceridemia and diminishment of High-density lipoprotein cholesterol (HDL-C). In severe forms of insulin resistance, Low-density lipoprotein cholesterol (LDL-C) may also be elevated. Hypertriglyceridemia is due to an increase in the rate of synthesis of very low-density lipoprotein cholesterol (VLDL-C) in the liver and a reduction in their breakdown by the lipoprotein lipase in non-hepatic tissue [5].

The earliest changes in the treatment naïve HIV patients are probably dyslipidemia with plummeting of HDL levels. As the disease progresses, LDL-C decreases followed by an increase in triglycerides, apolipoprotein levels and VLDL in the advance course of the disease. Hypertriglyceridemia may be due to decreased clearance of triglycerides and increased production of VLDL [6].

Once the patients are initiated on HAART, the impact on the components of MetS is more pronounced. Some of the initial changes found in the early stages of HIV infection get exacerbated with addition of more components. These changes depend on the medications on the HAART regime. Hypertriglyceridemia in general worsens with Ritonavir based PI (Protease Inhibitor) regime with an increase of up to 83% in one study and could be due to effect of Ritonavir’s inhibitory effect on degradation of apolipoprotein B [7].

Insulin resistance can occur in HIV patients on therapy, but probably the mechanism is different from the general population. Multiple antiretroviral drugs - zidovudine, lamivudine, stavudine, efavirenz and most of the protease inhibitors have been found to have influence on glucose metabolism though by different mechanisms some of which are still not well understood. Studies have shown that PIs selectively inhibit glucose transport in adipocytes without affecting early insulin-signaling events or translocation of intracellular GLUT4 transporters to the cell surface [8].

The resultant effects of HIV infection with or without therapy lead to a state of immune dysfunction with profound influence on lipid metabolism, body habitus and vascular architecture leading to a prothrombotic state thereby enhancing the risk of cardiovascular diseases manifold [9].

Metabolic complications and abnormal fat distribution were frequently observed after a few years of antiretroviral therapy and, as the array of antiretroviral drugs became broader, long term metabolic alterations are becoming far more common worldwide. Nevertheless, the risk of not being on HAART is overwhelmingly greater than the metabolic adverse events in terms of morbidity and mortality events [10]. 

HIV/HAART-induced metabolic imbalances overlap to some extent the components of Metabolic Syndrome (MetS) and its high rates in the HIV population place infected individuals in an elevated CVD risk category [11].

The introduction and widespread use of highly active antiretroviral therapy (HAART), has led HIV-infected individuals to experience a dramatic decline in immunodeficiency-related events, including causes of death [12-14]. As a consequence, life-expectancy increased, which exposed them to the effects of aging itself, including the influence of the same environmental risk factors known to act in the general population and contributing to the occurrence of obesity, diabetes mellitus (DM), and cardiovascular diseases (CVD) [15-16]. However long term toxicities are emerging after prolonged exposure to antiretroviral therapy and are becoming challenges to successful HIV management. Exposure to combination antiretroviral treatment, for instance increased the incidence of MI by 26% per year in developed nations [17].

According to the Third National Health and Nutrition Examination Survey, prevalence of MetS in the general US population has been estimated as 25% and this number has been growing continuously over time [18]. MetS encompasses a cluster of risk factors leading to CVD as primary clinical outcome and contribute to higher risks of DM. Such factors include obesity (mainly central adiposity), defective glucose metabolism (DM, impaired glucose tolerance, or impaired fasting glycaemia), raised blood pressure, and elevated TG and low HDL-C levels [10-11].

Of all the nucleoside reverse transcriptase inhibitors (NRTI’s), Stavudine is most commonly cited antiretroviral agent that is being associated with MetS and HIV related fat accumulation [19]. Moreover Protease Inhibitors (PI) in general have been reported to be highly associated with MetS [20]. The pathways underlying such alterations are not always known but an in vitro assay with PIs and NRTIs showed altered adipocyte functions and decreased adiponectin, a positive regulator of insulin sensitivity, due to an increased expression and secretion of pro-inflammatory cytokines [21]. Even without commencing ART, elevated lipid levels have been linked with HIV infection itself [22].

Disorders in lipid and glucose metabolism, accompanied by body shape abnormalities and alterations in fat distribution also began to be described. A syndrome, named "HIV-associated lipodystrophy syndrome", was coined to classify these clinical spectrum aspects. This syndrome involves not only metabolic alterations but also fat redistribution, the most visible effect being facial lipoatrophy (fat loss), increased upper trunk fat (buffalo hump), lipoatrophy of the arms and legs, and abdominal obesity. HIV patients also experience increased prevalence of ectopic fat distribution in liver and muscles [5,4]. This is not seen in treatment naive HIV patients, but more common once HAART is initiated with PI based regimes and also with stavudine, which mercifully is now rarely used. Central obesity as a consequence of lipodystrophy is a component of MetS. Also these patients have abdominal subcutaneous lipoatrophy more pronounced in the abdomen with consequent loss of hip circumference and spuriously elevated waist hip ratio. This makes inclusion of waist hip ratio an unreliable component in the diagnosis of HIV induced metabolic syndrome. These changes in body shape are very important to be recognized, as they are associated with worse morbidity and mortality particularly CVD [23].

The link between HIV infection and development of hypertension is at best tenuous. Epidemiological studies have not found an increased incidence of hypertension in treatment naive HIV patients [24]. However, use of effective antiretroviral therapy has been linked to development of hypertension though some reports have implicated protease inhibitors as the cause. Increase in BMI after effective antiretroviral therapy has been postulated as the cause of hypertension [25].

This cross sectional study was conducted in Department of Medicine in collaboration with ART Centre, Rajindra Hospital, Patiala. Hundred HIV positive patients between the age group of 18 to 70 years and fulfilling inclusion criteria were selected from various wards of Rajindra Hospital Patiala and those reporting to ART centre from November 2014 to August 2016.

All patients were examined thoroughly. Anthropometric and Laboratory data was collected and results were statistically analysed. All the patients and their relatives were informed about the study in their vernacular language. Written consent was taken. Clinical examination and all the relevant investigations were performed. Results were tabulated and subjected to statistical analysis using SPSS and represented in the form of bar diagrams and pie charts as and where required.

Inclusion Criteria

• Previously or newly diagnosed HIV positive patients (ART and Pre-ART)

• Age more than 18 years

Exclusion Criteria

• Withdrawal of combination ART 

• Evidence of clinical signs of active AIDS in the 3 months before entry Because of their possible impact on anthropometric and laboratory parameters

• Pregnant women and anyone who switched ART combination regimen for any reason

Blood Pressure measurements -3 readings were taken and the mean of second and third recordings was taken. In all the patients venous blood sample was collected after overnight fasting of 8-12 hours in a standard empty vial. Serum Triglycerides were estimated by GPO/PAP method, HDL-C was estimated by PEG/CHOD-PAP method and FPG by Glucose Oxidase method.

As shown in the table-1 above, 46% (n = 46) of patients had Triglycerides levels of <150 mg/dl, while 54% (n = 54) had TG levels of more than or equal to 150 mg/dl. Mean TG’s levels were 172.63+59.411 mg/dl and range was 100-350 mg/dl.

Table 1: Triglycerides Distribution

Table 2: Hdl-C Distribution

Table 3: Blood Pressure Distribution

Table 4: Fasting Glucose Distribution

As shown in the Table 2 above, 30% (n = 30) of patients had High density Lipoprotein Cholesterol levels less than cutoff values for the diagnosis of MetS i.e <50 mg/dl in females or < 40 mg/dl in males, while 70% (n = 70) had HDL-C levels in normal range.

In our study of 100 patients, 34% of patients (n = 34) had High Blood Pressure, i.e either Systolic (SBP) >130 mm hg or Diastolic (DBP) >85 mm hg or patient was on antihypertensive medication while 66% of patients (n = 66) were below the said cuttoff values. (Table 3)

As shown in the table 4 above, Most of the patients had Fasting glucose levels <100 mg/dl i.e 69% (n = 69) while 31% of patients had Fasting glucose levels in the impaired range of >100 mg/dl.Mean FPG levels were 103.52 mg/dl with 32.75 standard deviation.Range was 75-260.

Recent observations have suggested that chronic infectious diseases like HIV and chronic hepatitis B and C are associated with MetS. High blood levels of pro-inflammatory cytokines like CRP have been found in these conditions indicating enhanced inflammation. However, the infectious disease which has been conclusively linked with MetS for more than two decades has been HIV infection even if the patient has responded to antiretroviral therapy [26-27]. However, the Literature is scanty regarding the prevalence of MetS in HIV infected patients in India and particularly in Punjab. Thus study has been contemplated to asess the prevalence of MetS in HIV infected patients in this direction.

It has been observed that the earliest changes in the treatment naïve HIV patients are probably dyslipidemia with plummeting of HDL levels. As the disease progresses, LDL-C decreases followed by an increase in triglycerides, apolipoprotein levels and VLDL in the advance course of the disease. Hypertriglyceridemia may be due to decreased clearance of triglycerides and increased production of VLDL [6].

As per various studies conducted in evaluating prevalence of metabolic syndrome, the most common abnormality associated with diagnosis of metabolic syndrome is dyslipidemia, primarily hypertriglyceridemia and low High density lipoprotein cholesterol. In our study also we found that the most deranged parameter was hypertriglyceridemia, prevalence of hypertriglyceridemia was 54%, i.e out of 100 patients, 54 had elevated TG’s (>150 mg/dl).Mean TG in our study was 172.63 mg/dl with SD 59.411. This finding is comparable to various studies done by Gazarusso C et al. [28], Elgalib A et al. [29] and Bajaj Sarita et al. [30].

In our study the prevalence of reduced High density lipoprotein cholesterol is 30%, i.e out of 100 patients ,30 had reduced HDL-C (<50 mg/dl in females and <40 mg/dl in males).This finding is comparable to study done by Elgalib et al. [29] in 2011, 

High prevalence of Reduced HDL-C in studies done by Gazarusso C et al. [28] and Bajaj Sarita et al. [30] may be attributed to different demography and sample size of population.

Another derangement in MetS may be that of raised Blood pressure, in our study out of 100 patients, 34 patients had either high Systolic or diastolic pressure or patient was on anti hypertensive agent i.e prevalence of high BP was 34% in our study.This finding is comparable to earlier studies by Gazarusso C et al. [28] and Ngatchou W et al. [31].

In our study, prevalence of impaired fasting glucose was 31% i.e 31 out of 100 patients in our study group had Fasting Plasma Glucose of >100mg/dl. This finding is comparable to that observed in a study by Gazarusso C et al. [28] in 2002.

Low prevalence of Dysglycemia in Elgalib A et al. [29] may be due to High cutoff value of Fasting plasma glucose as per unrevised NCEP ATP III guidelines. Also high prevalence of FPG in study done by Ngatchou W et al. [31] may be attributed to Demographic factors and ethnicity of sample population. Mean Fasting plasma glucose in our study was 103.57 mg/dl with SD of 32.75. This is also comparable to that found in the study conducted by Silva EF et al. [32] in 2009. They found the mean FPG to be 101 mg/dl.

In our study, 54% of patients had dyslipidemia i.e atleast one or both of Hypertriglyceridemia or reduced HDL-C with most common abnormality being Hypertriglyceridemia, prevalence being 54% (n = 54).Prevalence of reduced HDL-C was 30% (n = 30). Both are significantly associated with prevalence of Metabolic Syndrome on statistical analysis (p<0.05). In our study, 34% of patients (n = 34) had hypertension or were taking antihypertensive medication.Out of these 16 patients were diagnosed as having Metabolic syndrome. In our study, 31% of patients (n = 31) had impaired fasting plasma glucose out of which 18 patients were labelled as MetS cases. Mean FBS levels were 103.52 mg/dl with standard deviation of 32.75 and range of 75-260 mg/dl. In our study of 100 HIV patients, 28% of patients didn’t meet any specified criteria for MetS, 29% patients met 1 criteria, 22% of patients met 2 criteria, 21% of patients (n = 21) had > = 3 criteria and were subsequently labelled as having MetS. So Most important derangement seen in these patients is dyslipidemia in the form of Hypertriglyceridemia and reduced HDL-C. As these patients are at an increased risk for Cardiovascular diseases and Diabetes mellitus, our aim should be to screen these patients at risk and manage accordingly to further reduce morbidity and mortality among HIV infected patients.

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