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Ind. J. Sci. Res. and Tech. 2013 1(1):53-61/Gowdaiah et al ISSN:-2321-9262 (Online)
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Research Article
PLASMA LIPIDS AND HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; A
PROSPECTIVE STUDY
*Prakash Kikkeri Gowdaiah1, Rajiv Elkal Neminatha2, Madhu Sudan Channappa1, Sandeep Sreerama
Reddy1 and Debasish Barik1
1Department of Medicine, Bangalore Medical College and Research Institute, Bangalore 2Department of Nephrology, Institute of Nephrourology, Bangalore *Author for Correspondence
ABSTRACT
Background: With the introduction of HAART, people with HIV infection live longer and considerable morbidity
and mortality they experience now is not from AIDS related illness, but from adverse effects of ART drugs.
Dyslipidemia is an important adverse effect of HAART, which can contribute adversely to overall cardiovascular
risk profile of the patient. Hence, we undertook this study to determine the impact of WHO recommended NRTI
based antiretroviral therapy on the lipid profile of HIV infected patients. Materials and Methods: This was a
prospective study, conducted from October 2010 to September 2012 at Bangalore Medical College and Research
Institute, Bangalore, India. 100 treatment naïve HIV infected patients with normal lipid profile as per NCEP ATP III
guidelines were recruited. 50 patients were assigned randomly to zidovudine based NRTI regimen (zidovudine
group) and another 50 to stavudine based regimen (stavudine group). They were followed up at regular intervals (6th
week, 6th month and at one year). At each visit, lipid profile was determined after an overnight fast, and
dyslipidemia diagnosed according to US National Cholesterol Education Programme III criteria. Data was compiled
and the results were analyzed using suitable software and appropriate statistical methods. Results: Both the groups
were age and sex matched. Maximum number of patients was in 31– 40 years age group. Hypertriglyceridemia was
the most common and earliest dyslipidemia to appear. 44% of patients in stavudine group and 21% of zidovudine
group had hypertriglyceridemia. Second most common dyslipidemia was increased total cholesterol, present in 38%
of stavudine and 12% of patients in zidovudine groups. This was followed by increased LDL-cholesterol, present in
29% patients of stavudine and 7% of patients in zidovudine groups. HDL-cholesterol showed marginal decrease in
both the treatment groups. Conclusion: The incidence of dyslipidemia in patients taking long term WHO
recommended NRTI based HAART (especially stavudine containing) is high. This may contribute adversely to
overall cardiovascular risk profile of the patient. Hence, patients should be closely monitored for this complication
and suitable interventions, either in the form of lifestyle modifications, lipid lowering drugs or introduction of
alternative HAART regimens containing tenofovir and abacavir should be considered.
Key Words: Highly Active Antiretroviral Therapy (HAART), NACO Guidelines and Dyslipidemia
INTRODUCTION
Highly active antiretroviral therapy has transformed HIV infection into a chronic manageable disease, which has led
to marked improvement in life expectancy for those infected with the virus. Despite reductions in the incidence of
AIDS with effective treatment, patients continue to experience considerable morbidity and mortality from non AIDS
illnesses such as premature cardiovascular disease, liver failure and renal failure. The implicated causes could be
either acute drug toxicities or long term morphologic effects like abnormalities in body fat distribution and
metabolic complications like dyslipidemia, insulin resistance, diabetes mellitus, hyperlactemia and osteopenia (Eoin
& Patrick, 2011; Vicente & Joquim 2011).
One of the principal drivers behind the well documented increase in the risk of cardiovascular disease in HIV
infected patients is dyslipidemia. Abnormalities in lipid metabolism of persons infected with HIV virus potentially
induced by the disease itself and also by the medications used to treat the disease; were first reported in the early
1990s. Hypertrigyceredimia and a decrease in total cholesterol and HDL cholesterol occuring in advanced phases of
HIV infection are considered as markers of chronic inflammation (Grunfeld, 2010; Shor-Posner et al., 1993).The
charecteristic pattern of dyslipidemia induced by HAART includes elevated triglycerides (40-80%), elevated LDL
cholesterol (40-80%) and total cholesterol (10-50%) (Sherer, 2003; Riddler et al., 2003 & 2007).
In HAART induced metabolic dysfunctions, many features are similar to those observed in non alcoholic fatty liver
disease (NAFLD). Enhanced endoplasmic reticulum stress (PI) and mitochondrial toxicity (NRTI) are the proposed
biochemical mechanisms causing dyslipidemia. Protease inhibitors (PI) and Nucleoside reverse transcriptase
inhibitors (NRTI) based regimens were implicated in inducing maximum dyslipidemia, while switch over from PI to
NNRTI based regimens attenuated dyslipidemia (Domingos et al., 2009; Galli et al., 2002).
Ind. J. Sci. Res. and Tech. 2013 1(1):53-61/Gowdaiah et al ISSN:-2321-9262 (Online)
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Research Article
In a developing country like India, the data regarding HAART induced dyslipidemia is limited. There are only a few
Indian studies on the subject (Pujari et al., 2005; Kalyan et al., 2012; Padmapriyadarshini et al., 2011; Jain et al.,
2013) and the majority of them are cross sectional in design. Hence, we undertook this prospective study with the
aim of quantifying the magnitude of change in plasma lipids over a period of 12 months, following initiation of
HAART (non PI based) in a cohort of HIV/AIDS patients treated in a large tertiary care institution.

MATERIALS AND METHODS
This was a prospective study conducted over a period of 2 years from October 2010 to September 2012. The study
included 100 treatment naïve patients with confirmed HIV infection attending ART centre at Victoria Hospital
which is a tertiary care Hospital attached to Bangalore Medical College, Bangalore. All the patients were 18 years or
older and met NACO guidelines to initiate HAART. All of them had normal lipid profile at baseline as per NCEP
Adult Treatment Panel III guidelines (Riddler et al., 2007). Acutely ill patients were excluded. Other exclusion
criteria were; patients on antilipidemic drugs, diabetics or patients with Thyroid dysfunction. Four WHO
recommended first line HAART regimens used in the study were; d4T+3TC+NVP, d4T+3TC+EFV,
AZT+3TC+NVP and AZT+3TC+EFV.
After obtaining an informed written consent, blood was drawn for baseline laboratory investigations such as CD4
count, 12 hours fasting lipid profile, Liver function tests, Renal function tests, FBS and PPBS. Then the patients
were assigned randomly to one of the abovementioned HAART regimens.
They were followed up for a period of 12 months with regular study visits at 6th week, 6th month and one year from
the date of initiating the treatment. At each visit, they were assessed for adherence to treatment regimen and a 12
hour fasting lipid profile was obtained. In accordance with US National Cholesterol Education Program Adult
Treatment Panel III (NCEP, ATP- III) guidelines (NCEP, 1995), abnormal lipid profile was defined as follows:
Total Cholesterol (TC) ≥ 200mg/dl Low density lipoprotein cholesterol (LDL-C) ≥ 130 mg/dl Triglycerides (TG) ≥ 150 mg/dl High density lipoprotein cholesterol (HDL-C) < 40mg/dl All the data were recorded in a printed Performa. This study was approved by the Institutional Ethics Committee.
Statistical methods
Descriptive statistical analysis was carried out in this study using software SPSS 15.0, Stata 8. Results on continuous
measurements were presented as mean ± SD, and results on categorical measurements were presented in number
(%). Significance was assessed at 5% level. Student test was used to find the significance of study parameters on
continuous scale between two groups (Inter group analysis). Chi square/ Fisher Exact test was used to find the
significance of study parameters on categorical scale between two groups.
RESULTS
Out of 100 patients who were enrolled into the study, 25 patients each were randomly assigned to one of the four
treatment groups mentioned earlier. But, for descriptive and statistical analysis they were grouped into two
categories as follows:
Stavudine group (50 patients) Zidovudine group (50 patients) As shown in Table 1. Both the groups were evenly sex and age matched. The maximum numbers of patients were
aged between 31 – 40 years (Fig. 1).

Table 1: Age and Sex distribution of study population
Stavudine group
Zidovudine group
Significance P value
Ind. J. Sci. Res. and Tech. 2013 1(1):53-61/Gowdaiah et al ISSN:-2321-9262 (Online)
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Figure 1: Showing age distribution pattern

At the end of one year follow up, it was found that there was significant increase in mean serum levels of
triglycerides (TG), total cholesterol (TC), and LDL cholesterol in both groups of patients (Table 2). This significant
change in lipids was noticed to occur from as early as 6th month of follow up. Maximum change occurred in
triglyceride levels, and patients in stavudine group showed greater percentage increase from baseline levels in all the
lipid parameters (except HDL cholesterol) when compared to zidovudine group as summerised and shown in Table
3.
Table 2: Depicting change in mean serum levels of lipid parameters from baseline to various intervals of
follow up to one year, between two groups of patients
Lipid parameters
Baseline
At 6th week
(mean value)
6th month
Total cholesterol Triglycerides(TG) Ind. J. Sci. Res. and Tech. 2013 1(1):53-61/Gowdaiah et al ISSN:-2321-9262 (Online)
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Table 3: showing summary of lipid changes in percentage values

Stavudine
Zidovudine
Reference fig number
Percentage increase in total cholesterol (TC) Percentage increase in triglyceride (TG) levels Percentage Increase in LDL cholesterol (LDL-C) Figure 2: Showing changes in mean total cholesterol levels over different intervals of follow up
Figure 3: Showing changes in mean serum triglyceride levels over different intervals of follow up
Ind. J. Sci. Res. and Tech. 2013 1(1):53-61/Gowdaiah et al ISSN:-2321-9262 (Online)
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Figure 4: Showing changes in mean serum LDL-cholesterol levels over different intervals of follow up
HDL cholesterol decreased by 1.3% and 0.44% in stavudine and zidovudine groups respectively (statistically not significant) (Fig. 5). Figure 5: Showing changes in mean serum HDL-cholesterol levels over different intervals of follow up
Analysis of the patient data on individual basis i.e number (%) of patients showing dyslipidemia over 12 month period (Table 4) was similar to that of changes in mean levels of lipid parameters. Hyper triglyceridemia occurred in maximum number of patients and it was the earliest lipid abnormality to occur. More number of patients in the stavudine group showed dyslipidemia when compared to zidovudine group as summarized in Table 5. Ind. J. Sci. Res. and Tech. 2013 1(1):53-61/Gowdaiah et al ISSN:-2321-9262 (Online)
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Table 4: Showing number (%) of patients with lipid abnormalities over different time Intervals of follow up
to one year
Lipid parameters
Baseline
At 6th week
At one year

Table 5: Showing summary of number (%) of patients with dyslipidemia

Stavudine group
Zidovudine group
Hypertriglyceridemia 23 (44%) patients 9 (21%) patients. ( Fig. 6) Hypercholesterolemia 20 (38%) patients 8 (12%) patients. ( Fig. 7) 16 (29%) patients 3 (7%) patients. ( Fig. 8) HDL cholesterol decreased in 3 (6%) patients in stavudine group, and in 1(2%) patient of zidovudine group. Figure 6: Showing percentage of patients with hypertriglyceridemia (Triglycerides ≥ 150 mg/dl) over
different time intervals of follow up
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Figure 7: Showing percentage of patients with hypercholesterolemia (Total cholesterol ≥ 150 mg/dl) over
different time intervals of follow up
Figure 8: Showing percentage of patients with raised LDL cholesterol (LDL-C ≥ 130mg/dl) over different
time intervals of follow up

DISCUSSION
We recruited 100 patients who fulfilled the inclusion criteria, and 50 patients were put on stavudine based HAART,
and another 50 were put on zidovudine based HAART randomly, according to NACO guidelines. Both the groups
were age and sex matched, with normal serum lipid levels at the start of therapy. We followed them up at regular
intervals of 6th week, 6th month and 12th month. At each visit the patients were assessed for adherence to therapy and
underwent a thorough physical examination and laboratory investigations which included a 12 hour fasting serum
lipid estimation. Our results showed that (Table 2, Table 4), significant dyslipidemia starts as early as 6 months of
Ind. J. Sci. Res. and Tech. 2013 1(1):53-61/Gowdaiah et al ISSN:-2321-9262 (Online)
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initiating an NRTI based HAART. Patients who were treated with stavudine containing regimens showed the
earliest and significant increase in serum lipids. Eric et al., (2011), in a cross sectional study involving 138 patients,
on stavudine based regimen also noticed significant dyslipidemia beginning to appear at or around 6 months of
initiation of therapy. Hypertriglyceridemia was the most common lipid abnormality, which was found in 44% of
patients on stavudine based regimens and 21% of patients on zidovudine based regimens. Pujari et al., (2005)
reported 45% incidence, Oosterhout et al., (2012) reported 37.6% and Llibrea et al., (2006) reported 43% incidence
of hypertriglyceridemia in their cross sectional studies with stavudine based regimens, which is similar to the results
of the present study.
Increase in total cholesterol (hypercholesterolemia) was the second most common lipid abnormality in our study,
which was present in 38% of patients on stavudine based regimens and 12% of patients on zidovudine based
regimens. This was followed by increase in LDL cholesterol which was present in 16% and 7% of patients on
stavudine and zidovudine based regimens,respectively. Pujari et al., (2005) reported 41.3% incidence, and Llibrea et
al., (2006) reported 35% incidence of hypercholesterolemia in stavudine based regimens, which is similar to the
results of the present study. There were no statistically significant changes in HDL cholesterol levels in both groups
of patients.

CONCLUSION
From the results of our study, it can be concluded that significant dyslipidemia occurs in NRTI based HAART
regimens especially those containing stavudine. Significant change in blood level of lipids starts as early as 6th
month of initiation of therapy, and hypertriglyceridemia is the commonest lipid abnormality noticed in our study,
followed by increase in total cholesterol and LDL cholesterol. This dyslipidemia associated with HAART is an
important cardiovascular risk factor and may contribute to significant morbidity and mortality, not directly related to
HIV infection. Hence, to mitigate this risk the recommendations of European AIDS clinical society guidelines on
non infectious co morbidities may be followed as given below:
Lipid parameters (TG, TC, LDL-c, HDL-c) should be estimated prior to initiating HAART and at least annually
after starting a new regimen.
In patients with dyslipidemia, and especially in those with other cardiovascular risk factors, lifestyle modifications
such as smoking cessation, diet and exercise should be recommended first. If NCEP lipid goals are not achieved
despite this, the use of lipid lowering drugs like statins and fibrates should be considered.
Additionally, modification of ART regimen like switching from stavudine and zidovudine to abacavir or tenofovir
may also be considered.
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