Insulin Resistance, Dyslipidemia and Cardiovascular Disease Risk in HIV-1 Infected Adults Receiving Protease Inhibitor based Combined Antiretroviral Therapy in the Art Clinic of Tikur Anbessa Referral Hospital.
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Date
2011-12
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Addis Abeba University
Abstract
Treatment with highly active antiretroviral therapy (HAART) has improved the prognosis of patients
with AIDS. However, it has also increased the incidence of various metabolic disorders, in particular
insulin resistance accompanied by dyslipidaemia, hyperglycaemia and lipodystrophy. This is often
predispose to type 2 diabetes and increased mortality from cardiovascular disease which is more common
in protease inhibitor based regimen.
This cross sectional study was designed to assess the occurrence of insulin resistance, dyslipidemia and
cardiovascular disease risk in HIV-1 infected adults taking protease inhibitor based combined
antiretroviral therapy and to compare with those taking NNRTI-based regimen in a total of 134 subjects
that contain equal number of cases and controls. Accordingly, variables like age, sex, type of regimen,
duration of ART were collected and anthropometric variables and blood pressure was measured.
Moreover, biochemical variables like glucose, insulin and lipid profile were determined using standard
and calibrated clinical chemistry analyzers along with a parallel control run in a fasting serum sample
collected from the patients. HOMA and total cholesterol to HDL ratio as well as triglyceride to HDL ratio
were also calculated using a standard formula.
The results revealed an elevated serum triglyceride concentration and a trend toward increase in insulin
resistance on patients treated with PI-based regimen (cases), compared to NNRI-based regimen (controls).
Insulin resistance was observed in 34.3% of the cases as compared to 28.4% in the controls as assessed by
HOMA-IR. HOMA-IR mean values were similar and did not differ significantly between the two groups.
Dyslipidemia was also more prevalent among the cases as compared to the controls. Accordingly, 58.2%
patients on PI based regimen and 47.8% on NNRTI-based regimen had high cholesterol levels (> 5.1
mmol/L). However, the difference was not statistically significant (p = 0.226) and the same is true for
their means (210 ± 41versus 200 ± 35, P = 0.137). Equally higher percentage of patients had high LDL
level (>2.6 mmol/L) on both groups and there was no statistically significant difference in the proportions
as well as mean values between the two groups (65.7% versus 64.2%, p = 0.856; 109 ± 32 versus 112 ±
31, p = 0.584). In this study, it appeared that hypertriglyceridemia (>1.7 mmol/L) affected almost three
fourth (74.6%) of the patients on PI-based regimen and 34.3% on NNRTI-based regimen (p<0.001).
Statistically significant difference was also observed between the mean values of triglyceride (210 ±
41versus 169 ± 124, p = 0.003). Similar trends were apparent when comparing the TG/HDL ratio in both
groups, with 74.6% of patients on PI-based regimen and 38.8% on NNRTI-based regimen presenting with
high TG/HDL ratio (> 3.8) (p <0.001). Further aggravating the cardiovascular risk, a significantly higher
proportion of patients on PI-based regimen had higher total cholesterol /HDL ratio (61.2%) as compared
with those on NNRTI-based regimen, 40.3% (p=0.016). Likewise, the mean differences between the two
groups were also statistically significant for both TG/HDL and TC/HDL (6.96 ± 4.6 versus 3.98 ± 2.69
and 5.7±1.7 versus 5.0 ± 1.4) with p values 0.026 and <0.001 respectively. Moreover a significantly
higher proportion of patients on PI-based regimen were found to have metabolic syndrome as compared
to the controls (32.8% versus 17.9%, P = 0.047), with 10.4% of patients on PI-based regimen estimated to
have an intermediate (10-20%) risk of developing cardiovascular disease in the coming ten years as
compared to only 1.5% on NNRTI-based regimen(P = 0.029)
Taken together, this study concluded that patients on PI- based cART have higher risk of developing
insulin resistance and cardiovascular problems.
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Keywords
Protease inhibitors, Insulin resistance, Dyslipidemia, HOMA, Metabolic syndrome