ABSTRACT

The introduction of highly active antiretroviral therapy (HAART) has significantly improved life expectancy among HIV positive individuals. However the impact of this treatment on individual micronutrients, other biochemical parameters and cardiovascular risk has not been well elucidated in this environment.

This study evaluated cardiovascular risk factors, selenium, zinc, magnesium, lipid profile, fasting blood sugar, haemoglobin, CD4 count and transaminases

among human immunodeficiency virus (HIV) afflicted Nigerian subjects on

HAART.

Subjects are HIV afflicted adult patients who presented consecutively at Imo State University Teaching Hospital Orlu, who are HAART naïve and agreed to written consent. A total of 99 volunteers comprising 51 patients and 48 HIV sero-negative adults as control participated. Their body weight, height, blood pressure, arterial pulse rate were measured, 10 ml of fasting venous blood samples were also taken before commencing HAART and at 6 months on

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HAART. Samples were analyzed for lipid profile, blood sugar, magnesium, zinc, selenium, haemoglobin and CD4.

Serum magnesium, zinc and selenium were significantly lower in HIV patients before HAART (p < 0.05) compared with control. However, serum levels of these minerals significantly increased after HAART compared to pre-HAART values.

Serum aspartate aminotransferase (AST) concentration was significantly higher after HAART compared with control.

Serum triglyceride (TG) significantly increased following HAART compared to control while high density lipoprotein (HDL) increased compared to pre-HAART values (p<0.05). There was no significant change in total cholesterol before or after HAART compared to control.

CD4 count increased significantly in HIV patients while on HAART compared

to values before HAART. However these values were lower than control value. Haemoglobin (Hb) significantly increased in HIV patients while on HAART when compared to these patients before HAART.

Blood sugar levels were similar in all groups.

In conclusion, HAART was beneficial to the patients as it enhanced CD4 count,

haemoglobin, and HDL but it increased serum triglyceride. HAART also improved low magnesium, zinc and selenium observed in HIV. This study

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suggests that the non protease inhibitor-based HAART may however predispose HIV patients to cardiovascular risk and that supplementation of these minerals may not be necessary in HAART.

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CHAPTER ONE

INTRODUCTION

1.1 Background

The introduction of the Highly Active Antiretroviral Therapy (HAART) has spectacularly changed the prognosis of Human Immunodeficiency Virus (HIV) infection by greatly prolonging the life span of subjects. Unfortunately HAART is associated with increased cardiovascular risks resulting in myocardial infarction occurring in younger age groups (SoRelle , 1998; Sklar and Masur, 2003 ) . Poor lipid profile, impaired glucose tolerance and in a few cases frank diabetes mellitus, redistribution of body fat (lipodystrophy) including abdominal obesity have all been reported (Shaw et al, 1998; Green, 2002; Riddler et al, 2003; Domingo et al, 2008 ). Other studies showed similar metabolic changes, although to a lower extent in HIV positive subjects not on any antiretroviral medication and concluded that HIV infection itself was in part responsible for the increased cardiovascular events (Carl and Tien, 2004; Caarr and Ory, 2006; Gross, 2006; Mujawar et al, 2006; Rasheed et al, 2008.). Initially it was thought that the protease inhibitors (PI’s)

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were responsible for these changes. It is now known that non PI-based HAART also has the same metabolic effect, although the PI’s are worst, with ritonavir at the lead (Papdopoloulos et al, 1998; Levy et al, 2000; Shahmahesh et al, 2001; Fontas et al, 2004.). A study showed a clear evidence that HIV-1 protein and antiretroviral drugs cause endothelial dysfunction, a key step in cardiovascular disease , although the extent of contribution of each is unclear (Kline and Sutliff, 2008) . Most of these studies were done in advanced countries; a record was found of a study done in Africa, still this was a case report of HAART - induced diabetes mellitus (Bakari et al, 2007). The well documented racial \ ethnic and social variation in cardiovascular risk makes it important to evaluate the changes in cardiovascular risk factors in HIV positive black subjects on HAART in a developing country with racial and social environment widely apart from those of advanced countries. A study had found a strong race / ethnic difference in plasma lipids in HIV-1-infected individuals on antiretroviral therapy (Foulkes et al, 2006).

Besides, the high rate of cellular turnover of the immune system make it a major user of nutrients, hence, immune function depend highly on nutritional status. This nutritional need increases even further in acute or chronic infection including HIV.

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This explains in part the deficiencies in nutrients including trace elements widely reported in HIV infected subjects. (Baum et al ,1997; Wellinghausen et al, 2000; Jonenz-Exposito et al, 2002; Foulkes et al, 2006; Jones et al, 2006; Bakari et al, 2007; Khalili et al, 2008.) . The severity of nutrient deficiency has been shown to be a strong determinant of disease progression (Baum et al, 1997).

Selenium deficiency was found to be an independent predictor of survival in HIV infection (Baum et al, 1997). Supplementation of this mineral increased serum concentration by 50% and reduced coronary heart disease risk by 24% (even though this is inconclusive) and also reduced symptoms of heart disease although it did not reverse immunological and heamatological parameters (Cirelli et al, 1991). Another study showed that selenium deficiency worsened cardiovascular risk factors in healthy Saudi males (Alisa et al, 2008). Another team of researchers suggested that selenium supplementation in HIV-infection could be of great interest in protecting cells from oxidative stress and improve survival (Delmas-Beauvleux, 1996).

Zinc deficiency was found in 23% of HIV-infected persons, with serum concentration comparable in treated and untreated patients (Wellinghausen et al,

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2000). Another team reported zinc deficiency in 40% men and 36% women on HAART (Jones et al, 2006).

Low plasma and erythrocyte magnesium was reported in HIV, but even lower in HIV subjects who consume alcoholic beverages (regularly) (Bogden et al, 2000 ). In children infected with HIV, however, routine monitoring of serum micronutrients may be unnecessary in the absence of any specific clinical indication of deficiency (Henderson et al, 1997).

Again reports of these nutrient deficiencies on black HIV subjects are very few. Besides, there are no reports on nutrient changes in HIV subjects after HAART is commenced.

Hepatotoxicity is one of the complications of HAART. Life threatening acute toxic hepatitis was reported in Turkey of a HIV positive patient on HAART (Gokengin and Yamazhan, 2002) including nevirapine, a non nucleoside reverse transcriptase inhibitor (NNRTI). Mitochondrial toxicity induced by nucleoside reverse transcriptase inhibitors (NRTI’s) is believed to be responsible for various adverse effects of NRTI’s. The NRTI , didanosine was found to be associated with the lowest peripheral blood mononuclear cells (PBMC’s) mitochondrial DNA (mtDNA) thus with the highest risk of long-term adverse effects (Saitoh et al,

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