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 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="" after="" before="" change="" cholesterol="" compared="" control.="" haart="" in="" no="" or="" significant="" span="" there="" to="" total="" was="">
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 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.
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) 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.
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, 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, 2007). Drug history, liver enzyme studies among others could
identify the probable cause of liver disease in 78% of HIV infected patients on
HAART (Ocama et al, 2008; ). Significantly low prealbumin was found in HIV
infected subjects (Baum et al, 1997). Analysis of serum levels of liver enzymes
in Nigerian subjects on HAART may then be useful.
1.2 Design
This was a prospective study with HIV positive cohorts
recruited from the Institute of Human Virology of Nigeria (IHVN)-assisted
HIV/AIDS treatment unit of the Imo State University Teaching Hospital (IMSUTH)
Orlu, a new Teaching Hospital located in a sub-urban area of South Eastern
Nigeria. All consecutive eligible subjects who gave consent were recruited.
The local ethics standard of the hospital for biomedical
research was respected and written approval secured from the Hospital Ethics
Committee.
The research also
conformed to the Helsinki declaration on biomedical research.
Written informed
consent was secured from each participant.
Only male and female subjects 18 years and over were
recruited. All eligible participants had laboratory confirmation of HIV
infection, were drug (antiretroviral) naïve and were prequalified by the
hospital clinician responsible for HAART administration as suitable to commence
HAART based on WHO recommendations.
1.3 Aim
The aim of this study is to evaluate the side effects of
HAART and its effects on serum minerals on HIV positive Nigerians.
1.4 Objective
The objective of this study is to evaluate the changes in
cardiovascular risk factors in HIV positive black subjects in a developing
country receiving HAART.
To evaluate possible nutritional (micronutrient and body
mass index) changes in HIV infected African subjects as they commence HAART.
To evaluate the
changes in liver enzymes and lipid profile in HIV subjects receiving HAART.
To make suggestions
based on identified cardiovascular risks and depleted micronutrients that will
improve the management of these patients.
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Item Type: Project Material | Size: 106 pages | Chapters: 1-5
Format: MS Word | Delivery: Within 30Mins.
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