ASSESSMENT OF HAEMATOLOGICAL PARAMETERS IN ANTI-RETROVIRAL THERAPY (ART)-NAÏVE HIV POSITIVE CHILDREN IN ENUGU, NIGERIA

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                                                     ABSTRACT
The Human immunodeficiency virus (HIV) infection is one of the most important emerging infections of this century. The haematological complications such as anaemia, neutropenia and thrombocytopenia are associated with HIV disease progression and reduced survival and they have been documented to be the second most common causes of morbidity and mortality in children. Hence, this study sought to assess the haematological parameters in HIV positive ART-naïve children and compare with the HIV negative children. This study was a prospective observational study involving a total of 200 children (100 test subjects and 100 test controls). Biodata was collected with a proforma and blood samples were subsequently collected and analyzed for full blood count (FBC) and CD4 counts. Data generated were analyzed with Statistical Package for Social Sciences (SSPS) version 22. The result showed that anaemia with a prevalence of 60%, is significantly associated with HIV infections unlike neutropenia and thrombocytopenia. It was also shown that the age of the children was inversely and significantly associated with anaemia but not with neutropenia and thrombocytopenia. Likewise, CD4 count was inversely and significantly associated with anaemia. It is concluded that anaemia is quite common and more prominent with decreasing age of the children. Results suggest that haemoglobin concentration estimations can be useful as one of the criteria for commencement of anti-retroviral medications especially in resource poor centers or localities where CD4 count is not readily available.  It is recommended that haemoglobin concentration less than 10mg/dl can be used as a cut-off mark for diagnosing anaemia.

TABLES OF CONTENTS

Title
Table of Contents
List of Figures
List of Abbreviations
Abstract

Chapter One: Introduction
1.1     Justification for the Study
1.2      Aims and Objectives
1.2.1.   Specific Aim
1.2.2.   General Objectives

Chapter Two: Literature Review
2.1.    Anaemia
2.2.    Thrombocytopenia
2.3.    Neutropenia
2.4.    CD4 Count and Cytopenias

Chapter Three: Methodology
3.1.0.     Study Design
3.2.0.     Clinical and Laboratory Data
3.3.0.     Laboratory Methods
3.4.0.     Study Area
3.5.0.     Study Site
3.6.0.     Study Population
3.7.0.     Ethical Clearance and Consent
3.8.0.     Sample Size Estimation
3.9.0.     Inclusion Criteria
3.10.0.   Exclusion Criteria
3.11.0.   Data Presentation and Analysis

Chapter Four: Results
4.1.0.     Sex and Age Distribution of Subjects and Controls
4.2.0.     Comparison of Haematological Parameters in the Subjects and Controls
4.3.0.     Prevalence of Haematological Abnormalities and Their Associations with Subjects and
Controls
4.4.0.     Comparison of Haematological Parameters in Male and Female Subjects
4.4.1.     Comparison of Haematological Parameters in Male and Female Controls
4.5.0.     Relationship between Age and Haematological Parameters in the Subjects
4.5.1.     Relationship between Age and Haematological Parameters in the Controls
4.6.0.     Prevalence of Different Levels of  CD4 Counts in the Subjects
4.7.0.     Relationship between Levels of Haematological Parameters and CD4 Counts of the
Subjects
4.8.0.     Relationship between Levels of Haemoglobin Concentrations and CD4 Counts of the
Subjects
4.8.1.     Relationship between Levels of Absolute Neutrophil Counts and CD4 Counts of the
Subjects
4.8.2.      Relationship between Levels of Platelet Counts and CD4 Counts of the Subjects

Chapter Five: Discussions, Conclusion and Recommendation
5.1.0.   References
 5.2.0   Appendices

CHAPTER ONE
                                                    INTRODUCTION
The Human Immunodeficiency Virus (HIV) is one of the most important emerging infections of this century. The HIV infection causes the Acquired Immunodeficiency Syndrome (AIDS), which is a systemic disorder characterized by deficiency in cellular immune responses. It is probably one of the diseases with multiple impacts on persons, families, communities and the entire society. Over 3 million children were noted to be living with HIV around the world at the end of 2013 (UNAIDS, 2014).
 Haematological complications have been documented to be the second most common causes of morbidity and mortality in HIV positive persons (Adetifa et al, 2006). A variety of haematological manifestations is seen at every stage of HIV and often life-threatening and impairs the quality of life of these patients (Coyle, 1997). Haematological abnormalities have been documented as strong independent predictors of morbidity and mortality in HIV infected children (Coyle, 1997).   Although it is not part of the criteria for initiating therapy nor used by the World Health Organization (WHO) for staging HIV, peripheral blood cell abnormalities in an abnormal haemogram are important prognostic tools for morbidity in HIV infection and AIDS (Coyle, 1997). Haematological manifestations in HIV infected patients often pose a great challenge in the comprehensive management of such patients and may cause symptoms that are life-threatening and impair the quality of life of these patients (Volberding, 2003; Baker, 2003; Levine, 2003). These complications in HIV infected ART-naïve patients usually result in poor ART- treatment outcome when they will eventually become eligible for ART and strongly predict poor prognosis and increase mortality (Liebman, 2008). These complications when present must be addressed appropriately and in good time.
Anaemia in children is defined as haemoglobin level less than 10g/dl and is the most common haematological abnormalities in HIV patients. Its prevalence ranges from 1.3% to 95%, normocytic normochromic anaemia being the predominant type followed by microcytic anaemia (Patwardhan et al, 2002).  Several factors play a role in the development of anaemia in patients with HIV including chronic disease, opportunistic infections, nutritional deficiencies and toxicities from medications (Patwardhan et al, 2002). The consequences of untreated anaemia may lead to multisystem disabling symptoms and fatigue, exhaustion, increased risk of HIV dementia and poor quality of life. On the other hand, survival time in HIV infected persons may be enhanced after recovery from anaemia (Mocroft et al, 1999).
Thrombocytopenia is defined as platelet level less than 150,000 cells/mm3 and is the second most frequent complication of HIV infection which is found in 3 to 40% of individual with HIV infection and could occur at any stage of HIV infection. The possible mechanisms that have been reported are immune-mediated destruction of platelets by antibodies, cross-reacting antibodies that are directed towards HIV proteins, particularly gp120 and p-24 (Kouri et al, 2008). This type of platelet destruction is called immune thrombocytopenic purpura (ITP) which is characterized by low platelet counts with normal haematocrit and white blood cell count (Liebman, 2007; Stasi, 2007). Thrombocytopenia has been identified as a strong independent predictor for mortality in HIV positive patients. Increased platelet destruction due to an autoimmune etiology offers an explanation for the decrease lifespan of platelets that is observed in the context of HIV-associated thrombocytopenia (Alcantara, 2009).
Neutropenia is defined as absolute neutrophil count less than 1500 cells/mm3 and is the most common leucopenia occurring in HIV infected individuals. Neutropenia is common and its incidence rises from 13% to 44% with disease progression from HIV to AIDS (Dikshit, 2009).   HIV infection suppresses the bone marrow and leads to decreased levels of granulocyte colony-stimulating factor, the factor that stimulates production of white blood cells in the bone marrow and affects the granulocte-macrophage lineage, resulting in leucopenia and neutropenia (Dikshit, 2009). Neutropenia can also result from other opportunistic infections including cytomegalovirus, tuberculosis, histoplasmosis and leishmaniasis. Hence, HIV patients with cytopenias may require bone marrow examination to determine the cause and to direct therapy (Dikshit et al, 2009).

 Low CD4 count is defined as CD4 count less than 500 cells/mm3. Low CD4 count has been associated with prevalent anaemia, neutropenia and thrombocytopenia (Levine et al, 2001). HIV preferentially infects CD4 cells causing their destruction. It has been calculated that each day, more than 1 billion CD4 cells are destroyed. The decline in CD4 count is linked to viral load and is used as a measure of disease progression (Davidson’s principles and practice of medicine, 2009).......

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