CHAPTER ONE

1.0 INTRODUCTION

 Human immunodefficiency virus (HIV) types 1 and 2 are lentiviruses belonging to the family Retroviridae, and the etiologic agents of acquired immune defficiency syndrome (AIDS). The acquired immune syndrome was first described in 1981, and HIV-1 was isolated by the end of 1983 (Brooks et al., 2010). Human Immunodefficiency Virus attacks the body's immune system. Normally, the immune system produces white blood cells and antibodies that attack viruses and bacteria. The infection fighting cells are called T-cell lymphocytes. Months to years after a person is infected with HIV, the virus destroys all the T-cell lymphocytes. This disables the immune system to defend the body against diseases and tumors. Various infections will be able to develop, these opportunistic infections take advantage of the body's weakened immune system. These infections which normally not cause severe or fatal health problems will eventually cause the death of the HIV patient (FMOH, 2010a).

 Infection with Hepatitis B virus (HBV) is a widespread problem. Epidemiological survey showed that about 5% of the world populations are asymptomatic carriers (Omer, 1995). Chronic HBV infection is a major cause of mortality and 50% of chronic carriers are expected to die from the disease due to liver cirrhosis or hepatocellular carcinoma (Omer,1995). Approximately, 350 million people are infected with HBV worldwide (Liu and Hou, 2006).

 The virus has been detected in peripheral mononuclear cells, tissues of pancrease, spleen, kidney and skin, and fluids like saliva, semen, sweat, breast milk, tears, urine and vaginal secretion (Willey et al., 2008; Chen et al., 2009). Some factors affecting the prevalence of chronic HBV include age at time of infection and mode of acquisition, which vary geographically. In the United States and Western Europe, HBV often is acquired in adolescence or adulthood via sexual contact or injection drug use (Luetkemeyer, 2010). Although spontaneous clearance of HBV acquired in adulthood occurs in over 90% of immunocompetent individuals, HIV-infected persons are half as likely as HIV-uninfected persons to spontaneously clear HBV (Luetkemeyer, 2010). Therefore, chronic HBV infection occurs in 5-10% of HIVinfected individuals who are exposed to HBV, a rate 10 times higher than that for the general population (Luetkemeyer, 2010). Hepatitis B virus is a DNA virus that forms stable circular covalently closed (ccc) DNA that can persist in the liver indefinitely (Pungpapong et al., 2007). Individuals with evidence of past infection (core antibody positivity) are at risk of HBV reactivation, particularly in the setting of severe immunocompromise, prolonged steroid use, or chemotherapy (Luetkemeyer, 2010).

Hepatitis B virus is classified into nine different genotypes using alphabetical nomenclature (A through I)  (Firnhaber and Ive, 2010) with the coexistence of genotypes A and

E in Nigeria and West Africa (Olinger et al., 2006), genotypes A and D predominant in South Africa. Genotype A is divided into at least 6 subgenotypes, A1 to A6. Subgenotype A1, which is found in South Africa, has unique characteristics that differentiate it from the other subgenotypes of A and genotype D. In genotype A, loss of hepatitis B e-antigen (HBeAg) cannot occur as a result of the precore stop codon mutation classically shown to cause truncation of the HBeAg precursor. In subgenotype A1, HBeAg seroconversion occurs as a result of mutations in both the basic core promoter and precore regions that affect HBeAg expression at the transcriptional, translational, and post-translational levels. These mutations may lead to loss of HBeAg expression without the expected reduction in viral loads, producing false-negative results via traditional serologic methods used for the diagnosis of actively replicating HBV (Firnhaber and Ive, 2010). Genotype G may be predictive of more severe fibrosis in HIV co-infected patients, and genotypes C and D may be more responsive to interferon (Luetkemeyer, 2010). However, in general, knowledge of the HBV genotype is not consistently associated with a response to nucleoside therapy and therefore is not particularly useful in clinical care of HIV and HBV coinfection, as nucleosides are the mainstays of HBV treatment (Luetkemeyer, 2010). Hepatitis B virus is the leading cause of chronic liver disease and liver-related death worldwide, with the majority of these cases occurring in areas of Africa and Asia where HBV prevalence is high (Hoffmann  and Thio, 2007). 

Co-infection of HIV and HBV is a state in which an individual is infected with both the HIV and the HBV viruses (Omonkhelin et al., 2010). The risk of co-infection is not uncommon especially in areas of high prevalence and people at high risk for parenteral infection (Liu and Hou, 2006).

Co-infections with HIV and HBV is common, with 70-90% of HIV-infected individuals in the United States having evidence of past or active infection with HBV (Luetkemeyer, 2010). Many of the countries that are affected by hepatitis B are also affected by a high HIV burden, leading to frequent HIV and HBV co-infection (Hoffmann and Thio, 2007).

In the United States, HIV and HBV co-infection rates are highest among men who have sex with men (MSM) and injection drug users (Luetkemeyer, 2010). In contrast, in Asia and subSaharan Africa, vertical and early childhood exposure are the most common modes of transmission, respectively, there is an overall high prevalence of HBV (Luetkemeyer, 2010). The prevalence of HBV among HIV-infected individuals also is higher, at an estimated 20-30%

(Luetkemeyer, 2010). The prevalence of HIV and HBV co-infection in ante-natal populations in Nigeria is as high as 8.9% (Adesina et al., 2010)

The consequences of co-infection, including increased liver-related morbidity and mortality, increased hepatitis B viral replication, immune reconstitution to HBV in the situation of antiretroviral therapy, and hepatotoxicity from antiretroviral drugs, are especially important in regions with expanding antiretroviral programmes (Hoffmann and Thio, 2007). Infection with HIV not only increases the risk of persons progressing from acute infection to chronic HBV infection, but also accelerates the progression to liver disease (Puoti et al., 2002).  

 Human immunodeficiency virus  and HBV have overlapping transmission routes, hence many people are infected with both viruses (Uneke et al., 2005). Rates of hepatitis B in the population as a whole have fallen dramatically since the advent of routine childhood HBV vaccination, but trends among people with HIV have not been well studied (Chun et al., 2010).

A majority of HIV negative individuals infected with HBV as adults spontaneously clear the virus without treatment, but 5-10% develop chronic infection lasting more than 6 months

(Brooks et al., 2010).  There are two main reasons for considering HBV therapy as a priority in HIV and HBV co-infected patients: Firstly, liver disease may progress more rapidly in those patients co-infected with HIV and HBV and could lead to serious liver disease complications such as cirrhosis and liver cancer at younger ages. Secondly, there is a higher risk of developing hepatotoxicity following the initiation of antiretroviral therapy in HIV patients co-infected with HBV than in patients infected with HIV alone (Highleyman, 2009).

1.1     Statement of Problem

Hepatitis B virus  infection is a dynamic disease and co-infection with HIV impacts directly on the outcome of HBV infection, considerably complicating its natural history, diagnosis, and management (Aghasadeghi et al., 2011). Few studies have addressed the issue of co-infection of HBV in HIV infected pregnant women to date, and in particular, there are few data on the prevalence of HBV and HIV co-infection in ante-natal populations (Landes et al., 2008).

Many of the countries that are affected by hepatitis B are also affected by a high HIV burden, leading to frequent HIV and HBV co-infection (Hoffmann and Thio, 2007). In patients infected with HBV, HIV can lead to higher rates of chronicity, decreased rates of anti-HBe and anti-HBs seroconversion, and increased viral replication, probably due to the impairment of the body’s immune responses (Hoffmann and Thio, 2007). 

Human Immunodefficiency virus  and HBV are both major global health concerns as they cause high mortality and morbidity in the developing countries. Due to the overlapping transmission routes; sexual contacts, blood transfusion, mother to child, use of unsterilized sharp objects such as needles, razor etc, many people are infected with both viruses (Willey et al., 2008). In immunocompromised pregnant women co-infection of HIV and HBV results in higher risk of maternal complications, and vertical transmission with higher rate of fetal and neonatal infections leading to liver disease that increases maternal mortality and morbidity (Elinav et al., 2006).

1.2 Justification 

                           Whereas 40 million individuals are estimated to be infected with HIV worldwide, nearly

400 million people are chronic HBV carriers (Hoffmann and Thio, 2007). Hepatitis B virus and

HIV are endemic in the same world regions, although HBV is more infectious than HIV (Hoffmann and Thio, 2007). Hepatitis B virus infection in Nigeria has remained a public health issue. It is a major cause of mortality, especially in developing countries (Eke et al., 2011). Vertical transmission of HBV infection is thought to be a major route of transmission in low resource areas. In spite of this, routine ante-natal screening for hepatitis B infection is not yet practiced in many Nigerian hospitals (Eke et al., 2011). Knowledge of the immune status of pregnant women if known will help the clinical management of the woman and reduce vertical transmission risks. 

           This will also help in advising and taking precautionary measures to protect the mothers and their unborn children, and provide information required for prevention or management of HIV and HBV. Testing for HBV infection in pregnancy is important in view of the morbidity and mortality of the host (pregnant women), its effect on the process of parturition, and the risk of vertical transmission from mother-to-child (Landes et al., 2008). The infected newborn most often remains a chronic carrier with the attendant consequences of liver cirrhosis, and hepatocellular carcinoma (HCC). Mother-to-child transmission can be avoided by vaccination of the newborn.  This intervention to stop vertical transmission can only be applied when the status of the pregnant woman is known (Landes et al., 2008). Therefore understanding the epidemiology of HBVand HIV co-infection in pregnant women is important because of vertical transmission risks and to inform clinical management (Landes et al., 2008).

1.3   Aim

 The aim of the study is to determine the prevalence of HIV and HBV co-infection and the effect on CD4+ cell count levels among pregnant women attending ante-natal care in some hospitals in Kaduna metropolis.

1.4 Specific Objectives 

1.   To determine the seroprevalence of HIV and HBV and their co-infection rate among pregnant women attending ante-natal care in some selected hospitals in Kaduna metropolis.

2.   To determine the effects of co-infection of HIV and HBV on the CD4+ cell count levels.

3.   To determine some possible risk factors associated with HIV and HBV infection.

1.5   Research Question

1.   What is the prevalence of HIV among pregnant women attending ante-natal care in some selected hospitals in Kaduna metropolis?

2.   What is the prevalence of HBV among pregnant women attending ante-natal care in some selected hospitals in Kaduna metropolis?

3.   What is the co-infection rate of HIV and HBV among the pregnant women attending ante-natal care in the selected hospitals in Kaduna metropolis?

4.   What are the demographic and risk factor(s) associated with co-infection with HIV and    HBV in the study population in Kaduna metropolis?

1.6   Research Hypothesis

Null hypothesis (Ho): There is no co-infection of HIV and HBV among pregnant women

attending ante-natal care in some selected hospitals in Kaduna metropolis.

Alternative hypothesis (Ha): There is co-infection of HIV and HBV among pregnant women attending ante-natal care in some selected hospitals in Kaduna metropolis. 

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