Essay: Complications associated with Human Immunodeficiency Virus (HIV)

INTRODUCTION
1.1 Background of the study
Complications associated with Human Immunodeficiency Virus (HIV) infection since it was first reported has become a global issue worthy of research (Leao et al., 2009; Frezzini et al., 2005; Nath, 2015). Newer complications are emerging frequently (Nath, 2015); which may be due to immune reorganisation, opportunistic infection, or the viral activities, posing therapeutic challenges for the clinicians. HIV infected patients on antiretroviral therapy (ART) have increasing signs of immune-mediated syndromes. As such, patients living longer are exposed to comorbidities such as stroke associated with hepatitis B&C co-infection, metabolic syndrome, drug abuse, and psychological trauma are significant contributory factors to the morbidity experienced (WHO, 2013; Nath, 2015).
About 44.2 million people are infected with the disease in sub Saharan African, making it the highest region with the disease and Nigeria as the most populace black nation in the country has experienced a steady increase from 1991(1.8%) to 2001 (5.6%) (WHO, 2005) and a gradual decrease to 3.17% as at 2014; with 15-49 years as the prevalent age group (CIA, 2014).
In this dispensation, morbidity and mortality resulting from HIV infection has been relegated to a far-below red alert level; this could only be attributed to the superior understanding of the disease mechanism and a resultant follow up by more effective therapy such as highly active antiretroviral therapy (HAART) (Pacheco et al., 2009; Grinsztejn et al., 2013; Swam, 2016). However, following the introduction of combination ART, fresh issues have been stirred among patients using, and clinician administering these regimens ((Barbaro, 2006; Kaur, 2014; Currier, 2015) with non-communicable diseases becoming a major health challenge around the world (Swam, 2016; Obirikorang et al., 2016).
Cardiovascular diseases (CVD), with the inclusion of atherosclerosis are the major contributors to mortality and morbidity worldwide (Yokozawa et al., 2003). Though numerous factors, such as indiscriminate consumption of cheap, high cholesterol food, age, genetics and life style play a significant role in triggering heart malfunction, the elevated cholesterol levels particularly Low density lipoproteins (LDL) cholesterol are chiefly the cause for the onset of Coronary heart disease CHDs (Farias et al., 1996; Yokozawa et al., 2003).
Cardiovascular disease (CVD) has emerged as an important
health issue for HIV-infected individuals. Not only are HIV-
infected individuals growing older, but they are also at
increased risk for CVD as compared with the general
population [1]. Both antiretroviral therapy (ART) and HIV
Cardiovascular disease (CVD) has emerged as an important
health issue for HIV-infected individuals. Not only are HIV-
infected individuals growing older, but they are also at
increased risk for CVD as compared with the general
population [1]. Both antiretroviral therapy (ART) and HIV
More concerns are emerging following increased prevalence of fat redistribution, central obesity and visceral abdominal lipoaccumulation (Carr et al., 1999; Currier, 2015), lipoatrophy (Dubé et al., 1997; Carr et al., 1998), not also forgetting alteration of cardiac structure; which are known risk factor for development of cardiovascular diseases (CVD) (Grinspoon and Carr, 2005; Lau et al., 2005). In addition to the changes in fat disorder, other metabolic abnormalities identified in patients on combination ART included disorder of lipoprotein metabolism, diabetes, irresponsiveness to insulin, and steatohepatitis (Barbaro, 2006). Studies have shown that CVD is an increasing, significant health problem for HIV-infected individuals (Edwards-Jackson et al., 2011; North and Sinclair, 2012). It well known that aging increases susceptibility to CVD (Lakatta and Levy, 2003; North and Sinclair, 2012), however its risk increases to a large percentage in HIV patient as when compared with normal population (Law et al., 2003; Triant et al., 2007). It has been suggested that both antiretroviral therapy (ART) and HIV are contributors to this increased risk (D:A:D study group, 2003; SMART study group, 2006) which may be partly explained by changes in what were originally described as cardiovascular risk factors (Bergersen et al., 2004; Mondy et al., 2007). Syed and Sani (2013) stated that HIV-associated pulmonary hypertension is significantly more common in sub-Saharan Africa than in developed countries, possibly as a result of interactions between HIV and other infectious agents, with very limited treatment options.
itself may contribute to this increased risk [2,3], which may
be partially explained by changes in traditional cardiovas-
cular risk factors [4,5].
Location and access to HAART have unprecedented influences on targets structures of the cardiovascular system (which include, the pericardium, myocardium, coronary arteries and pulmonary arteries) of people infected with HIV (). The close relationship between HIV, cART and CVD has been well known for a decade, with substantial epidemiological evidence (Obel et al., 2007; Triant et al., 2007). A global INTERHEART study had shown that many specific modifiable cardiovascular disease risk factors are preventive by adapting the right measures. However, Study indicating that the risk of heart disease is higher in the initial period of combination antiretroviral therapy (cART) (Currier et al., 2003; Obel et al., 2007).
In sub-Saharan Africa, with widespread tuberculosis infection and limited access to HAART, the prevailing type of HIV-associated cardiac disease are pericardial tuberculosis and cardiomyopathy. However, in countries with good industrial capacity, with occasional tuberculosis incidence and easy access to HAART, coronary artery disease is the leading cause of morbidity and mortality in these patients. Observational data suggest that HAART, by preserving immune function, reduces the incidence of myopericardial disease and pulmonary hypertension (Ntsekhe and Mayosi, 2009). However other works have shown that some of combination ART have complex mechanism in increasing the indices of risk factors of cardiovascular diseases (Friis-Moller et al., 2003; Friis-Moller et al., 2007; Baker et al., 2007; Freiberg and So‐Armah, 2016).
Therefore, the campaign is heavily on the development of optimal strategies to reduce the risk of vascular disease in the populations of countries with industrial advantage, with a greater focus on the prevention and treatment strategies for HIV-related cardiac disease in developing countries.
1.2 Statement of the problem
A large proportion of the world most especially underdeveloped and developing nations depend on tradomedical intervention as complementary chemotherapy for health care. The use of acclaimed potent herbal preparations for managing various disease; especially HIV is common in sub-Saharan African communities (Monera et. al., 2010). Moringa Seed, Leaf and tree back extract have been acknowledged to be rich in protein, vitamins, calcium, macrominerals and trace minerals, and tetraterpenoids (Peter, 2008; Leone et al., 2015; Gopalakrishnan et al., 2016) as well as antioxidant (Dillard and German, 2000); which makes it a likely therapeutic agent for managing HIV even to the extent of negeleting the importance of ART.
Unfortunately, some researcher, most especially in underdeveloped countries has in a way or another tried to elevate Moringa as a stand-alone therapeutic intervention for HIV infected patient; even when the adverse effect have not fully been investigated, neither has the complementary and independent effect in the various groups of HIV-patient been fully evaluated.
Experimental investigations have suggested that M. Oleifera reduces dyslipidemia (Mehta et al., 2003), attenuates nutritional and drug induced metabolic disorder (Burger et al., 2002); normalizes the activities of myocadial marker enzymes and possess cardiac protective qualities (Gunjal et al., 2010). Therefore, it is pertinent to investigate the effect of a known, acceptable M. Oleifera supplement on cardiac risk factors in other to assess its interventionary potentials in HIV patients.
1.3 Aim and objectives of the study
This studied was undertaken to investigate the effect of Moringa supplement on cardiac risk factors; so as to determine its interventionary qualities in immuno-susceptible HIV patients.
1.3.1 Objectives
 To determine the atherogenic lipid indices of HIV infected patients on ART (TDF).
 To evaluate the effect of Moringa supplement on atherogenic index (Log [TC/HDL-C]) in HIV infected patients on ART.
 To evaluate the effect of Moringa on cholesterol ratios (HDL/LDL), (Tchol/HDL) in HIV infected patients on ART.
 To determine any time dependent changes in lipid indices influenced by Moringa administration
1.4 Research Questions
I. Does ART (TDF) have any significant effect on atherogenic lipoprotein indices in HIV infected patients on ART?
II. Does Moringa have the potential to significantly reduce the atherogenic index of HIV patients on ART?
III. Does Moringa have the potential to significantly reduce cholesterol ratios (HDL/LDL), (Tchol/HDL) of HIV patients on ART.
IV. Does Moringa administration cause any change in atherogenic lipoprotein indices with time in HIV infected patients?
1.5 Significance of the study
Since it has been scientifically proven that moringa has nutritional as well as medicinal properties, with almost all part of the tree being utilized as an alternative chemotherapy. It would be worthwhile to investigate how well an approved supplement can assist in alleviating cardiovascular disease susceptibility by eliminating or reducing weight, blood pressure and atherogenic index.
Research has suggested that the root-bark of Moringa is used as anti-inflammatory, analgesic and antiviral (Burger, 2002; Khosa, 2011). While its stem-bark and flowers are hypoglycaemic (Khosa, 2011; Iwara et al., 2014). Infusion of seed is anti-inflammatory, antispasmodic and diuretic, also given in venereal diseases (Khosa, 2011). Moringa have been praised for its support in maintaining normal blood-glucose levels, healthy cardiovascular system, excellent anti-inflammatory mechanisms support, stimulate blood formation and support immune system (Dhar and Gupta, 1982).
Clinicians in developed setting and tradomedical practitioners in the deficient health system would benefit from the outcome of this research; as it will form the background for more professional advice to HIV patients who may be involved in self-administration, so as to assure improvement in their quality of life and overall life expectancy.
Additionally, the result of this work will either validate or refute claims of the therapeutic effect of moringa on HIV infected patients which will form a basis for management of HIV in the clinical sphere.
1.6 Scope of the study
This is randomised comparative assessment of the effect of NAFDAC approved Moringa supplement (Forumale-K) on atherogenic lipoprotein indices of HIV patients attending HIV clinic in the University of Port Harcourt Teaching Hospital.
The study was limited to atherogenic lipoprotein indices (Log (TG/HDL), TC/HDL cholesterol ratio and LDL/HDL cholesterol ratio).
This study involves HIV patients divided into two (2) groups. Group (A) is the test group consisting of HIV patients to be administered the test drug (Moringa supplement) and group (B), consisting of HIV patients on Anti-retroviral therapy alone. The experimentation was conducted in 3 phases namely; baseline (commencement) 4weeks follow-up and 12 weeks post commencement of supplements (end of study).
CHAPTER TWO
LITERATURE REVIEW
This section reviewed work that provides theoretical clarifications as well as empirical or experimental evidences with respect to the research topic.
2.1 THEORETICAL REVIEW
2.1.1 Human immunodeficiency virus (HIV)
From the historical account, HIV and AIDS were usually detected at the time of illness, fear and death; however, the development of highly effective antiretroviral drugs brought some succour to persons living with the disease (AVERT, 2016). There are various historical moments that define the HIV epidemic over the past 30 years. From a family tree developed from the original viral strain, it is widely believed that HIV originated in Kinshasa; sometime in 1920, when it crossed species from chimpanzees to humans (Mann, 1989). Prior to 1981 when cases of a rare lung infection called Pneumocystis carinii pneumonia (PCP) was found in some young males in California (Hymes, 1981; CDC, 1981; CDC, 1982a) and Kaposi Sarcoma among young homosexual males and drug abusers (Masur et al., 1981; CDC, 1982; 1982b; 1982c), there were already reports in some Africa, Australia, Europe, South and North American countries (Mann, 1989).
The terminal stage infection by the retrovirus (lentivirus), Human Immunodeficiency Virus (HIV) is Acquired Immunodeficiency Syndrome (AIDS) which signifies the irreversible damage and end-stage immunocompromised system (Gallo et al., 2003; NIH, 2010). HIV virus attacks white blood cells, which are called T-helper cells or CD4 cells (receptors of CD4 and chemokine-CCR5 and CXCR4) (AIDSinfo, 2015). HIV is incapable of self-replication; instead, it produces new copies of itself inside CD4 cells, eventually depleting them; thus, destroying the immune system overtime, leaving the system susceptible to opportunistic infections and diseases. HIV could pass on from one person to another, through body fluids and blood products such as; sex, mother to child infections, contaminated syringe, blood transfusion (AVERT, 2015). Up till this period, HIV is still regarded as a major global health problem, with an approximate death toll of about 1.0–1.5 million people (in Africa) dying of AIDs in 2014 and (WHO, 2015).
2.1.2 Anti-Retroviral drugs
As soon as the HIV virus infects a host, the virus begins to attack and destroy the CD4 cells. Without treatment, the virus gradually invades and overwhelms the immune system and progresses to AIDS (Alimonti et al., 2003). Antiretroviral medications shield the immune system by blocking HIV at various stages of the viral life cycle (Moore et al., 1999). The life cycle of the virus involves various molecular processes such as binding, fusion and entry, reverse transcription and integration, proviral transcription, cytoplasmic expression (Pattman et al., 2010), replication, assembly and budding, release, maturation. The HIV virus attaches to the CD4 cell receptors, using the CCR5 receptors. CCR5 antagonists are classes of drugs capable of blocking the binding HIV to CD4 receptors by fuseing with the membrane of the CD4 cell (Bryntesson, 2009; Pattman et al., 2010). A class of drugs that inhibit this action are called fusion inhibitors (Lieberman et al., 2008). As soon as fusion takes place, the virus releases its enzyme (reverse transcriptase), which translates the genetic component (HIV RNA) to DNA. This conversion enables HIV to penetrate the CD4 nucleus and attach to the cell genetic component. The classes of drugs that act at this point are the NNRTIs and NRTIs (Das et al., 2013). While inside a CD4 nucleus, the virus releases integrase to incorporate its viral DNA into CD4 DNA. The class of drugs that inhibit this step are called integrase inhibitors (Métifiot et al., 2013). If the integration is successful, the virus uses the components of the CD4 cell to produce chains of the HIV proteins. These protein chains form the building block of more HIV virons. Consequently, the new proteins relocate to the surface of the cell; assembling into mature HIV, that is finally pushed outside the host CD4 cell through the release of protease. This step is blocked by Protease Inhibitors (PT’s) (Wensing et al., 2010).
In 1987, Zidovudine was the first drug launched for HIV treatment; nevertheless, it took ten years for sustained suppression of HIV replication. Combination antiretroviral therapy (cART) was introduced in 1996. It consisted of the use of at least three drugs from at least two classes of HIV medication. This led to sustained, well reported reduction of AIDS-related mortality and morbidity among ART users (Mocroft et al., 2007).
There are presently 6 drug classes that target different pathways, in the life cycle of the virus. The drug classes are: NRTI’s, NNRTI’s, integrase inhibitors, CCR5 receptor antagonists, fusion, inhibitors and protease inhibitors.
[1] Nucleoside/nucleotide reverse transcriptase inhibitors (NRTI’s)
NRTIs were the first drug class approved by the FDA. They are given as prodrug and they depend on the entry into the host cell and cellular kinases phosphorylation before its antiviral effect (Mitsuya et al., 1985). The drugs eventually terminate growing viral DNA chain (Balzarini, 2000). Eight FDA-approved NRTIs include: Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Tenofovir, Zalcitabine, and Zidovudine
[2] Non- nucleoside reverse transcriptase inhibitors (NNRIT’s)
These class of drugs, decrease reverse transcriptase activity of HIV, by allosteric inhibition. Nevirapine and Efavirenz were the first in the market (Spence et al., 1995).
[3] Protease inhibitors
Protease inhibitors inhibit the protease enzyme in HIV and prevent cleavage of gag-pol protein, preventing the viral particles from reaching an infectious state (Flexner, 1998).
[4] CCR5 antagonists
HIV interacts with CD4 and uses CCR5 as additional co-receptor. Maraviroc was accepted as the drug for management of HIV infection in 2007. It inhibits HIV-1 from entering host cells by antagonism at the CCR5 co-receptor. It is useful in only strains that use CCRs as co-receptor for cell entrance (Carter, 2007).
[5] Fusion inhibitors
Enfuvirtide was approved in 2003 and it is the first fusion inhibitor, that binds with the HIV envelop glycoprotein, thereby preventing fusion of viral and cellular membrane. It is administered subcutaneously (Dando et al., 2003).
[6] Integrase inhibitors
The life Raltegravir was approved in 2007 as the first HIV integrase inhibitor. It targets HIV intergase and prevents integration of HIV DNA, into the genome of the human host cell (Hazuda et al., 2000).
2.1.3 Antiretroviral Therapy
HIV infection has a well-orchestrated progression pattern, in which the virus eventually overwhelms the immune system but the continuous use of antiretroviral therapy (ART) prevent the HIV virus from multiplying and progressing to AIDS. Antiretroviral therapy, involves the use of medications in the management of HIV. It is recommended for everyone infected with the virus (ARCC, 2008). The loss of CD4 cells, resulting from infection with HIV, makes it almost impossible for immunologic defence against infections and other HIV related cancers. ART tends to restore the loss in CD4 cells (Lederman et al., 1998).
The goal of anti-retroviral therapy is to make infected patients live a better and longer life, reduce the risk of non HIV related illness and reduce possibilities of transmission to others (Granich, 2008).
These drugs are called by different names like cocktail, ART and HAART. Most regimes take three different anti-retroviral drugs from at least two different classes (Brechtl et al., 2001). This regimen is the standard HIV care and helps the immune system to successfully control the virus’s replication, thereby protecting the host. It also helps to minimize the risk of HIV drugs resistance.
2.1.4 Cardiovascular risk factors
Well-established risk factors for CVD have been classified into two major groups;
1. Non-modifiable risk factors
2. Modifiable risk factors
Non-modifiable risk factors
These are factors which cannot be changed as they occur as part of human development and existence. These include age, sex (men are more at risk than women) and family history of heart disease (Fedele et al., 2011). Independent of the LDL cholesterol level the risk for CVD increases with older age (Wilson, 1998). Age to a large extent reflects physiologic degenerative progression of structural and hemodynamic changes in the cardiovascular system (Fedele et al., 2011), as a result of decrease in elasticity and an increase in stiffness of the arterial system (Cheitlin, 2003) resulting in loss of arterial compliance (Pugh and Wei, 2001), oxidative stress, and endothelial dysfunction, with the involvement of atherogenic risk factors (Fedele et al., 2011). Thus, on average, older people are more susceptible to coronary atherosclerosis than their younger counterparts.
The implication of sex in predisposition to CVD is not fully understood; however, due to faster elevations of LDL cholesterol and blood pressure, and reduced HDL cholesterol in men (Fedele et al., 2011; Mosca et al., 2011) and hormonal protection in premenopausal women, men are more predisposed to earlier onset of CVDs (Fedele et al., 2011). Confirmed family history of CVD amounts to risk factor in both sexes; as various studies indicate that a family history of CHD is an independent risk factor in the presence and absence of other risk factors (Fedele et al., 2011; Ranthe et al., 2012); with a higher chances when a first-degree relative had presented with CVDs (Li et al., 2000; Williams et al., 2001).
Researchers have suggested many risk factors such as; blood pressure, lipids and lipoproteins, and obesity are influenced genetically; however, such presentations only accounts for proportion of the total CVDs observed in families (Snowden et al., 1982; Khaw and Barrett-Connor, 1986).
Modifiable risk factors
Some risk factors are described modifiable, because something can be done about them to put them in check. Especially, adjustment of lifestyle assure the control of such risk factors.
Smoking
Smoking has been documented as a significant contributor to risk for coronary artery disease and other forms of CVDs (Ezzati et al., 2005; CDC, 2010; Fedele et al., 2011). Beyond its status as an independent risk factor, it appears to have a multiplicative and complicated interaction with the other major risk factors for CHD (CDC, 2010). The risks of CVDs appear to remain slightly elevated after persons stopped smoking; for up to 10 years (CDC, 2010), however, some studies in some studies have shown that such risk do not pose any significant effect (Dagenais et al., 1990; Kawachi et al., 1994; Qiao et al., 2000).
Dyslipidemia
It is often characterised by elevated plasma cholesterol, triglycerides (TGs), or a combination of both, or a reduced level of high-density lipoprotein (HDL). Studies have shown that there is association between elevated plasma cholesterol and the onset of infraction, and angina pectoris (Assmann et al., 1996). Studies have suggested that high plasma cholesterol is a predispository factor for CVD, however the combination of both is a more s a powerful risk factor for cardiac events or coronary heart disease CHD death, (Pöss et al., 2011; Fedele et al., 2011).
Studies have also shown that non-lipid risk factors such as obesity, sedentary life style, diabetes, hypertension, steroid abuse and cigarette smoking are also interrelated with triglycerides fluctuation (Tenkanen et al., 1995; Hodis et al., 1994; Assmann et al., 1996; Cullen et al., 2000) so as several other emerging factors such as fat redistribution, visceral abdominal lipoaccumulation (Carr et al., 1999; Currier, 2015), lipoatrophy (Dubé et al., 1997; Carr et al., 1998a) and irresponsiveness to insulin (Isomaa et al., 2001).
Hypertension
Elevated blood pressure is a well-known risk factor for CVD as well as other conditions such as peripheral vascular disease, cerebrovascular disease, renal failure, and heart failure, (Fedele et al., 2011; Cappuccio and Miller, 2016). Also Hypertetion induced structural changes in the vasculature of heart (Hamsten et al., 1985), increase oxidative process and release of free radicals which in turn promotes inflammatory activities, thus enhancing the atherosclerotic process (Abdel-Maksoud et al., 2008).
Diabetes
Diabetes mellitus is also considered to be an equivalent of cardiovascular risk; that places such an individual in the position to be called a risk of future CVD events. That is, his/her condition is considered an equivalent of someone who is suffering myocardial infarction (Fedele et al., 2011). Death arising from CVD-related diabetes mellitus complications account for approximately 50-75% of all deaths among patients (Gibbons and Dzau, 1994). Obesity and type 2 diabetes are strongly linked which is clearly demonstrated in type 2 diabetes rise consequent to a rise in obesity (Meigs, 2010).
Due to the high risk associated with diabetes, the management strategy for such patient involves both pharmacological intervention (drugs), change in life style (such as; feeding pattern, sedentary life and management of stress) (Fedele et al., 2011).
Metabolic syndrome
Metabolic syndrome which is an intercorrelation and cluster of lipid and non-lipid risk factors (Wilson et al., 1991; Meigs et al., 1997) such as fat redistribution, generalized and regional obesity (NCEP, 2001; Carr et al., 1999), lipoatrophy, dyslipidemia (Mbunkah et al., 2014), disorder of lipoprotein metabolism, diabetes (Chow et al., 2006), irresponsiveness to insulin (Isomaa et al., 2001), steatohepatitis (Barbaro, 2006) as well as high blood pressure (Carr et al., 1998a) is associated with increased CVD risk (Meigs, 2010).
However, NCEP specifically defined metabolic syndrome as diagnostic presentation with 3 or more of the following 5 cardiovascular risk factors:
1. Central obesity (using waist circumference: men >102cm; women >88cm);
2. Reduced high-density lipoprotein (HDL) cholesterol (to <40 mgdl-1 in men and <50 mgdl-1 in women);
3. Elevated triglycerides (TGL≥150 mgdl-1);
4. Systemic hypertension (≥130/≥85 mm Hg); and
5. Elevated fasting glucose (≥110 mgdl-1) (NCEP, 2001; Grundy et al., 2004)
Most of the above listed conditions are interrelated as abdominal obesity is closely associated with elevated of serum triglycerides and a higher TGL level is often results in lower HDL cholesterol concentrations (Pearson et al., 2003; Julien et al., 1997).
2.1.5 Cardiovascular diseases in HIV-infected patients
Since the first appearance of HIV in 1981, various cardiovascular abnormalities have been identified as a probable complications (Cohen et al., 1986; Stotka et al., 1989; Karve et al., 1992; Heidenreich et al., 1995). Clinical investigation through a meta-analytical stand point has proven to be difficult in determining the association of CVD and HIV; however the mystery behind such interaction cannot just be solved; as an indebt investigative controlled clinical trials is required, which will involve an intensive collaborations between cardiologists and infectivologists (De Gaetano Donati et al., 2010).
Pericarditis
The aetiology of pericardial effusion in HIV-infected patients has proven to be difficult to identify (Rakhlin et al., 2010) as various clinical investigation such as; pericardial fluid culture has often not revealed much. Although not fully studied with concrete findings, such occurrences have been related to enhance expression of cytokines in the later stage of HIV infection (Rakhlin et al., 2010). However, research has documented pericarditis in HIV-infected patients; with the possible presentation of large effusions or cardiac tampon blockage (Stotka et al., 1989; Karve et al., 1992; Heidenreich et al., 1995).
Research on HIV-infected patients have linked pericardial effusions with bacteriologic and cytologic out of which lymphoma and Staphylococcus aureus, Mycobacterium avium have been identified (Hsia and Ross, 1994). However, are isolated case reports of pathogens such as; Cryptococcus neoformans (Schuster et al., 1985) herpes simplex (Freedberg et al., 1985), Mycobacterium tuberculosis (D\’Cruz et al., 1986; Dalli et al., 1987; de Miguel et al., 1990), Staphylococcus aureus,( Stechel et al., 1986; Decker and Tuazon, 1994) as causes of pericarditis.
Myocarditis
HIV induced myocardial inflammation and other related infections has been implicated as a significant provoking factor in the development of HIV-associated cardiomyopathy (HIVAC) (Lumsden and Bloomfield, 2016). Myocarditis is trigger after infection with HIV and subsequent co-infections with other viruses and opportunistic infections which leads to the release of local cytokine and consequent B-cells clonal expansion invasion of the myocardium (Via et al., 1990; Magnani and Dec, 2006). Patients with myocarditis often presents with CD4 counts less than 400 cellsmm-3 and a higher fraction of untreated AIDS presenting histopathological evidence of myocarditis on autopsy (Barbarini and Barbaro, 2003; Magnani and Dec, 2006; Frustaci et al., 2014).
Myocarditis were often coinfected with cardiotropic viruses (Herskowitz et al., 1994; Barbaro et al., 1998; Longo-Mbenza et al., 1998; Barbaro, 2005). However, researchers have documented a reduction in opportunistic infections in patients on ART; which has been attributed to drastic reduction in myocarditis rates and prevalence of HIVAC observed in High income countries (HICs) (Barbaro et al., 2011; Pugliese et al., 2000).
Cardiac Autoimmunity
Autoantibody has been seem concentrations correlate with increased death in HIV-infected patients (Currie et al., 1992; Lumsden and Bloomfield, 2016). Opportunistic viruses have the ability to expedite the onset of myocardial abnormalities (Calabarese et al., 1984). Cardiac autoimmunity in HIV-infected individuals occur as a result of viral-induced alteration of the surface antigens on cardia muscle cells; thus uncovering hidden cell surface epitopes, consequently initiating abnormal autoimmune responses against endogenous cardiomyocytes (Currie et al., 1992).This is common among cardiotropic viruses like Cytomegalovirus (Herskowitz et al., 1994).
Pulmonary Hypertension
Severe pulmonary disease frequently present in patients with advanced HIV disease and cardiac abnormalities (Rakhlin et al., 2005). Patients with terminal stage HIV infection disease have been reported to with pulmonary hypertension (proven by cardiac catheterization) as well as hypertrophy of the right ventricular (Himelman et al., 1989; Piette et al., 1992; Weiss et al., 1995; Petitpretz et al., 1994). It has also been reported in HIV-infected patients without any history of cardiac associated infection (Pellicelli et al., 2001). However, some authors have reported that HIV-associated pulmonary hypertension correlates strongly with improper prognosis (Himelman et al., 1989; Weiss et al., 1995; Mehta et al., 2000).
How ART affects pulmonary hypertension is unknown; however, Zuber et al., 2004 reported higher incidence of pulmonary artery pressure increase in HIV-untreated patients when compared to ART-treated patients.
2.1.6 Moringa oleifera (M. Oleifera)
Various names exist for the tree called M. oleifera. Most countries generally recognise it as simply moringa, however other names that exist include, ben-oil-tree, horse radish tree, drumstick (due to its long, slender, triangular seed-pods) and horseradish tree (because of the taste of the roots) (CSIR, 1962; Anwar and Bhanger, 2003). M. oleifera is a plant widely distributed across the globe, but native to northern Indians (Anwar et al., 2007; Leone et al., 2015). Apart from its medicinal, and nutritional value, its tree, leaves and flowers have ornamental characteristics (see Figure 1.1).
The plant can be grown as a planation or cultivated with the house yards as it is very resistant to drought and flourishes in the tropical climate. It is however, grown in various parts of the world (Little and Wadsworth, 1964; Jahn et al., 1986; Lahjie and Siebert, 1987; Vivien, 1990; Francis and Liogier, 1991); as well as Nigeria (Adejumo et al., 2010; Zaku et al., 2015) and Ghana (Amaglo et al., 2010). The cultivation of M. oleifera can be intensively carried out with or without irrigation and fertilization and its seeds have no latency period, hence planting can be done as soon as they are mature (Fuglie, 1999; Zaku et al., 2015). It grows with minimal difficulty in humid environment or hot dry areas, as drought does not affect it much and it survives even in poor soil (Morton, 1991).
The young seed pods and leaves of Moringa (Figure 1.2) are often consumed as vegetables and dietary enhancer (Zaku et al., 2015). Due to its application in stimulating milk production in lactating women, it has been described as the mother’s best friend (Estrella et al., 2000; Siddhuraju and Becker, 2003; Chukwuebuka, 2015) as well as the purifying tree (Von, 1986; Olsen, 1987). It is can also be used as tradomedical intervention (Anwar et al., 2007; Leone et al., 2015). Seed, Leaf and tree back extract of Moringa have been acknowledged to be rich in protein, vitamins, calcium, macrominerals and trace minerals, and tetraterpenoids (Peter, 2008; Leone et al., 2015; Gopalakrishnan et al., 2016). The plant’s antioxidant constituent helps to boost the durability of fat containing foods (Dillard and German, 2000).
Taxonomy of Moringa
Moringa which grows to heights of 12m (Parotta, 1993) and is native to sub-Himalayan territories of Northern India and obtained its name from murungai the Indian (Tamil) vernacular name for drumstick (Olson, 2010; Sharma et al., 2012). It is the only genus in the family Moringaceae (Roloff et al., 2009; Khawaja et al., 2010; Paliwal and Sharma, 2011; Leone et al., 2015), with about 13 species indigenous to some part of Africa and Asia (Mabberley, 1997; Janick and Paull, 2008). M. oleifera is a diploid species with 28 chromosomes, with numerous other species possessing valuable use, which includes but not limited to the following (Ganguly and Guha, 2008; Leone et al., 2015; Prabsattroo et al., 2015);
 Sources of food (Wangcharoen and Gomolmanee, 2011)
 fibre
 medicine
 plant growth enhancers (Al-Kharusi et al., 2009)
 Water purification (Olsen, 1987)
 Industrial use (Vegetable oil) (Ramachandran et al., 1980)
Species of Moringa
Various research has suggested that all 13 recognised species of Moringa are of significant therapeutic and nutritional value (Jahn et al., 1986; Morton, 1991; Roloff et al., 2009; Monera and Maponga, 2010). M. Oleifera supplementations have been found to be commonly used by HIV infected patients with studies indicating that M. oleifera is an excellent immune booster (Monera and Maponga, 2010). Reports have also strengthened the advocacy of M. oleifera administration as a substitute therapy to enhance the immune systems of HIV infected patients particularly in regions with linical drugs inaccessibility (Burger et al., 2002).
Phytochemistry
Many biological active compounds are present in M. oleifera leaves; grouped as vitamins, carotenoids, flavinoids, polyphenols, alkaloids, glucosinolates, phenolic acids, isothiocyinates, tannins, saponins, oxalates and phytates (Leone et al., 2015).
Vitamins and Minerals
According to (Ramachandran et al., 1980) M. oleifera leaves comprise of 11,300-23,000 IU of Vitamin A, which play a vital role in physiological processes like vision, reproduction, immune competence cell differentiation, cell proliferation, apoptosis and brain function. Vitamin deficiency which is common in developing countries is linked with high child and maternal mortality (Alvarez et al., 2003).
The leaves of M. oleifera have a rich supply of Beta carotene. Beta carotene concentration is much higher in the dried leaves, ranging between 17.6 – 39.6 mg/100g of DW (Moyo, 2013).The Vitamin C content acts as an antioxidantat a concentration of about 200mg/l00g (Ramachandran et al., 1980). It is vital in the synthesis and metabolism of folic acid, tryptophan as well as tyrosine. It is also involved in the transformation of cholesterol into bile acids. Vitamin C also increases the uptake of iron in the gastrointestinal system (Chambial et al., 2013). Due to its quick oxidation when exposed to heat as well as oxygen, the concentration reduces when the leaves are dried, ranging between 18.7-140 mg/100 g of DW (Price, 1985; Joshi et al., 2010).
Vitamin B functions as a cofactor of numerous enzymes. It has been implicated in nutrients metabolism in addition to energy production (Leone et al., 2015).M. oleifera leaves comprise of between 0.06 and 0.6mg /100g, 0.05 and 0.17 mg/100g and 0.8 and 0.82mg /100g of thiamin, riboflavin and niacin respectively (Ramachandran et al., 1980).
There is also a rich supply of Vitamin E (at conc. up to 74.5–122.2 mg/100 g of DW) (Price, 1985; Sanchez-Machado etal., 2006; Moyo et al., 2011); especially α-tocopherol. The amount is approximately 9.0 mg/100 g which is similar to the amounts found in nuts (Ching et al., 2001). Vitamin E, which is fat soluble acts as an antioxidant and like Vitamin B it also has modulatory effects on gene expression and signalling, inhibition of cell proliferation, adhesion of monocyte, platelet aggregation as well as bone mass regulation (Borel, 2013; Leone et al., 2015).
Polyphenoles
The dried leaves of M. oleifera are abundant in polyphenols which includes flavonoids and phenolic acids. The amounts are between 2090 to 12,200 mgGAE/100g (Prakash, 2007; Sreelatha et al., 2009)
Flavinoids
Flavinoids which have a benzoic-v-pyrone structure are produced secondary to microbial infections (Kumar et al., 2013). According to some studies, increased intake of flavinoids, have a protective effect against a lot of infections as well as degenerative diseases (Pandey, 2009). Moringa leaves contain between 5.06 – 12.16mg.g-1 of flavinoids (Yang et al., 2008). The chief flavinoids include; quercetin (0.21-7.57 mg.g-1 of DW), myricetin (5.8 mg.g-1 of DW), and kaempferol (insignificant quantity; -4.59 mg.g-1 of DW) (Sultana et al., 2008; Coppin, 2013).
Phenolic acids
They are hydroxycinnamates and hydroxybenzoic acid derivatives. They are existent in vegetation with antioxidant, anti-mutagenic, anti-inflammatory and anticancer properties (Verma et al., 2013; El-Seedi et al., 2013). They are also abundant in fruits and vegetables as well and its concentration in the Moringa leaves is about 1.05 mg.g-1 (Prakash et al., 2005).
Alkaloids
Alkaloids are chemical compounds occurring naturally; composed mainly of basic nitrogen atoms. They are confirmed to be present in Moringa leaves though their concentration is still unknown (Panda et al., 2013).
Glucosinolates (β-thioglucoside-N-hydroxysulfates) and isothiocyanates
Glucosinolates naturally occur in plants with sharp- strong taste or smell and are products of plant secondary metabolism (Leone et al., 2015). They are synthesized from amino acids. Considerable amounts are present in M. oleifera leaves which are in the range of between 116 and 63mg/g of DW (Bennett et al., 2003). This is close to and in some cases higher compared to vegetables (Ciska et al., 2000).
Tannins
The concentration of Tannins in M. oleifera ranges from 13.2-20.6g TAE kg (Makkar et al., 1997) and it possess anti-inflammatory, anti-hepatotoxic,anti-carcinogenic, and anti-HIV replication action (Kancheva et al., 2013).
Saponins
These are natural compounds made up of isoprenoidal derived aglylone covalently interconnected to one or more sugar moieties (Augustin et al., 2011). Some saponins have hemolytic side effects and are also currently being evaluated for possible anti-cancer effects (Tian et al., 2013). The Moringa leaves contain about 50 gDE.kg-1 of DW of saponin (Makkar et.al., 1996). The concentration of saponins in M. oleifera is higher than that in other plants (Edeoga et al., 2005).
Oxalates and phytates
These are antinutritious compounds which bind minerals thereby inhibiting their absorption. Dried Moringa leaves have concentration of oxalate from 43-1050mg/100g of DW (Joshi et al., 2010) while the concentration of phytates are within the range of 15-31g/kg DW (Makkar et al., 1996).