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Prognostic markers are important tools for monitoring the HIV disease progression. Proper monitoring of the disease may reduce the morbidity as well as mortality rate.
Some markers have been identified for monitoring the HIV disease progression. It is also the strongest predictor of subsequent disease progression and survival according to findings from clinical trials and cohort studies [ 22 , 26 ]. Thus, the most important use of the viral load is to monitor the effectiveness of therapy after initiation of HAART. The minimal changes in the viral load is considered to be statistically significant 2 standard deviations when there is a three-fold change equivalent to a 0.
Data from previous studies and clinical trials reported that reduction in viral load following initiation of HAART are associated with reduced risk of progression to AIDS or death [ 30 ]. Therefore, RNA viral load measurement is an established surrogate marker for treatment response. Beta-2 microglobulin is a low molecular weight protein, which comprises the light chain of class 1 MHC proteins and is noncovalently bound to the heavy chain [ 2 ]. It is present on the surface of all nucleated cells.
Dissociation during metabolism and degradation leads to its release to all biological fluids. In HIV disease, an increased level of Beta-2 microglobulin in cerebrospinal fluid CSF correlates with the disease progression and a decrease level indicates successful therapy [ 32 ]. Similarly, neopterin, a marker of immune activation is a low molecular weight compound derived from guanosine triphosphate [ 5 ].
The production is increased in HIV infection and infection by intracellular organisms such as parasite, autoimmune disease, malignant tumours, allograft rejection, neurological as well as cardiovascular disease [ 33 ]. However, it has slightly low predictive value compared to beta-2 microglobulin [ 5 ]. Oxidative stress is a condition in which there is increased amounts of reactive oxygen or nitrogen species.
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This condition is now recognized to be a prominent feature of many acute and chronic disease and even in normal ageing process. Lipid peroxidation was found to be one of the biomarkers to assess oxidative stress status in human disease including HIV [ 23 ]. A study done by Friis-Moller et al.
Besides, high plasma levels of malondialdehyde MDA , reduced plasma glutathione GSH and decreased superoxide dismutase activities were also found [ 36 ]. Haemopoiesis is the formation of blood or blood cells in the living body.
It involves the production of three 3 major cell lines which are red blood cells, white blood cells and platelets [ 37 ]. In humans, this process occurs in the bone marrow. In certain diseases, the process can be altered either directly or indirectly. Patients with HIV infection will have altered haemopoiesis [ 38 ], affecting both red and white blood cells and platelet formation. Haemopoietic stem cells HSCs are the earliest cells recognized in the bone marrow Figure 2.
HSCs produce all blood cells [ 37 ]. Growth factors, also play an important role for production and differentiation of blood cells in the bone marrow. Erythropoietin, a type of hormone which is mainly produced by the kidney and thrombopoietin, which is mainly produced by the liver, are the growth factors that are necessary for production and proliferation of red blood cells and platelets respectively. White blood cells have five 5 major components which include neutrophil, monocyte, eosinophil, basophil and lymphocyte.
The lymphocytes are further subdivided into B-lymphocytes and T-lymphocytes, which are important for functional activity. In most circumstances, HIV infection causes reduction in blood cell formation [ 40 ]. These include red blood cell anaemia , platelet thrombocytopenia and white blood cell leucopenia or any combination of these lineages Table 6. The cause of these changes in HIV infection are not fully understood.
Haematological abnormalities are common complications of HIV infection. These abnormalities increase as the disease advances. On both antiretroviral-treated and untreated individuals, different types of haematological abnormalities are common [ 41 , 42 , 43 , 44 ] Table 6.rikonn.biz/wp-content/2020-09-14/localizzazione-cellulari-gps.php
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Since the impact of HIV infection can be found in the peripheral blood and bone marrow, disorders of the haemopoietic system include anaemia, leucopenia, thrombocytopenia and thrombosis. These could be because of direct effects of the virus on the bone marrow, suppression of bone marrow by secondary infections or neoplasms causing ineffective haematopoiesis, nutritional deficiencies or side effects of the drugs used [ 44 ].
The disorders commonly occur throughout the course of HIV infection. The majority of the HIV cases present haematological abnormalities in the middle or advanced stages of the infection. However, some of the changes such as low haemoglobin and platelets have been reported in the early stages of HIV infection [ 44 ].
Anaemia refers to decrease in the haemoglobin Hb concentration with reference to healthy individuals of the same age group, sex, physiological state and environment altitude.
Cytokines in Hemopoiesis, Oncology, and AIDS | SpringerLink
This can be classified based on the etiology or morphology of the red blood cell. The normal red blood cell shows a normochromic normocytic morphology. Anaemia can be the earliest haematological manifestation, especially in children with HIV infection. Normochromic normocytic anaemia is the usual feature, but sometimes the HIV patients can present with a hypochromic microcytic anemia [ 45 , 46 , 47 , 48 , 49 ].
The causes of anemia in HIV patients are multifactorial. Inflammatory cytokines released by lymphocytes such as tumour necrosis factor TNF , Interleukin-1 IL-1 and interferon gamma play an important role in the pathogenesis of anaemia. These cytokines have been shown to inhibit red cell production erythropoiesis in vitro [ 51 ].
TNF levels were found to be consistently elevated in HIV infection and this condition is correlated with viral load [ 52 ]. Presence of dyserythropoiesis and opportunistic infections have also resulted in functional and morphological abnormalities of red blood cells [ 41 ]. This can alter the normal function of red blood cell as oxygen carrier or alter its normal biconcave shape.
Other factors that contribute to the development of anaemia include underlying chronic disease, mixed nutritional deficiencies, opportunistic infections and side effects from the treatment [ 53 ]. As HIV disease progresses, the prevalence and severity of anaemia also increases [ 48 , 54 ]. Another isolated red cell disorder, chronic pure red cell aplasia has been reported in HIV patients infected with parvovirus B19 [ 55 ]. This indicates that the underlying infection due to immunosuppression can give rise to anaemia.
Nutritional anaemia in HIV patients frequently arises from an inadequate balanced diet intake and malabsorption.
Infection and drug toxicity are common causes of gastrointestinal disease. Vitamin B12 deficiency is seen in up to one-third of HIV-positive subjects. Iron and folate deficiency are also common in this type of patients [ 38 ]. Bone marrow infiltration by tumour, such as lymphoma, is more common among HIV patients as compared to the normal population. The infiltration can suppress the production of red blood cells which can lead to anaemia. Anaemia is known to occur as an adverse effect of drug therapy for HIV infection or its complications. Myelosuppression can be caused by dose limiting toxicity of zidovudine [ 56 ].
Other drugs such as primaquine, dapsone and ganciclovir can lead to anaemia in HIV patients [ 52 ].