*3.4.2. Virologic marker of infection*

partially explain the susceptibility of HIV-infected individuals to infection by intracellular microbes. In addition, Th2 cytokines also may inhibit macrophage-mediated killing of microbes [13] and consequently lead to failure of macrophage activation in the killing process

114 Trends in Basic and Therapeutic Options in HIV Infection - Towards a Functional Cure

Tumour necrosis factor-alfa (TNF)-α, IL-1 and IL-6 which are produced by monocytes and macrophages, play an important role in activation of neutrophils, monocytes and macrophages to initiate bacterial and tumor cell killing, increase adhesion molecule expression on the surface of neutrophils and endothelial cells, stimulate T and B lymphocytes proliferation as well as initiate the production of other proinflammatory cytokines [1, 2]. In addition, these cytokines can cause systemic symptoms such as fever and weight loss as well as influence the production of acute phase protein in the liver [1]. Inflammation is one of the components of innate immune response. Thus, production of appropriate amounts of TNF, IL-1 and IL-6 is important in response to infection [1]. Increased production of these cytokines, particularly TNF-α has been found in acute and inflammatory conditions (e.g., trauma, sepsis, infection, rheumatoid arthritis) [18]. The observed increase in proinflammatory and inflammatory cytokines

Normal levels of protein S, protein C and antithrombin activities are necessary for coagulation process. In HIV patients, protein S, protein C and antithrombin activities decrease with an increase in plasma D-dimer [19, 20]. Binding of viral and bacterial components to Toll-like receptors (TLRs) stimulate the procoagulant tissue factor to initiate the coagulation cascade. This leads to thrombin activation which then cleaves the fibrinogen to fibrin [21]. Plasmin cleaves the fibrin to produce fibrin degradation products. An increase in monocyte tissue factor expression leads to increase in D-dimer in HIV infection [21]. Decrease protein S, protein C and antithrombin activities as well as increase in plasma D-dimer are the predisposing factors

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. The markers is classified as immunologic (CD4+ T cells), virologic (RNA viral load), serologic (serum β2microglobulin and neopterin) [22] as well as biomarkers (lipid peroxidation) [23]. Among the markers, CD4+ T cell count and RNA viral load are two most commonly used prognostic markers for clinical

The CD4+ T cell count is the most important laboratory indicator of immune function in HIVinfected patients. It is also the strongest predictor of subsequent disease progression and

survival according to findings from clinical trials and cohort studies [22, 26].

following cell injury or infection subsequently leads to immune dysfunction.

of the virus.

*3.3.3.2. Coagulopathy in HIV patients*

which will increase the risk HIV patients to thrombosis.

**3.4. Prognostic markers of HIV infection**

progression of HIV infection [24, 25].

*3.4.1. Immunologic marker of infection*

RNA viral load is the best indicator of progression to AIDS and death followed by CD4+ T cell count, serum neopterin levels and serum β2microglobulin. It strongly predicts the rate of decrease in CD4+ T cell counts and progression to AIDS and eventual death, but the prognosis of HIV is best predicted by combination of both plasma HIV-1 RNA and CD4+ T cells [21].

In addition, it is also a marker of response to HAART. The main goal of HAART is to achieve and maintain durable viral suppression. A patient's pre-HAART viral load level and the magnitude of viral load decline after initiation of HAART provide prognostic information about the probability of disease progression [30]. 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 0.5 log10 copies/mL change) in the viral load [31]. Optimal viral suppression is defined as presence of persistent viral load below the level of detection (HIV RNA <20 to 75 copies/mL, depending on the assay used) [31].

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.
