*3.3.2. Loss of function of CD4+ T cells*

**\*\*Category C:**

**AIDS-Indicator Conditions**

⋅ Bacterial pneumonia, recurrent (two or more episodes in 12 months)

⋅ Candidiasis of the bronchi, trachea, or lungs

⋅ Cervical carcinoma, invasive, confirmed by biopsy ⋅ Coccidioidomycosis, disseminated or extrapulmonary

⋅ Histoplasmosis, disseminated or extrapulmonary ⋅ Isosporiasis, chronic intestinal ("/>1-month in duration)

⋅ *Mycobacterium tuberculosis*, pulmonary or extrapulmonary

⋅ *Pneumocystis jiroveci* (formerly *carinii*) pneumonia (PCP) ⋅ Progressive multifocal leukoencephalopathy (PML) ⋅ *Salmonella* septicemia, recurrent (nontyphoid)

⋅ Cryptosporidiosis, chronic intestinal ("/>1 month in duration) ⋅ Cytomegalovirus disease (other than liver, spleen, or nodes)

⋅ Herpes simplex: chronic ulcers ("/>1 month in duration), or bronchitis,

⋅ Lymphoma, Burkitt, immunoblastic, or primary central nervous system ⋅ *Mycobacterium avium* complex (MAC) or *Mycobacterium kansasii*,

⋅ *Mycobacterium*, other species or unidentified species, disseminated or

⋅ Wasting syndrome caused by HIV (involuntary weight loss "/>10% of baseline body weight) associated with either chronic diarrhea (two or more loose stools per day for ≥1 month) or chronic weakness and documented

T cells in the mucosal tissue [10] while chronic infection

⋅ Candidiasis, esophageal

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

⋅ Cryptococcosis, extrapulmonary

⋅ Encephalopathy, HIV-related

pneumonitis, or esophagitis

disseminated or extrapulmonary

⋅ Kaposi sarcoma

extrapulmonary

⋅ Toxoplasmosis of brain

Untreated HIV-1 infection is associated with a gradual loss of peripheral CD4<sup>+</sup> T cells. Loss of

is characterized by immune activation which is associated with massive production of proinflammatory cytokines [11]. This subsequently leads to decrease in peripheral CD4<sup>+</sup> T cells

The major mechanism of CD4<sup>+</sup> T cell depletion in HIV patients is due to apoptosis, in which the number of apoptotic cells exceed the number of HIV-infected cells [12]. Other causes

 T cells and systemic immune activation are the major hallmarks of HIV infection [9]. There are two major phases of HIV disease, acute and chronic infection. Acute infection is

fever for ≥1 month

**Table 5.** B and \*\*C Clinical Categories of HIV infection [7].

**3.3. Immunologic changes in HIV infection**

associated with gradual loss of CD4<sup>+</sup>

and profound immunodeficiency.

CD4<sup>+</sup>

*3.3.1. Depletion of CD4+T cells causes immunodeficiency*

Functional defects in the immune system of HIV-infected individuals exacerbate the immune deficiency caused by depletion of CD4+ T cells. These functional defects include a decrease in T cell responses to antigens as well as weak humoral immune responses even though total serum Ig levels may be elevated [13]. The defects might be due to the direct effects of HIV on CD4+ T cells through:


In addition, HIV-infected T cells are unable to form tight synapses with APCs, therefore interferes with T cell activation [13]. Failure of the activation process will lead to incapability of the T cells particularly CD4+ T cells to interact with other immune cells and subsequently lead to failure of elimination of the virus [13].
