Porth's Essentials of Pathophysiology, 4e

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Disorders of the Immune Response

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doubling time of approximately 0.3 days during the first 2 to 3 weeks of infection. The problem is that, over years, the CD4 + T-cell count gradually decreases through this process, and the number of viruses detected in the blood of persons infected with HIV increases. The depletion of CD4 + T cells after infection is due to the cytopathic effect of the virus, resulting from production of viral particles, as well as death of unaffected cells. Other infected cells, such as macrophages and dendritic cells, may also die, resulting in destructive changes in the lymphoid organs. Until the CD4 + T-cell count falls to a very low level, a person infected with HIV can remain asymp- tomatic, although active viral replication is still taking place and serologic tests can identify antibodies to HIV. These antibodies, unfortunately, do not convey protec- tion against the virus. Although symptoms are not evi- dent, the infection proceeds on a microbiologic level, including the invasion and selective destruction of CD4 + T cells. The continual decline of CD4 + T cells, which are pivotal cells in the immune response, strips the HIV- infected person of protection against common organ- isms and cancerous cells. Classification and Stages of HIV Infection The definitions and classification systems for HIV and AIDS have been evolving, due in part to improvements in diagnostic and therapeutic capabilities, including increased use of new HIV-testing technologies. In 1993, the Centers for Disease Control and Prevention (CDC) developed a classification system that emphasized the clinical importance of the CD4 + T-cell count along with a list of AIDS-defining conditions (Chart 16-3). 56 The 1993 classification system, which was revised in 2008, highlights the central importance of the CD4 + T-cell count and percentages, which are objective measures of immunosuppression routinely used in the care of HIV- infected persons 57 (Table 16-2). It distinguishes three stages of HIV infection based on CD4 + T-cell counts and total T-cell percentages: stage one >500 cells/ μ L (29%); stage two 200 to 499 cells/ μ L (14% to 28%); and stage three (AIDS) <200 cells/ μ L (<14%). An undetermined stage has also been included. Clinical Course. The typical course of HIV infection is characterized by three phases, which usually occur over a period of 8 to 12 years. These are the primary infec- tion phase, chronic asymptomatic or latency phase, and overt AIDS phase (Fig. 16-9). 56 When initially infected with HIV, many persons have an acute mononucleosis-like syndrome known as primary infection. This acute phase (stage 1) may include fever, fatigue, myalgias, sore throat, night sweats, gastrointestinal problems, lymphadenopathy, maculopapular rash, and headache. Fever and malaise are the symptoms most commonly associated with pri- mary infection. 46,57 During primary infection, there is an increase in viral replication, which leads to very high viral loads, sometimes greater than 1,000,000 copies/ mL, and a decrease in the CD4 + T-cell count. The signs

CHART 16-3   Conditions Included in the 1993 AIDS Surveillance Case Definition

and symptoms of primary HIV infection usually appear 1 to 4 weeks after exposure to HIV, and have an aver- age duration of 7 to 10 days. 57 After several weeks, the immune system acts to control viral replication and reduces the viral load to a lower level, where it often remains for several years. This relatively stable level of virus is referred to as the set point. People who are diagnosed with HIV infection while they are in the pri- mary infection phase may have a unique opportunity for treatment. Some experts hypothesize that treatment, if started early, may reduce the number of HIV-infected CD4 + memory T cells; protect the functioning of HIV- infected CD4 + T cells and cytotoxic T cells; and poten- tially help to maintain a homogeneous viral population that will be better controlled by antiretroviral therapy and the immune system. 46,58 disseminated or extrapulmonary Pneumocystis jiroveci pneumonia Pneumonia, recurrent* Progressive multifocal leukoencephalopathy Salmonella septicemia, recurrent Toxoplasmosis of the brain Wasting syndrome due to HIV *Added to the 1993 expansion of the AIDS surveillance case definition. From Centers for Disease Control and Prevention. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep. 1992;41(RR-17):19. Candidiasis of bronchi, trachea, or lungs Candidiasis, esophageal Cervical cancer, invasive* Coccidioidomycosis, disseminated or extrapulmonary Cryptococcosis, extrapulmonary Cryptosporidiosis, chronic intestinal (>1 month duration) Cytomegalovirus disease (other than liver, spleen, or nodes) Cytomegalovirus retinitis (with loss of vision) Encephalopathy, HIV related Herpes simplex: chronic ulcer(s) (>1 month duration) or bronchitis, pneumonitis, or esophagitis Histoplasmosis, disseminated or extrapulmonary Isosporiasis, chronic intestinal (>1 month’s duration) Kaposi sarcoma Lymphoma, Burkitt (or equivalent term) Lymphoma, immunoblastic (or equivalent term) Lymphoma, primary, of brain Mycobacterium avium-intracellulare complex or Mycobacterium kansasii, disseminated or extrapulmonary Mycobacterium tuberculosis, any site (pulmonary* or extrapulmonary) Mycobacterium, other species or unidentified species,