HIV Disease

Almost everyone who becomes infected with HIV develops HIV disease, marked by slow destruction of their immune system, eventually ending in AIDS.

Symptoms

The first symptoms of HIV disease appear after an incubation period of 6 days to 6 weeks and usually consist of fever, headache, sore throat, muscle aches, enlarged lymph nodes, and a generalized rash. Some subjects develop central nervous system symptoms ranging from moodiness and confusion to seizures and paralysis. These symptoms constitute the acute retroviral syndrome (ARS), and they typically subside within 6 weeks. Many HIV infections are asymptomatic, however, or the symptoms are mild and attributed to the "flu." Following the acute illness, if any, there is an asymptomatic period that typically lasts for years, even though the disease advances in the infected person and can be transmitted to others. The asymptomatic period may end with persistent enlargement of the person's lymph nodes, a condition known as lymphadenopathy syndrome (LAS). Other symptoms heralding immunodeficiency include fever, weight loss, fatigue, and diarrhea, referred to as the AIDS-related complex (ARC). The first symptoms in many cases are those due to tumors or opportunistic infections resulting from severe immunodeficiency. As one might

Nester-Anderson-Roberts: I IV. Infectious Diseases I 29. HIV Disease and I I © The McGraw-Hill

Microbiology, A Human Complications of Companies, 2003

Perspective, Fourth Edition Immunodeficiency

29.1 Human Immunodeficiency Virus (HIV) Infection and AIDS 741

Table 29.1 AIDS-Defining Conditions*

Cancer of the uterine cervix, invasive

Candidiasis involving the esophagus, trachea, bronchi, or lungs

Coccidioidomycosis, of tissues other than the lung

Cryptococcosis, of tissues other than the lung

Cryptosporidiosis of duration greater than 1 month

Cytomegalovirus disease of the retina with vision loss or other involvement outside liver, spleen, or lymph nodes

Encephalopathy (brain involvement with HIV)

Herpes simplex virus causing ulcerations lasting 1 month or longer or involving the esophagus, bronchi, or lungs

Histoplasmosis of tissues other than the lung

Isosporiasis (a protozoan disease of the intestine) of more than 1 month's duration

Kaposi's sarcoma

Lymphomas, such as Burkitt's, or arising in the brain

Mycobacterial diseases, including tuberculosis

Pneumocystosis (pneumonia due to Pneumocystis carinii)

Pneumonias occurring repeatedly

Progressive multifocal leukoencephalopathy (a brain disease caused by the JC polyomavirus)

Salmonella infection of the bloodstream, recurrent

Toxoplasmosis of the brain

Wasting syndrome (weight loss of more than 10% due to HIV); also known as slim disease

'Additional conditions are used in surveillance of childhood AIDS

expect, symptoms at this stage of the disease vary widely according to the kind of infection. For example, a frequently encountered symptom is a fuzzy white patch on the tongue, hairy leukoplakia (figure 29.2), a result of latent Epstein-Barr virus (EBV) reactivation. Severe skin rashes, cough and chest pain, stiff neck, confusion, visual problems, and diarrhea are manifestations of other infections. ■ Epstein-Barr virus, p. 727

Causative Agent

In the United States, and most other parts of the world, AIDS is usually caused by human immunodeficiency virus, type 1 (HIV-1), a single-stranded RNA virus of the retrovirus family. There are many kinds of retroviruses, naturally infecting hosts as diverse as fish and humans. HIV-1 belongs to the lentivirus subgroup of the retroviruses, which characteristically infect mononuclear phagocytes.

HIV-1 viruses can be classified into subtypes based on nucleic acid sequences. In the M (for "major") group of HIV-1 viruses, 10

Hairy Leukoplakia
Figure 29.2 Hairy Leukoplakia This AIDS-related condition is probably due to activation of latent Epstein-Barr virus infection.

subtypes, clades, have been described, designated A through J. Members of each clade are closely related, as determined by sequencing their genomes. Infection by two different subtypes can give rise to "hybrids" having properties of both. Other HIV-1 groups such as O (for "outlier") and N differ from M group viruses. The importance of being able to recognize all these differing strains of HIV-1 viruses is to aid epidemiological studies and to ensure that the tests for HIV reliably detect infection.

Human immunodeficiency viruses, type 2 (HIV-2), are lentiviruses similar in structure to HIV-1, but antigenically distinct, their genomes differing from HIV-1 by more than 55%. They are a prominent cause of AIDS in parts of West Africa and India, and have appeared in the United States and other countries. HIV-2 transmission has generally been less efficient that HIV-1, and disease progression slower. Otherwise, the biology of HIV-2 is quite similar to HIV-1. For the remainder of this chapter, we will use the term HIV to indicate HIV-1.

The structure of HIV is shown schematically in figure 29.3a. The locations of its important antigens are indicated. The numerous knobs projecting from the surface of the virion represent gp120 (SU, for "surface") antigen, partly responsible for attachment to the host cell. The gp stands for glycoprotein, indicating that sugar molecules are attached to the protein. The gp41 (TM, for "transmembrane") antigen traverses the viral envelope and is closely associated with SU; it probably plays a role in entry ofthe virus into the host cell. The p17 (MA) matrix protein, located inside the viral envelope, helps maintain viral structure, transport the viral genome to the host cell nucleus, and assemble new virions. The core of the virion is composed of the p24 (CA) capsid antigen, two copies of the single-stranded RNA viral genome, and various proteins, including nucleocapsid (NC) and three important viral enzymes, reverse transcriptase (RT), protease (PR), and integrase (IN).

The HIV genome is shown schematically in figure 29.3b. The first two genes,gag (from "group antigen") and pol (from "polymerase"), can be translated as a unit from the full-length viral

gag vif tat nef

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