Human Immunodeficiency Virus
In June 1981, the CDC’s Morbidity and Mortality Weekly Report highlighted 5 homosexual men in Los Angeles, California, who had biopsy-confirmed Pneumocystis jirovecii (formerly called Pneumocystis carinii) pneumonia. In 1982, the CDC used the term AIDS for the first time and released the first case definition; by the next year the major routes of transmission for AIDS were identified. In 1983, HIV, a newly recognized retrovirus, was identified as the cause of AIDS.
HIV is a blood-borne virus and is transmitted via sexual intercourse, shared intravenous drug paraphernalia, blood transfusion, and from mother to child during birth or breastfeeding. Although HIV infection may be transmitted via blood or blood products, the risk of transmission by accidental needle-stick appears quite low (less than 0.5%).
The CDC estimated that as of the end of 2015, 1.1 million persons aged 13 years and older were living with HIV infection in the United States. The most affected population for new HIV diagnosis in the United States in 2016 was black men who have sex with men. Worldwide, more than 70 million people have been infected with HIV, and 35 million people have died from HIV infection. At the end of 2016, 36.7 million people worldwide had HIV, with the majority in sub-Saharan Africa; 2.1 million of the infected individuals were children younger than 15 years of age.
Etiology and Pathogenesis
HIV belongs to a family of viruses known as retroviruses. A retrovirus encodes its genetic information in RNA and uses a unique viral enzyme named reverse transcriptase to copy its genome into DNA. HIV has 2 subtypes, HIV-1 and HIV-2. HIV-1 is further classified into several groups, including M, N, and O. Thus far, there are 9 known serotypes of HIV-1 group M, and 1 each of HIV-1 groups N and O. In the United States, HIV-1 group M, serotype B is the most common form of HIV. HIV-2, another human T-lymphotropic retrovirus, has been isolated in West African individuals and is closely related to simian immunodeficiency virus.
HIV preferentially infects T lymphocytes, especially helper T (CD4+) lymphocytes. The virus infects mature T lymphocytes in vitro, although other cells can serve as targets. CD4 is the phenotypic marker for this subset and is identified by monoclonal antibodies OKT4 and Leu-3.
The hallmark of the immunodeficiency in AIDS is a depletion of the CD4+ helper-inducer T lymphocytes. HIV selectively infects these lymphocytes as well as macrophages; with HIV replication, the helper T lymphocytes are killed. Because the helper T lymphocytes are central to the immune response, loss of this subset results in a profound immune deficiency, leading to the life-threatening opportunistic infections indicative of AIDS. This selective depletion of CD4+ helper T lymphocytes leads to the characteristic inverted CD4+/CD8+ ratio (also known as the T4/T8 ratio), where the ratio drops to less than 1.0, in comparison to the normal CD4+/CD8+ ratio, which is around 2. Years may pass between the initial HIV infection and the development of these immune abnormalities.
In addition to cellular immunodeficiency, patients with AIDS have abnormalities of B-lymphocyte function. These patients are unable to mount an antibody response to novel T lymphocyte–dependent B-lymphocyte challenges, although they have B-lymphocyte hyperfunction with polyclonal B-lymphocyte activation, hypergammaglobulinemia, and circulating immune complexes. This B-lymphocyte hyperfunction may be a direct consequence of HIV infection: studies have demonstrated that polyclonal activation can be induced in vitro by adding HIV to B lymphocytes.
HIV has also been documented to infect macrophages in the brains of patients with AIDS. It is thought that HIV infection of the brain is responsible for the HIV encephalopathy syndrome.
Excerpted from BCSC 2020-2021 series: Section 1 - Update on General Medicine. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.