15.3.1.2.3: HIV and AIDS
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Learning Objectives
- Describe the mode of transmission, mechanisms of infection, treatment options, and WHO and CDC classifications for the human immunodeficiency virus (HIV)
Human immunodeficiency virus infection / acquired immunodeficiency syndrome (HIV/ AIDS ) is a disease of the human immune system caused by the human immunodeficiency virus (HIV ). During the initial infection a person may experience a brief period of influenza-like illness. This is typically followed by a prolonged period without symptoms. As the illness progresses it interferes more and more with the immune system, making people much more likely to get infections, including opportunistic infections, and tumors that do not usually affect people with working immune systems.
HIV is transmitted primarily via unprotected sexual intercourse (including anal and even oral sex), contaminated blood transfusions and hypodermic needles, and from mother to child during pregnancy, delivery, or breastfeeding. Some bodily fluids, such as saliva and tears, do not transmit HIV. Prevention of HIV infection, primarily through safe sex and needle-exchange programs, is a key strategy to control the spread of the disease. There is no cure or vaccine; however, antiretroviral treatment can slow the course of the disease and may lead to a near-normal life expectancy. While antiretroviral treatment reduces the risk of death and complications from the disease, these medications are expensive and may be associated with side effects.
Virology
HIV is the cause of the spectrum of disease known as HIV/AIDS. HIV is a retrovirus that primarily infects components of the human immune system such as CD4+ T cells, macrophages and dendritic cells. It directly and indirectly destroys CD4+ T cells.HIV is a member of the genus Lentivirus, part of the family of Retroviridae. Lentiviruses share many morphological and biological characteristics. Many species of mammals are infected by lentiviruses, which are characteristically responsible for long-duration illnesses with a long incubation period. Lentiviruses are transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon entry into the target cell, the viral RNA genome is converted (reverse transcribed) into double-stranded DNA by a virally encoded reverse transcriptase that is transported along with the viral genome in the virus particle. The resulting viral DNA is then imported into the cell nucleus and integrated into the cellular DNA by a virally encoded integrase and host co-factors. Once integrated, the virus may become latent, allowing the virus and its host cell to avoid detection by the immune system. Alternatively, the virus may betranscribed, producing new RNA genomes and viral proteins that are packaged and released from the cell as new virus particles that begin the replication cycle anew. Two types of HIV have been characterized: HIV-1 and HIV-2. HIV-1 is the virus that was originally discovered (and initially referred to also as LAV or HTLV-III). It is more virulent, more infective, and is the cause of the majority of HIV infections globally. The lower infectivity of HIV-2 as compared with HIV-1 implies that fewer people exposed to HIV-2 will be infected per exposure. Because of its relatively poor capacity for transmission, HIV-2 is largely confined to West Africa.
Classifications of HIV infection
Two main clinical staging systems are used to classify HIV and HIV-related disease for surveillance purposes: the WHO disease staging system for HIV infection and disease, and the CDC classification system for HIV infection. The CDC’s classification system is more frequently adopted in developed countries. Since the WHO’s staging system does not require laboratory tests, it is suited to the resource-restricted conditions encountered in developing countries, where it can also be used to help guide clinical management. Despite their differences, the two systems allow comparison for statistical purposes.
The World Health Organization first proposed a definition for AIDS in 1986. Since then, the WHO classification has been updated and expanded several times, with the most recent version being published in 2007. The WHO system uses the following categories:
Primary HIV infection: May be either asymptomatic or associated with acute retroviral syndrome.
Stage I : HIV infection is asymptomatic with a CD4+ T cell count (also known as CD4 count) greater than 500/uL. May include generalized lymph node enlargement.
Stage II : Mild symptoms which may include minor mucocutaneous manifestations and recurrent upper respiratory tract infections. A CD4 count of less than 500/uL.
Stage III : Advanced symptoms which may include unexplained chronic diarrhea for longer than a month, severe bacterial infections including tuberculosis of the lung as well as a CD4 count of less than 350/uL.
Stage IV or AIDS : severe symptoms which includes toxoplasmosis of the brain, candidiasis of the esophagus, trachea, bronchi or lungs and Kaposi’s sarcoma. A CD4 count of less than 200/uL.
The United States Center for Disease Control and Prevention also created a classification system for HIV, and updated it in 2008. In this system HIV infections are classified based on CD4 count and clinical symptoms, and describes the infection in three stages:
Stage 1 : CD4 count ≥ 500 cells/uL and no AIDS defining conditions
Stage 2 : CD4 count 200 to 500 cells/uL and no AIDS defining conditions
Stage 3 : CD4 count ≤ 200 cells/uL or AIDS defining conditions
Unknown : if insufficient information is available to make any of the above classificationsFor surveillance purposes, the AIDS diagnosis still stands even if, after treatment, the CD4+ T cell count rises to above 200 per µL of blood or other AIDS-defining illnesses are cured.
Antiviral therapy
Abacavir, a nucleoside analog reverse transcriptase inhibitor (NARTI or NRTI) is used to treat HIV. Current HAART options are combinations (or “cocktails”) consisting of at least three medications belonging to at least two types, or “classes,” of antiretroviralagents. Initially treatment is typically a non-nucleoside reverse transcriptase inhibitor (NNRTI) plus two nucleoside analogue reverse transcriptase inhibitors(NRTIs). Typical NRTIs include: zidovudine (AZT) or tenofovir (TDF) and lamivudine (3TC) or emtricitabine (FTC). Combinations of agents which include a protease inhibitors (PI) are used if the above regime loses effectiveness.
Key Points
- During the initial HIV infection a person may experience a brief period of influenza-like illness. This is typically followed by a prolonged period without symptoms.
- HIV is transmitted primarily via unprotected sexual intercourse (including anal and even oral sex), contaminated blood transfusions and hypodermic needles, and from mother to child during pregnancy, delivery, or breastfeeding.
- Abacavir, a nucleoside analog reverse transcriptase inhibitor (NARTI or NRTI) is used to treat HIV. Current HAART options are combinations (or “cocktails”) consisting of at least three medications belonging to at least two types, or “classes,” of antiretroviralagents.
Key Terms
- immunodeficiency : A depletion in the body’s natural immune system, or in some component of it.
- AIDS : an infectious disease, caused by HIV, that causes the gradual degeneration of the body’s immune system