Long-term nonprogressors

Long-term nonprogressors are a group of individuals who are infected with HIV, but whose infection does not progress to AIDS. The elite controllers are a subset of this group who show an ability to suppress the HIV viral load to extremely low, often undetectable levels for an indefinite length of time. Some have been HIV positive for 30 years without developing the clinical symptoms of AIDS, despite the fact that they have never been been treated. These individuals have been the subject of a great deal of research, as it is presumed that an understanding of their ability to control HIV infection may lead to better anti-HIV drugs or a vaccine against HIV.^[1]

See also: HIV disease progression rates

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It is estimated that as many as 1 in 100 people are long-term nonprogessors, and as many as 1 in 300 are elite controllers. Since many of the individuals never develop the symptoms of AIDS, it is believed many of them do not know they are infected. ^[2]

It is currently not known why long-term nonprogressors and elite controllers do not progress to full-blown AIDS. However, it has been shown that they are not simply infected with a weakened or inactive form of HIV. Many theories have been put forth suggesting the underlying mechanism of their resistance to infection. Most point to an inherited genetic trait that confers greater resistance or more robust immune response to HIV infection.

• Receptor mutations. A high percentage of long-term nonprogressors have been shown to have inherited mutations of the CCR5 receptor of T cell lymphocytes. HIV uses CCR5 to enter these cells. It is believed that the Δ32 (delta 32) variant of CCR5 impairs HIV ability to infect cells and cause disease. An understanding of this mechanism led to the development of a class of HIV medicines, the entry inhibitors. ^[3]

• Antibody production. All individuals with HIV make antibodies against HIV. For reasons not completely understood, these antibodies do not prevent disease progression. However, the antibodies made against HIV by long-term nonprogressors do seem to keep the virus in check. These antibodies seem to be targeted against highly conserved regions of HIV surface proteins, especially gp120 and gp41. Induction of similar antibodies in healthy individuals is a potential strategy for a HIV vaccine.^[4]

References