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, in spite of never having been treated with HAART. They have been the subject of a great deal of research, since an understanding of their ability to control HIV infection may lead to better anti-HIV drugs or a vaccine against HIV. ["Understanding Long-term Nonprogressors." International AIDS Vaccine Initiative. [http://www.iavireport.org/vax/primers/vaxprimer28.asp] accessed Dec 2007.]

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. [Walker BD. "Elite control of HIV Infection: implications for vaccines and treatment." Top HIV Med. 2007 Aug-Sep;15(4):134-6. PMID 17720999]

It is currently not known why long-term nonprogressors and elite controllers do not progress to 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. [Olivier Lambotte, Faroudy Boufassa, Yoann Madec, Ahn Nguyen, et al. "HIV controllers: a homogeneous group of HIV-1-infected patients with spontaneous control of viral replication." Clinical Infectious Diseases. Chicago: Oct 1, 2005. Vol. 41, Iss. 7; pg. 1053 PMID 16142675]

* 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. [Djordjevic A, Veljkovic M, Antoni S, Sakarellos-Daitsiotis M, Krikorian D, Zevgiti S, Dietrich U, Veljkovic N, Branch DR. "The presence of antibodies recognizing a peptide derived from the second conserved region of HIV-1 gp120 correlates with non-progressive HIV infection." Curr HIV Res. 2007 Sep;5(5):443-8. PMID 17896963]

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