Long-term nonprogressor
Long-term nonprogressors (LTNPs), less commonly called elite controllers, are rare individuals who are infected with HIV, but control the infection without antiretroviral therapy. Many of these patients have been HIV positive for 30 years without progressing to the point of needing to take medication in order not to develop AIDS.[citation needed] They have been the subject of a great deal of research, since an understanding of their ability to control HIV infection may lead to the development of immune therapies or a therapeutic vaccine.[1]
Long-term nonprogressors typically have viral loads under 10,000 copies RNA/ml blood,[2] do not take antiretrovirals, and have CD4+ counts within the normal range.[3] Most people with HIV not on medication have viral loads which are much higher.
It is estimated that around 1 in 500 people with HIV are long-term nonprogressors.[4] Without the symptoms of AIDS, many LTNP patients may not know they are infected.[5] The clinical relevance of the classification "Long-term non-progressor" is not definitive because some patients classified in this category have gone on to develop AIDS. It is likely, however, that these patients were not true LTNP patients.
Genetic traits that confer greater resistance or more robust immune response to HIV are thought to explain why LTNP patients progress to the point of needing to take medication in order not to develop AIDS more slowly than most HIV-infected people.[6][7] Some LTNP are infected with a weakened or inactive form of HIV, but it is now known that many LTNP patients carry a fully virulent form of the virus. Genetic traits that may affect progression include:
- Gene mutation. A mutation in the FUT2 gene affects the progression of HIV-1 infection.[8] 20% of Europeans who have that mutation are called "non secretor" because of their absence of a certain type of antigen that provide also a strong resistance against norovirus[8][9]
- Mitochondrial DNA. Different types of Mitochondrial DNA in humans gives an increased or a decreased rate of HIV progression.[10]
- Receptor mutations. A low 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.[11] The presence of this mutation, however, is not a unifying theme among LTNPs and is observed in a exceedingly small number of these patients.
- HLA type has also been correlated with long-term non-progressor cohorts. In particular, a high percentage of people possessing HLA-B*5705 and/or HLA-B*2705 are more likely to exhibit control over HIV (Migueles et al., 2000).[weasel words]
- Antibody production. All individuals with HIV make antibodies against the virus. In most patients, broadly neutralizing antibodies do not emerge until ~4 years after the initial infection. At this point, the latent reservoir has already been established and the presence of broadly neutralizing antibodies is not enough to prevent disease progression. In some rare patients, these antibodies emerge earlier and can result in a delayed disease course. These patients, however, are not typically classified as LTNPs, but rather as slow progressors, who will eventually develop AIDS. Induction of broadly neutralizing antibodies in healthy individuals is a potential strategy for a preventive HIV vaccine.[citation needed]
References
- ^ Understanding Long-term Nonprogressors. International AIDS Vaccine Initiative. [1] accessed Dec 2007.[dead link]
- ^ Poropatich, Kate; Sullivan, David J. (2010). "Human immunodeficiency virus type 1 long-term non-progressors: the viral, genetic and immunological basis for disease non-progression". Journal of General Virology 92 (2).
- ^ Rhodes DI, Ashton L, Solomon A, Carr A, Cooper D, Kaldor J, Deacon N (November 2000). "Characterization of three nef-defective human immunodeficiency virus type 1 strains associated with long-term nonprogression. Australian Long-Term Nonprogressor Study Group". J. Virol. 74 (22): 10581–8. PMC 110932. PMID 11044102. Retrieved 2010-10-13.
- ^ National Institute of Allergy and Infectious Diseases, http://www.niaid.nih.gov/volunteer/hivlongterm/Pages/default.aspx, accessed July 5, 2011
- ^ Walker BD. Elite control of HIV Infection: implications for vaccines and treatment. Top HIV Med. 2007 Aug-Sep;15(4):134-6. PMID 17720999
- ^ O’connell, K. A.; Bailey, J. R.; Blankson, J. N. (2009). "Elucidating the elite: mechanisms of control in HIV-1 infection". Trends in Pharmacological Sciences 30 (12): 631–637. doi:10.1016/j.tips.2009.09.005. PMID 19837464.
- ^ Blankson, J. N. (2009). "Effector mechanisms in HIV-1 infected elite controllers: Highly active immune responses?". Antiviral Research 85 (1): 295–302. doi:10.1016/j.antiviral.2009.08.007. PMC 2814919. PMID 19733595.
- ^ a b http://journals.lww.com/aidsonline/Fulltext/2006/03210/A_nonsense_mutation__428G__A__in_the.7.aspx
- ^ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1315998/?tool=pubmed
- ^ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699618/
- ^ 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
12. "Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization" http://www.sciencemag.org/content/340/6133/751.abstract
