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{{Cite check|date=July 2010}}
{{Cite check|date=July 2010}}
'''Long-term nonprogressors''' (LTNPs), sometimes also called "elite controllers", are individuals infected with [[HIV]], who maintain a CD4 count greater than 500 without [[Highly active antiretroviral therapy|antiretroviral therapy]] with a detectable viral load.<ref>http://www.aidsmap.com/HIV-non-progressor-status-established-soon-after-infection/page/1432975/</ref> 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|date=October 2010}} 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.<ref>''Understanding Long-term Nonprogressors.'' International AIDS Vaccine Initiative. [http://www.iavireport.org/vax/primers/vaxprimer28.asp] accessed Dec 2007. {{webarchive |url=https://web.archive.org/web/20061009103120/http://www.iavireport.org/vax/primers/vaxprimer28.asp |date=October 9, 2006 }}</ref> The classification "Long-term non-progressor" is not permanent, because some patients in this category have gone on to develop AIDS.
'''Long-term nonprogressors''' (LTNPs), sometimes also called "elite controllers", are individuals infected with [[HIV]], who maintain a CD4 count greater than 500 without [[Highly active antiretroviral therapy|antiretroviral therapy]] with a detectable viral load.<ref>{{cite web|author=Michael Carter Published: 12 January 2009 |url=http://www.aidsmap.com/HIV-non-progressor-status-established-soon-after-infection/page/1432975/ |title=HIV & AIDS Information :: HIV non-progressor status established soon after infection |publisher=Aidsmap.com |date=2009-01-12 |accessdate=2017-01-17}}</ref> 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|date=October 2010}} 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.<ref>''Understanding Long-term Nonprogressors.'' International AIDS Vaccine Initiative. [http://www.iavireport.org/vax/primers/vaxprimer28.asp] accessed Dec 2007. {{webarchive |url=https://web.archive.org/web/20061009103120/http://www.iavireport.org/vax/primers/vaxprimer28.asp |date=October 9, 2006 }}</ref> The classification "Long-term non-progressor" is not permanent, because some patients in this category have gone on to develop AIDS.


Long-term nonprogressors typically have viral loads under 10,000 copies RNA/ml blood,<ref>{{cite journal|last=Poropatich|first=Kate|author2=Sullivan, David J. |title=Human immunodeficiency virus type 1 long-term non-progressors: the viral, genetic and immunological basis for disease non-progression|journal=Journal of General Virology|year=2010|volume=92|issue=2|doi=10.1099/vir.0.027102-0 |url=http://vir.sgmjournals.org/content/92/2/247.full|pages=247–268}}</ref> do not take antiretrovirals, and have CD4+ counts within the normal range.<ref name="pmid11044102">{{cite journal |vauthors=Rhodes DI, Ashton L, Solomon A, Carr A, Cooper D, Kaldor J, Deacon N | title = Characterization of three nef-defective human immunodeficiency virus type 1 strains associated with long-term nonprogression. Australian Long-Term Nonprogressor Study Group | journal = [[J. Virol.]] | volume = 74 | issue = 22 | pages = 10581–8 |date=November 2000 | pmid = 11044102 | pmc = 110932 | doi = 10.1128/jvi.74.22.10581-10588.2000| url = http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=11044102 | issn = | accessdate = 2010-10-13}}</ref> Most people with HIV not on medication have viral loads which are much higher.
Long-term nonprogressors typically have viral loads under 10,000 copies RNA/ml blood,<ref>{{cite journal|last=Poropatich|first=Kate|author2=Sullivan, David J. |title=Human immunodeficiency virus type 1 long-term non-progressors: the viral, genetic and immunological basis for disease non-progression|journal=Journal of General Virology|year=2010|volume=92|issue=2|doi=10.1099/vir.0.027102-0 |url=http://vir.sgmjournals.org/content/92/2/247.full|pages=247–268}}</ref> do not take antiretrovirals, and have CD4+ counts within the normal range.<ref name="pmid11044102">{{cite journal |vauthors=Rhodes DI, Ashton L, Solomon A, Carr A, Cooper D, Kaldor J, Deacon N | title = Characterization of three nef-defective human immunodeficiency virus type 1 strains associated with long-term nonprogression. Australian Long-Term Nonprogressor Study Group | journal = [[J. Virol.]] | volume = 74 | issue = 22 | pages = 10581–8 |date=November 2000 | pmid = 11044102 | pmc = 110932 | doi = 10.1128/jvi.74.22.10581-10588.2000| url = http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=11044102 | issn = | accessdate = 2010-10-13}}</ref> Most people with HIV not on medication have viral loads which are much higher.
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[[Genetic trait]]s that confer greater resistance or more robust immune response to HIV are thought to explain why LTNP patients are able to live much longer with HIV than patients who are not LTNP.<ref>{{Cite journal | doi = 10.1016/j.tips.2009.09.005 | title = Elucidating the elite: mechanisms of control in HIV-1 infection | year = 2009 | last1 = O’connell | first1 = K. A. | last2 = Bailey | first2 = J. R. | last3 = Blankson | first3 = J. N. | journal = Trends in Pharmacological Sciences | volume = 30 | pages = 631–637| pmid = 19837464 | issue = 12 }}</ref><ref>{{Cite journal | pages = 295–302 | pmid = 19733595 | issue = 1 | pmc = 2814919| volume = 85 | journal = Antiviral Research | title = Effector mechanisms in HIV-1 infected elite controllers: Highly active immune responses? | year = 2009 | last1 = Blankson | first1 = J. N. | doi = 10.1016/j.antiviral.2009.08.007 }}</ref> 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:
[[Genetic trait]]s that confer greater resistance or more robust immune response to HIV are thought to explain why LTNP patients are able to live much longer with HIV than patients who are not LTNP.<ref>{{Cite journal | doi = 10.1016/j.tips.2009.09.005 | title = Elucidating the elite: mechanisms of control in HIV-1 infection | year = 2009 | last1 = O’connell | first1 = K. A. | last2 = Bailey | first2 = J. R. | last3 = Blankson | first3 = J. N. | journal = Trends in Pharmacological Sciences | volume = 30 | pages = 631–637| pmid = 19837464 | issue = 12 }}</ref><ref>{{Cite journal | pages = 295–302 | pmid = 19733595 | issue = 1 | pmc = 2814919| volume = 85 | journal = Antiviral Research | title = Effector mechanisms in HIV-1 infected elite controllers: Highly active immune responses? | year = 2009 | last1 = Blankson | first1 = J. N. | doi = 10.1016/j.antiviral.2009.08.007 }}</ref> 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.<ref name="journals.lww.com">http://journals.lww.com/aidsonline/Fulltext/2006/03210/A_nonsense_mutation__428G__A__in_the.7.aspx</ref> 20% of Europeans who have that mutation are called "non secretor" because of their absence of a certain type of antigen that also provides strong resistance against [[norovirus]].<ref name="journals.lww.com"/><ref>{{cite journal | pmc=1315998 | pmid=16306606 | doi=10.1128/JVI.79.24.15351-15355.2005 | volume=79 | title=A homozygous nonsense mutation (428G--&gt;A) in the human secretor (FUT2) gene provides resistance to symptomatic norovirus (GGII) infections | year=2005 | journal=J. Virol. | pages=15351–5 |vauthors=Thorven M, Grahn A, Hedlund KO, Johansson H, Wahlfrid C, Larson G, Svensson L }}</ref>
* '''Gene mutation.''' A mutation in the [[FUT2]] gene affects the progression of HIV-1 infection.<ref name="journals.lww.com">{{cite journal |doi=10.1097/01.aids.0000216368.23325.bc|pmid=16514298|title=A nonsense mutation (428G→A) in the fucosyltransferase FUT2 gene affects the progression of HIV-1 infection|journal=AIDS|volume=20|issue=5|pages=685|year=2006|last1=Kindberg|first1=Elin|last2=Hejdeman|first2=Bo|last3=Bratt|first3=Göran|last4=Wahren|first4=Britta|last5=Lindblom|first5=Bertil|last6=Hinkula|first6=Jorma|last7=Svensson|first7=Lennart}}</ref> 20% of Europeans who have that mutation are called "non secretor" because of their absence of a certain type of antigen that also provides strong resistance against [[norovirus]].<ref name="journals.lww.com"/><ref>{{cite journal | pmc=1315998 | pmid=16306606 | doi=10.1128/JVI.79.24.15351-15355.2005 | volume=79 | issue=24 | title=A homozygous nonsense mutation (428G--&gt;A) in the human secretor (FUT2) gene provides resistance to symptomatic norovirus (GGII) infections | year=2005 | journal=J. Virol. | pages=15351–5 |vauthors=Thorven M, Grahn A, Hedlund KO, Johansson H, Wahlfrid C, Larson G, Svensson L }}</ref>
* '''Mitochondrial DNA.''' Different [[mitochondrial DNA]] [[haplotype]]s in humans may increase or decrease rates of AIDS progression. Haplotypes associated with more loosely coupled [[Oxidative phosphorylation|mitochondrial respiration]], with reduced [[Adenosine triphosphate|ATP]] and [[Reactive oxygen species|ROS]] generation, have been associated with faster progression and vice versa.<ref name="HendricksonHutcheson2008">{{cite journal|last1=Hendrickson|first1=S. L.|last2=Hutcheson|first2=H. B.|last3=Ruiz-Pesini|first3=E.|last4=Poole|first4=J. C.|last5=Lautenberger|first5=J.|last6=Sezgin|first6=E.|last7=Kingsley|first7=L.|last8=Goedert|first8=J. J.|last9=Vlahov|first9=D.|last10=Donfield|first10=S.|last11=Wallace|first11=D. C.|last12=OʼBrien|first12=S. J.|title=Mitochondrial DNA haplogroups influence AIDS progression|journal=AIDS|volume=22|issue=18|date=2008-11-30|pages=2429–2439|issn=0269-9370|doi=10.1097/QAD.0b013e32831940bb|pmid=19005266|pmc=2699618}}</ref>
* '''Mitochondrial DNA.''' Different [[mitochondrial DNA]] [[haplotype]]s in humans may increase or decrease rates of AIDS progression. Haplotypes associated with more loosely coupled [[Oxidative phosphorylation|mitochondrial respiration]], with reduced [[Adenosine triphosphate|ATP]] and [[Reactive oxygen species|ROS]] generation, have been associated with faster progression and vice versa.<ref name="HendricksonHutcheson2008">{{cite journal|last1=Hendrickson|first1=S. L.|last2=Hutcheson|first2=H. B.|last3=Ruiz-Pesini|first3=E.|last4=Poole|first4=J. C.|last5=Lautenberger|first5=J.|last6=Sezgin|first6=E.|last7=Kingsley|first7=L.|last8=Goedert|first8=J. J.|last9=Vlahov|first9=D.|last10=Donfield|first10=S.|last11=Wallace|first11=D. C.|last12=OʼBrien|first12=S. J.|title=Mitochondrial DNA haplogroups influence AIDS progression|journal=AIDS|volume=22|issue=18|date=2008-11-30|pages=2429–2439|issn=0269-9370|doi=10.1097/QAD.0b013e32831940bb|pmid=19005266|pmc=2699618}}</ref>
* '''Receptor mutations.''' A low percentage of long-term nonprogressors have been shown to have inherited mutations of the [[CCR5]] receptor of [[T cell]] [[lymphocyte]]s. HIV uses CCR5 to enter these cells. It is believed that the [[CCR5#CCR5-.CE.9432|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]].<ref>{{cite journal |author1=Lambotte Olivier |author2=Boufassa Faroudy |author3=Madec Yoann |author4=Nguyen Ahn | year = 2005 | title = HIV controllers: a homogeneous group of HIV-1-infected patients with spontaneous control of viral replication | url = | journal = Clinical Infectious Diseases | volume = 41 | issue = 7| pages = 1053–6 | doi = 10.1086/433188 | pmid = 16142675 |display-authors=etal}}</ref> The presence of this mutation, however, is not a unifying theme among LTNPs and is observed in an exceedingly small number of these patients.
* '''Receptor mutations.''' A low percentage of long-term nonprogressors have been shown to have inherited mutations of the [[CCR5]] receptor of [[T cell]] [[lymphocyte]]s. HIV uses CCR5 to enter these cells. It is believed that the [[CCR5-D32|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]].<ref>{{cite journal |author1=Lambotte Olivier |author2=Boufassa Faroudy |author3=Madec Yoann |author4=Nguyen Ahn | year = 2005 | title = HIV controllers: a homogeneous group of HIV-1-infected patients with spontaneous control of viral replication | url = | journal = Clinical Infectious Diseases | volume = 41 | issue = 7| pages = 1053–6 | doi = 10.1086/433188 | pmid = 16142675 |display-authors=etal}}</ref> The presence of this mutation, however, is not a unifying theme among LTNPs and is observed in an exceedingly small number of these patients.
* '''[[HLA type]]''' has also been correlated with long-term non-progressor cohorts. In particular, strong correlations have been found between possessing the class 1 [[HLA-B57|HLA-B*57]]01,<ref name="MiguelesSabbaghian2000">{{cite journal|last1=Migueles|first1=S. A.|last2=Sabbaghian|first2=M. S.|last3=Shupert|first3=W. L.|last4=Bettinotti|first4=M. P.|last5=Marincola|first5=F. M.|last6=Martino|first6=L.|last7=Hallahan|first7=C. W.|last8=Selig|first8=S. M.|last9=Schwartz|first9=D.|last10=Sullivan|first10=J.|last11=Connors|first11=M.|title=HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors|journal=Proceedings of the National Academy of Sciences|volume= 97|issue= 6|date= 2000-02-29|pages= 2709–2714|issn= 0027-8424|doi= 10.1073/pnas.050567397|pmid=10694578|pmc=15994}}</ref> HLA-B*5703,<ref name = "Costello_1999">{{cite journal | last = Costello | first = C. |author2=Tang, J. |author3=Rivers, C. |author4=Karita, E. |author5=Meizen-Derr, J. |author6=Allen, S. |author7= Kaslow, R. A. | title = HLA-B*5703 independently associated with slower HIV-1 disease progression in Rwandan women | journal = AIDS | volume = 13 | issue = 14 | pages = 1990–1991 | date = 1999-10-01 | url = http://journals.lww.com/aidsonline/Fulltext/1999/10010/HLA_B_5703_independently_associated_with_slower.31.aspx | pmid = 10513667 | accessdate = 2013-06-12 | doi=10.1097/00002030-199910010-00031}}
* '''[[HLA type]]''' has also been correlated with long-term non-progressor cohorts. In particular, strong correlations have been found between possessing the class 1 [[HLA-B57|HLA-B*57]]01,<ref name="MiguelesSabbaghian2000">{{cite journal|last1=Migueles|first1=S. A.|last2=Sabbaghian|first2=M. S.|last3=Shupert|first3=W. L.|last4=Bettinotti|first4=M. P.|last5=Marincola|first5=F. M.|last6=Martino|first6=L.|last7=Hallahan|first7=C. W.|last8=Selig|first8=S. M.|last9=Schwartz|first9=D.|last10=Sullivan|first10=J.|last11=Connors|first11=M.|title=HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors|journal=Proceedings of the National Academy of Sciences|volume= 97|issue= 6|date= 2000-02-29|pages= 2709–2714|issn= 0027-8424|doi= 10.1073/pnas.050567397|pmid=10694578|pmc=15994}}</ref> HLA-B*5703,<ref name = "Costello_1999">{{cite journal | last = Costello | first = C. |author2=Tang, J. |author3=Rivers, C. |author4=Karita, E. |author5=Meizen-Derr, J. |author6=Allen, S. |author7= Kaslow, R. A. | title = HLA-B*5703 independently associated with slower HIV-1 disease progression in Rwandan women | journal = AIDS | volume = 13 | issue = 14 | pages = 1990–1991 | date = 1999-10-01 | url = http://journals.lww.com/aidsonline/Fulltext/1999/10010/HLA_B_5703_independently_associated_with_slower.31.aspx | pmid = 10513667 | accessdate = 2013-06-12 | doi=10.1097/00002030-199910010-00031}}
</ref> and/or [[HLA-B27|HLA-B*27]]05<ref name="AlmeidaPrice2007">{{cite journal|last1=Almeida|first1=J. R.|last2=Price|first2=D. A.|last3=Papagno|first3=L.|last4=Arkoub|first4=Z. A.|last5=Sauce|first5=D.|last6=Bornstein|first6=E.|last7=Asher|first7=T. E.|last8=Samri|first8=A.|last9=Schnuriger|first9=A.|last10=Theodorou|first10=I.|last11=Costagliola|first11=D.|last12=Rouzioux|first12=C.|last13=Agut|first13=H.|last14=Marcelin|first14=A.-G.|last15=Douek|first15=D.|last16=Autran|first16=B.|last17=Appay|first17=V.|title=Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover|journal=Journal of Experimental Medicine|volume=204|issue=10|date=2007-09-24|pages=2473–2485|issn=0022-1007|doi=10.1084/jem.20070784}}</ref> alleles and ability to exert control over HIV.
</ref> and/or [[HLA-B27|HLA-B*27]]05<ref name="AlmeidaPrice2007">{{cite journal|last1=Almeida|first1=J. R.|last2=Price|first2=D. A.|last3=Papagno|first3=L.|last4=Arkoub|first4=Z. A.|last5=Sauce|first5=D.|last6=Bornstein|first6=E.|last7=Asher|first7=T. E.|last8=Samri|first8=A.|last9=Schnuriger|first9=A.|last10=Theodorou|first10=I.|last11=Costagliola|first11=D.|last12=Rouzioux|first12=C.|last13=Agut|first13=H.|last14=Marcelin|first14=A.-G.|last15=Douek|first15=D.|last16=Autran|first16=B.|last17=Appay|first17=V.|title=Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover|journal=Journal of Experimental Medicine|volume=204|issue=10|date=2007-09-24|pages=2473–2485|issn=0022-1007|doi=10.1084/jem.20070784}}</ref> alleles and ability to exert control over HIV.


* '''Antibody production.''' All individuals with HIV make [[antibodies]] against the virus. In most patients, broadly neutralizing antibodies do not emerge until approximately 2–4 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, as is the elicitation of these antibodies through rationally designed immunogens. Direct production of these antibodies in somatic tissue through plasmid transfection also pose a viable method for making these antibodies available in a large number of humans. {{Citation needed|date=October 2010}}
* '''Antibody production.''' All individuals with HIV make [[antibodies]] against the virus. In most patients, broadly neutralizing antibodies do not emerge until approximately 2–4 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, as is the elicitation of these antibodies through rationally designed immunogens. Direct production of these antibodies in somatic tissue through plasmid transfection also pose a viable method for making these antibodies available in a large number of humans. {{Citation needed|date=October 2010}}
* '''[[APOBEC3G]] protein production'''. In a small number of people infected with HIV, the virus is naturally suppressed without medical treatment. These people may carry high quantities of a protein called [[APOBEC3G]] that disrupts viral replication in cells. APOBEC3G, or "A3" for short, is a protein that sabotages reverse transcription, the process HIV relies on for its replication. This process involves the virus transcribing its singe-stranded RNA genome into double-stranded DNA that is incorporated into the cell's genome. A3 usually stops dormant viruses in the human genome, called [[endogenous retrovirus]]es, from reawakening and causing infections.<ref name="Virus-sabotaging protein may help people defy HIV">http://www.newscientist.com/article/dn24426-virussabotaging-protein-may-help-people-defy-hiv.html</ref>
* '''[[APOBEC3G]] protein production'''. In a small number of people infected with HIV, the virus is naturally suppressed without medical treatment. These people may carry high quantities of a protein called [[APOBEC3G]] that disrupts viral replication in cells. APOBEC3G, or "A3" for short, is a protein that sabotages reverse transcription, the process HIV relies on for its replication. This process involves the virus transcribing its singe-stranded RNA genome into double-stranded DNA that is incorporated into the cell's genome. A3 usually stops dormant viruses in the human genome, called [[endogenous retrovirus]]es, from reawakening and causing infections.<ref name="Virus-sabotaging protein may help people defy HIV">{{cite web|last=Coghlan |first=Andy |url=http://www.newscientist.com/article/dn24426-virussabotaging-protein-may-help-people-defy-hiv.html |title=Virus-sabotaging protein may help people defy HIV |doi=10.1371/journal.pone.0076002 |publisher=New Scientist |date=2013-10-17 |accessdate=2017-01-17}}</ref>


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
*{{cite journal |doi=10.1126/science.1233989|pmid=23661761|title=Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization|journal=Science|volume=340|issue=6133|pages=751|year=2013|last1=Georgiev|first1=I. S.|last2=Doria-Rose|first2=N. A.|last3=Zhou|first3=T.|last4=Do Kwon|first4=Y.|last5=Staupe|first5=R. P.|last6=Moquin|first6=S.|last7=Chuang|first7=G.-Y.|last8=Louder|first8=M. K.|last9=Schmidt|first9=S. D.|last10=Altae-Tran|first10=H. R.|last11=Bailer|first11=R. T.|last12=McKee|first12=K.|last13=Nason|first13=M.|last14=O'Dell|first14=S.|last15=Ofek|first15=G.|last16=Pancera|first16=M.|last17=Srivatsan|first17=S.|last18=Shapiro|first18=L.|last19=Connors|first19=M.|last20=Migueles|first20=S. A.|last21=Morris|first21=L.|last22=Nishimura|first22=Y.|last23=Martin|first23=M. A.|last24=Mascola|first24=J. R.|last25=Kwong|first25=P. D.}}
12. "Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization" http://www.sciencemag.org/content/340/6133/751.abstract


==External links==
==External links==

Revision as of 10:35, 17 January 2017

Long-term nonprogressors (LTNPs), sometimes also called "elite controllers", are individuals infected with HIV, who maintain a CD4 count greater than 500 without antiretroviral therapy with a detectable viral load.[1] 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.[2] The classification "Long-term non-progressor" is not permanent, because some patients in this category have gone on to develop AIDS.

Long-term nonprogressors typically have viral loads under 10,000 copies RNA/ml blood,[3] do not take antiretrovirals, and have CD4+ counts within the normal range.[4] Most people with HIV not on medication have viral loads which are much higher.

It is estimated that around 1 in 300 people with HIV are long-term nonprogressors.[5] Without the symptoms of AIDS, many LTNP patients may not know they are infected.[6]

Genetic traits that confer greater resistance or more robust immune response to HIV are thought to explain why LTNP patients are able to live much longer with HIV than patients who are not LTNP.[7][8] 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.[9] 20% of Europeans who have that mutation are called "non secretor" because of their absence of a certain type of antigen that also provides strong resistance against norovirus.[9][10]
  • Mitochondrial DNA. Different mitochondrial DNA haplotypes in humans may increase or decrease rates of AIDS progression. Haplotypes associated with more loosely coupled mitochondrial respiration, with reduced ATP and ROS generation, have been associated with faster progression and vice versa.[11]
  • 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.[12] The presence of this mutation, however, is not a unifying theme among LTNPs and is observed in an exceedingly small number of these patients.
  • HLA type has also been correlated with long-term non-progressor cohorts. In particular, strong correlations have been found between possessing the class 1 HLA-B*5701,[13] HLA-B*5703,[14] and/or HLA-B*2705[15] alleles and ability to exert control over HIV.
  • Antibody production. All individuals with HIV make antibodies against the virus. In most patients, broadly neutralizing antibodies do not emerge until approximately 2–4 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, as is the elicitation of these antibodies through rationally designed immunogens. Direct production of these antibodies in somatic tissue through plasmid transfection also pose a viable method for making these antibodies available in a large number of humans. [citation needed]
  • APOBEC3G protein production. In a small number of people infected with HIV, the virus is naturally suppressed without medical treatment. These people may carry high quantities of a protein called APOBEC3G that disrupts viral replication in cells. APOBEC3G, or "A3" for short, is a protein that sabotages reverse transcription, the process HIV relies on for its replication. This process involves the virus transcribing its singe-stranded RNA genome into double-stranded DNA that is incorporated into the cell's genome. A3 usually stops dormant viruses in the human genome, called endogenous retroviruses, from reawakening and causing infections.[16]

References

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External links

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