258:
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 poses a viable method for making these antibodies endogenously.
25:
117:
293:
received antiretroviral therapy but stopped treatment at some point. The
Argentinian patient took antiretroviral therapy only while pregnant, but her viral load was nevertheless reported to be undetectable years after treatment discontinuation. This could inform the development of a "sterilising cure."
292:
Recently, there have been reports of elite controllers who maintain undetectable viral loads. In 2019, an
American named Loreen Willenberg was announced as the first such case. In 2021, an Argentinian dubbed "the Esperanza patient" after the town in which she lives was also identified. Willemberg had
244:
HIV controllers exhibit a highly skewed TCR repertoire dominated by specific TRAV24 and TRBV2 variable genes, with shared CDR3 motifs and public clonotypes that possess high affinity for HIV antigens. These TCRs, capable of cross-restriction across multiple HLA-DR alleles, can confer enhanced antigen
155:
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. Some LTNP are infected with a weakened or inactive form of HIV, but it is now known that many LTNP patients carry a fully
271:
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 single-stranded RNA genome into double-stranded DNA that is incorporated into the
1001:
Daniela Benati, Moran
Galperin, Olivier Lambotte, Stéphanie Gras, Annick Lim, Madhura Mukhopadhyay, Alexandre Nouël, Kristy-Anne Campbell, Brigitte Lemercier, Mathieu Claireaux, Samia Hendou, Pierre Lechat, Pierre de Truchis, Faroudy Boufassa, Jamie Rossjohn, Jean-François Delfraissy, Fernando
1389:
Georgiev, I. S.; Doria-Rose, N. A.; Zhou, T.; Do Kwon, Y.; Staupe, R. P.; Moquin, S.; Chuang, G.-Y.; Louder, M. K.; Schmidt, S. D.; Altae-Tran, H. R.; Bailer, R. T.; McKee, K.; Nason, M.; O'Dell, S.; Ofek, G.; Pancera, M.; Srivatsan, S.; Shapiro, L.; Connors, M.; Migueles, S. A.; Morris, L.;
141:
with a detectable viral load. 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. They have been the subject of a great deal of research, since an understanding of their ability to control HIV
257:
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
943:
Almeida, J. R.; Price, D. A.; Papagno, L.; Arkoub, Z. A.; Sauce, D.; Bornstein, E.; Asher, T. E.; Samri, A.; Schnuriger, A.; Theodorou, I.; Costagliola, D.; Rouzioux, C.; Agut, H.; Marcelin, A.-G.; Douek, D.; Autran, B.; Appay, V. (2007-09-24).
145:
Long-term nonprogressors typically have viral loads under 10,000 copies /mL blood, do not take antiretrovirals, and have CD4+ counts within the normal range. Most people with HIV not on medication have viral loads which are much higher.
142:
infection may lead to the development of immune therapies or a therapeutic vaccine. The classification "Long-term non-progressor" is not permanent, because some patients in this category have gone on to develop AIDS.
167:
gene affects the progression of HIV-1 infection. 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
1324:
Turk, Gabriela; Seiger, Kyra; Lian, Xiaodong; Sun, Weiwei; Parsons, Elizabeth M.; Gao, Ce; Rassadkina, Yelizaveta; Polo, Maria Laura; Czernikier, Alejandro; Ghiglione, Yanina; Vellicce, Alejandra (2021-11-16).
737:
Hendrickson, S. L.; Hutcheson, H. B.; Ruiz-Pesini, E.; Poole, J. C.; Lautenberger, J.; Sezgin, E.; Kingsley, L.; Goedert, J. J.; Vlahov, D.; Donfield, S.; Wallace, D. C.; OʼBrien, S. J. (2008-11-30).
1231:
Jiang, Chenyang; Lian, Xiaodong; Gao, Ce; Sun, Xiaoming; Einkauf, Kevin B.; Chevalier, Joshua M.; Chen, Samantha M. Y.; Hua, Stephane; Rhee, Ben; Chang, Kaylee; Blackmer, Jane E. (26 August 2020).
835:
Migueles, S. A.; Sabbaghian, M. S.; Shupert, W. L.; Bettinotti, M. P.; Marincola, F. M.; Martino, L.; Hallahan, C. W.; Selig, S. M.; Schwartz, D.; Sullivan, J.; Connors, M. (2000-02-29).
499:
35:
267:: 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
1047:
149:
It is estimated that around 1 in 500 people with HIV are long-term nonprogressors. Without the symptoms of AIDS, many LTNP patients may not know they are infected.
218:
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
230:
has also been correlated with long-term non-progressor cohorts. In particular, strong correlations have been found between possessing the class 1
447:-defective human immunodeficiency virus type 1 strains associated with long-term nonprogression. Australian Long-Term Nonprogressor Study Group"
495:
245:
sensitivity and polyfunctionality when transferred to healthy T cells, suggesting their potential role in immunotherapeutic strategies for HIV.
222:. The presence of this mutation, however, is not a unifying theme among LTNPs and is observed in an exceedingly small number of these patients.
138:
690:"A homozygous nonsense mutation (428G→A) in the human secretor (FUT2) gene provides resistance to symptomatic norovirus (GGII) infections"
1174:
1117:"Lower HIV Provirus Levels Are Associated with More APOBEC3G Protein in Blood Resting Memory CD4+ T Lymphocytes of Controllers In Vivo"
402:"Human immunodeficiency virus type 1 long-term non-progressors: the viral, genetic and immunological basis for disease non-progression"
96:
1089:
68:
374:
350:
75:
837:"HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors"
946:"Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover"
1394:; Kwong, P. D. (2013). "Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization".
552:
O'Connell, K. A.; Bailey, J. R.; Blankson, J. N. (2009). "Elucidating the elite: mechanisms of control in HIV-1 infection".
82:
639:
Kindberg, Elin; Hejdeman, Bo; Bratt, Göran; Wahren, Britta; Lindblom, Bertil; Hinkula, Jorma; Svensson, Lennart (2006).
1062:
43:
64:
1480:
54:
39:
186:
1115:
De
Pasquale, MariaPia; Kourteva, Yordanka; Allos, Tara; d'Aquila, Richard T.; Unutmaz, Derya (16 October 2013).
796:"HIV controllers: a homogeneous group of HIV-1-infected patients with spontaneous control of viral replication"
303:
1460:
185:
in humans may increase or decrease rates of AIDS progression. Haplotypes associated with more loosely coupled
641:"A nonsense mutation (428G→A) in the fucosyltransferase FUT2 gene affects the progression of HIV-1 infection"
194:
190:
1041:
902:
Costello, C.; Tang, J.; Rivers, C.; Karita, E.; Meizen-Derr, J.; Allen, S.; Kaslow, R. A. (1999-10-01).
273:
1403:
1244:
1128:
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503:
281:
89:
328:
203:: A low percentage of long-term nonprogressors have been shown to have inherited mutations of the
1437:
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670:
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1260:
1207:
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1029:
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884:
866:
817:
776:
758:
719:
662:
618:
569:
534:
525:
Walker, BD (2007). "Elite control of HIV Infection: implications for vaccines and treatment".
477:
423:
318:
308:
179:
688:
Thorven, M; Grahn, A; Hedlund, KO; Johansson, H; Wahlfrid, C; Larson, G; Svensson, L (2005).
441:
Rhodes, DI; Ashton, L; Solomon, A; Carr, A; Cooper, D; Kaldor, J; Deacon, N (November 2000).
1419:
1411:
1354:
1338:
1268:
1252:
1146:
1136:
1019:
1011:
973:
957:
915:
904:"HLA-B*5703 independently associated with slower HIV-1 disease progression in Rwandan women"
874:
856:
807:
766:
750:
709:
701:
652:
608:
600:
561:
467:
459:
413:
219:
1391:
1199:
1175:"Loreen Willenberg's HIV seems to have disappeared. Is this good news for the rest of us?"
589:"Effector mechanisms in HIV-1 infected elite controllers: Highly active immune responses?"
323:
1407:
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1132:
852:
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378:
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Lambotte, Olivier; Boufassa, Faroudy; Madec, Yoann; Nguyen, Ahn; et al. (2005).
313:
152:
1441:
674:
604:
280:
The 'long-term nonprogressors' term is used for HIV carriers only but the wide term
401:
1327:"A Possible Sterilizing Cure of HIV-1 Infection Without Stem Cell Transplantation"
1141:
754:
215:
156:
virulent form of the virus. Genetic traits that may affect progression include:
565:
1256:
1004:"Public T cell receptors confer high-avidity CD4 responses to HIV controllers"
254:
211:
1350:
1264:
1211:
969:
870:
762:
1415:
1233:"Distinct viral reservoirs in individuals with spontaneous control of HIV-1"
451:
272:
cell's genome. A3 usually stops dormant viruses in the human genome, called
182:
169:
1433:
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268:
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generation, have been associated with faster progression and vice versa.
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53:
if you can. Unsourced or poorly sourced material may be challenged and
1342:
1015:
208:
1003:
812:
795:
16:
HIV-infected individual who does not progress to immune deficiency
1455:
1200:"A Woman May Have Been Cured of H.I.V. Without Medical Treatment"
214:. HIV uses CCR5 to enter these cells. It is believed that the
204:
164:
134:
130:
18:
351:"HIV non-progressor status established soon after infection"
739:"Mitochondrial DNA haplogroups influence AIDS progression"
377:. International AIDS Vaccine Initiative. Archived from
50:
500:
National
Institute of Allergy and Infectious Diseases
1090:"Virus-sabotaging protein may help people defy HIV"
1063:"Immune Responses in Controllers of HIV Infection"
634:
632:
1300:"Rare case of woman's body ridding itself of HIV"
238:05 alleles and ability to exert control over HIV.
841:Proceedings of the National Academy of Sciences
49:Please review the contents of the article and
400:Poropatich, Kate; Sullivan, David J. (2010).
8:
1046:: CS1 maint: multiple names: authors list (
1294:
1292:
276:, from reawakening and causing infections.
1423:
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1023:
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919:
878:
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811:
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284:is well known for many other infections.
1061:Abena K Kwaa , Joel N Blankson (2024).
1002:Arenzana-Seisdedos, Lisa A Chakrabarti.
375:"Understanding Long-term Nonprogressors"
1456:The International HIV Controllers Study
341:
129:(LTNPs), are individuals infected with
1039:
319:Timothy Ray Brown (The Berlin patient)
496:"HIV+ Long-Term Non-Progressor Study"
7:
324:Adam Castillejo (the London patient)
658:10.1097/01.aids.0000216368.23325.bc
1198:Mandavilli, Apoorva (2020-08-26).
706:10.1128/JVI.79.24.15351-15355.2005
554:Trends in Pharmacological Sciences
464:10.1128/jvi.74.22.10581-10588.2000
349:Michael Carter (12 January 2009).
14:
1008:Journal of Clinical Investigation
950:Journal of Experimental Medicine
921:10.1097/00002030-199910010-00031
253:: All individuals with HIV make
115:
23:
605:10.1016/j.antiviral.2009.08.007
502:. June 23, 2010. Archived from
137:count greater than 500 without
1390:Nishimura, Y.; Martin, M. A.;
51:add the appropriate references
1:
1142:10.1371/journal.pone.0076002
1088:Coghlan, Andy (2013-10-17).
800:Clinical Infectious Diseases
755:10.1097/QAD.0b013e32831940bb
1331:Annals of Internal Medicine
443:"Characterization of three
406:Journal of General Virology
36:reliable medical references
1497:
566:10.1016/j.tips.2009.09.005
1257:10.1038/s41586-020-2651-8
187:mitochondrial respiration
65:"Long-term nonprogressor"
42:or relies too heavily on
587:Blankson, J. N. (2009).
304:Innate resistance to HIV
127:Long-term nonprogressors
1416:10.1126/science.1233989
274:endogenous retroviruses
234:01, HLA-B*5703, and/or
862:10.1073/pnas.050567397
419:10.1099/vir.0.027102-0
288:Clearance of the virus
216:Δ32 (delta 32) variant
139:antiretroviral therapy
1461:The Zephyr Foundation
962:10.1084/jem.20070784
282:asymptomatic carrier
163:: A mutation in the
1408:2013Sci...340..751G
1249:2020Natur.585..261J
1133:2013PLoSO...876002D
853:2000PNAS...97.2709M
329:HIV-positive people
251:Antibody production
1204:The New York Times
593:Antiviral Research
381:on October 9, 2006
265:protein production
201:Receptor mutations
1481:HIV/AIDS research
1243:(7824): 261–267.
956:(10): 2473–2485.
309:HIV/AIDS research
180:mitochondrial DNA
176:Mitochondrial DNA
133:, who maintain a
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1067:Annu Rev Immunol
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1016:10.1172/JCI83792
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847:(6): 2709–2714.
832:
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700:(24): 15351–55.
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542:
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506:on July 19, 2011
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458:(22): 10581–88.
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1402:(6133): 751–6.
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914:(14): 1990–91.
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749:(18): 2429–39.
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560:(12): 631–637.
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44:primary sources
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1450:External links
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61:Find sources:
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32:This article
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1308:. Retrieved
1306:. 2021-11-16
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