PMID- 27122576
OWN - NLM
STAT- MEDLINE
DCOM- 20170510
LR  - 20220317
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 90
IP  - 13
DP  - 2016 Jul 1
TI  - Long-Term Spontaneous Control of HIV-1 Is Related to Low Frequency of Infected 
      Cells and Inefficient Viral Reactivation.
PG  - 6148-6158
LID - 10.1128/JVI.00419-16 [doi]
AB  - HIV establishes reservoirs of infected cells that persist despite effective 
      antiretroviral therapy (ART). In most patients, the virus begins to replicate 
      soon after treatment interruption. However, a low frequency of infected cells at 
      the time of treatment interruption has been associated with delayed viral 
      rebound. Likewise, individuals who control the infection spontaneously, so-called 
      HIV-1 controllers (HICs), carry particularly low levels of infected cells. It is 
      unclear, however, whether and how this small number of infected cells contributes 
      to durable viral control. Here we compared 38 HICs with 12 patients on effective 
      combined antiretroviral therapy (cART) and found that the low frequency of 
      infected cells in the former subjects was associated both with less efficient 
      viral reactivation in resting CD4(+) T cells and with less efficient virion 
      production ex vivo We also found that a potent HIV-specific CD8(+) T cell 
      response was present only in those HICs whose CD4(+) T cells produced virus ex 
      vivo Long-term spontaneous control of HIV infection in HICs thus appears to be 
      sustained on the basis of the inefficient reactivation of viruses from a limited 
      number of infected cells and the capacity of HICs to activate a potent 
      HIV-specific CD8(+) T cell response to counteract efficient viral reactivation 
      events. IMPORTANCE: There is a strong scientific interest in developing 
      strategies to eradicate the HIV-1 reservoir. Very rare HIV-1-infected patients 
      are able to spontaneously control viremia for long periods of time (HIV-1 
      controllers [HICs]) and are put forward as a model of HIV-1 remission. Here, we 
      show that the low viral reservoirs found in HICs are a critical part of the 
      mechanisms underlying viral control and result in a lower probability of HIV-1 
      reactivation events, resulting in limited HIV-1 release and spread. We found that 
      those HICs in whom viral reactivation and spread from CD4(+) T cells in vitro 
      were the most difficult were those with diminished CD8(+) T cell responses. These 
      results suggest that, in some settings, low HIV-1 reservoirs decisively 
      contribute to at least the temporary control of infection without antiretroviral 
      therapy. We believe that this work provides information of relevance in the 
      context of the search for HIV-1 remission.
CI  - Copyright (c) 2016, American Society for Microbiology. All Rights Reserved.
FAU - Noel, Nicolas
AU  - Noel N
AD  - Universite Paris Sud, UMR-1184, Paris, France.
AD  - CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Fontenay-aux-Rose, France.
AD  - INSERM, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, 
      Le Kremlin Bicetre, France.
AD  - APHP, Service de Medecine Interne-Immunologie Clinique, Hopitaux Universitaires 
      Paris Sud, Le Kremlin Bicetre, France.
FAU - Pena, Ruth
AU  - Pena R
AD  - AIDS Research Institute-IrsiCaixa, Institut d'Investigacio en Ciencies de la 
      Salut Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Spain.
FAU - David, Annie
AU  - David A
AD  - Institut Pasteur, Unite HIV Inflammation et Persistance, Paris, France.
FAU - Avettand-Fenoel, Veronique
AU  - Avettand-Fenoel V
AD  - APHP, Hopital Necker, Service de Virologie, Paris, France.
AD  - Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, EA7327, 
      Paris, France.
FAU - Erkizia, Itziar
AU  - Erkizia I
AD  - AIDS Research Institute-IrsiCaixa, Institut d'Investigacio en Ciencies de la 
      Salut Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Spain.
FAU - Jimenez, Esther
AU  - Jimenez E
AD  - AIDS Research Institute-IrsiCaixa, Institut d'Investigacio en Ciencies de la 
      Salut Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Spain.
FAU - Lecuroux, Camille
AU  - Lecuroux C
AD  - Universite Paris Sud, UMR-1184, Paris, France.
AD  - INSERM, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, 
      Le Kremlin Bicetre, France.
FAU - Rouzioux, Christine
AU  - Rouzioux C
AD  - APHP, Hopital Necker, Service de Virologie, Paris, France.
AD  - Universite Paris Descartes, Sorbonne Paris Cite, Faculte de Medecine, EA7327, 
      Paris, France.
FAU - Boufassa, Faroudy
AU  - Boufassa F
AD  - INSERM, U1018, Faculte de Medecine Paris Sud, Le Kremlin-Bicetre, France.
FAU - Pancino, Gianfranco
AU  - Pancino G
AD  - Institut Pasteur, Unite de Regulation des Infections Retrovirales, Paris, France.
FAU - Venet, Alain
AU  - Venet A
AD  - Universite Paris Sud, UMR-1184, Paris, France.
FAU - Van Lint, Carine
AU  - Van Lint C
AD  - Service de Virologie Moleculaire, IBMM, Universite Libre de Bruxelles (ULB), 
      Gosselies, Belgium.
FAU - Martinez-Picado, Javier
AU  - Martinez-Picado J
AD  - AIDS Research Institute-IrsiCaixa, Institut d'Investigacio en Ciencies de la 
      Salut Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Spain.
AD  - Universitat de Vic, Barcelona, Spain.
AD  - Institucio Catalana de Recerca i EstudisAvancats (ICREA), Barcelona, Spain.
FAU - Lambotte, Olivier
AU  - Lambotte O
AD  - Universite Paris Sud, UMR-1184, Paris, France.
AD  - CEA, DSV/iMETI, Division of Immuno-Virology, IDMIT, Fontenay-aux-Rose, France.
AD  - INSERM, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, 
      Le Kremlin Bicetre, France.
AD  - APHP, Service de Medecine Interne-Immunologie Clinique, Hopitaux Universitaires 
      Paris Sud, Le Kremlin Bicetre, France.
FAU - Saez-Cirion, Asier
AU  - Saez-Cirion A
AD  - Institut Pasteur, Unite HIV Inflammation et Persistance, Paris, France 
      asier.saez-cirion@pasteur.fr jgarciaprado@irsicaixa.es.
FAU - Prado, Julia G
AU  - Prado JG
AD  - AIDS Research Institute-IrsiCaixa, Institut d'Investigacio en Ciencies de la 
      Salut Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Spain 
      asier.saez-cirion@pasteur.fr jgarciaprado@irsicaixa.es.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160610
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Anti-HIV Agents)
RN  - 0 (RNA, Viral)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anti-HIV Agents/therapeutic use
MH  - CD4-Positive T-Lymphocytes/*virology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Female
MH  - HIV Infections/drug therapy/*virology
MH  - HIV-1/growth & development/isolation & purification/*physiology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - RNA, Viral/blood
MH  - *Virus Activation
MH  - Virus Latency
MH  - Virus Replication
PMC - PMC4907242
EDAT- 2016/04/29 06:00
MHDA- 2017/05/11 06:00
PMCR- 2016/12/10
CRDT- 2016/04/29 06:00
PHST- 2016/03/01 00:00 [received]
PHST- 2016/04/18 00:00 [accepted]
PHST- 2016/04/29 06:00 [entrez]
PHST- 2016/04/29 06:00 [pubmed]
PHST- 2017/05/11 06:00 [medline]
PHST- 2016/12/10 00:00 [pmc-release]
AID - JVI.00419-16 [pii]
AID - 00419-16 [pii]
AID - 10.1128/JVI.00419-16 [doi]
PST - epublish
SO  - J Virol. 2016 Jun 10;90(13):6148-6158. doi: 10.1128/JVI.00419-16. Print 2016 Jul 
      1.