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Defective proviruses rapidly accumulate during acute HIV-1 infection

Although antiretroviral therapy (ART) suppresses viral replication to clinically undetectable levels, human immunodeficiency virus type 1 (HIV-1) persists in CD4(+) T cells in a latent form that is not targeted by the immune system or by ART. This latent reservoir is a major barrier to curing indivi... Full description

Journal Title: Nature medicine 2016, Vol.22 (9), p.1043-1049
Main Author: Bruner, Katherine M
Other Authors: Murray, Alexandra J , Pollack, Ross A , Soliman, Mary G , Laskey, Sarah B , Capoferri, Adam A , Lai, Jun , Strain, Matthew C , Lada, Steven M , Hoh, Rebecca , Ho, Ya-Chi , Richman, Douglas D , Deeks, Steven G , Siliciano, Janet D , Siliciano, Robert F
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: United States: Nature Publishing Group
ID: ISSN: 1078-8956
Link: https://www.ncbi.nlm.nih.gov/pubmed/27500724
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title: Defective proviruses rapidly accumulate during acute HIV-1 infection
format: Article
creator:
  • Bruner, Katherine M
  • Murray, Alexandra J
  • Pollack, Ross A
  • Soliman, Mary G
  • Laskey, Sarah B
  • Capoferri, Adam A
  • Lai, Jun
  • Strain, Matthew C
  • Lada, Steven M
  • Hoh, Rebecca
  • Ho, Ya-Chi
  • Richman, Douglas D
  • Deeks, Steven G
  • Siliciano, Janet D
  • Siliciano, Robert F
subjects:
  • 1 Biological
  • 2 Factors relating to physical environment
  • Acute Disease
  • Adult
  • Aged
  • Anti
  • Anti-HIV Agents - therapeutic use
  • Article
  • Bayes Theorem
  • Care and treatment
  • CD4-Positive T-Lymphocytes - virology
  • Cohort Studies
  • Development and progression
  • Disease Progression
  • endogenous factors
  • Female
  • Health Sciences
  • Highly active antiretroviral therapy
  • HIV Agents
  • HIV infection
  • HIV Infections
  • HIV Infections - drug therapy
  • HIV Infections - metabolism
  • HIV Infections - virology
  • HIV-1
  • Human immunodeficiency virus 1
  • Humans
  • Immunology
  • Infection
  • Infectious Diseases
  • Lentivirus
  • Lymphocytes
  • Male
  • Medical
  • Middle Aged
  • Observations
  • Patient outcomes
  • Polymerase Chain Reaction
  • Positive T
  • Proviruses
  • Proviruses - metabolism
  • Retroviridae
  • Viral Load
  • Virulence (Microbiology)
  • Virus Latency
  • Virus Replication
  • Young Adult
ispartof: Nature medicine, 2016, Vol.22 (9), p.1043-1049
description: Although antiretroviral therapy (ART) suppresses viral replication to clinically undetectable levels, human immunodeficiency virus type 1 (HIV-1) persists in CD4(+) T cells in a latent form that is not targeted by the immune system or by ART. This latent reservoir is a major barrier to curing individuals of HIV-1 infection. Many individuals initiate ART during chronic infection, and in this setting, most proviruses are defective. However, the dynamics of the accumulation and the persistence of defective proviruses during acute HIV-1 infection are largely unknown. Here we show that defective proviruses accumulate rapidly within the first few weeks of infection to make up over 93% of all proviruses, regardless of how early ART is initiated. By using an unbiased method to amplify near-full-length proviral genomes from HIV-1-infected adults treated at different stages of infection, we demonstrate that early initiation of ART limits the size of the reservoir but does not profoundly affect the proviral landscape. This analysis allows us to revise our understanding of the composition of proviral populations and estimate the true reservoir size in individuals who were treated early versus late in infection. Additionally, we demonstrate that common assays for measuring the reservoir do not correlate with reservoir size, as determined by the number of genetically intact proviruses. These findings reveal hurdles that must be overcome to successfully analyze future HIV-1 cure strategies.
language: eng
source:
identifier: ISSN: 1078-8956
fulltext: no_fulltext
issn:
  • 1078-8956
  • 1546-170X
url: Link


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descriptionAlthough antiretroviral therapy (ART) suppresses viral replication to clinically undetectable levels, human immunodeficiency virus type 1 (HIV-1) persists in CD4(+) T cells in a latent form that is not targeted by the immune system or by ART. This latent reservoir is a major barrier to curing individuals of HIV-1 infection. Many individuals initiate ART during chronic infection, and in this setting, most proviruses are defective. However, the dynamics of the accumulation and the persistence of defective proviruses during acute HIV-1 infection are largely unknown. Here we show that defective proviruses accumulate rapidly within the first few weeks of infection to make up over 93% of all proviruses, regardless of how early ART is initiated. By using an unbiased method to amplify near-full-length proviral genomes from HIV-1-infected adults treated at different stages of infection, we demonstrate that early initiation of ART limits the size of the reservoir but does not profoundly affect the proviral landscape. This analysis allows us to revise our understanding of the composition of proviral populations and estimate the true reservoir size in individuals who were treated early versus late in infection. Additionally, we demonstrate that common assays for measuring the reservoir do not correlate with reservoir size, as determined by the number of genetically intact proviruses. These findings reveal hurdles that must be overcome to successfully analyze future HIV-1 cure strategies.
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subject1 Biological ; 2 Factors relating to physical environment ; Acute Disease ; Adult ; Aged ; Anti ; Anti-HIV Agents - therapeutic use ; Article ; Bayes Theorem ; Care and treatment ; CD4-Positive T-Lymphocytes - virology ; Cohort Studies ; Development and progression ; Disease Progression ; endogenous factors ; Female ; Health Sciences ; Highly active antiretroviral therapy ; HIV Agents ; HIV infection ; HIV Infections ; HIV Infections - drug therapy ; HIV Infections - metabolism ; HIV Infections - virology ; HIV-1 ; Human immunodeficiency virus 1 ; Humans ; Immunology ; Infection ; Infectious Diseases ; Lentivirus ; Lymphocytes ; Male ; Medical ; Middle Aged ; Observations ; Patient outcomes ; Polymerase Chain Reaction ; Positive T ; Proviruses ; Proviruses - metabolism ; Retroviridae ; Viral Load ; Virulence (Microbiology) ; Virus Latency ; Virus Replication ; Young Adult
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descriptionAlthough antiretroviral therapy (ART) suppresses viral replication to clinically undetectable levels, human immunodeficiency virus type 1 (HIV-1) persists in CD4(+) T cells in a latent form that is not targeted by the immune system or by ART. This latent reservoir is a major barrier to curing individuals of HIV-1 infection. Many individuals initiate ART during chronic infection, and in this setting, most proviruses are defective. However, the dynamics of the accumulation and the persistence of defective proviruses during acute HIV-1 infection are largely unknown. Here we show that defective proviruses accumulate rapidly within the first few weeks of infection to make up over 93% of all proviruses, regardless of how early ART is initiated. By using an unbiased method to amplify near-full-length proviral genomes from HIV-1-infected adults treated at different stages of infection, we demonstrate that early initiation of ART limits the size of the reservoir but does not profoundly affect the proviral landscape. This analysis allows us to revise our understanding of the composition of proviral populations and estimate the true reservoir size in individuals who were treated early versus late in infection. Additionally, we demonstrate that common assays for measuring the reservoir do not correlate with reservoir size, as determined by the number of genetically intact proviruses. These findings reveal hurdles that must be overcome to successfully analyze future HIV-1 cure strategies.
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authorBruner, Katherine M ; Murray, Alexandra J ; Pollack, Ross A ; Soliman, Mary G ; Laskey, Sarah B ; Capoferri, Adam A ; Lai, Jun ; Strain, Matthew C ; Lada, Steven M ; Hoh, Rebecca ; Ho, Ya-Chi ; Richman, Douglas D ; Deeks, Steven G ; Siliciano, Janet D ; Siliciano, Robert F
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abstractAlthough antiretroviral therapy (ART) suppresses viral replication to clinically undetectable levels, human immunodeficiency virus type 1 (HIV-1) persists in CD4(+) T cells in a latent form that is not targeted by the immune system or by ART. This latent reservoir is a major barrier to curing individuals of HIV-1 infection. Many individuals initiate ART during chronic infection, and in this setting, most proviruses are defective. However, the dynamics of the accumulation and the persistence of defective proviruses during acute HIV-1 infection are largely unknown. Here we show that defective proviruses accumulate rapidly within the first few weeks of infection to make up over 93% of all proviruses, regardless of how early ART is initiated. By using an unbiased method to amplify near-full-length proviral genomes from HIV-1-infected adults treated at different stages of infection, we demonstrate that early initiation of ART limits the size of the reservoir but does not profoundly affect the proviral landscape. This analysis allows us to revise our understanding of the composition of proviral populations and estimate the true reservoir size in individuals who were treated early versus late in infection. Additionally, we demonstrate that common assays for measuring the reservoir do not correlate with reservoir size, as determined by the number of genetically intact proviruses. These findings reveal hurdles that must be overcome to successfully analyze future HIV-1 cure strategies.
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