Cited by 745HIV Research and TreatmentHIV/AIDS drug development and treatmentVirus-based gene therapy research

Defective proviruses rapidly accumulate during acute HIV-1 infection

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Bruner, Katherine M, Murray, Alexandra J, Pollack, Ross A, Soliman, Mary G, Laskey, Sarah B, Capoferri, Adam A, Lai, Jun, Strain, Matthew C +7 more·2016·Nature Medicine

Abstract

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.

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Authors
Bruner, K. M., Murray, A. J., Pollack, R. A., Soliman, M. G., Laskey, S. B., Capoferri, A. A., Lai, J., Strain, M. C., Lada, S. M., Hoh, R., Ho, Y.-C., Richman, D. D., Deeks, S. G., Siliciano, J. D., & Siliciano, R. F.
Affiliations
  • Johns Hopkins University (US)
  • Howard Hughes Medical Institute (US)
  • University of California San Diego (US)
  • VA San Diego Healthcare System (US)
  • University of California, San Francisco (US)
Corresponding author
Siliciano, Robert F
Venue
Nature Medicine
Published
2016-08-08
Volume
22
Issue
9
Pages
1043-1049
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
OpenAlex
W2512878063
Cited by
737
References
46
Citations by year
2026: 48 · 2025: 55 · 2024: 71 · 2023: 70 · 2022: 55 · 2021: 78 · 2020: 119 · 2019: 86 · 2018: 82 · 2017: 65 · 2016: 7
FWCI
55.22
Type
journal article
Language
en
Open access
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institute of General Medical Sciences (T32GM007309, T32GM008752)
  • National Institute of Allergy and Infectious Diseases (R21AI113147, U19AI096109, R01AI043222, R33AI104283, U19AI096113, P30AI036214, P30AI094189, P30AI027763)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
Keywords
HIV-1, defective proviruses, acute HIV-1 infection, latent viral reservoir, antiretroviral therapy timing, early treatment, HIV cure strategies, CD4+ T cells
MeSH terms
Acute Disease, Adult, Aged, Bayes Theorem, Female, Humans, Male, Middle Aged, Proviruses, Virus Replication, Cohort Studies, CD4-Positive T-Lymphocytes, HIV-1, HIV Infections, Polymerase Chain Reaction, Virus Latency, Disease Progression, Anti-HIV Agents, Viral Load, Young Adult

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