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A minor population of macrophage-tropic HIV-1 variants is identified in recrudescing viremia following analytic treatment interruption.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 May 05; Vol. 117 (18), pp. 9981-9990. Date of Electronic Publication: 2020 Apr 16. - Publication Year :
- 2020
-
Abstract
- HIV-1 persists in cellular reservoirs that can reignite viremia if antiretroviral therapy (ART) is interrupted. Therefore, insight into the nature of those reservoirs may be revealed from the composition of recrudescing viremia following treatment cessation. A minor population of macrophage-tropic (M-tropic) viruses was identified in a library of recombinant viruses constructed with individual envelope genes that were obtained from plasma of six individuals undergoing analytic treatment interruption (ATI). M-tropic viruses could also be enriched from post-ATI plasma using macrophage-specific (CD14) but not CD4+ T cell-specific (CD3) antibodies, suggesting that M-tropic viruses had a macrophage origin. Molecular clock analysis indicated that the establishment of M-tropic HIV-1 variants predated ATI. Collectively, these data suggest that macrophages are a viral reservoir in HIV-1-infected individuals on effective ART and that M-tropic variants can appear in rebounding viremia when treatment is interrupted. These findings have implications for the design of curative strategies for HIV-1.<br />Competing Interests: The authors declare no competing interest.
- Subjects :
- Anti-Retroviral Agents pharmacology
Antiretroviral Therapy, Highly Active
CD4-Positive T-Lymphocytes pathology
HIV Infections pathology
HIV Infections virology
HIV Seropositivity
HIV-1 pathogenicity
Humans
Macrophages immunology
Macrophages pathology
Proviruses genetics
Viral Load genetics
Viremia pathology
Viremia virology
Biological Clocks genetics
HIV Infections genetics
HIV-1 genetics
Viremia genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 117
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 32300019
- Full Text :
- https://doi.org/10.1073/pnas.1917034117