1. A minor population of macrophage-tropic HIV-1 variants is identified in recrudescing viremia following analytic treatment interruption.
- Author
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Andrade VM, Mavian C, Babic D, Cordeiro T, Sharkey M, Barrios L, Brander C, Martinez-Picado J, Dalmau J, Llano A, Li JZ, Jacobson J, Lavine CL, Seaman MS, Salemi M, and Stevenson M
- 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
- 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., Competing Interests: The authors declare no competing interest.
- Published
- 2020
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