Widespread tissue distribution of transcriptionally active, clonally expanded HIV-1 proviruses despite suppressive antiretroviral therapy
Hiromi Imamichi, Ven Natarajan, Francesca Scrimieri, Mindy Smith, Yunden Badralmaa, Marjorie Bosche, Jack Hensien, Thomas Buerkert, Weizhong Chang, Brad Sherman, Kanal Singh, H. Clifford Lane
Hiromi Imamichi, Ven Natarajan, Francesca Scrimieri, Mindy Smith, Yunden Badralmaa, Marjorie Bosche, Jack Hensien, Thomas Buerkert, Weizhong Chang, Brad Sherman, Kanal Singh, H. Clifford Lane
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Research Letter AIDS/HIV Infectious disease Virology

Widespread tissue distribution of transcriptionally active, clonally expanded HIV-1 proviruses despite suppressive antiretroviral therapy

Abstract

Authors

Hiromi Imamichi, Ven Natarajan, Francesca Scrimieri, Mindy Smith, Yunden Badralmaa, Marjorie Bosche, Jack Hensien, Thomas Buerkert, Weizhong Chang, Brad Sherman, Kanal Singh, H. Clifford Lane

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Figure 1

HIV-DNA and cell-associated HIV-RNA were measured in all 13 donors across 31 tissue compartments and peripheral blood, with most HIV-1 proviruses representing clonally expanded sequences.

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HIV-DNA and cell-associated HIV-RNA were measured in all 13 donors acros...
(A) Levels of HIV-DNA (copies/2 μg of genomic DNA) and cell-associated (CA) HIV-RNA (copies/1 μg of total RNA) in the ‘Active’ group (HIV-1 levels ≥ 4.9 copies/2 μg gDNA or 1 μg gRNA) in blood at autopsy, n = 5) and ‘Suppressed’ group (HIV-1 levels < 4.9 copies/2 μg gDNA or 1 μg gRNA), n = 8). HIV-DNA ranged from 5 to 11,340 copies; CA HIV-RNA ranged from 7 to 7,814 copies. (B) Proportions of full-length intact (black) and clonally expanded (colored) HIV-1 proviruses in each donor. (C) Correlation between the number of distinct identical HIV-1 sequence types and the total sequences per donor (Spearman test) (5, 6). (D) In participant 12, 12 distinct HIV-1 clones were distributed across ≥ 4 tissue compartments. Numbers in parentheses indicate total sequences per tissue. The outer ring reflects CA HIV-RNA levels using the same gradient as A. Similar data for participants 1–3, 6–9, 11, and 13 are in Supplemental Figure 3. (E) Proportions of clonally expanded defective HIV-1 proviruses in 19 tissue compartments and blood from participant 12.