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J Clin Invest. 2018 Aug 31;128(9):4074-4085. doi: 10.1172/JCI120549. Epub 2018 Aug 20.

HIV-1 proviral landscapes distinguish posttreatment controllers from noncontrollers.

Author information

1
Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
2
Harvard PhD Program in Virology, Division of Medical Sciences, Harvard University, Boston, Massachusetts, USA.
3
Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
4
Simon Fraser University, Burnaby, British Columbia, Canada.
5
British Columbia Centre for Excellence in HIV/AIDS, Vancouver, British Columbia, Canada.
6
Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
7
University of Alabama at Birmingham, Birmingham, Alabama, USA.
8
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
9
Temple University, Philadelphia, Pennsylvania, USA.
10
University of Massachusetts Medical School-Baystate, Springfield, Massachusetts, USA.
11
UNC School of Medicine, Chapel Hill, North Carolina, USA.
12
UCLA, Los Angeles, California, USA.
13
Gladstone Center for AIDS Research, UCSF, San Francisco, California, USA.
14
University of Arizona College of Medicine, Tucson, Arizona, USA.
15
Case Western Reserve University, Cleveland, Ohio, USA.

Abstract

HIV posttreatment controllers (PTCs) represent a natural model of sustained HIV remission, but they are rare and little is known about their viral reservoir. We obtained 1,450 proviral sequences after near-full-length amplification for 10 PTCs and 16 posttreatment noncontrollers (NCs). Before treatment interruption, the median intact and total reservoir size in PTCs was 7-fold lower than in NCs, but the proportion of intact, defective, and total clonally expanded proviral genomes was not significantly different between the 2 groups. Quantification of total but not intact proviral genome copies predicted sustained HIV remission as 81% of NCs, but none of the PTCs had a total proviral genome greater than 4 copies per million peripheral blood mononuclear cells (PBMCs). The results highlight the restricted intact and defective HIV reservoir in PTCs and suggest that total proviral genome burden could act as the first biomarker for identifying PTCs. Total and defective but not intact proviral copy numbers correlated with levels of cell-associated HIV RNA, activated NK cell percentages, and both HIV-specific CD4+ and CD8+ responses. These results support the concept that defective HIV genomes can lead to viral antigen production and interact with both the innate and adaptive immune systems.

KEYWORDS:

AIDS vaccine; AIDS/HIV; Infectious disease

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