HIV-1 proviral landscapes distinguish posttreatment controllers from noncontrollers.

TitleHIV-1 proviral landscapes distinguish posttreatment controllers from noncontrollers.
Publication TypeJournal Article
Year of Publication2018
AuthorsSharaf R, Lee GQ, Sun X, Etemad B, Aboukhater LM, Hu Z, Brumme ZL, Aga E, Bosch RJ, Wen Y, Namazi G, Gao C, Acosta EP, Gandhi RT, Jacobson JM, Skiest D, Margolis DM, Mitsuyasu R, Volberding P, Connick E, Kuritzkes DR, Lederman MM, Yu XG, Lichterfeld M, Li JZ
JournalJ Clin Invest
Volume128
Issue9
Pagination4074-4085
Date Published2018 Aug 31
ISSN1558-8238
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.

DOI10.1172/JCI120549
Alternate JournalJ. Clin. Invest.
PubMed ID30024859
PubMed Central IDPMC6118642
Grant ListUM1 AI069501 / AI / NIAID NIH HHS / United States
R01 AI098487 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
U01 AI069501 / AI / NIAID NIH HHS / United States
R56 AI125109 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States