The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time
Language: 
English
Abstract: 

The source and dynamics of persistent HIV-1 during long-term combinational antiretroviral therapy (cART) are critical to understanding the barriers to curing HIV-1 infection. To address this issue, we isolated and genetically characterized HIV-1 DNA from naïve and memory T cells from peripheral blood and gut-associated lymphoid tissue (GALT) from eight patients after 4-12 y of suppressive cART. Our detailed analysis of these eight patients indicates that persistent HIV-1 in peripheral blood and GALT is found primarily in memory CD4(+) T cells [CD45RO(+)/CD27((+/-))]. The HIV-1 infection frequency of CD4(+) T cells from peripheral blood and GALT was higher in patients who initiated treatment during chronic compared with acute/early infection, indicating that early initiation of therapy results in lower HIV-1 reservoir size in blood and gut. Phylogenetic analysis revealed an HIV-1 genetic change between RNA sequences isolated before initiation of cART and intracellular HIV-1 sequences from the T-cell subsets after 4-12 y of suppressive cART in four of the eight patients. However, evolutionary rate analyses estimated no greater than three nucleotide substitutions per gene region analyzed during all of the 4-12 y of suppressive therapy. We also identified a clearly replication-incompetent viral sequence in multiple memory T cells in one patient, strongly supporting asynchronous cell replication of a cell containing integrated HIV-1 DNA as the source. This study indicates that persistence of a remarkably stable population of infected memory cells will be the primary barrier to a cure, and, with little evidence of viral replication, this population could be maintained by homeostatic cell proliferation or other processes.

Author(s): 
Josefsson, Lina
von Stockenstrom, Susanne
Faria, Nuno R.
Sinclair, Elizabeth
Bacchetti, Peter
Killian, Maudi
Epling, Lorrie
Tan, Alice
Ho, Terence
Lemey, Philippe
Shao, Wei
Hunt, Peter W.
Somsouk, Ma
Wylie, Will
Douek, Daniel C.
Loeb, Lisa
Custer, Jeff
Hoh, Rebecca
Poole, Lauren
Deeks, Steven G.
Hecht, Frederick
Palmer, Sarah
Item Type: 
Journal Article
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America
Journal Abbreviation: 
Proc. Natl. Acad. Sci. U.S.A.
Publication Date: 
Dec 17, 2013
Publication Year: 
2013
Pages: 
E4987-4996
Volume: 
110
Issue: 
51
ISSN: 
1091-6490
DOI: 
10.1073/pnas.1308313110
Library Catalog: 
NCBI Published Medical (?)
Extra: 
PMID: 24277811 PMCID: PMC3870728

Turabian/Chicago Citation

Lina Josefsson, Susanne von Stockenstrom, Nuno R. Faria, Elizabeth Sinclair, Peter Bacchetti, Maudi Killian, Lorrie Epling, Alice Tan, Terence Ho, Philippe Lemey, Wei Shao, Peter W. Hunt, Ma Somsouk, Will Wylie, Daniel C. Douek, Lisa Loeb, Jeff Custer, Rebecca Hoh, Lauren Poole, Steven G. Deeks, Frederick Hecht and Sarah Palmer. Dec 17, 2013. "The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time." Proceedings of the National Academy of Sciences of the United States of America 110: 51: E4987-4996. 10.1073/pnas.1308313110.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1073/pnas.1308313110 | issn = 1091-6490 | volume = 110 | pages = E4987-4996 | last = Josefsson | first = Lina | coauthors = von Stockenstrom, Susanne, Faria, Nuno R., Sinclair, Elizabeth, Bacchetti, Peter, Killian, Maudi, Epling, Lorrie, Tan, Alice, Ho, Terence, Lemey, Philippe, Shao, Wei, Hunt, Peter W., Somsouk, Ma, Wylie, Will, Douek, Daniel C., Loeb, Lisa, Custer, Jeff, Hoh, Rebecca, Poole, Lauren, Deeks, Steven G., Hecht, Frederick, Palmer, Sarah | title = The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time | journal = Proceedings of the National Academy of Sciences of the United States of America | date = Dec 17, 2013 | pmid = | pmc = }} </ref>