Emergence of CXCR4-using human immunodeficiency virus type 1 (HIV-1) variants in a minority of HIV-1-infected patients following treatment with the CCR5 antagonist maraviroc is from a pretreatment CXCR4-using virus reservoir.

Journal of Virology
Mike WestbyElna van der Ryst

Abstract

Antagonists of the human immunodeficiency virus type 1 (HIV-1) coreceptor, CCR5, are being developed as the first anti-HIV agents acting on a host cell target. We monitored the coreceptor tropism of circulating virus, screened at baseline for coreceptor tropism, in 64 HIV-1-infected patients who received maraviroc (MVC, UK-427,857) as monotherapy for 10 days. Sixty-two patients harbored CCR5-tropic virus at baseline and had a posttreatment phenotype result. Circulating virus remained CCR5 tropic in 60/62 patients, 51 of whom experienced an HIV RNA reduction from baseline of >1 log(10) copies/ml, indicating that CXCR4-using variants were not rapidly selected despite CCR5-specific drug pressure. In two patients, viral load declined during treatment and CXCR4-using virus was detected at day 11. No pretreatment factor predicted the emergence of CXCR4-tropic virus during maraviroc therapy in these two patients. Phylogenetic analysis of envelope (Env) clones from pre- and posttreatment time points indicated that the CXCR4-using variants probably emerged by outgrowth of a pretreatment CXCR4-using reservoir, rather than via coreceptor switch of a CCR5-tropic clone under selection pressure from maraviroc. Phylogenetic analysis was also ...Continue Reading

References

Apr 1, 1995·Journal of Clinical Microbiology·R A FouchierH Schuitemaker
Jan 1, 1996·Methods in Enzymology·D G HigginsT J Gibson
Mar 4, 1997·Proceedings of the National Academy of Sciences of the United States of America·C C BleulC R Mackay
Jan 24, 1998·Nature·E A BergerR A Weiss
Feb 22, 2001·The Journal of Clinical Investigation·S PhilpottH Burger
Sep 20, 2001·Current Medicinal Chemistry·M Gurrath
Oct 9, 2002·Medicinal Research Reviews·Erik De Clercq
Jan 14, 2003·Annual Review of Immunology·Daniel C DouekRichard A Koup
Mar 15, 2003·The New England Journal of Medicine·Jacob P LalezariUNKNOWN TORO 1 Study Group
May 30, 2003·The New England Journal of Medicine·Adriano LazzarinUNKNOWN TORO 2 Study Group
Mar 27, 2004·Current HIV Research·Sean M Philpott
Jun 29, 2004·Journal of Virology·Cristina PastoreDonald E Mosier
Jul 13, 2004·Reviews in Medical Virology·Theodore C PiersonStefan Pöhlmann
Jan 14, 2005·Current Opinion in Infectious Diseases·Eoin CoakleyJeannette M Whitcomb
Feb 18, 2005·The Journal of Infectious Diseases·Graeme J MoyleBrian G Gazzard
Jul 5, 2005·The Journal of Infectious Diseases·Zabrina L BrummeP Richard Harrigan

❮ Previous
Next ❯

Citations

Oct 27, 2006·Current Infectious Disease Reports·Caitlin Reed, Eric S Daar
Apr 2, 2013·Antiviral Research·Aiman A Haqqani, John C Tilton
Nov 17, 2011·Journal of Medicinal Chemistry·Won-Tak ChoiJing An
Dec 1, 2007·Nature Reviews. Drug Discovery·Erik De Clercq
Oct 4, 2008·The New England Journal of Medicine·Gerd FätkenheuerUNKNOWN MOTIVATE 1 and MOTIVATE 2 Study Teams
Dec 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Alonso HerediaRobert R Redfield
Mar 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·Cleo G AnastassopoulouJohn P Moore
Jun 6, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Rodger D MacArthur, Richard M Novak
Sep 12, 2008·The Journal of Infectious Diseases·James C ShepherdJoseph B Margolick
Apr 10, 2010·The Journal of Infectious Diseases·Jeffrey M JacobsonWilliam C Olson
Aug 7, 2007·AIDS Research and Human Retroviruses·A BritoJ Casseb
Mar 31, 2009·AIDS Research and Human Retroviruses·Rebecca M LynchCynthia A Derdeyn
Jan 9, 2010·AIDS Research and Human Retroviruses·John C TiltonRobert W Doms
Apr 27, 2013·AIDS Research and Human Retroviruses·Anthony Kebira NyamacheSamoel A Khamadi
Feb 7, 2009·Stem Cells and Development·Malgorzata Simm
Mar 1, 2013·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Jonathan Z Li, Daniel R Kuritzkes
Aug 13, 2009·The Journal of Antimicrobial Chemotherapy·Miguel GenebatManuel Leal
Jan 14, 2010·The Journal of Antimicrobial Chemotherapy·Mercedes Armand-UgónJosé A Esté
Mar 1, 2012·The Journal of Antimicrobial Chemotherapy·Silvia BaroncelliMarco Floridia
Apr 3, 2009·Current Opinion in HIV and AIDS·Donald E Mosier
Apr 3, 2009·Current Opinion in HIV and AIDS·William C Olson, Jeffrey M Jacobson
Dec 20, 2007·AIDS·Cathia SouliéVincent Calvez
Nov 5, 2008·AIDS·Vincent SorianoJuergen Rockstroh
Sep 3, 2009·AIDS·Pierre Corbeau, Jacques Reynes
Feb 6, 2009·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Matthew Bidwell GoetzUNKNOWN Long-Term Monitoring Study (CPCRA 060) and Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA)
Jul 31, 2010·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Timothy J WilkinRoy M Gulick
Jun 29, 2011·Journal of Acquired Immune Deficiency Syndromes : JAIDS·Ashika SinghThumbi Ndung'u
Apr 5, 2012·Cold Spring Harbor Perspectives in Medicine·Eric J Arts, Daria J Hazuda
Oct 2, 2008·HIV Medicine·B G GazzardUNKNOWN BHIVA Treatment Guidelines Writing Group
May 2, 2012·Antimicrobial Agents and Chemotherapy·Alejandro Gonzalez-SernaEzequiel Ruiz-Mateos
Jan 24, 2008·Antimicrobial Agents and Chemotherapy·Roger G PtakBrigitte Rosenwirth
Dec 5, 2012·Antimicrobial Agents and Chemotherapy·P Recordon-PinsonUNKNOWN S AC11 Resistance Study Group

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.