Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy
Authors
Sharkey, Mark E.Teo, Ian
Greenough, Thomas
Sharova, Natalia
Luzuriaga, Katherine
Sullivan, John L.
Bucy, R. Pat
Kostrikis, Leondios G.
Haase, Ashley
Veryard, Claire
Davaro, Raul E.
Cheeseman, Sarah H.
Daly, Jennifer S.
Bova, Carol A.
Ellison, Richard T. III
Mady, Brian
Lai, Kwan Kew
Moyle, Graeme
Nelson, Mark
Gazzard, Brian
Shaunak, Sunil
Stevenson, Mario
UMass Chan Affiliations
Program in Molecular MedicineDepartment of Medicine, Division of Infectious Diseases and Immunology
Department of Pediatrics
Office of Research
Center for Infectious Disease and Vaccine Research
Graduate School of Nursing
Document Type
Journal ArticlePublication Date
2000-01-01Keywords
Anti-HIV AgentsBase Sequence
CD4 Lymphocyte Count
DNA Primers
Drug Therapy, Combination
HIV Infections
*HIV Long Terminal Repeat
HIV-1
Humans
Lymphocytes
RNA, Viral
Reference Values
Reverse Transcriptase Inhibitors
Viral Load
Virus Replication
Immunology of Infectious Disease
Immunoprophylaxis and Therapy
Virus Diseases
Metadata
Show full item recordAbstract
Treatment of HIV-1-infected individuals with a combination of anti-retroviral agents results in sustained suppression of HIV-1 replication, as evidenced by a reduction in plasma viral RNA to levels below the limit of detection of available assays. However, even in patients whose plasma viral RNA levels have been suppressed to below detectable levels for up to 30 months, replication-competent virus can routinely be recovered from patient peripheral blood mononuclear cells and from semen. A reservoir of latently infected cells established early in infection may be involved in the maintenance of viral persistence despite highly active anti-retroviral therapy. However, whether virus replication persists in such patients is unknown. HIV-1 cDNA episomes are labile products of virus infection and indicative of recent infection events. Using episome-specific PCR, we demonstrate here ongoing virus replication in a large percentage of infected individuals on highly active anti-retroviral therapy, despite sustained undetectable levels of plasma viral RNA. The presence of a reservoir of 'covert' virus replication in patients on highly active anti-retroviral therapy has important implications for the clinical management of HIV-1-infected individuals and for the development of virus eradication strategies.Source
Nat Med. 2000 Jan;6(1):76-81. Link to article on publisher's siteDOI
10.1038/71569Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34559PubMed ID
10613828Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1038/71569