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      Rapid HIV RNA rebound after antiretroviral treatment interruption in persons durably suppressed in Fiebig I acute HIV infection

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          Abstract

          Antiretroviral therapy (ART) during the earliest stage of acute HIV infection (Fiebig I) might minimize establishment of a latent HIV reservoir and thereby facilitate viremic control after analytical treatment interruption (ATI). We show that 8 participants, who initiated treatment during Fiebig I and were treated for a median of 2.8 years, all experienced rapid viral load rebound following ATI, indicating that additional strategies are required to control or eradicate HIV.

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          Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy.

          J. Gallant, R Brookmeyer, J Margolick … (1998)
          The hypothesis that quiescent CD4+ T lymphocytes carrying proviral DNA provide a reservoir for human immunodeficiency virus-type 1 (HIV-1) in patients on highly active antiretroviral therapy (HAART) was examined. In a study of 22 patients successfully treated with HAART for up to 30 months, replication-competent virus was routinely recovered from resting CD4+ T lymphocytes. The frequency of resting CD4+ T cells harboring latent HIV-1 was low, 0.2 to 16.4 per 10(6) cells, and, in cross-sectional analysis, did not decrease with increasing time on therapy. The recovered viruses generally did not show mutations associated with resistance to the relevant antiretroviral drugs. This reservoir of nonevolving latent virus in resting CD4+ T cells should be considered in deciding whether to terminate treatment in patients who respond to HAART.
          Article 0 comments Cited 736 times – based on 0 reviews     Review now
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            Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy.

            T Chun, L Stuyver, S. B. Mizell … (1997)
            Although highly active antiretroviral therapy (HAART) in the form of triple combinations of drugs including protease inhibitors can reduce the plasma viral load of some HIV-1-infected individuals to undetectable levels, it is unclear what the effects of these regimens are on latently infected CD4+ T cells and what role these cells play in the persistence of HIV-1 infection in individuals receiving such treatment. The present study demonstrates that highly purified CD4+ T cells from 13 of 13 patients receiving HAART with an average treatment time of 10 months and with undetectable (<500 copies HIV RNA/ml) plasma viremia by a commonly used bDNA assay carried integrated proviral DNA and were capable of producing infectious virus upon cellular activation in vitro. Phenotypic analysis of HIV-1 produced by activation of latently infected CD4+ T cells revealed the presence in some patients of syncytium-inducing virus. In addition, the presence of unintegrated HIV-1 DNA in infected resting CD4+ T cells from patients receiving HAART, even those with undetectable plasma viremia, suggests persistent active virus replication in vivo.
            Article 0 comments Cited 267 times – based on 0 reviews     Review now
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              Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy

              David T W Chun, L Stuyver, S. B. Mizell … (1997)
              Article 0 comments Cited 255 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-journal-id): 9502015
                Journal ID (pubmed-jr-id): 8791
                Journal ID (nlm-ta): Nat Med
                Journal ID (iso-abbrev): Nat. Med.
                Title: Nature medicine
                ISSN (Print): 1078-8956
                ISSN (Electronic): 1546-170X
                Publication date Nihms-submitted: 25 March 2018
                Publication date (Electronic): 11 June 2018
                Publication date (Print): July 2018
                Publication date PMC-release: 11 December 2018
                Volume: 24
                Issue: 7
                Pages: 923-926
                Affiliations
                [1 ]SEARCH, Thai Red Cross AIDS Research Centre, Bangkok, Thailand
                [2 ]U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA
                [3 ]Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA
                [4 ]Centre de Recherche du CHUM and Department of microbiology, infectiology et immunology, Université de Montréal, QC, Canada
                [5 ]Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
                [6 ]Chulalongkorn Vaccine Research Center, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
                [7 ]Department of Medicine, Division of Infectious Diseases & HIV Medicine at Drexel University College of Medicine. Philadelphia, PA, USA
                [8 ]HIV-NAT, Thai Red Cross AIDS Research Center, Bangkok, Thailand
                [9 ]AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA
                [10 ]Division of AIDS, National Institute of Allergy and Infectious Diseases, Rockville, MD, USA
                [11 ]Department of Retrovirology, Armed Forces Research Institute of Medical Sciences United States Component, Bangkok, Thailand
                [12 ]Present address: International Vaccine Institute, Seoul, Korea
                [13 ]Department of Global Health, University of Amsterdam, Amsterdam, The Netherlands
                Author notes
                Corresponding author: Jintanat Ananworanich, MD, PhD, Associate Director for Therapeutics Research, US Military HIV Research Program, 6720A Rockledge Drive, Suite 400, Bethesda, MD, USA 20817, Tel: +1 301 500 3949, jananworanich@ 123456hivresearch.org
                Article
                Manuscript ID: NIHMS954408
                DOI: 10.1038/s41591-018-0026-6
                PMC ID: 6092240
                PubMed ID: 29892063
                SO-VID: e2f5428b-472f-4abb-bb3b-566fc9bb20ce
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                Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms

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