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      Re-examining the HIV ‘functional cure’ oxymoron: Time for precise terminology?

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          Abstract

          For over a decade, the binary concepts of ‘sterilizing’ versus ‘functional’ cure have provided an organizing framework for the field of HIV cure-related research. In this article, we examine how the expression ‘functional cure’ is employed within the field, published literature, and community understanding of HIV cure research. In our synthesis of the different meanings attributed to ‘functional cure’ within contemporary biomedical discourse, we argue that employing the ‘functional cure’ terminology poses a series of problems. The expression itself is contradictory and inconsistently used across a wide array of HIV cure research initiatives. Further, the meaning and acceptability of ‘functional cure’ within communities of people living with and affected by HIV is highly variable. After drawing lessons from other fields, such as cancer and infectious hepatitis cure research, we summarize our considerations and propose alternative language that may more aptly describe the scientific objectives in question. We call for closer attention to language used to describe HIV cure-related research, and for continued, significant, and strategic engagement to ensure acceptable and more precise terminology.

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          Most cited references75

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          The need for a new medical model: a challenge for biomedicine.

          The dominant model of disease today is biomedical, and it leaves no room within tis framework for the social, psychological, and behavioral dimensions of illness. A biopsychosocial model is proposed that provides a blueprint for research, a framework for teaching, and a design for action in the real world of health care.
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            HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation

            A cure for HIV-1 remains unattainable as only one case has been reported, a decade ago1,2. The individual-who is known as the 'Berlin patient'-underwent two allogeneic haematopoietic stem-cell transplantation (HSCT) procedures using a donor with a homozygous mutation in the HIV coreceptor CCR5 (CCR5Δ32/Δ32) to treat his acute myeloid leukaemia. Total body irradiation was given with each HSCT. Notably, it is unclear which treatment or patient parameters contributed to this case of long-term HIV remission. Here we show that HIV-1 remission may be possible with a less aggressive and toxic approach. An adult infected with HIV-1 underwent allogeneic HSCT for Hodgkin's lymphoma using cells from a CCR5Δ32/Δ32 donor. He experienced mild gut graft-versus-host disease. Antiretroviral therapy was interrupted 16 months after transplantation. HIV-1 remission has been maintained over a further 18 months. Plasma HIV-1 RNA has been undetectable at less than one copy per millilitre along with undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. Quantitative viral outgrowth assays from peripheral CD4 T lymphocytes show no reactivatable virus using a total of 24 million resting CD4 T cells. CCR5-tropic, but not CXCR4-tropic, viruses were identified in HIV-1 DNA from CD4 T cells of the patient before the transplant. CD4 T cells isolated from peripheral blood after transplantation did not express CCR5 and were susceptible only to CXCR4-tropic virus ex vivo. HIV-1 Gag-specific CD4 and CD8 T cell responses were lost after transplantation, whereas cytomegalovirus-specific responses were detectable. Similarly, HIV-1-specific antibodies and avidities fell to levels comparable to those in the Berlin patient following transplantation. Although at 18 months after the interruption of treatment it is premature to conclude that this patient has been cured, these data suggest that a single allogeneic HSCT with homozygous CCR5Δ32 donor cells may be sufficient to achieve HIV-1 remission with reduced intensity conditioning and no irradiation, and the findings provide further support for the development of HIV-1 remission strategies based on preventing CCR5 expression.
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              Culture, illness, and care: clinical lessons from anthropologic and cross-cultural research.

              Major health care problems such as patient dissatisfaction, inequity of access to care, and spiraling costs no longer seem amenable to traditional biomedical solutions. Concepts derived from anthropologic and cross-cultural research may provide an alternative framework for identifying issues that require resolution. A limited set of such concepts is described as illustrated, including a fundamental distinction between disease and illness, and the notion of the cultural construction of clinical reality. These social science concepts can be developed into clinical strategies with direct application in practice and teaching. One such strategy is outlined as an example of a clinical social science capable of translating concepts from cultural anthropology into clinical language for practical application. The implementation of this approach in medical teaching and practice requires more support, both curricular and financial.
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                Author and article information

                Contributors
                Journal
                J Virus Erad
                J Virus Erad
                Journal of Virus Eradication
                Elsevier
                2055-6640
                2055-6659
                14 October 2020
                November 2020
                14 October 2020
                : 6
                : 4
                : 100017
                Affiliations
                [a ]UNC Gillings School of Global Public Health, Chapel Hill, NC, USA
                [b ]Zephyr LTNP Foundation, Inc., Sacramento, CA, USA
                [c ]AIDS Action Baltimore, Baltimore, MD, USA
                [d ]amfAR Institute for HIV Cure Research Community Advisory Board (CAB), Palm Springs, CA, USA
                [e ]Delaney AIDS Research Enterprise (DARE) CAB, Baltimore,MD and Los, Angeles, CA, USA
                [f ]Martin Delaney Collaboratory CAB, Baltimore, MD; Seattle, WA; Palm Springs, CA; Ithaca, NY, Los Angeles, CA, USA
                [g ]DefeatHIV CAB, Seattle, WA, USA
                [h ]HIV + Aging Research Project – Palm Springs (HARP-PS), Palm Springs, CA, USA
                [i ]University of California AntiViral Research Center CAB, San Diego, CA, USA
                [j ]BEAT-HIV CAB, Philadelphia, PA, USA
                [k ]Department of Science and Technology Studies, Cornell University, Ithaca, NY, USA
                [l ]Collaboratory of AIDS Researchers for Eradication (CARE) CAB, Chapel Hill, USA
                [m ]Institute of Global Health and Infectious Diseases (IGHID), University of North Carolina at Chapel Hill, NC, USA
                [n ]Charles R. Drew University of Medicine and Science, Los Angeles, CA, USA, UCLA, Los Angeles, CA, USA
                [o ]University of California Riverside School of Medicine, Riverside, CA, USA
                [p ]Center for Healthy Communities, Department of Social Medicine and Population Health, University of California Riverside School of Medicine, Riverside, CA, USA
                [q ]Division of Prevention Science, Center for AIDS Prevention Studies, University of California, San Francisco, CA, USA
                [r ]Division of HIV, Infectious Diseases and Global Medicine, University of California, San Francisco, CA, USA
                Author notes
                []Corresponding author. karine_dube@ 123456med.unc.edu
                Article
                S2055-6640(20)31466-7 100017
                10.1016/j.jve.2020.100017
                7646673
                33251025
                707b0cc5-27b5-43c0-8b48-b6f906623ff8
                © 2020 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 12 April 2020
                : 29 September 2020
                : 2 October 2020
                Categories
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                hiv,hiv cure research,functional cure,suppression,control,immunity,terminology,language,community engagement,journal of virus eradication

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