Please use this identifier to cite or link to this item: http://hdl.handle.net/11434/1251
Title: Impact of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy with Sezary syndrome.
Epworth Authors: McMahon, James
Prince, Miles
Other Authors: Rasmussen, Thomas
Chang, Judy
Symons, Jori
Michael, Roche
Dantanarayana, Ashanti
Okoye, Afam
Hiener, Bonnie
Palmer, Sarah
Lee, Wen Shi
Kent, Stephen
Van Der Weyden, Carrie
Cameron, Paul
Lewin, Sharon
Keywords: HIV
Antiretroviral Therapy
ART
Sezary Syndrome
Alemtuzumab
HIV-DNA
CD4+ T Cells
Flow Cytometry
T Cells
Malignant
Non-Malignant
Primary Cutaneous Anaplastic Large-Cell Lymphoma
Immune Recovery
Internal Medicine Clinical Institute, Epworth HealthCare, Victoria, Australia
Cancer Services Clinical Institute, Epworth HealthCare, Victoria, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne and Epworth Healthcare, Victoria, Australia
Issue Date: Aug-2017
Publisher: Lippincott Williams & Wilkins
Citation: AIDS. 2017 Aug 24;31(13):1839-1845
Abstract: OBJECTIVE: To study the effects of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy (ART) with Sezary syndrome, a rare malignancy of CD4+ T cells. DESIGN: Case report. METHODS: Blood was collected 30 and 18 months prior to presentation with Sezary syndrome, at the time of presentation and during alemtuzumab. T-cell subsets in malignant (CD7−CD26−TCR−VBeta2+) and nonmalignant cells were quantified by flow cytometry. HIV-DNA in total CD4+ T cells, in sorted malignant and nonmalignant CD4+ T cells, was quantified by PCR and clonal expansion of HIV-DNA assessed by full-length next-generation sequencing. RESULTS: HIV–hepatitis B virus coinfection was diagnosed and antiretroviral therapy initiated 4 years prior to presentation with Sezary syndrome and primary cutaneous anaplastic large cell lymphoma. The patient received alemtuzumab 10 mg three times per week for 4 weeks but died 6 weeks post alemtuzumab. HIV-DNA was detected in nonmalignant but not in malignant CD4+ T cells, consistent with expansion of a noninfected CD4+ T-cell clone. Full-length HIV-DNA sequencing demonstrated multiple defective viruses but no identical or expanded sequences. Alemtuzumab extensively depleted T cells, including more than 1 log reduction in total T cells and more than 3 log reduction in CD4+ T cells. Finally, alemtuzumab decreased HIV-DNA in CD4+ T cells by 57% but HIV-DNA remained detectable at low levels even after depletion of nearly all CD4+ T cells. CONCLUSION: Alemtuzumab extensively depleted multiple T-cell subsets and decreased the frequency of but did not eliminate HIV-infected CD4+ T cells. Studying the effects on HIV persistence following immune recovery in HIV-infected individuals who require alemtuzumab for malignancy or in animal studies may provide further insights into novel cure strategies.
URI: http://hdl.handle.net/11434/1251
DOI: 10.1097/QAD.0000000000001540
PubMed URL: https://www.ncbi.nlm.nih.gov/pubmed/28514279
ISSN: 0269-9370
Journal Title: AIDS
Type: Journal Article
Affiliated Organisations: The Peter Doherty Institute for Infection and Immunity, The University of Melbourne and Royal Melbourne Hospital, Victoria, Australia
Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark
Department of Infectious Diseases, Alfred Hospital and Monash University, Melbourne, Victoria, Australia
Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton
Oregon National Primate Research Center, Hillsboro, Oregon, USA
The Westmead Institute for Medical Research, The University of Sydney, Westmead, New South Wales
Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria
Type of Clinical Study or Trial: Case Reports
Appears in Collections:Internal Medicine

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