Impact of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy with Sezary syndrome. (24th August 2017)

• Record Type: Journal Article
• Authors: Rasmussen, Thomas A.; McMahon, James; Chang, J. Judy; Symons, Jori; Roche, Michael; Dantanarayana, Ashanti; Okoye, Afam; Hiener, Bonnie; Palmer, Sarah; Lee, Wen Shi; Kent, Stephen J.; Van Der Weyden, Carrie; Prince, H. Miles; Cameron, Paul U.; Lewin, Sharon R.
• Is Part Of: AIDS. Volume 31:Number 13(2017)
• Publication Date: 2017-08-24
• Subjects: alemtuzumab -- HIV -- HIV cure -- HIV eradication -- HIV latency -- HIV reservoir; AIDS (Disease) -- Periodicals; Acquired Immunodeficiency Syndrome; AIDS (Disease); Periodicals; Periodicals; 616.9792005
• DOI: 10.1097/QAD.0000000000001540
• Languages: English
• ISSNs: 0269-9370

Abstract

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. Abstract : Supplemental Digital Content is available in the text