Impact of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy with Sezary syndrome

Thomas A. Rasmussen, James McMahon, J. Judy Chang, Jori Symons, Michael Roche, Ashanti Dantanarayana, Afam Okoye, Bonnie Hiener, Sarah Palmer, Wen Shi Lee, Stephen J. Kent, Carrie Van Der Weyden, H. Miles Prince, Paul U. Cameron, Sharon R. Lewin

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1839-1845
Number of pages7
JournalAIDS
Volume31
Issue number13
DOIs
StatePublished - Aug 24 2017

Fingerprint

Sezary Syndrome
HIV
T-Lymphocytes
Therapeutics
DNA
T-Lymphocyte Subsets
alemtuzumab
Primary Cutaneous Anaplastic Large Cell Lymphoma
Defective Viruses
Coinfection
DNA Sequence Analysis
Hepatitis B virus
Neoplasms

Keywords

  • alemtuzumab
  • HIV
  • HIV cure
  • HIV eradication
  • HIV latency
  • HIV reservoir

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Rasmussen, T. A., McMahon, J., Chang, J. J., Symons, J., Roche, M., Dantanarayana, A., ... Lewin, S. R. (2017). Impact of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy with Sezary syndrome. AIDS, 31(13), 1839-1845. https://doi.org/10.1097/QAD.0000000000001540

Impact of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy with Sezary syndrome. / 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.

In: AIDS, Vol. 31, No. 13, 24.08.2017, p. 1839-1845.

Research output: Contribution to journalArticle

Rasmussen, TA, McMahon, J, Chang, JJ, Symons, J, Roche, M, Dantanarayana, A, Okoye, A, Hiener, B, Palmer, S, Lee, WS, Kent, SJ, Van Der Weyden, C, Prince, HM, Cameron, PU & Lewin, SR 2017, 'Impact of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy with Sezary syndrome', AIDS, vol. 31, no. 13, pp. 1839-1845. https://doi.org/10.1097/QAD.0000000000001540
Rasmussen TA, McMahon J, Chang JJ, Symons J, Roche M, Dantanarayana A et al. Impact of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy with Sezary syndrome. AIDS. 2017 Aug 24;31(13):1839-1845. https://doi.org/10.1097/QAD.0000000000001540
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. / Impact of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy with Sezary syndrome. In: AIDS. 2017 ; Vol. 31, No. 13. pp. 1839-1845.
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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.",
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AU - Symons, Jori

AU - Roche, Michael

AU - Dantanarayana, Ashanti

AU - Okoye, Afam

AU - Hiener, Bonnie

AU - Palmer, Sarah

AU - Lee, Wen Shi

AU - Kent, Stephen J.

AU - Van Der Weyden, Carrie

AU - Prince, H. Miles

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N2 - 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.

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