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

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.

• Authors: 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
• Journal: AIDS (London, England) (AIDS) Vol. 31 Issue 13 Pg. 1839-1845 (08 24 2017) ISSN: 1473-5571 [Electronic] England
• PMID: 28514279 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Retroviral Agents
• Antineoplastic Agents, Immunological
• DNA, Viral
• Alemtuzumab

Topics

• Alemtuzumab (administration & dosage)
• Anti-Retroviral Agents (therapeutic use)
• Antineoplastic Agents, Immunological (administration & dosage)
• CD4-Positive T-Lymphocytes (virology)
• DNA, Viral (analysis)
• Flow Cytometry
• HIV (isolation & purification)
• HIV Infections (complications, drug therapy)
• Humans
• Immunophenotyping
• Male
• Middle Aged
• Sezary Syndrome (drug therapy)
• Skin Neoplasms (drug therapy)
• T-Lymphocyte Subsets (immunology)