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.