Advertisement

 

 

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

Impact of alemtuzumab on HIV persistence in an HIV-infected individual on antiretroviral therapy with Sezary syndrome.
Author Information (click to view)

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,


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, (click to view)

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,

Advertisement
Share on FacebookTweet about this on TwitterShare on LinkedIn

AIDS (London, England) 31(13) 1839-1845 doi 10.1097/QAD.0000000000001540

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.

Submit a Comment

Your email address will not be published. Required fields are marked *

1 × 3 =

[ HIDE/SHOW ]