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Open AccessArticle

Enhancement of Antiviral CD8+ T-Cell Responses and Complete Remission of Metastatic Melanoma in an HIV-1-Infected Subject Treated with Pembrolizumab

1
IrsiCaixa AIDS Research Institute, 08916 Badalona, Spain
2
Autonomous University of Barcelona, 08193 Cerdanyola del Vallès, Barcelona, Spain
3
Infectious Diseases Department, University Hospital “Germans Trias i Pujol”, 08916 Badalona, Spain
4
Medical Oncology Service—Badalona Applied Research Group in Oncology (B-ARGO Group), University Hospital “Germans Trias i Pujol”—Catalan Insitute of Oncology (ICO), 08916 Badalona, Spain
5
Department of Dermatology, University Hospital “Germans Trias i Pujol”, 08916 Badalona, Spain
6
Department of Oncology, University of Lausanne, CH-1015 Lausanne, Switzerland
7
Chair in Infectious Diseases and Immunity, Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), 08500 Vic, Spain
8
Germans Trias i Pujol Research Institute (IGTP), 08916 Badalona, Spain
9
Catalan Institution for Research and Advanced Studies (ICREA), 08010 Barcelona, Spain
*
Authors to whom correspondence should be addressed.
O.B.-L. and C.G. share first authorship.
J. Clin. Med. 2019, 8(12), 2089; https://doi.org/10.3390/jcm8122089
Received: 16 October 2019 / Revised: 14 November 2019 / Accepted: 22 November 2019 / Published: 1 December 2019
(This article belongs to the Section Immunology)
Background: Pembrolizumab is an immune checkpoint inhibitor against programmed cell death protein-1 (PD-1) approved for therapy in metastatic melanoma. PD-1 expression is associated with a diminished functionality in HIV-1 specific-CD8+ T cells. It is thought that PD-1 blockade could contribute to reinvigorate antiviral immunity and reduce the HIV-1 reservoir. Methods: Upon metastatic melanoma diagnosis, an HIV-1-infected individual on stable suppressive antiretroviral regimen was treated with pembrolizumab. A PET-CT was performed before and one year after pembrolizumab initiation. We monitored changes in the immunophenotype and HIV-1 specific-CD8+ T-cell responses during 36 weeks of treatment. Furthermore, we assessed changes in the viral reservoir by total HIV-1 DNA, cell-associated HIV-1 RNA, and ultrasensitive plasma viral load. Results: Complete metabolic response was achieved after pembrolizumab treatment of metastatic melanoma. Activated CD8+ T-cells expressing HLA-DR+/CD38+ transiently increased over the first nine weeks of treatment. Concomitantly, there was an augmented response of HIV-1 specific-CD8+ T cells with TNF production and poly-functionality, transitioning from TNF to an IL-2 profile. Furthermore, a transient reduction of 24% and 32% in total HIV-1 DNA was observed at weeks 3 and 27, respectively, without changes in other markers of viral persistence. Conclusions: These data demonstrate that pembrolizumab may enhance the HIV-1 specific-CD8+ T-cell response, marginally affecting the HIV-1 reservoir. A transient increase of CD8+ T-cell activation, TNF production, and poly-functionality resulted from PD-1 blockade. However, the lack of sustained changes in the viral reservoir suggests that viral reactivation is needed concomitantly with HIV-1-specific immune enhancement. View Full-Text
Keywords: Immune checkpoint inhibitors; pembrolizumab; HIV-1 reservoir; HIV-specific CD8+ T cells; HIV-1 curative strategies Immune checkpoint inhibitors; pembrolizumab; HIV-1 reservoir; HIV-specific CD8+ T cells; HIV-1 curative strategies
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Blanch-Lombarte, O.; Gálvez, C.; Revollo, B.; Jiménez-Moyano, E.; Llibre, J.M.; Manzano, J.L.; Boada, A.; Dalmau, J.; E. Speiser, D.; Clotet, B.; G. Prado, J.; Martinez-Picado, J. Enhancement of Antiviral CD8+ T-Cell Responses and Complete Remission of Metastatic Melanoma in an HIV-1-Infected Subject Treated with Pembrolizumab. J. Clin. Med. 2019, 8, 2089.

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