Journal
JOURNAL OF CLINICAL MEDICINE
Volume 8, Issue 12, Pages -Publisher
MDPI
DOI: 10.3390/jcm8122089
Keywords
Immune checkpoint inhibitors; pembrolizumab; HIV-1 reservoir; HIV-specific CD8(+) T cells; HIV-1 curative strategies
Categories
Funding
- Merck Sharp & Dohme Espana, S.A [IISP 57699]
- National Health Institute Carlos III [PI17/00164]
- National Health Institute Carlos III (ISCIII) [CPII15/00014]
- Catalan Government [AGAUR-FI_B 00582]
- Spanish Ministry of Education, Culture and Sport [FPU15/03698]
- Redes Tematicas de Investigacion en SIDA [ISCIII RETIC RD16/0025/0041]
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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.
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