OAB0203
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Title
Effects of immune-check point inhibitors on anti-HIV specific immune responses and HIV-reservoir in people living with HIV (PLHIV) and cancer
Presenter
Marine Baron
Authors
M. Baron * (1), C. Soulié (2), L. Assoumou (3), J. Anna-Tine (3), B. Abbar (1), A. Rousseau (1), M. Veyri (4), D. Costagliola (3), C. Katlama (5), B. Autran (1), J. Cadranel (6), A. Lavolé (6), A. Saez-Cirion (7), O. Lambotte (8), J.-P. Spano (4), A.-G. Marcellin (2), A. Guihot (1), ANRS CO24 ONCOVIHAC Study Group
Institutions
(1) CIMI, UMR 1135, Paris, France, (2) INSERM-Sorbonne Université, UMR_S 1136, Paris, France, (3) INSERM-Sorbonne Université, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Paris, France, (4) Hôpital Pitié-Salpêtrière, Assistance-Publique Hôpitaux de Paris, Medical Oncology, Paris, France, (5) Hôpital Pitié-Salpêtrière, Assistance-Publique Hôpitaux de Paris, Infectious Diseases, Paris, France, (6) Hôpital Tenon, Assistance-Publique Hôpitaux de Paris, Pneumology, Paris, France, (7) Institut Pasteur, Unité HIV, Inflammation et Persistance, Paris, France, (8) Hôpital Kremlin-Bicêtre, Assistance-Publique Hôpitaux de Paris, Internal Medicine and Clinical Immunology, Paris, France

BACKGROUND: Immune checkpoint inhibitors (ICPi) are a major advance in cancer treatment. Whether they can act as a latency reversal agent towards an HIV cure is yet unknown, with still sparse immune-virological data.
METHODS: OncoVIRIM is a biological sub-study of the ongoing ANRS CO-24 OncoVIHAC prospective multicenter cohort including virally suppressed PLHIV treated with anti-PD1 for cancer. Blood samples were obtained at baseline and before different cycles (cycles 2, 3/4, 9, 15/18, 27/36, 51). Were evaluated by flow cytometry: T cell counts (CD3, CD4, CD8), T cell differentiation and activation markers (CD45RA, CCR7, CD27 and CD69, CD27, CD38, Ki67, HLA-DR), ICP expression, and HIV-specific T cells measured by intracellular cytokine staining (ICS) ; by PCR: ultrasensitive plasma HIV-RNA and total cell associated HIV-DNA.
RESULTS:







Median baseline
(range)		Median delta (D) or median fold change (FC) from C2 to D0 (n=)
Median delta (D) or median fold change (FC) from last point to D0 (n=)
p between C2 and D0
(Wilcoxon signed-rank test)		p between last point and D0
(Wilcoxon signed-rank test)
CD4 HLA-DR+
3,48% (0,52-6,17)2,91 (D, n=10)
-0,26 (D, n=12)
0,0039
0,5693
CD8 PD1+ 28,8% (20-42)-24,1 (D, n=10)
-23,335 (D, n=11)
0,0195
0,001
CD8 CTLA4+
0,05% (0.01-0.25)-0,015 (D, n=10)
0,0005 (D, n=12)
0,625
0,6621
CD8 TIM3+
5,66% (2-17)-0,27 (D, n=10)
1,115 (D, n=12)
0,7695
0,2734
HIV-specific-CD8+
1,42% (0,1-6,52)0,0025 (D, n=5)
0,0003 (D, n=6)
0,81250,8468
HIV-RNA
20 cp/mL (1-47)1 (FC, n=6)1 (FC, n=7)0,750,8539
HIV-DNA
218 cp/10^6 cells (40-620)0,486 (FC, n=6)0,501 (FC, n=7)0,6250,4375

Fourteen patients had been enrolled (median age 61 years), from January 2018 to June 2019. The median follow-up was 6 months (range 1-18), 4 patients stopped treatment and 6 died. The median baseline CD4 cell count value was 373/mm3 (range 90-888), CD4/CD8 ratio was 0.8 (range 0.1-2.1). At C2 and at last time point, there was no significant change in CD4 and CD8 cell counts or in T cell subsets distribution. However, proportions of HLA-DR+ CD4 T cells increased by 85% at C2 without change in other activation markers. PD1 expression dramatically decreased by 95% at C2 without change in CTLA4 and TIM3 expression overtime. Frequencies of HIV-specific-CD8 T cells remained stable overtime, but with higher PD1 expression on IFN-γ+ HIV-specific-CD8 T cells compared to non-HIV-specific-CD8 T cells at baseline (70% vs 38%, p=0.0012). HIV-RNA and DNA remained stable overtime (final median values: 10.5 cp/mL and 80 cp /10^6 cells).
CONCLUSIONS: In a context of HIV infection and cancer, these preliminary data on a limited number of patients suggest that ICPi used in monotherapy do not significantly impact the clinical biology of HIV infection.