Kaposi disease in HIV-infected patients Oral Presentation – Wednesday 25th July 2018 Session: Keep your eyes on Ois and STIs Abstract number: WEAB0105 Kaposi disease in HIV-infected patients with suppressed HIV viremia: the experience of the French national multidisciplinary committee ONCOVIH R. Palich*, M. Veyri, M.-A. Valantin, A.-G. Marcelin, F.Boué, A. Guihot, C. Solas, H. Ait-Mohand, V. Martinez, I. Poizot-Martin, D. Costagliola, J.-P. Spano, C. Katlama, for the CancerVIH study group * Service des Maladies Infectieuses et Tropicales, Hôpital Pitié-Salpêtrière, AP-HP, Paris, France Logos INSERM et SORBONNE UNIVERSITE

Changing epidemiology on highly active antiretroviral therapy Introduction Kaposi disease (KD) Incidence of KD in HIV-positive patients over time1 Changing epidemiology on highly active antiretroviral therapy Decrease in the incidence of KD since 1996 (PI/r, triple therapies)1 Numéroter les références Référence RR = 35 « comparativement aux personnes HIV-negative » Despite immunological and virological control on ART, high risk of developing KD for HIV-positive patients2 Incident and recurrent KD in HIV-controlled patients 1. Shils, Curr Opin HIV AIDS, 2017. 2. Yanik, JCO, 2016

The French committee ONCOVIH Introduction The French committee ONCOVIH + DOM-TOM + Switzerland Experts’ discussion about cases of cancers occurring in HIV-infected patients Every 15 days, by teleconference Specific form completed by clinicians of the different French centers Goal: to provide advices for diagnosis, therapeutic approaches and prevention of drug-drug interactions « fiches remplies par les cliniciens des centres français » et « téléconférence » From May 2014 to December 2017 530 records (427 patients) 90 centers

The French committee ONCOVIH Introduction The French committee ONCOVIH Lung Kaposi NHL Anus ENT Breast Bladder Rectum Pancreas Liver Hodgkin Indeterminate Esophagus Skin Colon Distribution of cancers referred to the ONCOVIH committee from May 2014 to December 2017 « fiches remplies par les cliniciens des centres français » et « téléconférence » From May 2014 to December 2017 530 records (427 patients) 90 centers

Objective, definition of cases Objective: to describe the clinical, biological and therapeutic characteristics of virally-suppressed HIV-infected patients with Kaposi disease Current episode of KD Patients with suppressed viremia First episode: patients who had never had Kaposi lesions in their history Recurrent episode: new lesions of Kaposi in patients with previous KD in their history HIV plasma viral load <50 cp/ml at time of KD diagnosis (current episode) and On ART for at least 12 months

Methodology ONCOVIH forms: Back to the centers: Observational study from ONCOVIH committee data, from May 2014 to November 2017 ONCOVIH forms: Data on patients (demographic and clinical information, virological and therapeutic history) Data on KD (first episode or recurrent disease, localisations, previous treatments) Back to the centers: To complete missing information To update patients’ evolution

N = 72 patients with Kaposi disease Results Repartition of KD cases N = 72 patients with Kaposi disease Patients with suppressed viremia Patients with unsuppressed viremia N = 12 missing data N = 21 N = 39 pVL <50 cp/ml and on ART >12 months pVL >50 cp/ml or on ART <12 months 13 centers 26 centers

Number of patients with available data Results Patients’ characteristics Number of patients with available data Male 81% N=17/21 Origin: metropolitan France 45% N=9/20 DOM-TOM 5% N=1/20 Africa 50% N=10/20 Age (years) 54 (35-61) N=21 Time from HIV diagnosis (years) 14 (6-22) Time of virological suppression (years) 3 (2-5) N=17 CD4 nadir (/mm3) 196 (84-329) N=19 ART regimen: 2 NRTI + NNRTI 32% N=6/19 2 NRTI + PI/r 21% N=4/19 2 NRTI + INSTI 47% N=9/19 CD4 at time of KD diagnosis (/mm3) 449 (241-625) CD4/CD8 ratio at time of KD diagnosis 0,58 (0,33-0,65) N=12

Patients’ characteristics Results Patients’ characteristics Number of patients with available data Male 81% N=17/21 Origin: metropolitan France 43% N=9/21 DOM-TOM 5% N=1/21 Africa 48% N=10/21 Age (years) 54 (35-61) N=21 Time from HIV diagnosis (years) 14 (6-22) Time of virological suppression (months) 36 (24-60) N=17 CD4 nadir (/mm3) 196 (84-329) N=19 ART regimen: 2 NRTI + NNRTI 32% N=6/19 2 NRTI + PI/r 21% N=4/19 2 NRTI + INSTI 47% N=9/19 CD4 at time of KD diagnosis (/mm3) 449 (241-625) CD4/CD8 ration at time of KD diagnosis 0,58 (0,33-0,65) N=12 Distribution of CD4 count at time of KD diagnosis Patients’ characteristics Median CD4 count according to the KD status First episode: 375 (165-609) Recurrent episode: 478 (345-649)

Status of Kaposi disease Results Kaposi diseases’ characteristics Status of Kaposi disease Localisations 27% lymph nodes (N=6/21) 100% skin (N=21/21) 40% first episodes (N=8/20) 18% bones (N=4/21) 18% bronchi (N=4/21) 60% recurrent episodes (N=12/20) 5% mucous (N=1/21) 14% esophagus, stomach (N=3/21)

53% 47% Kaposi diseases’ characteristics not yet treated Results Kaposi diseases’ characteristics Previous treatments for the current episode of KD (at time of case presentation to ONCOVIH committee) 53% not yet treated (N=10/19) 47% Previously treated (N=9/19) Anthracyclines (78%) Taxanes (33%) 2 patients had received other treatments (bleomycin, IFN-α)

ONCOVIH committee proposals (N=21) Results Therapeutic management ONCOVIH committee proposals (N=21) Kaposi disease ART 14 treatment initiations Antracycline (7) Taxane (4) Other (3): bleomycine, etoposide, lenalidomide Radiotherapy (1) 3 treatment continuations 2 therapeutic abstentions 2 awaiting further examinations 17 treatment continuations With monitoring of renal function in one case 4 treatment modifications Drug-drug interaction (3) Resistance for ongoing treatment (1)

Evolution of Kaposi disease Results Follow-up Evolution of Kaposi disease at time of analysis* (N=16) 87% N=13/15 Regression Progress Stabilization N=6 N=4 ONCOVIH committee proposals (N=21) Kaposi disease ART * Median time from cases presentation to ONCOVIH committee from analysis: 25 months (14-34) 14 initiations of treatment Antracycline (7) Taxane (4) Other (3): bleomycine, etoposide, lenalidomide Radiotherapy (1) 3 continuations of treatment 2 therapeutic abstentions 2 awaiting further examinations 17 continuations of treatment With monitoring of renal function in one case 4 modifications of treatment 87% N=13/15 88% N=14/16 16 back to the medical records from associated centers Drug-drug interaction (3) Resistance for ongoing treatment (1)

Conclusion Highlighting Kaposi disease in HIV-infected individuals with sustained virological suppression Controlled immunological and virological situation More than 10 years of HIV infection evolution 3 years of virological suppression CD4 at 450/mm3 Therapeutic concerns Majority of patients referred due to recurrent KD Many patients previously treated for KD Patients progressing despite ongoing treatments Toxicity of conventional chemotherapies: therapeutic dead-end

Discussion Limitations Perspectives Retrospective cohort Missing data ONCOVIH specific form not suitable for clinical research Small number of cases Selection bias (most problematic cases) Perspectives CancerVIH working group to federate a large number of centers in France Constitution of a prospective cohort Low CD4/CD8 ratio as a risk factor of developing KD in virally-suppressed patients1 Alteration of HHV-8-specific immunity in HIV-positive patients developing KD2 This immunity should be explored in HIV-controlled patients Evaluation of alternative therapeutic strategies as immunotherapies (anti-PD-1) 1. Caby, Abs. TUPEC 265, AIDS 2018, Amsterdam. 2. Guihot, JID, 2006

Aknowledgment CancerVIH Study Group Associated Centers Isabelle Poizot-Martin Jean-Philippe Spano François Boué Christine Katlama Anne-Geneviève Marcelin Dominique Costagliola Caroline Solas Marc-Antoine Valantin Sylvain Choquet Rodolphe Garrafo Amélie Guihot Brigitte Autran Armelle Lavolé Jacques Cadranel Project leader: Marianne Veyri T. Lecompte D. Makhloufi V. Martinez C. Merle de Boever A. Montoya-Ferrer J. Pacanowski S. Patrat-Delon S. Pavel M.-C. Thiebaut-Drobacheff M.-O. Vareil D. Vittecoq Associated Centers T. Allègre K. Belhouari N. Bernard S. Bouchez R. Calin A. Canestri P. Chiarello L. Cotte C. Flateau H. Hitoto B. Hoen N. Landgraf

Number of patients with available data Results HIV-replicative patients Number of patients with available data Age (years) 44 (35-49) N=39 Time from HIV infection diagnosis (years) 4 (3-6) CD4 nadir (/mm3) 93 (34-173) N=35 CD4 at time of KD diagnosis (/mm3) 170 (51-367) KD concomittant of HIV infection diagnosis 64% N=23/36 KD occuring during an ART discontinuation 36% N=13/36 Patients’ characteristics