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Background: Human Immunodeficiency Virus (HIV) infection is associated with an increased risk of classical Hodgkin (cHL) and non-Hodgkin lymphomas (NHL). In the combined antiretroviral therapy (cART) era, while the incidence of NHL has declined, HL incidence has remained stable. In comparison to their HIV-negative counterpart, HIV-associated HLs present frequent high-risk characteristics: 1- mixed cellularity histological subtype, 2- advanced stage, presence of B symptoms and higher International Prognostic Score (IPS). Methods: The national prospective cohort of HIV-related lymphomas (ANRS CO16 Lymphovir cohort sponsored by Inserm-ANRS) enrolled adult patients in 40 centers since July 2008. Pathological materials were centralized and reviewed. Diagnoses were based on World Health Organization criteria. Patients have been followed every 6 months during 5 years. HIV HL patients were compared to a series of HIV-negative adult patients consecutively diagnosed with HL during the same period in Paris Saint-Louis hospital. Results: Among 159 HIV-infected patients, 68 (43%) were diagnosed with cHL. Mixed cellularity (MC) subtype was predominant (n=42), followed by nodular sclerosing (11). Fifteen cases could not be subclassified mainly because of small needle biopsies. Median age was 44 years (ranging from 20 to 65), male/female ratio was 5.8. Most patients (75%) had advanced clinical stage (III/IV). HIV infection had been diagnosed for a median of 13 years (maximum of 26 years) before the diagnosis of cHL. Median CD4 T-cell count was 380/μl (range 37-1742) and plasma HIV RNA was < 50 in 78% of the patients. All except one patient had been treated with cART prior to cHL diagnosis. They were all treated with cART after diagnosis. Front-line chemotherapy with standard anthracyclin based regimen (ABVD) was given to 64 out of 68 patients, BEACOPP in 4 patients. ABVD was followed by radiotherapy in limited stages. Five patients died from early disease progression (n=2), sepsis during chemotherapy (1) and after relapse (2). Two-year overall survival and Progression Free Survivals (PFS) were 94% [95%CI 88, 100] and 89% [82, 97], respectively. The only factor associated with PFS was age with a relative risk of 8.09 [0.97; 67.18] above 45 years (Table). IPS and CD4 count were not significantly associated with PFS. In comparison with HIV-negative patients, patients with HIV infection displayed higher risk features for all prognostic factors of HL (older age, male predominance, MC subtype, more advanced stages, lower lymphocytic counts). Treatment of HIV-negative patients was similar to HIV-positive patients: ABVD (79%), BEACOPP (21%), with addition of radiotherapy in limited stages. Overall, the outcomes of the HIV-infected patients did not differ significantly from those of HIV-negative patients (Figure). Conclusion : Although high risk features still predominate in HIV-HL, the prognostic of these patients has markedly improved in the recent cART era. We report 2-years OS and PFS of 94% and 89%, respectively, in patients mainly treated with cART and ABVD. The outcome of HL in HIV infected patients now resembles to those of non HIV infected patients. Table: Univariate analysis of Progression Free Survival in HIV associated Hodgkin Lymphoma (Cox model) (N=68) N Progression or Death, N RR 95 % CI p-value Gender 0.95 F 9 1 1 M 59 6 0.94 [0.11 ; 7.77] Age 0.05 =40 18 1 1 0.2 45 4 1 ≤0.2 21 3 1.64 [0.37 ; 7.32] RR: Relative Risk CI: Confidency interval *: 3 missing values **: 8 missing values ***: 2 missing values Median follow-up: HIV(-) cHL: 37 months (IQR=37) Lymphovir: 33 months (IQR=34) 2- year PFS: HIV(-) cHL: 0.86 CI95%=[ 0.82, 0.90 ] Lymphovir: 0.89 CI95%=[ 0.82, 0.97 ] Figure: Progression free survival (PFS) of HIV associated Hodgkin’s Lymphoma (N= 68) compared with HIV negative patients (N=336) Figure:. Progression free survival (PFS) of HIV associated Hodgkin’s Lymphoma (N= 68) compared with HIV negative patients (N=336) IQR: Interquartile range CI: Confidency interval Disclosures Brice: Seattle Genetics, Inc.: Research Funding; Takeda Pharmaceuticals International Co.: Honoraria, Research Funding; Roche: Honoraria.

Abstract 2147 Background: Human Immunodeficiency Virus (HIV) infection is associated with an increased risk of Hodgkin lymphoma (HL) and B-cell non-Hodgkin lymphoma (NHL). Increased risk of NHL is strongly correlated to the severity of the underlying immunodeficiency. Introduction of combined antiretroviral therapy (cART) has reduced the incidence of NHL -but not of HL's- among HIV-infected individuals. Outcomes are reported to be poorer among HIV-infected patients with HL or NHL than among non-HIV-infected patients. We carry out a cohort with the aim to study the characteristics and outcome of HIV-related lymphomas. Methods: The multicentric prospective Cohort of HIV related lymphomas (ANRS-CO16 Lymphovir cohort) enrolled 116 adult patients in 32 centers between October 2007 and April 2012. Investigations were performed after approval of the ethic committee. Patients were included at diagnosis of lymphoma (n=108) or at first relapse (1 HL, 7 NHL). Data collection concerned HIV infection history, clinical, biological and histological presentation, treatment and evolution of lymphoma. Pathological materials were centralized and 91 cases were reviewed. Diagnoses were based on World Health Organization criteria. Each patient was followed every 6 months during 5 years. Results: Among the 116 patients, 39.7% (46) were diagnosed with HL and 60.3% (70) with NHL. Median age was 43.5 years (ranging from 20 to 61) among patients with HL and 47 years (23 to 67) among those with NHL. Gender (male/female) ratio was 8.2 (41/5) among patients with HL, 1.7 (44/26) among those with NHL. The histological distribution of NHL were diffuse large B-cell lymphoma (DLBCL) 54.3% (38), Burkitt lymphomas (BL) 18.6% (13), plasmablastic lymphoma 10% (7), marginal zone/lymphoplasmocytic lymphoma 7.1% (5), others 10%: PTLD- like lymphoma (2), primary effusion lymphoma (1), follicular lymphoma (1), anaplastic lymphoma (1), unclassified (2). There was a predominance of clinical stages III/IV versus I/II among HL (76.7%, 33/43) and NHL patients (73.5%, 50/68). Among patients with DLBCL, LDH level was elevated in 68.4% (26/38) and performance status altered (2–4 versus 0–1) in 38.5% (15/39). HIV infection had been diagnosed for a median of 151 months (0 to 312) among HL patients and 117 (0 to 327) among those with NHL. The interval between diagnoses of HIV infection and lymphoma was shorter than 3 months for 2 patients with HL and 13 with NHL. All other patients except 6 NHL patients had been treated with ART at diagnosis of lymphoma. Median durations of ARV were 128 months (2 to 238) among HL patients and 119 months (1 to 236) among those with NHL. Patients with HL had a median CD4 T-cell count at diagnosis of lymphoma of 353/mm3 (range 37–1120), those with NHL, 261/mm3 (range 7–1322)]. The median interval between lymphoma occurrence and last follow-up was 21 months (range 0–41). During follow-up, all patients were treated with ARV. Among first-line HL patients, 39 out of 40 were treated with ABVD. Out of 40 patients with DLBCL or BL, 30 received chemotherapies combined with rituximab. At 24 months, overall survival is 95% among patients with HL and 78% among those with NHL (Figure 1). Two HL patients died during follow-up: one HL patient included in relapse from progression, another from a second cancer. Sixteen NHL patients died during follow-up: there were 10 early deaths ( Conclusions: The present study points out the high proportion of HL among HIV infection with lymphoma in the cART era and their favourable outcome compared to previous reports. This study also strengthens the heterogeneity of HIV-related lymphomas and the frequency of early deaths among patients with NHL. Disclosures: No relevant conflicts of interest to declare.

Abstract 4156 Introduction: Human Immunodeficiency Virus (HIV) and hepatitis C virus (HCV) infections are both associated with an increased risk of B-cell non-Hodgkin lymphoma (B-NHL). They are known to be preferentially diffuse large B-cell lymphoma (DLBCL), and Burkitt lymphoma subtypes in HIV infection, while marginal zone lymphoma (MZL) and DLBCL represent the main subtypes in HCV infected patients. The absence of increased risk of B-NHL in HIV-HCV co-infected patients compared to HIV infected patients was reported in epidemiological studies, but the clinico-pathological characteristics of B-NHL in the setting of such co-infection particularly in the era of HAART remains unclear. Patients and methods: We present the data of adult patients with B-NHL and HIV-HCV co-infection from the French ANRS CO16 Lymphovir cohort. This multicentric prospective cohort includes HIV infected patients with lymphoma. Each patient is followed every 6 months during 5 years. At each follow-up, a blood sample is withdrawn allowing ancillary studies. Data collection concerns clinical presentation, treatment and evolution of B-NHL and HIV and HCV infections. Pathological and cytological materials are centralized in order to allow their review and a concerted analysis by a group of expert hematopathologists (MR, SP, DC), haematologists and immunologists. Results: Among the 49 patients with B-NHL included in the cohort, 6 were HIV-HCV coinfected, [5 men and 1 woman, median age 47 years (range 36–67)]. They were included between october 2007 and august 2009 in 6 French centres. Transmission risk was intravenous drug abuse (n=4) and heterosexual transmission (n=2). Median duration from HIV diagnosis to B-NHL was 11 years (range 1–20), and the median nadir CD4 T-cell count was 194/mm3 (range 151–746) (nadir not available for 2 patients). Only one patient had developed AIDS before the diagnosis of NHL. HCV genotypic distribution was: genotype 1 (n=3), 2 (n=1), 4 (n=1), and not available (n=1). Median HCV viral load was 6.0 log (range 5.4–7.1). One patient had compensated cirrhosis and none of the patients were tested for cryoglobulinemia. Immunological assays showed the presence of monoclonal IgM Kappa in 1 patient and no positive rheumatoid factor. At the diagnosis of B-NHL, 4 patients received HAART and had an undetectable HIV load. In contrast, none of the patients were treated for HCV infection. The median interval between B-NHL diagnosis and last follow-up is 17 months (range 0.1–32 months). The histological subtype distribution is 4 MZL -including 2 extranodal MZL of MALT, 1 splenic lymphoma with villous lymphocytes (SLVL) and 1 lymphoplasmacytic lymphoma- and 2 EBV-negative DLBCL. All patients have extranodal involvement, including digestive tract (n=3), liver (n=2), bone marrow (n=2) and spleen (n=1). Median CD4 T-cell count at B-NHL diagnosis was 582/mm3 (range 235–1322) in MZL patients and 274/mm3 (200 and 347) in DLBCL patients. Following diagnosis, all patients were treated with HAART, associated with peg-interferon plus ribavirin in 1 patient. The 2 patients with DLBCL received R-CHOP, associated with methotrexate in 1 case. One patient with a partial response exhibited a neuromeningeal relapse and was treated with COPADM and CYVE regimen, allowing a complete and sustained response. The other patient died of serious infection after 2 courses of chemotherapy. Among patients with MZL, one patient received R-CVP and one received chlorambucil, allowing a complete response in both patients. The patient with SLVL received HAART then peg-interferon plus ribavirin, allowing normalization of lymphocytes count (5.89 at baseline vs. 1.69 × 109/L at 12 weeks of anti-HCV therapy) with a correlation between HCV virological and hematological response. Patient with lymphoplasmacytic lymphoma died of cardiac ischemia before the initiation of chemotherapy. Conclusions: This study describes the resurgence of MZL in HIV-HCV co-infected patients with restored immunity under HAART. Such B-NHL, very rarely described in HIV patients, occurs mainly in patients with control of HIV without history of AIDS but with active HCV infection. Histological subtypes and localizations resemble more to that observed in HCV infected patients than in HIV infected patients. These findings suggest the role of chronic antigenic stimulation by HCV and/or HIV and question about the interest of HCV antiviral therapy on NHL in co-infected patients. Disclosures: No relevant conflicts of interest to declare.