Abstract 1827 Prior studies suggest that HIV+ patients have a higher prevalence of paraproteinemia. Paraproteinemia is a known risk factor for development of hematological malignancy (HM) in non HIV patients. However the pathogenesis of paraproteinemia and the additional risk conferred by it to development of HM in HIV remains unclear. We describe our findings from a large database of HIV+ patients in Montefiore Medical Center with and without paraprotein for differences in HIV status, comorbidities and incidence of HM. Our de-identified patient database, Clinical Looking Glass, was used to identify all documented HIV+ patients who underwent at least one serum protein electrophoresis test (SPEP) after the HIV test between January 1st 2001 and December 31st 2011. Patients were classified into SPEP+ and SPEP-, and SPEP+ patients further stratified into distinct (D-SPEP) or faint/multiple/oligoclonal (F-SPEP) cases by visual assessment of gel electrophoresis. Laboratory data was reviewed for comorbidities and HIV status. Results of all biopsies undergone by each patient were reviewed to identify HM diagnoses. A total of 17,961 HIV+ patients were identified of which 2,095 patients had at least one SPEP test. Of those tested, 21.2% were SPEP+ (D-SPEP: 4%; F- SPEP:17.2%). 3.3% had a missing result. IgG was the commonest subtype on immunofixation (85.4%). All 3 groups (SPEP-, D-SPEP and F-SPEP) had a similar median duration of HIV before testing for SPEP. Mean CD4+ value measured around the time of the SPEP test (3 months before or after) was significantly higher in the F-SPEP group compare to both other groups. Patients in the D-SPEP and F-SPEP groups were more likely to be seropositive for Hepatitis C and Rheumatoid Factor (RF) than those who were SPEP-. A significantly higher proportion of patients were biopsied in the D-SPEP and F-SPEP groups than the SPEP-. Overall the incidence of HM in D-SPEP was significantly higher but when adjusted for patients who were biopsied, the higher incidence in D-SPEP did not reach statistical significance. 50–60% of HM were diagnosed within 6 months of the index SPEP; the D-SPEP group had the shortest time to diagnosis of HM after SPEP. The pattern of HM was different among the three groups with the D-SPEP patients mostly developing plasma cell dyscrasias, while the F-SPEP and SPEP- groups had a higher proportion of high grade B and T cell neoplasms. (Table 1). To our knowledge this is the largest published sample of HIV+ patients tested for paraproteinemia. The higher prevalence of Hepatitis C in SPEP+ patients suggests its role in pathogenesis of paraproteinemia. The higher incidence of HM, especially plasma cell dyscrasias diagnosed close to the index SPEP in the D-SPEP group suggests that D-SPEP may reflect malignant clonal proliferation. In contrast, the F-SPEP group had a similar HM incidence to SPEP- and a higher CD4+ count than the other groups. These suggest that faint/oligoclonal paraproteins may require T cell mediated B cell activation to develop and maybe directed against viral antigens rather than reflect premalignant or malignant proliferation. Understanding antigen specificity of paraproteins may shed light on the risk of HM in HIV+ SPEP+ patients.Table 1Differences between HIV+ SPEP-, HIV+D-SPEP and HIV+F-SPEPCharacteristicHIV+SPEP- (n=1596)HIV+DSPEP+ (n=82)HIV+FSPEP+ (n=348)pAge (yrs)49.4 (SE:0.29)50.5 (SE:1.35)49.9 (SE:0.58)0.604Male (%)53.2%47.6%47.1%0.088Median HIV duration before SPEP (days)8908117600.554Mean CD4 for patients tested (/uL)264 (SE:7.41)295 (SE:32.41)329 (SE:17.88)0.001*Mean HIV viral load for patients tested (copies/ml)127310 (SE:15094)118218 (SE:31448)98378 (SE:27968)0.691Median follow up after SPEP test (days)65410477340.362Hepatitis C+ of total tested patients494 (36.3%)33 (50.8%)125 (41.8%)0.018*Hepatitis B+ of total patients tested96 (9.9%)7 (13.2%)29 (12.4%)0.441ANA +of total patients tested89 (13.7%)5 (18.5%)17 (11.3%)0.531RF + of total patients tested88 (22.7%)11 (45.8%)43 (39.8%)0.000*Patients with HM (% of total N)66 (4.1%)10 (12.2%)21 (6%)0.004*Number of patients s/p biopsy268 (16.8%)22 (26.8%)90 (25.9%)0.000*Number of patients with HM of those biopsied66 (24.8%)10 (45.5%)21 (23.3%)0.087Number of total HM diagnosed after index SPEP37 (56.1%)6 (60%)11 (52.4%)0.918Median time from SPEP test to HM diagnosis (d)56363290.016* No relevant conflicts of interest to declare.