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BackgroundNicotine replacement therapy, bupropion, and varenicline are smoking cessation medications (SCMs) shown to be similarly effective in people with and without human immunodeficiency virus (PWH and PWoH, respectively), although rates of receipt of these medications are unknown.MethodsWe identified patients in the Veterans Aging Cohort Study with electronic health record-documented current smoking using clinical reminder data for tobacco use (2003–2018). We measured receipt of SCMs using Veterans Affairs pharmacy data for outpatient prescriptions filled 0–365 days after current smoking documentation. We used log-linear, Poisson-modified regression models to evaluate the relative risk (RR) for receiving SCM by human immunodeficiency virus (HIV) status, the annual rate of receipt, and rate difference among PWH relative to PWoH.ResultsThe sample included 92 632 patients (29 086 PWH), reflecting 381 637 documentations of current smoking. From 2003 to 2018, the proportion receiving SCMs increased from 15% to 34% for PWH and from 17% to 32% among PWoH. There was no statistical difference in likelihood of receiving SCM by HIV status (RR, 1.010; 95% confidence interval [CI], .994–1.026). Annual rates of receiving SCM increased for PWH by 4.3% per year (RR, 1.043; 95% CI, 1.040–1.047) and for PWoH by 3.7% per year (RR, 1.037; 95% CI, 1.036–1.038; rate difference +0.6% [RR, 1.006; 95% CI, 1.004–1.009]).ConclusionsIn a national sample of current smokers, receipt of SCM doubled over the 16-year period, and differences by HIV status were modest. However, fewer than 35% of current smokers receive SCM annually. Efforts to improve SCM receipt should continue for both groups given the known dangers of smoking.

Background Protection offered by five different forms of immunity, combining natural and vaccine immunity, was investigated against symptomatic SARS-CoV-2 infection from Omicron BA.1 or BA.2, and severe, critical, or fatal COVID-19 from BA.1 or BA.2, in Qatar, between December 23, 2021 and February 21, 2022. Methods Six national, matched, test-negative case-control studies were conducted on a sample of 272,861 PCR-positive tests and 669,628 PCR-negative tests to estimate effectiveness of BNT162b2 (Pfizer-BioNTech) vaccine, mRNA-1273 (Moderna) vaccine, natural immunity due to prior infection with pre-Omicron variants, and hybrid immunity from prior infection and vaccination. Results Effectiveness of prior infection alone against symptomatic BA.2 infection was 46.1% (95% CI: 39.5-51.9%). Effectiveness of two-dose BNT162b2 vaccination alone was negligible at -1.1% (95% CI: -7.1-4.6), but nearly all individuals received their second dose >6 months earlier. Effectiveness of three-dose BNT162b2 vaccination alone was 52.2% (95% CI: 48.1-55.9%). Effectiveness of hybrid immunity of prior infection and two-dose BNT162b2 vaccination was 55.1% (95% CI: 50.9-58.9%). Effectiveness of hybrid immunity of prior infection and three-dose BNT162b2 vaccination was 77.3% (95% CI: 72.4-81.4%). Meanwhile, prior infection, BNT162b2 vaccination, and hybrid immunity all showed strong effectiveness ( >70%) against severe, critical, or fatal COVID-19 due to BA.2. Similar patterns of effectiveness were observed for BA.1 and for the mRNA-1273 vaccine. Figure 1.Effectiveness of prior infection, vaccination, and hybrid immunity against symptomatic Omicron infection and against severe, critical, or fatal COVID-19 for the BA.1 (panels A and B, respectively) and BA.2 (panels C and D, respectively) subvariants in the BNT162b2-vaccine study.Figure 2.Effectiveness of prior infection, vaccination, and hybrid immunity against symptomatic Omicron infection and against severe, critical, or fatal COVID-19 for the BA.1 (panels A and B, respectively) and BA.2 (panels C and D, respectively) subvariants in the mRNA-1273-vaccine study. Conclusion There are no discernable differences between BA.1 and BA.2 in the effects of prior infection, vaccination, and hybrid immunity. Vaccination enhances the protection of those with a prior infection. Hybrid immunity resulting from prior infection and recent booster vaccination conferred the strongest protection. Disclosures Adeel A. Butt, MBBS, Gilead Sciences: Grant/Research Support.

Background Comparative effectiveness of coronavirus disease 2019 (COVID-19) vaccines across patient subgroups is poorly understood and essential to precisely targeting vaccination strategies. Methods We used the US Department of Veterans Affairs COVID-19 Shared Data Resource to identify veterans who utilize VA health care and had no documented severe acute respiratory syndrome coronavirus 2 infection before December 11, 2020. Using a test-negative case–control design (TND), we used conditional logistic regression with adjustment for covariates to estimate vaccine effectiveness (VE) over time for veterans who received 2 doses of mRNA vaccines or 1 dose of Ad26.Cov2.S. Results We identified 4.8 million veterans with a mean age of 64 years, of whom 58% had ≥1 chronic disease. Vaccine effectiveness for symptomatic infections, hospitalizations, and ICU admission or death declined over time and varied by the type of vaccine (P 1 chronic disease. Conclusions mRNA-1273 was more effective than BNT162b2 in older veterans and those with chronic diseases.

Background Qatar experienced a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic that disproportionately affected the craft and manual worker (CMW) population, who comprise 60% of the total population. This study aimed to assess ever and/or current infection prevalence in this population. Methods A cross-sectional population-based survey was conducted during July 26 to September 09, 2020, to assess both anti-SARS-CoV-2 positivity through serological testing and current infection positivity through polymerase chain reaction (PCR) testing. Associations with antibody and PCR positivity were identified through regression analyses. Results The study included 2641 participants, 69.3% of whom were Conclusions Six in every 10 CMWs in Qatar have been infected, suggestive of reaching the herd immunity threshold. Infection severity was low, with only 1 in every 200 infections progressing to be severe or critical. Only 1 in every 10 infections had been previously diagnosed, which is suggestive of mostly asymptomatic or mild infections.

Background The prevalence and risk of concurrent unhealthy drinking, cigarette use, and depression on mortality among persons living with HIV (PLWH) is unclear. This study applied a syndemic framework to assess whether these co-occurring conditions increase mortality and whether such risk is differential by HIV status. Methods We evaluated 6721 participants (49.8% PLWH) without baseline cancer from the Veterans Aging Cohort Study, a prospective, observational cohort of PLWH and matched uninfected veterans enrolled in 2002 and followed through 2015. Multivariable Cox proportional hazards regressions estimated risk of a syndemic score (number of conditions: that is, unhealthy drinking, cigarette use, and depressive symptoms) on all-cause mortality by HIV status, adjusting for demographic, health status, and HIV-related factors. Results Fewer than 10% of participants had no conditions; 25.6% had 1, 51.0% had 2, and 15.0% had all 3. There were 1747 deaths (61.9% PLWH) during the median follow-up (11.4 years). Overall, age-adjusted mortality rates/1000 person-years increased with a greater number of conditions: (0: 12.0; 1: 21.2; 2: 30.4; 3: 36.3). For 3 conditions, the adjusted hazard ratio of mortality was 36% higher among PLWH compared with uninfected participants with 3 conditions (95% confidence interval, 1.07–1.72; P = .013), after adjusting for health status and HIV disease progression. Among PLWH and uninfected participants, mortality risk persisted after adjustment for time-updated health status. Conclusions Syndemic unhealthy drinking, cigarette use, and depression are common and are associated with higher mortality risk among PLWH, underscoring the need to screen for and treat these conditions.

Background Progression of liver disease and clinical outcomes in HCV/HBV coinfected persons and how they differ from HCV monoinfected persons and HCV infected persons with resolved HBV infection are not well characterized. We compared incidence of cirrhosis, hepatic decompensation and overall mortality in these three groups. Methods Using the Electronically Retrieved Cohort of HCV-infected Veterans (ERCHIVES), we identified those with HCV infection only, HCV/HBV coinfection (HbsAg or HBV DNA or both positive) or HCV with resolved HBV (HbcAb+ in absence of HbsAg or HBV DNA positivity). We excluded those with HIV coinfection or hepatocellular carcinoma at or before baseline, and those who received any HCV or HBV treatment. Incident rates (95% CI) were determined for cirrhosis, first hepatic decompensation event and overall mortality in the three groups. Results We identified 60,368 HCV monoinfected (Gp A), 151 HCV/HBV coinfected (Gp B) and 19,802 HCV infected with resolved HBV infection (Gp C). Mean age was 61.0, 60.9, and 63.0 years in the three groups and 96.5%, 96.0%, and 97.9% were males. Median baseline FIB-4 index was 2.0, 2.2, and 2.1, respectively. Incident cirrhosis (among those without cirrhosis at baseline) was increased 2- to 2.5-fold in HCV/HBV coinfected persons with baseline FIB-4 of 1.46–3.25. Hepatic decompensation and mortality were also increased several-fold in the HCV/HBV coinfected who had minimal or mild/moderate fibrosis at baseline. However, among those with cirrhosis at baseline, the difference was small among HCV/HBV coinfected and the other groups. Conclusion HCV/HBV coinfected persons with minimal or mild/moderate fibrosis at baseline have a much higher risk of developing cirrhosis, hepatic decompensation and mortality. However, once cirrhosis has is established, the difference is diminished. This underscores the need to intervene early when HCV/HBV coinfected persons still have minimal or mild/moderate fibrosis. Disclosures All authors: No reported disclosures.

Background There are scant data regarding hepatitis C (HCV) virologic response to directly acting antiviral agents (DAAs) in chronic hepatitis B (HBV) and HCV coinfected persons. HCV treatment response in those with spontaneously cleared HBV infection is unknown. Methods All HCV-infected persons treated with a DAA regimen in ERCHIVES were identified and categorized into HBV/HCV-coinfected (HBsAg, HBV DNA or both positive), HCV-monoinfected, and resolved HBV (isolated HBcAb+). SVR rates were determined and compared for all groups. A logistic regression model was used to determine factors associated with SVR. Results Among 115 HCV/HBV-coinfected, 38,570 HCV-monoinfected persons, and 13,096 persons with resolved HBV, 31.6% of HCV/HBV-coinfected, 24.6% of HCV-monoinfected and 26.4% with resolved HBV had cirrhosis at baseline. SVR was achieved in 90.4% of HCV/HBV-coinfected, 83.4% of HCV-monoinfected and 84.5% of those with resolved HBV infection (P = 0.04 HCV/HBV vs. HCV monoinfected). In a logistic regression model, those with HCV/HBV were more likely to achieve SVR compared with HCV monoinfected (OR 2.25, 95% CI 1.17, 4.31). For HCV/HBV coinfected, the SVR rates dropped numerically with increasing severity of liver fibrosis (P-value non-significant). Factors associated with a lower likelihood of attaining SVR included cirrhosis at baseline (OR 0.85, 95% CI 0.80, 0.92), diabetes (OR 0.93, 95% CI 0.87, 0.99) and higher pretreatment HCV RNA (OR 0.86, 95% CI 0.84, 0.87). Conclusion HBV/HCV-coinfected persons have higher overall SVR rates with newer DAA regimens. The virologic response is graded, with decreasing SVR rates with increasing degree of liver fibrosis as determined by the FIB-4 scores. Disclosures All authors: No reported disclosures.

Background Knowledge about HCV treatment uptake, regimens and providers in the era of all-oral directly acting antiviral agents is critical for patients, providers, payers and policy makers. Our objective was to determine the number of persons initiated on HCV treatment over time, and trends in providers who initiate treatment Methods Among all HCV+ persons in ERCHIVES from 2001 to 2017, we identified all persons who initiated HCV treatment and medical specialty of the provider initiating treatment. Results were tabulated by VA fiscal year. Results A total of 108,133 persons were initiated on treatment (Figure 1). Sofosbuvir-based regimens were the most commonly used regimens, accounting for nearly two-thirds of all DAA regimens. Gastroenterologists/hepatologist were the most common initiators of treatment in the pre-DAA era accounting for 26.7% of all prescriptions in 2001–2011 but only 10.3% in 2017 (Figure 2). Allied health professionals accounted for only 7.2% of treatment initiations in the 2001–2011 period but were the most frequent prescribers in 2017 (22.2%). Ratio of persons initiated on treatment to new HCV diagnoses reversed in 2013 for HCV monoinfected persons and in 2014 for HCV/HIV coinfected persons, with new treatment initiations far outnumbering new infections. Conclusion There has been a dramatic increase in HCV treatment uptake in the VA healthcare system with the approval of newer all-oral DAA regimens. Treatment paradigm appears to be shifting toward lesser gastroenterologists/hepatologists and more allied health professionals treating HCV. Figure 1. New hepatitis C virus infection diagnoses and treatments initiated per month for Veterans with hepatitis C virus infection. Figure 2. Proportion of patients treated by each specialty by year of treatment initiation (excludes those classified as “other” and “missing”). Disclosures A. Ajwad Butt, Gilead: Grant Investigator, Research grant.

Background Studies reporting on the association between HCV and cardiovascular disease (CVD), and effect of HCV treatment upon future risk of CVD have shown mixed results. Methods Within ERCHIVES (Electronically Retrieved Cohort of HCV Infected Veterans), we identified all persons treated for ≥7 weeks and propensity-score-matched group who never received HCV treatment. We excluded those with HIV, HBV, or previously diagnosed CVD. Incidence rate (per 1,000 person-years) and risk factors for CVD events (Cox proportional hazards analysis) were determined for various treatment groups. CVD events were identified using ICD-9CM/ICD-10 codes. Kaplan–Meier plots were generated to show and compare CVD-free survival by treatment status and attainment of SVR. Results Among 32,575 treated and same number of untreated persons in the final dataset, median age was 58 years, 27% were Black race, and 96% were male. The incidence rate for CVD events/1,000 person-years (95% CI) among the treated was 19.10 (17.79, 20.50) vs. 32.37 (30.51, 34.33) among the untreated (P < 0.01). Treatment with a DAA regimen (vs. PEG/RBV; HR [95% CI] 0.68 [0.53,0.88]) and achieving SVR (HR [95% CI] 0.76 [0.63,0.92]) were associated with a lower risk of incidence CVD event (table). Kaplan–Meier curves demonstrated that untreated persons had a shorter CVD event-free survival during 30 months of follow-up compared with the treated persons. (figure; log-rank P < 0.0001) Conclusion HCV treatment is associated with a reduction in incident CVD events. Directly acting antiviral regimens (vs. PEG/RBV) and attainment of SVR (vs. no SVR) are associated with a lower risk of incident CVD events. Disclosures A. Ajwad Butt, Gilead: Grant Investigator, Research grant.

Background Treatment of HCV with directly acting antiviral agents (DAAs) is associated with a significant reduction in cardiovascular, metabolic and cancer risk. However, there are conflicting data regarding the risk of hepatocellular carcinoma (HCC) after DAA treatment. Risk of HCC in HCV genotype 3 infected persons after DAA therapy is not well known. Methods We prospectively studied HCV-infected persons initiated on treatment between October 2014 and March 2017 at two centers in Pakistan. All persons were free of HCC at study initiation. The occurrence of HCC was confirmed based on radiologic findings on a triphasic CT on 64 slice MDCT scanner. The treatment regimen was at the discretion of clinical care providers, taking into account the national guidelines and patient preferences. Patients were followed for 24 weeks after the completion of therapy. Informed consent was obtained from all participants. Results A total of 662 persons were initiated on treatment. Median age (IQR) was 50 (41, 57) years and 48.8% were male. At baseline, 49.4% were cirrhotic with 90% of cirrhotics having compensated cirrhosis. 91% were genotype 3 and SVR was attained in 91.9%. Treatment regimens used were: Sofosbuvir (SOF)/ribavirin (RBV)/pegylated interferon (PEG-IFN), 25.2%; SOF/RBV, 62.4%; SOF/RBV/daclatasavir (DCL), 10.6%; SOF/DCL, 2.0%. Incident HCC was detected in 42 patients (12.8%) in the six month period after treatment completion, and was exclusively observed in those with cirrhosis. In multivariable Cox regression analysis, SVR was associated with a reduction in HCC risk (HR, 95% CI: 0.35, 0.14,0.85) while SOF/RBV/DCL regimen (compared with SOF/RBV/PEG-IFN) was associated with an increased risk of HCC (HR, 95% CI: 17.32, 2.14,140.36). In K-M plots by treatment regimen, those treated with SOF/RBV, SOF/RBV/DCL, or SOF/DCL regimens had shorter HCC-free survival compared with those treated with a SOF/RBV/PEG-IFN regimen. (See figure) Conclusion In a predominantly genotype 3 cohort, incident HCC occurs commonly and early after treatment completion, and exclusively in those with pretreatment cirrhosis. SVR reduces but does not completely eliminate the risk of HCC. Treating HCV-infected persons before the development of cirrhosis may reduce future risk of HCC. Disclosures All authors: No reported disclosures.

Background Beneficial effect of hepatitis C virus (HCV) treatment with directly acting antiviral agents (DAAs) upon overall mortality is well-established. However, the effect of treatment upon liver-related mortality is not well documented. Methods We used ERCHIVES database to identify all chronic HCV-infected persons between January 1, 2002 and December 31, 2016. We excluded those with HIV or HBV coinfection or hepatocellular carcinoma. HCV treatment status was defined as prescription of pegylated interferon (PEG)/ribavirin (RBV) for >24 weeks, PEG/RBV plus boceprevir or telaprevir, or a newer DAA regimen for >8 weeks. Propensity score-matched untreated controls were identified for each treated person. We linked HCV+ cases to the National Death Index (NDI) data updated to the end of 2016. Cause of death was retrieved from the underlying cause listed on the death certificate by using ICD‐10 codes. The listed primary cause was assigned as the cause of death. Each cause of death was categorized as “Liver related” or “Not liver related” by two physician members of the study team. Liver-related causes included viral hepatitis-related causes, complications of liver disease, and hepatocellular carcinoma, but excluded any cause where alcohol or any other known liver disease other than viral hepatitis was specified. Discordant results were adjudicated by a third physician member. Results Among 34,412 treated and 21,287 untreated controls, there were 13,098 deaths, of which 2,474 (18.9%) were liver related. Overall liver-related mortality rate per 100 person-years of follow-up was 0.64 in the treated and 1.24 in the untreated group (P). Among the treated group, the liver-related mortality rate per 100 person-years was 0.14 for those who achieved SVR and 1.26 among those who did not achieve SVR. When stratified by treatment regimen, those treated with PG/RBV had a mortality rate of 0.73 vs. 0.24 for those treated with a DAA regimen. However, further stratification by attainment of SVR revealed that the difference between regimens was almost entirely driven by the difference in SVR rates (see table). Conclusion HCV-infected persons who receive treatment have a substantial reduction in liver-related mortality. This reduction is largely driven by attainment of SVR and is independent of the regimen use when stratified by SVR attainment. Disclosures All Authors: No reported Disclosures.

Background There are limited data describing carbapenem-resistant Enterobacteriaceae (CRE) from the Arabian Gulf region. Our aims were to describe the clinical, microbiological and molecular characteristics of CRE infections and to characterize the gene displaying resistance to carbapenem. Methods Retrospective and prospective review of clinical, microbiological and molecular characteristics of CRE isolated between April 2015 and November 2017 at 7 tertiary hospitals in Qatar. Susceptibility testing was performed and interpreted according to Clinical Laboratory Standards Institute methodology and breakpoints. Carbapenemase genes were identified using PCR. Whole-genome sequencing followed by bioinformatics analysis was performed on a subset of samples for accurate detection of resistant genes. SPSS V.21.0 was used for all statistical analyses. Results A total of 144 nonrepeating CRE strains were recovered from 137 individuals over the study period, of which 35 (24.3%) represented colonization. Klebsiella spp. (98, 68.1%) and E. coli (38, 26.4%) were the most predominant. The most prevalent carbapenemases were NDM (69, 47.9%), OXA-48 (36, 25.0%), and KPC (15, 10.4%). Sixteen (11.1%) strains possessed multiple carbapenemase genes but none were detected in 37 (25.7%) strains. Genomic analysis also detected the presence of NDM-7, NDM-5, NDM1, VIM4, and OXA48-like carbapenemase genes among 34 clinical samples. The majority of the strains were susceptible to tigecycline (124, 86.1%), fosfomycin (122, 84.7%) and amikacin (102, 70.8%). There were 109 CRE infections involving the urinary tract (40, 36.7%), bloodstream (31, 28.4%), and respiratory tract (17, 15.6%). Fifty-seven (52.3%) were males and the median age was 57 years (range 3–97). Baseline comorbidities included diabetes (57, 52.3%), chronic kidney disease (27, 24.8%), and cancer (27, 24.8%) (Table 1). Within the 30 days preceding CRE infection, 38 (34.9%) had received carbapenem therapy, 65 (59.6%) had undergone invasive procedures and 33 (30.3%) had had surgery. All-cause 30-day mortality was 29.4%. The only variable independently associated with mortality was baseline SAPS Score (Table 2). Conclusion NDM and OXA-48 are the predominant carbapenemases in Qatar. CRE infections are associated with high overall mortality. Disclosures All authors: No reported disclosures.

Background Newer directing antiviral agents against HCV (DAAs) are safe and efficacious in persons with chronic kidney disease (CKD). Whether availability of these newer DAAs has resulted in more persons with CKD initiating HCV treatment remains unknown. Methods We identified HCV+ persons in ERCHIVES. We excluded HIV+ and HBsAg+ and those with missing HCV RNA and eGFR data. We determined the CKD stage according to National Kidney Foundation criteria. We determined the number of persons initiated on any of the approved DAA-regimen (defined as >14 days of DAA prescription). Logistic regression analyses was used to determine factors associated with treatment initiation. Results Among 76,513 evaluable persons, 21.1% initiated DAA treatment. Initiation rates differed significantly by CKD stage: 21.1% (15,136/68,469) for eGFR>90mL/minute/1.73m2 and CKD stage-2; 14.0% 9853/6,086) for CKD stage 3; and 7.6% (148/1,958) for CKD stage-4/5. Those with CKD stage-3 were 35% less likely and those with CKD stage-4/5 were 65% less likely to initiate treatment with a DAA compared with those with baseline eGFR>90mL/minute/1.73m2. Those with Body Mass Index (BMI)>30 were more likely to initiate treatment (OR 1.24, 95% CI 1.19,1.29). Treatment initiation was less likely in HCV genotype 2 or 3 and those with diabetes (OR 0.82, 95% CI 0.78,0.86), cardiovascular disease (OR 0.73, 95% CI 0.68,0.78), alcohol abuse or dependence (OR 0.75, 95% CI 0.72,0.78) or cirrhosis (OR 0.85, 95% CI 0.80,0.89) at baseline. Conclusion Persons with more advanced CKD are less likely to receive treatment for HCV. Strategies are needed to improve treatment rates in the HCV/CKD population. Disclosures A. Butt, Merck: Investigator, Grant recipient. A. Puenpatom, Merck: Employee, Salary. J. M. Arduino, Merck: Employee, Salary. R. Kumar, Merck: Employee, Salary

Background Data are limited regarding the effect of paritaprevir/ritonavir, ombitasvir, dasabuvir regimen (PrOD) upon the rate of liver fibrosis progression and incidence of cirrhosis and hepatic decompensation after treatment for HCV. Methods Within ERCHIVES (Electronically Retrieved Cohort of HCV Infected Veterans), we identified HCV infected persons treated with PrOD and treatment-na•ve controls to determine the effect of PrOD treatment upon subsequent progression of fibrosis and incident cirrhosis and hepatic decompensation. Controls were propensity-score matched based on demographic and clinical characteristics. We excluded those with HIV coinfection, positive HBsAg, hepatocellular carcinoma at baseline and those with missing HCV RNA or FIB-4 scores. Fibrosis progression and liver cirrhosis were assessed using the FIB-4 score. Results The final propensity score matched sample included 1,473 PrOD-treated individuals, and an equal number of matched, untreated controls. PrOD-treated patients had significantly reduced median FIB-4 scores over time, compared with controls (median absolute change in FIB-4 = -0.7 [IQR -1.51, -0.3] vs. +0.06 [IQR -0.38, 0.49]; P < 0.0001). Compared with matched controls, PrOD-treated patients had an 86% relative reduction in the risk of incident cirrhosis over 2,241 patient-years of follow-up (adjusted HR 0.14 [95% CI 0.08-0.23]). Treatment with PrOD was also associated with delayed time to first hepatic decompensation event (P < 0.001). In sensitivity analysis, the exclusion of patients with baseline cirrhosis did not materially alter the estimates of effect. Conclusion Treatment with PrOD is associated with a significant reduction in fibrosis progression, a longer time to the development of cirrhosis, and reduced risk of hepatic decompensation. Our results demonstrate the long-term anti-fibrotic benefits associated with PrOD therapy for chronic HCV. Disclosures J. Kort, Abbvie: Employee and Shareholder, Salary; A. Butt, Merck: Investigator, Grant recipient

Background Chronic kidney disease (CKD) was a relative contraindication to HCV treatment in the interferon/ribavirin era due to poor tolerability and lower efficacy. Our aim was to determine the effectiveness treatment completion, and safety of sofosbuvir/ledipasvir (SOF/LDV) and paritaprevir/ritonavir/ombitasvir/dasabuvir (PrOD) regimens in persons with CKD. Methods We identified all persons started on a SOF/LDV or PrOD regimen in ERCHIVES before 30 April 2016. We excluded those with missing HCV genotype, or eGFR values. We determined treatment completion, sustained virologic response (SVR) rates and proportion of persons with worseningrenal function or developing grade 3/4 anemia. Results We identified 9,837 persons on SOF/LDV, 3,826 on SOF/LDV+RBV, 1,017 on PrOD and 2,944 on PrOD+RBV. Genotype 1a was the predominant genotype for SOF/LDV+RBV (77.3% no RBV; 70.0% with RBV) and PrOD+RBV (79.5%) groups, while only 4.3% of PrOD with no RBV group were genotype 1a. Among treated patients, the prevalence of patients with stage 4–5 CKD was 0.8% (SOF/LDV + RBV), 1.1% (SOF/LDVno RBV), 2.2% (PrOD +RBV) and 5.4% (PrOD no RBV). Among 13,663 total persons on SOF/LDV, 67.8% completed treatment while the treatment completion rate of those on PrOD was 74.0% (N = 2,932/3,961) (Table 1). The overall SVR rates of persons on SOF/LDV or PrOD regimens were 96.3%. A drop in treatment completion rates was seen in CKD stage 4–5 and those on PrOD+RBV, but the impact of RBV on SVR was unclear. While about one-third of the persons with a CKD stage 1–2 experienced a >10 mL/minute/1,73m2, about 15% decline among those with CKD stage 3. The incidence of grade3/4 anemia by CKD stages increased significantly across the treatment groups. Grade 3/4 anemia ranged from 9.7% (SOF/LDV) to 21.8% (PrOD) among patients with CKD stage 4–5 (Table 2). Conclusion SVR rates among persons treated with SOF/LDV or PrOD were high in the CKD population despite 22% not completing the treatment regimen. Incidence of grade3/4 anemia increased significantly in CKD stage 4–5 across the treatment groups. Disclosures A. Butt, Merck: Investigator, Grant recipient.A. Puenpatom, Merck: Employee, Salary. J. M. Arduino, Merck: Employee, Salary. R. Kumar, Merck: Employee, Salary

Background Reactivation of HBV infection has been reported in patients with HCV treated with newer directly acting antiviral agents (DAAs). Magnitude of this problem and its consequences are not fully understood. Methods Using ERCHIVES, a well-established national database of HCV infected Veterans, we identified all persons who received DAA treatment for >28 days. We determined the proportion of patients who had HBV viral reactivation (≥1 log10 increase in HBV DNA from baseline), seroconversion (from HBsAg or HBeAg seronegative to seropositive), or flare of hepatitis (HBV viral reactivation plus ALT increase ≥10 times baseline value) at anytime after initiating DAA treatment. We also determined factors associated with HBVr using Cox regression analysis. Results We identified 43,137 persons on DAA therapy. Among those with available follow-up data, overall HBV reactivation was observed in 795 persons. HBV viral reactivation was observed in 4.8% (17/352), clinical hepatitis in 0.3% (1/350), seroconversion in 16.0% (695/4339) and ALT flare in 0.2% (85/41652). In a Cox proportional hazards model, factors associated with increased risk of HBV reactivation were black race, male sex, alcohol use or dependence, and detectable HBV DNA at baseline (table). Treatment with any regimen was associated with a significantly lower risk (number of persons on sofosbuvir/daclatasvir and elbasvir/grazoprevir were small to make meaningful inferences) of HBV reactivation. Conclusion Among HCV infected persons treated with a DAA regimen, HBV viral reactivation and HBV seroconversion are common, but clinical hepatitis or ALT flares are rare. DAA regimens are not associated with HBV reactivation. Disclosures A. Butt, Merck: Investigator, Grant recipient

Background. End-stage liver disease (ESLD) is an important cause of morbidity among human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients. Qua.jpegying the risk of this outcome over time could help determine which coinfected patients should be targeted for risk factor modification and HCV treatment. We evaluated demographic, clinical, and laboratory variables to predict risk of ESLD in HIV/HCV-coinfected patients receiving antiretroviral therapy (ART). Methods. We conducted a retrospective cohort study among 6016 HIV/HCV-coinfected patients who received ART within the Veterans Health Administration between 1997 and 2010. The main outcome was incident ESLD, defined by hepatic decompensation, hepatocellular carcinoma, or liver-related death. Cox regression was used to develop prognostic models based on baseline demographic, clinical, and laboratory variables, including FIB-4 and aspartate aminotransferase-to-platelet ratio index, previously validated markers of hepatic fibrosis. Model performance was assessed by discrimination and decision curve analysis. Results. Among 6016 HIV/HCV patients, 532 (8.8%) developed ESLD over a median of 6.6 years. A model comprising FIB-4 and race had modest discrimination for ESLD (c-statistic, 0.73) and higher net benefit than alternative strategies of treating no or all coinfected patients at relevant risk thresholds. For FIB-4 >3.25, ESLD risk ranged from 7.9% at 1 year to 26.0% at 5 years among non-blacks and from 2.4% at 1 year to 14.0% at 5 years among blacks. Conclusions. Race and FIB-4 provided important predictive information on ESLD risk among HIV/HCV patients. Estimating risk of ESLD using these variables could help direct HCV treatment decisions among HIV/HCV-coinfected patients.

Background Viral central nervous system (CNS) infections are common causes of morbidity and mortality globally. There are no existing data about viral CNS infections in Gulf Cooperation Council countries. We conducted this study to determine the etiology, clinical and epidimiological characteristics, and outcomes of viral central nerveous system infection in patients in Qatar. Methods We retrospectively evaluated all cerebrospinal fluid findings from January 2011–March 2015 at any of the 7 hospitals in the Hamad Medical Corporation. We included those with an abnormal CSF findings and excluded those with missing medical records, no clinical evidence of CNS infection and those with proven bacterial infection. Based on pre-defined clinical and CSF (lab, culture, PCR) criteria, patients were classified as having meningitis, meningoencephalitis, encephalitis or myelitis. We reviewed the laboratory results to determine the proportion of persons with confirmed viral etiology. Results Among 7690 patients with available CSF results, 550 cases met the case definition criteria for viral CNS infection (meningitis 75%; meningoencephalitis 16%; encephalitis 9%; myelitis 0.4%). Two-thirds (65%) were male and 50% were between 16-60 years old. The most common presenting signs and symptoms are listed in the table. Persons of Southeast Asian origin accounted for 39.6% of all infections. A definitive virologic etiologic agent was found in 38%, with enterovirus being the most common (44.3%) followed by Epstein–Barr virus (31%) and varicella-zoster virus (12.4%). The clinical outcome was overall good, only 2 cases died and the rest were discharged to home. Among those with confirmed viral etiology, 83.8% received ceftriaxone (mean duration 7.3 ± 5.2 days), 38% received vancomycin (mean duration 2.7 ± 5.4 days) and 38% received at least one other antibiotic. Conclusion Viral etiology is common among those evaluated for CNS infection in Qatar, and is most commonly seen in Southeast Asian immigrants. Clinical outcomes are generally excellent in this group of patients. Antibiotics are overly used even when a viral etiology is confirmed. There is a need for clinician education regarding etiology and treatment of CNS infections. Disclosures A. Butt, Merck: Investigator, Grant recipient