Lisa I. Backus

Retention in Care: A Challenge to Survival with HIV Infection

BACKGROUND Patients with human immunodeficiency virus (HIV) infection need lifelong medical care, but many do not remain in care. The effect of poor retention in care on survival is not known, and we sought to quantify that relationship. METHODS We conducted a retrospective cohort study involving persons newly identified as having HIV infection during 1997-1998 at any United States Department of Veterans Affairs hospital or clinic who started antiretroviral therapy after 1 January 1997. To be included in the study, patients had to have seen a clinician at least once after receiving their first antiretroviral prescription and to have survived for at least 1 year. Patients were divided into 4 groups on the basis of the number of quarters in that year during which they had at least 1 HIV primary care visit. Survival was measured through 2002. Because data were available for only a small number of women, female patients were excluded from the study. RESULTS A total of 2619 men were followed up for a mean of >4 years each. The median baseline CD4(+) cell count and median log(10) plasma HIV concentration were 228x10(6) cells/L and 4.58 copies/mL, respectively. Thirty-six percent of the patients had visits in <4 quarters, and 16% died during follow-up. In Cox multivariate regression analysis, compared with persons with visits in all 4 quarters during the first year, the adjusted hazard ratio of death was 1.42 (95% confidence interval, 1.11-1.83; P<.01), 1.67 (95% confidence interval, 1.24-2.25; P<.001), and 1.95 (95% confidence interval, 1.37-2.78; P<.001) for persons with visits in 3 quarters, 2 quarters, and 1 quarter, respectively. CONCLUSIONS Even in a system with few financial barriers to care, a substantial portion of HIV-infected patients have poor retention in care. Poor retention in care predicts poorer survival with HIV infection. Retaining persons in care may improve survival, and optimal methods to retain patients need to be defined.

A Sustained Virologic Response Reduces Risk of All-Cause Mortality in Patients With Hepatitis C

BACKGROUND & AIMS The effectiveness of hepatitis C virus (HCV) treatment with pegylated interferon and ribavirin usually is evaluated by the surrogate end point of sustained virologic response (SVR), although the ultimate goal of antiviral treatment is to reduce mortality. The impact of SVR on all-cause mortality is not well documented by HCV genotype or in populations in routine medical practice with substantial comorbidities. METHODS From the US Department of Veterans Affairs (VA), we identified all patients infected with HCV genotypes 1, 2, or 3, without human immunodeficiency virus co-infection or hepatocellular carcinoma before HCV treatment with pegylated interferon and ribavirin, who started HCV treatment from January 2001 to June 2007, stopped treatment by June 2008, and had a posttreatment HCV RNA test result of SVR or no SVR. Mortality data from VA and non-VA sources were available through 2009. RESULTS HCV genotypes 1, 2, or 3 cohorts consisted of 12,166, 2904, and 1794 patients, respectively, with SVR rates of 35%, 72%, and 62%, respectively. Each cohort had high rates of comorbidities. During a median follow-up period of approximately 3.8 years, 1119 genotype-1, 220 genotype-2, and 196 genotype-3 patients died. In genotype-specific multivariate survival models that controlled for demographic factors, comorbidities, laboratory characteristics, and treatment characteristics, an SVR was associated with substantially reduced mortality risk for each genotype (genotype-1 hazard ratio, 0.70; P < .0001; genotype-2 hazard ratio, 0.64; P = .006; genotype-3 hazard ratio, 0.51; P = .0002). CONCLUSIONS An SVR reduced mortality among patients infected with HCV of genotypes 1, 2, or 3 who were being treated by routine medical practice and had substantial comorbidities.

Predictors of response of U.S. veterans to treatment for the hepatitis C virus

The currently recommended treatment for hepatitis C virus (HCV) infection is pegylated interferon alfa (PEG‐INF) and ribavirin, which can be difficult to tolerate. More information about predicting sustained virologic response (SVR) may allow more informed treatment decisions to be made. This retrospective observational cohort study identified predictors of SVR to PEG‐INF and ribavirin in routine medical practice at 121 Department of Veterans Affairs facilities. Among 5,944 patients infected with HCV genotypes 1, 2, or 3 who had been treated with PEG‐INF and ribavirin, SVR rates were 20%, 52%, and 43%, respectively, and discontinuation rates were 68% (prior to 48 weeks), 34% (24 weeks), and 41% (24 weeks), respectively. In multivariate analysis, significant predictors of decreased likelihood of genotype 1 patients having an SVR were being African American, clinical liver disease, diabetes, low cholesterol, low hemoglobin, low platelet count, and treatment at a low‐volume facility. Predictors of increased likelihood of genotype 1 patients having an SVR were low‐level HCV viremia, elevated ALT quotient, and receiving PEG‐INF 2A (rather than 2B). For genotype 2 patients, increasing body mass index, prior use of interferon, and low platelet count were negative predictors; only low‐level HCV viremia was a positive predictor. For genotype 3 patients, only receiving PEG‐INF 2A affected the likelihood of an SVR; its effect was positive. Conclusion: Among patients for whom HCV treatment is initiated during routine medical care, multiple factors including form of PEG‐INF received affect the SVR rate for genotype 1 patients. Few of these factors affect the rate for genotype 2 patients, and even fewer do so for genotype 3 patients. (HEPATOLOGY 2007.)

Clinical Case Registries: Simultaneous Local and National Disease Registries for Population Quality Management

The Department of Veterans Affairs (VA) has a system-wide, patient-centric electronic medical record system (EMR) within which the authors developed the Clinical Case Registries (CCR) to support population-centric delivery and evaluation of VA medical care. To date, the authors have applied the CCR to populations with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Local components use diagnosis codes and laboratory test results to identify patients who may have HIV or HCV and support queries on local care delivery with customizable reports. For each patient in a local registry, key EMR data are transferred via HL7 messaging to a single national registry. From 128 local registry systems, over 60,000 and 320,000 veterans in VA care have been identified as having HIV and HCV, respectively, and entered in the national database. Local and national reports covering demographics, resource usage, quality of care metrics and medication safety issues have been generated.

Real‐world effectiveness of ledipasvir/sofosbuvir in 4,365 treatment‐naive, genotype 1 hepatitis C‐infected patients

Real‐world effectiveness data are needed to inform hepatitis C virus (HCV) treatment decisions. The uptake of ledipasvir/sofosbuvir (LDV/SOF) regimens across health care settings has been rapid, but variations often occur in clinical practice. The aim of this study was to assess sustained virologic response (SVR) of LDV/SOF±ribavirin (RBV) in routine medical practice. This observational, intent‐to‐treat cohort was comprised of 4,365 genotype 1, treatment‐naive, HCV‐infected veterans treated with LDV/SOF±RBV. SVR rates were 91.3% (3,191/3,495) for LDV/SOF and 92.0% (527/573) for LDV/SOF+RBV (P = 0.65). African American race (odds ratio 0.70, 95% confidence interval 0.54‐0.90, P  = 0.004) and FIB‐4 >3.25 (odds ratio 0.56, 95% confidence interval 0.43‐0.71, P < 0.001) were independently associated with decreased likelihood of SVR; age, sex, body mass index, decompensated liver disease, diabetes, genotype 1 subtype, and regimen did not predict SVR. In models limited to those who completed 12 weeks of treatment, African American race was no longer a significant predictor of SVR but FIB‐4 >3.25 (odds ratio 0.35, 95% confidence interval 0.24‐0.50, P < 0.001) remained. Among those without cirrhosis (defined by FIB‐4 ≤3.25) and with baseline HCV RNA<6,000,000 IU/mL, SVR rates were 93.2% (1,020/1,094) for those who completed 8 weeks of therapy and 96.6% (875/906) for those who completed 12 weeks of therapy (P = 0.001). Conclusions: In this real‐world cohort, SVR rates with LDV/SOF±RBV nearly matched the rates reported in clinical trials and were consistently high across all subgroups; those without cirrhosis but with HCV RNA<6,000,000 IU/mL were less likely to achieve SVR with 8 weeks compared to 12 weeks of therapy, although the numeric difference in SVR rates was small. (Hepatology 2016;64:405‐414)

Predictors of retention in HIV care among a national cohort of US veterans.

Abstract Background: Poor retention in HIV care leads to poor survival. The predictors of poor retention in HIV care are not well understood, especially from US nationwide datasets. We determined the predictors of poor retention in HIV care among a group of US veterans and examined whether poor retention was confounded by other predictors of survival. Methods: We conducted a retrospective cohort study of 2,619 male US veterans who started antiretroviral therapy after January 1, 1998. Poor retention in HIV care was defi ned as having had at least 1 quarter-year without any primary care visit in the year after starting antiretroviral therapy. Survival was assessed through 2002. Logistic regression and Cox models were constructed. Results: Thirty-six percent of patients had poor retention in care. In multivariable analysis, younger age, Black race/ethnicity, CD4 cell count >350 ×106/L, hepatitis C infection, and illicit drug use were predictive of poor retention in care. Having a chronic medical comorbidity and being identifi ed as a man having sex with men (MSM) were associated with improved retention in care. In multivariable survival analyses, poor retention in care was not a confounder or moderator for other variables that predicted survival. Conclusions: Retention in HIV care is an independent predictor of survival. As routine HIV screening increases, more people with the characteristics predictive of poor retention in care will be identifi ed. Interventions to improve retention in care are needed.

HIV, hepatitis C and HIV/hepatitis C virus co-infection in vulnerable populations

Objective:To describe basic patient demographic and clinical characteristics of HIV-infected and HIV/hepatitis C virus (HCV)-co-infected patients receiving care in the Department of Veterans Affairs (VA) with a focus on some patient factors that place such patients at an increased risk of poor health outcomes. Design:An observational retrospective cohort study. Methods:The study cohort consisted of veterans in the VA Immunology Case Registry who received care in the VA in 2002. Results:Of 18 349 HIV-infected patients, 6782 (37.0%) were HCV seropositive. Compared with HIV-alone-infected patients, HIV/HCV-co-infected patients were older, more likely to be men, more likely to be black or Hispanic, and more likely to report intravenous drug use as a risk factor for HIV acquisition. HIV/HCV-co-infected patients were more likely to have diagnoses of mental health illness, depression, alcohol abuse, substance abuse and hard drug abuse compared with HIV-alone-infected patients. Co-infected patients were less likely to have a history of an AIDS opportunistic infection ever and were less likely to have received HIV antiretroviral drugs in 2002. Conclusion:The VAs HIV and HIV/HCV-co-infected patient populations have very high rates of additional comorbid conditions that complicate both the pharmacological therapy and clinical course of both HIV and HCV infections. Given the overlap in viral illness and comorbidities, optimal models of integrated care need to be developed for populations with HIV, HCV, and HIV/HCV co-infection and who need substance abuse treatment or mental healthcare.

Effectiveness of sofosbuvir-based regimens in genotype 1 and 2 hepatitis C virus infection in 4026 U.S. Veterans

Real‐world effectiveness data are needed to inform hepatitis C virus (HCV) treatment decisions.

Comparative effectiveness of the hepatitis C virus protease inhibitors boceprevir and telaprevir in a large U.S. cohort

Limited data exist on the effectiveness of boceprevir and telaprevir in routine practice.

Evaluation of hepatitis B reactivation among 62,920 veterans treated with oral hepatitis C antivirals

Reactivation of hepatitis B virus (HBV) has been reported in hepatitis C virus–infected individuals receiving direct‐acting antiviral (DAA) therapy. The overall risk among patients with current or prior HBV infection in the context of DAA treatment is unknown. The aim of this evaluation was to identify and characterize HBV reactivation among veterans treated with oral DAA therapy. This retrospective evaluation included 62,290 hepatitis C virus–infected veterans completing oral DAA treatment. Baseline HBV infection status for each veteran was identified from HBV laboratory data performed prior to DAA initiation. To assess for HBV reactivation and hepatitis we identified all hepatitis B surface antigen (HBsAg), HBV DNA, and alanine aminotransferase results obtained while on DAA treatment or 7 days after. HBV reactivation was defined as a >1000 IU/mL increase in HBV DNA or HBsAg detection in a person who was previously negative. Prior to DAA treatment 85.5% (53,784/62,920) had HBsAg testing and 0.70% (377/53,784) were positive; 84.6% (53,237/62,920) had a hepatitis B surface antibody test, of which 42.2% (22,479/53,237) were positive. In all, 9 of 62,290 patients treated with DAAs had evidence of HBV reactivation occurring while on DAA treatment. Eight occurred in patients known to be HBsAg‐positive, and 1 occurred in a patient known to be isolated hepatitis B core antibody–positive. Seventeen other patients had small increases in HBV DNA levels that did not qualify as HBV reactivation. Only 3 of the 9 patients identified with HBV reactivation in this cohort exhibited peak alanine aminotransferase elevations >2 times the upper limit of normal. Conclusion: HBV reactivation of varying severity, even in the setting of isolated hepatitis B core antibody, with or without accompanying hepatitis can occur—though the occurrence of accompanying severe hepatitis was rare. (Hepatology 2017;66:27–36).