Larry A. Mole

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.

The Impact of Active Herpes Simplex Virus Infection on Human Immunodeficiency Virus Load

The effect of a concurrent herpes simplex virus (HSV) infection on human immunodeficiency virus type 1 (HIV-1) load was evaluated. Sixteen subjects were identified with an active HSV infection and had pre-outbreak, acute-phase, and post-outbreak plasma (n = 16) and peripheral blood mononuclear cell (PBMC) (n = 8) samples for evaluation. All subjects were treated for an acute HSV outbreak with acyclovir for 10 days, followed by chronic prophylaxis. HIV-1 plasma RNA levels were determined by branched DNA, and intracellular HIV gag mRNA copy numbers were determined by quantitative reverse transcriptase-polymerase chain reaction ELISA. Plasma virus load increased a median of 3.4-fold during the acute outbreak (range, 0- to 10-fold; P = .002), while post-outbreak levels (30-45 days after the appearance of lesions) remained above pre-outbreak, baseline levels in some subjects. Intracellular HIV gag mRNA increased during the outbreak as well. Thus, an acute HSV episode can result in increased HIV transcription and plasma virus load.

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)

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).

National quality forum performance measures for HIV/AIDS care: the Department of Veterans Affairs' experience.

BACKGROUND Information technology promises to improve health care through reporting of standardized quality-of-care measures. In 2008, the National Quality Forum (NQF) first endorsed performance measures for human immunodeficiency virus (HIV)/AIDS care. Little is known about performance on these measures in routine medical practice. We assessed performance using available electronic data for the large, diverse population with HIV in the Department of Veterans Affairs (VA) and evaluated the influence of patient and resource factors. METHODS In a retrospective analysis of observational data for 21 564 patients with HIV receiving VA medical care in 2008, we determined performance rates for 10 NQF measures for HIV/AIDS care for the VA nationwide and for 73 facilities with caseloads of 100 or more patients with HIV. RESULTS National rates for 6 measures were greater than 80%; the remaining measures and their rates were as follows: annual syphilis screening (54%), tuberculosis screening (65%), Pneumocystis pneumonia prophylaxis (72%), and HIV RNA control (73%). For all measures, rates varied across facilities. In multivariate logistic regression models, African Americans and hard drug users were less likely to access care and less likely to receive HIV-specific care but more likely to receive indicated general medical care. Resource factors (number of primary care/infectious disease outpatient visits, duration of care, and larger facility caseload) were associated with increased likelihood of receipt of indicated general and HIV-specific care. CONCLUSIONS National performance rates were generally high, but variation in rates across facilities revealed room for improvement. Both patient and resource factors had an impact on the likelihood of receipt of indicated care.

Impact of Race/Ethnicity and Gender on HCV Screening and Prevalence Among US Veterans in Department of Veterans Affairs Care

OBJECTIVES We assessed HCV screening and prevalence among veterans and estimated the potential impact of complete birth cohort screening, accounting for the disparate HCV disease burden by race/ethnicity and gender. METHODS We used the Department of Veterans Affairs (VA) Corporate Data Warehouse to identify birth dates, gender, race/ethnicity, and laboratory tests for veterans with at least 1 VA outpatient visit in 2012. We calculated HCV screening rates, prevalence, and HCV infection incident diagnosis. RESULTS Among 5,499,743 veterans, 54.7% had HCV screening through the VA. In more than 2.9 million veterans screened, HCV prevalence was 6.1% overall and highest among Blacks (11.8%), particularly Black men born in 1945 to 1965 (17.7%). HCV infection incident diagnosis in 2012 was 5.9% for men and 2.3% for women. An estimated additional 48,928 male veterans, including 12,291 Black men, and 1484 female veterans would potentially be identified as HCV infected with full birth cohort screening. CONCLUSIONS HCV prevalence was markedly elevated among veterans born in 1945 to 1965, with substantial variation by race/ethnicity and gender. Full adoption of birth cohort screening may reveal substantial numbers of veterans with previously unknown HCV infection.

Decreased medical expenditures for care of HIV-seropositive patients. The impact of highly active antiretroviral therapy at a US Veterans Affairs Medical Center.

AbstractObjective: To identify any changes in expenditures and in morbidity and mortality with the progression of treatment of the HIV-seropositive population from monotherapy with a nucleoside reverse transcriptase inhibitor (NRTI) [1993] through dual NRTI therapy (1995) to highly active antiretroviral therapy (HAART) [1997]. Design and setting: This study retrospectively compared 3 separate years of the total expenditures encountered in the management of HIV-seropositive individuals seen at a US Veterans Affairs Medical Center. Interventions: Utilising a computerised hospital database, we identified those patients with HIV-related International Classification of Diseases, version 9 (ICD-9) codes and collected all healthcare-related expenditure data. The 3 eras selected for comparison were controlled for similar utilisation of prophylaxis against opportunistic infections, access to investigational antivirals, consistency between primary care providers and distribution of new anti-HIV therapies relative to that era. Cost data for inpatient and outpatient activities (visits and admissions) were derived from actual expenditures. Major categories were then compared, including total inpatient/outpatient expenditures and utilisation, laboratory and prescription costs, and morbidity and mortality rates. Main outcome measures and results: The 3 periods had similar patient populations, with 86, 86 and 82% of patients in 1993, 1995 and 1997, respectively, having some degree of immunosuppression (defined as CD4+ lymphocyte counts <500 cells/mm3). Morbidity and mortality were not changed by the addition of dual NRTI therapy. HAART therapy produced 60 and 70% declines in relative mortality when compared with the single and dual NRTI eras. Dual NRTI or HAART therapy decreased overall expenditures as compared with NRTI monotherapy. HIV-related outpatient resource utilisation other than pharmacy and laboratory costs fell by 25 and 59% in 1997 as compared with 1993 and 1995, respectively. The greatest fall in resource utilisation was for inpatient bed-days of care, where the average cost per patient fell by