Developing Treatment Guidelines During a Pandemic Health Crisis: Lessons Learned From COVID-19.

The development of the National Institutes of Health (NIH) COVID-19 Treatment Guidelines began in March 2020 in response to a request from the White House Coronavirus Task Force. Within 4 days of the request, the NIH COVID-19 Treatment Guidelines Panel was established and the first meeting took place (virtually-as did subsequent meetings). The Panel comprises 57 individuals representing 6 governmental agencies, 11 professional societies, and 33 medical centers, plus 2 community members, who have worked together to create and frequently update the guidelines on the basis of evidence from the most recent clinical studies available. The initial version of the guidelines was completed within 2 weeks and posted online on 21 April 2020. Initially, sparse evidence was available to guide COVID-19 treatment recommendations. However, treatment data rapidly accrued based on results from clinical studies that used various study designs and evaluated different therapeutic agents and approaches. Data have continued to evolve at a rapid pace, leading to 24 revisions and updates of the guidelines in the first year. This process has provided important lessons for responding to an unprecedented public health emergency: Providers and stakeholders are eager to access credible, current treatment guidelines; governmental agencies, professional societies, and health care leaders can work together effectively and expeditiously; panelists from various disciplines, including biostatistics, are important for quickly developing well-informed recommendations; well-powered randomized clinical trials continue to provide the most compelling evidence to guide treatment recommendations; treatment recommendations need to be developed in a confidential setting free from external pressures; development of a user-friendly, web-based format for communicating with health care providers requires substantial administrative support; and frequent updates are necessary as clinical evidence rapidly emerges.

Impact of Sustained Virologic Response with Direct-Acting Antiviral Treatment on Mortality in Patients with Advanced Liver Disease.

The impact of sustained virologic response (SVR) on mortality after direct-acting antiviral treatment is not well documented. This study evaluated the impact of direct-acting antiviral-induced SVR on all-cause mortality and on incident hepatocellular carcinoma (HCC) in 15,059 hepatitis C virus-infected patients with advanced liver disease defined by a FIB-4 >3.25. Overall, 1,067 patients did not achieve SVR (no SVR) and 13,992 patients achieved SVR. In a mean follow-up period of approximately 1.6 years, 195 no SVR patients and 598 SVR patients died. Mortality rates were 12.3 deaths/100 patient years of follow-up for no SVR patients and 2.6 deaths/100 patient years for SVR patients, a 78.9% reduction (P < 0.001). Among patients without a prior diagnosis of HCC, 140 no SVR patients and 397 SVR patients were diagnosed with incident HCC. HCC rates were 11.5 HCCs/100 patient years for no SVR patients and 1.9 HCCs/100 patient years for SVR patients, an 83.5% reduction (P < 0.001). In multivariable Cox proportional hazard models controlling for baseline demographics, clinical characteristics, and comorbidities, SVR was independently associated with reduced risk of death compared to no SVR (hazard ratio, 0.26; 95% confidence interval, 0.22-0.31; P < 0.001). A history of decompensated liver disease (hazard ratio, 1.57; 95% confidence interval, 1.34-1.83; P < 0.001) and decreased albumin (hazard ratio, 2.70 per 1 g/dL decrease; 95% confidence interval, 2.38-3.12; P < 0.001) were independently associated with increased risk of death. Conclusion: Those achieving SVR after direct-acting antiviral treatment had significantly lower all-cause mortality and lower incident HCC rates than those who did not achieve SVR.

Real-world effectiveness of daclatasvir plus sofosbuvir and velpatasvir/sofosbuvir in hepatitis C genotype 2 and 3.

BACKGROUND & AIM: Understanding the real-world effectiveness of all-oral hepatitis C virus (HCV) regimens informs treatment decisions. We evaluated the effectiveness of daclatasvir + sofosbuvir ±â€¯ribavirin (DCV + SOF ±â€¯RBV) and velpatasvir/sofosbuvir (VEL/SOF) ±â€¯RBV in patients with genotype 2 and genotype 3 infection treated in routine practice. METHODS: This observational analysis was carried out in an intent-to-treat cohort of patients with HCV genotype 2 and genotype 3. Sustained virologic response (SVR) analysis was performed in 5,400 patients initiated on DCV + SOF ±â€¯RBV or VEL/SOF ±â€¯RBV at any Department of Veterans Affairs facility. RESULTS: For genotype 2, SVR rates did not differ between DCV + SOF (94.5%) and VEL/SOF (94.4%) or between DCV + SOF + RBV (88.1%) and VEL/SOF + RBV (89.5%). For genotype 3, SVR rates did not differ between DCV + SOF (90.8%) and VEL/SOF (92.0%) or between DCV + SOF + RBV (88.1%) and VEL/SOF + RBV (86.4%). In multivariate models of patients with genotype 2 and 3 infection, the treatment regimen was not a significant predictor of the odds of SVR. For genotype 3, significant predictors of reduced odds of SVR were prior HCV treatment-experience (odds ratio [OR] 0.51, 95% CI 0.36-0.72; p <0.001), FIB-4 >3.25 (OR 0.60; 95%CI 0.43-0.84; p = 0.002) and a history of decompensated liver disease (OR 0.68; 95%CI 0.47-0.98; p = 0.04). For patients with genotype 2 and 3, treated with VEL/SOF ±â€¯RBV, 89% and 85% received 12-weeks of treatment, respectively. For DCV + SOF ±â€¯RBV, 56% and 20% of patients with HCV genotype 2 received 12-weeks and 24-weeks of treatment, respectively; while 53% and 23% of patients with HCV genotype 3 received 12-weeks and 24-weeks, with most direct-acting antiviral experienced patients receiving 24-weeks. CONCLUSIONS: In patients infected with HCV genotype 2 and 3, DCV + SOF ±â€¯RBV and VEL/SOF ±â€¯RBV produced similar SVR rates within each genotype, and the regimen did not have a significant impact on the odds of SVR. For patients with genotype 3, prior treatment-experience and advanced liver disease were significant predictors of reduced odds of SVR regardless of regimen. LAY SUMMARY: In clinical practice, cure rates for hepatitis C virus (HCV) genotype 2 were 94% and cure rates for HCV genotype 3 were 90%. The chance of achieving cure was the same whether a person received daclatasvir plus sofosbuvir or velpatasvir/sofosbuvir. Ribavirin did not affect cure rates. The chance of a cure was lowest in people who had received HCV medication in the past.

Real-world effectiveness of sofosbuvir/velpatasvir/voxilaprevir in 573 direct-acting antiviral experienced hepatitis C patients.

Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) provides a needed hepatitis C virus (HCV) antiviral option for direct-acting antiviral (DAA)-experienced patients. We evaluated the effectiveness of SOF/VEL/VOX for 12 weeks in DAA-experienced patients with genotype 1-4 treated in clinical practice. In this observational cohort analysis from the Veterans Affairs' Clinical Case Registry, 573 DAA-experienced patients initiating SOF/VEL/VOX were included: 490 genotype 1, 20 genotype 2, 51 genotype 3 and 12 genotype 4. Rates of cirrhosis were 32.7%, 30.0%, 49.0% and 58.3%; rates of prior NS5A-experience were 100.0%, 95.0%, 90.2% and 100.0% for genotypes 1-4, respectively. Overall SVR rates were 90.7% (429/473), 90.0% (18/20), 91.3% (42/46) and 100.0% (12/12) for genotypes 1-4, respectively, and were 91.3% (274/300), 88.9% (16/18), 90.2% (37/41) and 100.0% (11/11) for those with prior NS5A + NS5B experience. For genotype 1, SVR rates were similar in patients with prior regimens of ledipasvir/SOF (90.6%, 298/329), elbasvir/grazoprevir (91.2%, 73/80) and ombitasvir/paritaprevir/ritonavir/dasabuvir (90.9%, 70/77). SVR rates in genotype 1, 2 and 3 patients with prior SOF/VEL experience were 78.9% (15/19), 86.7% (13/15) and 84.6% (11/13). In genotype 1-4 patients completing 12 weeks of SOF/VEL/VOX, overall SVR rates were 95.1% (409/430), 89.5% (17/19), 93.3% (42/45) and 100% (12/12). In this diverse real-world cohort of heavily NS5A pretreated patients, SOF/VEL/VOX SVR rates in DAA-experienced patients were high across all genotypes. Genotype 1 patients who had prior experience with the most commonly prescribed NS5A regimens achieved similarly high SVR rates when retreated with SOF/VEL/VOX. For genotypes 1, 2 and 3, patients with prior SOF/VEL experience had lower SVR rates.

Direct-acting antiviral sustained virologic response: Impact on mortality in patients without advanced liver disease.

The impact of sustained virologic response (SVR) on mortality after direct-acting antiviral (DAA) treatment is not well documented in patients without advanced liver disease and affects access to treatment. This study evaluated the impact of SVR achieved with interferon-free DAA treatment on all-cause mortality in hepatitis C virus-infected patients without advanced liver disease. This observational cohort analysis was comprised of 103,346 genotype 1, 2, and 3, hepatitis C virus-monoinfected patients without advanced liver disease, defined by FIB-4 ≤3.25 and no diagnosis of cirrhosis, hepatic decompensation, or hepatocellular carcinoma or history of liver transplantation, identified from the Veterans Affairs Hepatitis C Clinical Case Registry. Among 40,664 patients treated with interferon-free DAA regimens, 39,374 (96.8%) achieved SVR and 1,290 (3.2%) patients were No SVR; 62,682 patients constituted the untreated cohort. The mortality rate for SVR patients of 1.18 deaths/100 patient-years was significantly lower than the rates for both No SVR patients (2.84 deaths/100 patient-years; P < 0.001) and untreated patients (3.84 deaths/100 patient-years; P < 0.001). SVR patients with FIB-4 <1.45 and 1.45-3.25 had a 46.0% (P = 0.036) and 63.2% (P < 0.001) reduction in mortality rates, respectively, compared to No SVR patients and 66.7% (P < 0.001) and 70.6% (P < 0.001) reduction in mortality rates, respectively, compared to untreated patients. In multivariate Cox proportional hazard models controlling for baseline demographics, clinical characteristics, and comorbidities, SVR was independently associated with reduced risk of death compared to No SVR (hazard ratio, 0.44; 95% confidence interval, 0.32-0.59; P < 0.001) and compared to untreated patients (hazard ratio, 0.32; 95% confidence interval, 0.29-0.36; P < 0.001). CONCLUSION: Successfully treating hepatitis C virus with DAAs in patients without clinically apparent advanced liver disease translates into a significant mortality benefit. (Hepatology 2018).

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).

Curing Hepatitis C Virus Infection: Best Practices From the U.S. Department of Veterans Affairs.

The U.S. Department of Veterans Affairs (VA) is the nation's largest care provider for hepatitis C virus (HCV)-infected patients and is uniquely suited to inform national efforts to eliminate HCV. An extensive array of delivery of services, policy guidance, outreach efforts, and funding has broadened the reach and capacity of the VA to deliver direct-acting antiviral (DAA) HCV therapy, supported by an infrastructure to effectively implement change and informed by extensive population health data analysis. The VA has treated more than 92 000 HCV-infected veterans since all-oral DAAs became available in January 2014, with cure rates exceeding 90%; only 51 000 veterans in VA care are known to remain potentially eligible for treatment. Key actions advancing the VA's aggressive treatment of HCV infection that are germane to non-VA settings include expansion of treatment capacity through the use of nonphysician providers, video telehealth, and electronic technologies; expansion of integrated care to address psychiatric and substance use comorbidities; and electronic data tools for patient tracking and outreach. A critical component of effective implementation has been building infrastructure through the creation of regional multidisciplinary HCV Innovation Teams, whose system redesign efforts have produced innovative HCV practice models addressing gaps in care while providing more efficient and effective HCV management for the populations they serve. Financing for HCV treatment and infrastructure resources coupled with reduced drug prices has been paramount to the VA's success in curing HCV infection. The VA is poised to share and extend best practices to other health care organizations and providers delivering HCV care, contributing to a concerted effort to reduce the overall burden of HCV infection.

Effectiveness of All-Oral Antiviral Regimens in 996 Human Immunodeficiency Virus/Hepatitis C Virus Genotype 1-Coinfected Patients Treated in Routine Practice.

BACKGROUND.: Large cohorts are needed to assess human immunodeficiency virus (HIV)/hepatitis C virus (HCV) real-world treatment outcomes. We examined the effectiveness of ledipasvir/sofosbuvir with or without ribavirin (LDV/SOF ± RBV) and ombitasvir/ paritaprevir/ritonavir plus dasabuvir (OPrD) ± RBV in HIV/HCV genotype 1 (GT1)-coinfected patients initiating HCV therapy in clinical practice. METHODS.: Observational intent-to-treat cohort analysis using the Veterans Affairs Clinical Case Registry to identify HIV/HCV GT1-coinfected veterans initiating 12 weeks of LDV/SOF ± RBV or OPrD ± RBV. Multivariate models of sustained virologic response (SVR) included age, race, cirrhosis, proton pump inhibitor (PPI) prescription, prior HCV treatment, body mass index, genotype subtype, and HCV treatment regimen. RESULTS.: Nine hundred ninety-six HIV/HCV GT1-coinfected veterans initiated therapy: 757 LDV/SOF, 138 LDV/SOF + RBV, 28 OPrD, and 73 OPrD + RBV. Overall SVR was 90.9% (823/905); LDV/SOF 92.1% (631/685), LDV/SOF + RBV 86.3% (113/131), OPrD 88.9% (24/27), and OPrD + RBV 88.7% (55/62). SVR was 85.9% (176/205) and 92.4% (647/700) in those with and without cirrhosis (P = .006). SVR was similar between African Americans (90.5% [546/603]) and all others (91.7% [277/302]). PPI use with LDV/SOF ± RBV did not affect SVR (89.7% [131/146] with PPI and 91.5% [613/670] without PPI). Cirrhosis was predictive of reduced SVR (0.51 [95% confidence interval {CI}, .31-.87]; P = .01). Median creatinine change did not differ among patients receiving LDV/SOF and tenofovir disoproxil fumarate (TDF) without a protease inhibitor (PI) (0.18 [interquartile range {IQR}, 0.08-0.30]; n = 372), LDV/SOF and TDF/PI (0.17 [IQR, 0.04-0.30]; n = 100), and LDV/SOF without TDF (0.15 [IQR, 0.00-0.30]; n = 423). CONCLUSIONS.: SVR rates in HIV/HCV GT1-coinfected patients were high. African American race or PPI use with LDV/SOF ± RBV was not associated with lower SVR rates, but cirrhosis was. Renal function did not worsen on LDV/SOF regimens with TDF.

Prevalence of Human Immunodeficiency Virus, Hepatitis C Virus, and Hepatitis B Virus Among Homeless and Nonhomeless United States Veterans.

BACKGROUND: Veterans are disproportionately affected by human immunodeficiency virus (HIV), hepatitis C virus (HCV), and hepatitis B virus (HBV). Homeless veterans are at particularly high risk for HIV, HCV, and HBV due to a variety of overlapping risk factors, including high rates of mental health disorders and substance use disorders. The prevalence of HIV, HCV, and HBV among homeless veterans nationally is currently unknown. This study describes national testing rates and prevalence of HIV, HCV, and HBV among homeless veterans. METHODS: Using data from the Department of Veterans Affairs (VA) Corporate Warehouse Data from 2015, we evaluated HIV, HCV, and HBV laboratory testing and infection confirmation rates and diagnoses on the Problem List for nonhomeless veterans and for veterans utilizing homeless services in 2015. RESULTS: Among 242740 homeless veterans in VA care in 2015, HIV, HCV, and HBV testing occurred in 63.8% (n = 154812), 78.1% (n = 189508), and 52.8% (n = 128262), respectively. The HIV population prevalence was 1.52% (3684/242740) among homeless veterans, compared with 0.44% (23797/5424685) among nonhomeless veterans. The HCV population prevalence among homeless veterans was 12.1% (29311/242740), compared with 2.7% (148079/5424685) among nonhomeless veterans, while the HBV population prevalence was 0.99% (2395/242740) for homeless veterans and 0.40% (21611/5424685) among nonhomeless veterans. CONCLUSIONS: To our knowledge this work represents the most comprehensive tested prevalence and population prevalence estimates of HIV, HCV, and HBV among homeless veterans nationally. The data demonstrate high prevalence of HIV, HCV, and HBV among homeless veterans, and reinforce the need for integrated healthcare services along with homeless programming.

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

UNLABELLED: 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).

Cascade of Care for Hepatitis C Virus Infection Within the US Veterans Health Administration.

OBJECTIVES: We measured the quality of HCV care using a cascade of HCV care model. METHODS: We estimated the number of patients diagnosed with chronic HCV, linked to HCV care, treated with HCV antivirals, and having achieved a sustained virologic response (SVR) in the electronic medical record data from the Veterans Health Administration's Corporate Data Warehouse and the HCV Clinical Case Registry in 2013. RESULTS: Of the estimated 233,898 patients with chronic HCV, 77% (181,168) were diagnosed, 69% (160,794) were linked to HCV care, 17% (39,388) were treated with HCV antivirals, and 7% (15,983) had achieved SVR. CONCLUSIONS: This Cascade of HCV Care provides a clinically relevant model to measure the quality of HCV care within a health care system and to compare HCV care across health systems.

Impact of provider type on hepatitis C outcomes with boceprevir-based and telaprevir-based regimens.

GOALS: To examine the effect of provider type on outcomes and safety in a large hepatitis C virus (HCV)-infected cohort treated in routine medical practice. BACKGROUND: Nonphysician providers (NPP) are uniquely positioned to expand health care infrastructure to meet HCV treatment demands. STUDY: Retrospective, observational cohort analysis of 820 HCV genotype 1-infected veterans initiated on peginterferon/ribavirin and boceprevir or telaprevir in routine medical practice at 94 VA facilities before January 1, 2012 and followed through July 30, 2013. Provider type was determined from prescription records and included physicians (MD) or NPPs (ie, nurse practitioners, physician assistants, and pharmacists). Inverse probability-of-treatment weighting and unweighted logistic regression analysis was used for comparison of sustained virologic response (SVR), treatment discontinuation rates, and adverse hematologic events. RESULTS: There was no significant difference in SVR by provider type overall (NPPs 52% vs. MDs 49%, P=0.33) and within patient subgroups, or in treatment discontinuation rates. In multivariate analyses, provider type was not associated with any significant difference in the odds of achieving SVR (NPP vs. MD; odds ratio 1.17; 95% confidence interval, 0.84-1.63; P=0.37 inverse probability of treatment weighting; odds ration 1.16, 95% confidence interval, 0.84-1.59, P=0.38 unweighted). Hematologic adverse event rates were similar: anemia: 57% NPP, 62% MD; thrombocytopenia: 43% NPP, 40% MD; neutropenia: 40% NPP, 39% MD. CONCLUSIONS: Treatment prescribed by NPPs was as likely to result in SVR as treatment prescribed by MDs, even after accounting for patient differences. Engaging more NPPs as HCV treatment providers may allow wider access to HCV treatment.

Impact of race/ethnicity and gender on HCV screening and prevalence among U.S. 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.

Early virologic responses and hematologic safety of direct-acting antiviral therapies in veterans with chronic hepatitis C.

BACKGROUND & AIMS: There are limited data on the early effectiveness of direct-acting antiviral (DAA) therapies for patients with hepatitis C virus (HCV) infection in routine medical practice. We aimed to evaluate real-world experience with DAA-based regimens. METHODS: By using the Veterans Affairs' Clinical Case Registry, we conducted a prospective observational intent-to-treat analysis of veterans infected with HCV genotype 1 who began treatment with pegylated interferon, ribavirin, and boceprevir (BOC, n = 661) or telaprevir (TVR, n = 198) before January 2012. We determined rates of virologic response at treatment weeks 4, 8, 12, and 24; futility; early discontinuation; and adverse hematologic events. RESULTS: About one third of patients discontinued treatment by week 24 (30% BOC, 34% TVR). A higher percentage of treatment-naive, noncirrhotic patients receiving BOC had undetectable levels of virus at week 24 than patients receiving TVR (74% vs 60%; P = .03). There were no significant differences in rates of early response within subgroups of cirrhotic patients, prior relapsers, prior partial responders, or prior null responders. By week 24, treatment was determined to be futile for 14% of patients receiving BOC and 17% of those receiving TVR. No differences were observed in overall rates of anemia (50% BOC, 49% TVR) or thrombocytopenia (16% BOC, 18% TVR); higher rates of neutropenia were observed in BOC-treated patients (34% BOC, 21% TVR; P = .008). CONCLUSIONS: HCV-infected veterans treated in routine medical practice with DAA-based regimens (BOC or TVR) had rates of early response comparable with those reported in clinical trials. However, they had higher rates of futility and early discontinuation than clinical trial participants. Further studies are needed to determine rates of sustained viral response.

Rural residence and adoption of a novel HIV therapy in a national, equal-access healthcare system.

Rural persons with HIV face barriers to care that may influence adoption of advances in therapy. We performed a retrospective cohort study to determine rural-urban variation in adoption of raltegravir-the first HIV integrase inhibitor-in national Veterans Affairs (VA) healthcare. There were 1,222 veterans with clinical indication for raltegravir therapy at time of its FDA approval in October 2007, of whom 223 (19.1%) resided in rural areas. Urban persons were more likely than rural to initiate raltegravir within 180 days (17.3% vs. 11.2%, P = 0.02) and 360 days (27.5% vs. 19.7%, P = 0.02), but this gap narrowed slightly at 720 days (36.3% vs. 31.8%, P = 0.19). In multivariable analysis adjusting for patient characteristics, urban residence predicted raltegravir adoption within 180 days (odds ratio 1.72, 95% CI 1.09-2.70) and 360 days (OR 1.63, 95% CI 1.13-2.34), but not 720 days (OR 1.26, 95% CI 0.84-1.87). Efforts are needed to reduce geographic variation in adoption of advances in HIV therapy.

Pharmacist-Led Management of HIV PrEP Within the Veterans Health Administration.

Background: Uptake and access to HIV preexposure prophylaxis (PrEP) is key to reducing incident HIV infections. Pharmacists are one of the most accessible health care professionals in the United States and are well suited to address this need. Observations: We describe a model of care at the Veterans Affairs Greater Los Angeles Healthcare System in which clinical pharmacist practitioners developed and implemented a pharmacy-led PrEP clinic colocated within an infectious disease clinic. Veterans Health Administration clinical pharmacists provide direct patient care under a scope of practice that includes ordering and interpreting laboratory tests and providing PrEP prescriptions. To improve access and patient acceptability, we also used novel telemedicine modes of care to ensure flexible appointment scheduling. Conclusions: This model can be used by other federal and community-based health care organizations to implement interdisciplinary pharmacist-managed PrEP clinics and expand telehealth modalities to deliver outpatient services.