bluuebunny/crossref_metadata_2025 huggingface dataset:
897. Trends and Correlation of HIV-1 Reservoir in Acute HIV Infection and Chronic HIV Infection in China
Authors: peng Shuang , wang Ming
Published: December 2021

Background

Among acute HIV infection （AHI）and chronic HIV infection（CHI）,the association of HIV-1 DNA and HIV-1 RNA is currently a hot spot of concern. We studied HIV-1 DNA levels in patients with AHI and CHI before initiation of ART to explore the growth characteristics of the HIV reservoir.

Methods

From 2016/10/31 to 2020/11/23, 97 patients were enrolled in the first hospital of Changsha in China. According to the patient’s epidemiological history, HIV-1 antibody conversion time, presence of opportunistic infection（OI）, to determine whether the patients were in the acute or chronic infection period, and divided into two arms: AHI and CHI. Lleukomonocyte, HIV-1 RNA, and CD4/8 of all patients were collected. The HIV-1 DNA in peripheral blood mononuclear (PBMC) was detected by PCR-Fluorescence Probing. The results were analyzed by SPSS 22.0 and GraphPad Prism 8.0. P-value < 0.05 were statistically significant.

Results

93 of 97 were male and 85 of 97 with sexual transmission. In AHI arm, the mean of HIV-1 RNA was 5.15 log10 copies/ml, and the mean of HIV-1 DNA was 2.83 log10 copies/106 PBMCs. In CHI Arm, the mean value of HIV-1 RNA was 4.90 log10 copies/ml, and the mean value of HIV-1 DNA was 3.19 log copies/106 PBMCs. The HIV-1 DNA of CHI group was higher than that of AHI group (p = 0.002) , but the HIV-1 RNA of CHI group was lower than that of AHI Group (p = 0.183) . There were no significant differences between AHI and CHI in age, sex, body weight, route of infection, ART, other viral infection, leukomonocyte, CD4+ T cell count, CD4+ T cell percentage, CD8+ T cell count, CD8+ T cell percentage and CD4/CD8 ratio (P > 0.05).In Group AHI, HIV-1 DNA was positively correlated with HIV-1 RNA (r = 0.548, p < 0.001), but not in Group CHI (r = 0.14, p = 0.347).

Conclusion

Patients with AHI have lower HIV-1 DNA levels and smaller viral reservoir than those with CHI. These data have illustrates the benefits of rapid treatment. The correlation between HIV-1 DNA and HIV-1 RNA in patients with acute infection is strong,the level of HIV-1 DNA increased with the increase of HIV-1 RNA level, but was not related to CD4 + T cells, CD8 + T cells and CD4/CD8 ratio.

Disclosures

All Authors: No reported disclosures
898. Effectiveness and Tolerability of DTG + 3TC in Clinical Practice: Evidence in PLHIV from Real-world Data
Authors: Evitt Lee A , Kumar Rahul , Kamath Rahul , Jha Diwakar , Parks Daniel , van Wyk Jean A , de Ruiter Annemiek
Published: December 2021

Background

Randomized controlled trials have shown dolutegravir (DTG) + lamivudine (3TC) to be an efficacious, well-tolerated and durable regimen for treatment-naive and treatment-experienced people living with HIV (PLHIV). Several observational studies have also concluded that it is effective in clinical practice. The objective of this meta-analysis was to estimate effectiveness and tolerability of DTG + 3TC in PLHIV by combining real-world evidence from clinical practice.

Methods

A systematic literature review using PubMed and Embase plus 24 regional and international conferences was conducted between January 2013 and December 2020 to identify studies of DTG + 3TC in treatment-experienced and treatment-naive PLHIV in clinical practice. Eligible published articles reporting virologic suppression, virologic failure and discontinuations at Weeks 48 and 96 were identified and extracted. Identified studies were included if they had an acceptable level of publication bias and heterogeneity determined using funnel plots and I2 statistics, respectively. One-arm meta-analyses using the DerSimonian and Laird method were conducted to estimate effect sizes for outcomes of interest for DTG + 3TC.

Results

One study of DTG + 3TC was identified reporting outcomes of interest at time points of interest in treatment-naive PLHIV, hence no meta-analysis was undertaken in this population. Eight studies (N=2366 PLHIV) undertaken in Europe reported data on treatment-experienced, virologically suppressed PLHIV on outcomes of interest at time points of interest (not all endpoints/time points were reported by all studies). The meta-analysis of available data from these 8 studies showed that among PLHIV switching to DTG + 3TC treatment, ≥ 95% maintained virologic suppression (per protocol) with ~1% virologic failures on DTG + 3TC at Weeks 48 and 96. Five of the 8 studies reported resistance data. Among participants with baseline resistance testing, no treatment-emergent integrase strand transfer inhibitor resistance mutations were observed.

Table. Meta-analysis Results in Treatment-Experienced PLHIV: Proportion with Virologic Failure, Virologic Suppression, and Discontinuations at Weeks 48 and 96

Conclusion

DTG + 3TC is an effective, tolerable and durable antiretroviral regimen with low rates of discontinuation in treatment-experienced PLHIV in clinical practice.

Disclosures

Lee A. Evitt, MSc Health Economics, ViiV Healthcare (Employee, Shareholder of GSK) Rahul Kumar, M Pharmacy, GlaxoSmithKline (Employee) Rahul Kamath, PharmD, GlaxoSmithKline (Employee) Diwakar Jha, Masters in Pharmaceutical Sciences, GlaxoSmithKline (Employee) Daniel Parks, PhD, GlaxoSmithKline (Employee, Shareholder) Jean A. van Wyk, MB,ChB, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Annemiek de Ruiter, MBBS FRCP, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)
899. Use of Dolutegravir/Rilpivirine in Treatment of HIV in PLWH with CKD and ESRD
Authors: Kang Jungwook , Kim Yae Ji
Published: December 2021

Background

Dolutegravir and rilpivirine is a novel two-drug single-tablet regimen for human immunodeficiency virus (HIV) that does not require dose adjustment in patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD). Although there are no studies proving the efficacy and safety of this regimen for patients with CKD and ESRD, there are a few studies that support the use of dolutegravir in hemodialysis.

Methods

A retrospective chart review was performed on patients who received dolutegravir and rilpivirine from November 2017 to July 2020 in the HIV clinic at SUNY Downstate Medical Center. The primary endpoint was the viral load suppression rate (defined as viral load less than 50 copies/ml) at 6 months of therapy compared between two groups of patients with varying kidney function: chronic kidney disease (defined as creatinine clearance (CrCl) under 60 mL/min) and normal kidney function (defined as CrCl higher than or equal to 60 mL/min). Viral load suppression rate was compared using logistic regression. Secondary outcomes were any reported adverse drug events and the discontinuations of the study medication.

Results

Overall viral load suppression at 6 months was achieved in 31 out of 36 patients (86.1%). 13 out of 14 patients (92.9%) with CrCl greater than or equal to 60 mL/min at baseline achieved viral load suppression at 6 months, whereas 18 out of 22 patients (81.8%) with CrCl under 60 mL/min at baseline achieved viral load suppression at 6 months (p=0.367). With adjustments for age, gender, and the history of Acquired Immunodeficiency Syndrome, the result was still insignificant. One adverse event of headache was reported in the group with baseline CrCl under 60 mL/min. Three cases of discontinuation were reported in this group due to resistance, headache, and drug-drug interaction.

Conclusion

The use of dolutegravir and rilpivirine for the treatment of HIV infection in adults with CKD or ESRD on hemodialysis was both safe and effective in African American population.

Disclosures

All Authors: No reported disclosures
901. Integrated Community Health Screening for COVID-19 and HIV Promotes HIV Diagnoses and Linkage to Care
Authors: Rosmarin-DeStefano Corey L , Martin Eugene G , Salaru Gratian , Tempalski Barbara , Finkel Diana , Scarinci Eileen
Published: December 2021

Background

New Jersey experienced a 64% decrease in HIV screening during the COVID-19 pandemic, hampering the Federal “End the Epidemic Initiative”. From March 2020- May 2021, North Jersey Community Research Initiative, a community-based organization in Newark, NJ, noted a HIV seropositivity of 3.1% despite a decrease of 25% in testing. Qualitative interviews conducted virtually with community individuals and focus groups during that time period indicated that COVID-19 suggested clients were taking more risks due to feelings of isolation, depression and anxiety. NJCRI in collaboration with Robert Wood Johnson Medical School in Somerset, NJ and five other community-based partners in NJ wanted to assess if offering community combination COVID-19 screening and HIV screenings during the pandemic would increase community screening for HIV.

Methods

CLIA Waived Screening for COVID-19 from two antigen assays, LumiraDx and BD Veritor was combined with a referenced laboratory based molecular screening from saliva Infinity Biologix under FDA emergency use authorization within CDC guidance with HIV Alere/Determine and INSTI in those individuals that identified as asymptomatic for COVID-19 but with high risk for HIV

Results

NJCRI began the COVID-19 and HIV rapid screening to clients on January 4, 2021.Clients tested for COVID-19 (N=274), 3% tested positive for HIV and < 3% are self-reported HIV+ (94% of the sample tested negative for HIV). Overall, 92% of clients tested negative for COVID-19. Clients testing positive for COVID-19 (N=19), there was a 6% positivity rate utilizing COVID-19 Antigen by nasal swab. Those positive via COVID-19 Molecular (N=19) method, results indicate clients also tested positive 6% of the time using a saliva indicator. Approximately, 5% of the study sample are confirmed COVID-19 positives via both testing methods (separately 1% Antigen and < 2% Molecular). 19% of the sample (N=3) tested positive for both HIV and COVID-19.

Figure 2. Demographics

Figure 3. Social and Economic Risk Factors

Conclusion

Newly diagnosed patients were treated the same day with antiretroviral therapy; linked to medical care, behavioral health and risk reduction services. Combining COVID-19 and HIV screening in a trusted community-based setting improved delivery of HIV care and linkage to care for newly diagnosed individuals in Newark, NJ.

Figure 4. Behavioral Risk Factors

Figure 3. Social and Behavioral Risk Factors

Disclosures

All Authors: No reported disclosures
902. Unreturned Pill Bottles in the 1489 and 1490 Clinical Trials: An Important Measure of Poor Adherence that Is Often Ignored in Pill Count Calculations
Authors: Acosta Rima K , Chen Grace Q , Huang Hailin , Liu Hui , White Kirsten L
Published: December 2021

Background

Adherence to antiretroviral therapy is important for HIV suppression. In clinical trials, adherence is commonly measured by pill count; limitations are that unreturned pills may not have been taken and unreturned pill bottle data are omitted. This analysis focuses on the relationship between unreturned pill bottles as a measure of poor adherence and the overall effect on virologic success rates across all treatment groups.

Methods

Pill bottle return category (all bottles returned or ≥1 bottle unreturned) and return rates for participants across all treatment groups from two treatment-naïve INSTI clinical trials (Studies 1489 and 1490) were calculated. Association of bottle return category or rates with virologic events through week 144, including last on-treatment observation carried forward (LOCF) outcome, was determined; comparisons used Fisher’s exact or Wilcoxon rank sum test.

Results

Virologic suppression with ≥95% adherence by pill count can differ for those with unreturned pill bottles (Figure). In these studies, 60% of participants returned all their pill bottles through week 144; if one visit with ≥1 unreturned bottle was allowed, this percentage increased to 81%. The mean bottle return rate was 94% and did not differ by study, treatment arm, or sex. Failure to return pill bottles was significantly associated with lower suppression rates. Additionally, significant differences in pill bottle return rate (p < 0.01) were observed by week 144 LOCF outcome (95% vs 77% mean return rate for those with HIV RNA < 50 c/mL vs ≥50 c/mL), need for resistance testing (95% vs 77% return rate for those not tested vs tested), confirmed virologic failure (VF) (94% vs 90% return rate for those without VF vs with VF) and blip status (95% vs 92% return rate for those without blips vs with blips).

HIV-1 Viral Loads of Two Participants with ≥95% Adherence by Pill Count through Week 144

Conclusion

In these treatment-naïve INSTI clinical trials, failure to return pill bottles was associated with lower suppression rates. Although the calculated adherence rates in these studies was relatively high (median ≥95%), these calculations did not account for unreturned pill bottles. We believe that assessing adherence by both pill count and pill bottle return rate may provide a more complete picture of adherence in clinical trials.

Disclosures

Rima K. Acosta, BS, Gilead Sciences, Inc. (Employee, Shareholder) Grace Q. Chen, BS, Gilead Sciences, Inc. (Employee) Hailin Huang, PhD, Gilead Sciences, Inc. (Employee, Shareholder) Hui Liu, PhD, Gilead Sciences, Inc. (Employee, Shareholder) Kirsten L. White, PhD, Gilead Sciences, Inc (Employee, Shareholder)
904. Improving Infectious Disease Screening and Hepatitis C Care Cascade Outcomes Among Adults Receiving Medication Assisted Treatment
Authors: Hoehnen Sarah , Blood Audra B , Austermiller Rachel
Published: December 2021

Background

This initiative increased infectious disease (ID) screening in an adult medication assisted treatment (MAT) population at a Federally Qualified Health Center (FQHC) by implementing opt-out screening for HIV, viral hepatitis, and sexually transmitted infections (STIs), and assessed the success of a co-located hepatitis C (HCV) treatment program.

Methods

ID providers maintained a standing lab order for HIV, hepatitis A, hepatitis B, HCV, syphilis, chlamydia/gonorrhea (GC/CT), and trichomoniasis (trich), with reflex to confirmatory for HIV/HCV/syphilis. For all existing and new adult MAT patients, a MAT RN provided education, ensured lab draw on the day of MAT induction, and scheduled an ID follow-up visit. The patient then had an in-person or telemedicine visit with the ID provider to review results, discuss risk reduction, and initiate treatment (HIV PrEP or treatment for STI, HCV, or HIV) as indicated. Data was compiled and monitored by a Prevention RN.

Plan, Do, Study, Act (PDSA) Model

PDSA model demonstrating implementation approach

Results

The rate of testing among MAT patients increased over a one-year period.

HCV treatment uptake in this setting exceeded that documented in published data for people who inject drugs (PWID).

HCV Care Cascade Outcomes

HCV screening and treatment outcomes within HCV Care Cascade model

Screening Outcomes

Screening rates among adult MAT population over a one-year measurement period

Conclusion

This study documents the successful implementation of an opt-out screening program among an adult substance use disorder (SUD) treatment population across urban, mixed, and designated rural environments. HCV treatment uptake in this setting exceeded that documented in published data for people who inject drugs (PWID).

Barriers to implementation included acceptance among patients with long-term MAT participation, acceptance/adoption by behavioral health nursing and provider staff, and functional workflow development – establishment of protocol, lab availability, scheduling, and “tough sticks.”

Modifications that increased effectiveness included an interdisciplinary approach and dedicated staff for monitoring results completion and patient outreach.

Run chart: HIV screening rates over a one-year period

HIV screening change among adult MAT patients over a one-year period

Run chart: HCV screening rates over a one-year period

HCV screening change among adult MAT patients over a one-year period

HCV Care Cascade: HCV screening and treatment outcomes

HCV screening and treatment outcomes presented in HCV Care Cascade for adult MAT population

Disclosures

All Authors: No reported disclosures
906. Characteristics of Chronic Hepatitis B Patients with Severe Outcomes in a Large Integrated Healthcare System - 2008-2019
Authors: Florea Ana , Gounder Prabhu , Sahota Amandeep , Pak Katherine J , Hong Vennis , Im Theresa M , Tartof Sara
Published: December 2021

Background

It is estimated that there are 1.59 million cases of chronic hepatitis B virus (HBV) infection (CHB) in the United States. HBV infection is highest among men and non-Hispanic Asian adults. CHB can lead to liver damage, cirrhosis, hepatocellular carcinoma, or death. However, the population that is most likely to develop severe outcomes is not as well-defined.

Methods

We evaluated electronic health record data from Kaiser Permanente Southern California adult members from 2008-2019 with at least 1 year of continuous membership, and with 2 successive, positive HBV lab results (HBV DNA, or HBsAg, or HBeAg) at least 6 months apart (indicative of CHB). Severe outcomes included incident hepatic decompensation, hepatocellular carcinoma (HCC), liver transplant and death, and prevalent and incident liver cirrhosis. For each outcome, we estimated the distribution of characteristics including age, sex, race/ethnicity, and lab values (alanine aminotransferase [ALT], alpha-fetoprotein [AFP], MELD score).

Results

Our final study population included 5,427 CHB-diagnosed patients with 411 (7.6%) cases of liver cirrhosis, 123 (2.3%) of hepatic decompensation, 65 (1.2%) of HCC, 8 (0.1%) of liver transplant, and 164 (3.0%) deaths. Compared to the total cohort, those who developed severe outcomes were older (median age for each outcome >50 years vs. 47 years in total CHB population). Among those with severe outcomes, the majority were male ( >56%) and Asian. Diabetes was more prevalent in patients with hepatic decompensation, HCC, and death versus the entire cohort (25% vs. 8%, respectively, P< 0.0001), and twice as prevalent among those with cirrhosis. All severe outcomes were associated with >2 x upper limit of normal ALT levels.

Conclusion

The characteristics of those with severe outcomes were consistent with those of overall CHB, although there was a 2-3 times higher prevalence of diabetes in those with severe outcomes. Identifying characteristics that are more prevalent in those with severe outcomes can help inform screening and management of CHB.

Disclosures

Ana Florea, PhD MPH, Gilead Inc. (Grant/Research Support) Prabhu Gounder, MD, Gilead Inc. (Grant/Research Support) Amandeep Sahota, MD, MS, Gilead Inc (Grant/Research Support) Katherine J. Pak, MS, Gilead (Grant/Research Support) Vennis Hong, MPH, Gilead Inc. (Research Grant or Support) Theresa M. Im, MPH, Gilead Inc. (Grant/Research Support) Sara Tartof, PhD, Gilead (Grant/Research Support, Scientific Research Study Investigator)
908. Dismantling Barriers to Hepatitis Elimination: Automated Hepatitis C Screening with Care and Cure by a Primary Care Based Team
Authors: Xu Binghong , Brogden Ruth P , Patel Ammie J , Gallipani Alyssa , Yango Jaymie , Adedeji Mary O , Wang Su
Published: December 2021

Background

Liver cancer rates are rising in the US, viral hepatitis accounting for more than 65% of the cases. Yet more than half of viral hepatitis infections remain undiagnosed. In response to the rise in HCV due to the opioid epidemic, the Centers for Disease Control and Prevention began recommending a one-time HCV test for all adults in 2020. Screening, linkage to care (LTC) and access to HCV curative therapy must be scaled up to reach the WHO goal of eliminating hepatitis by 2030.

Methods

In 2018, automated HCV screening utilizing electronic medical record protocols began in the emergency department (ED) based on the date of birth. Drug testing and peer recovery consults were added as eligibility criteria. Screening became universal and expanded to the inpatient units in 2020. Patient navigators (PN) received alerts of positive results and worked with patients to arrange LTC, one site being a primary care-based practice (PCP) where internists provided HCV care and support from ambulatory care clinical pharmacists.

Results

From Mar 2018 to Mar 2021, 50,873 people were screened for HCV, with 977 (1.9%) testing HCV Ab+, and 259 (0.5%) had confirmed infection by reflex HCV RNA. LTC 86.6% of patients, and 128 (49.4%) were newly diagnosed. Universal screening led to 35,482 testings from Jan 2020-Mar 2021. People born out of the 1945-65 birth cohort made up 75.8% of the screened and 39.1% of the infected. The PCP evaluated 47 HCV patients, initiated therapy in 38; 36 required prior authorization and 15 needed financial assistance. Treatment breakdown was: 29 (76.3%) glecaprevir/pibrentasvir, 6 (15.8%) sofosbuvir/velpatasvir & 3 (7.9%) ledipasvir/sofosbuvir. Pharmacist intervention with prior authorizations and financial assistance significantly reduced the cost (table 1). Thus far, 35 achieved cure with undetectable HCV RNA at 12 weeks.

Table 1. The Cost of Treatment before and after Pharmacist Assistance

Conclusion

Automated universal testing was an effective and seamless way to scale up HCV screening. Warm handoffs from a PN were important for engaging patients in care. A team approach assisted with removing barriers in therapy access, including prior authorization, specialist requirements, and financial assistance. Novel strategies utilizing ED and hospitals for testing with coordination to PCP are needed to find the missing millions and achieve hepatitis elimination.

Disclosures

Su Wang, MD MPH, Gilead Sciences (Grant/Research Support)Gilead Sciences (Grant/Research Support)
909. Treating Hepatitis C Virus (HCV) in Young Adult Active Drug Users Is Possible
Authors: Nahass Ronald G , Seneca Kathleen H , Homer Ruth A
Published: December 2021

Background

Successful treatment of HCV in persons who inject drugs (PWIDS), has been reported for patients who were older or who had used drugs more than 6 months prior. The young, < 35 year of age (yoa), active user has not been well studied or reported. We performed a pilot treatment study in a young cohort of PWIDS to evaluate cure rates of HCV in this population.

Methods

Young, active PWIDS using < 6months earlier, < 35 yoa were identified. Treatment for HCV with glecaprevir/pibrentasvir (G/P) and concurrent treatment for opiate use disorder with XR Naletrexone (XR-NTX) was provided. Two patients chose methadone. Patients were followed up to 12 months after enrollment. Patients were evaluated for adherence, side effects, alanine aminotransferase (ALT) levels, urine drug screens (UDS) and opioid craving scores using a visual analog scale (VAS) while on XR-NTX to assess management of their addiction. Rates of treatment completion, SVR 4 & 12 were determined.

Results

30 patients were recruited: 18 were women. Average age was 28 with a range of 23-35. Recent injection drug use was common with 22 (73%) having injected within the 30 days and all having injected within 3 months of recruitment. The average ALT on enrollment was 106. Genotypes were 1 (15), 3a (11), and unknown (4). Of the 30 patients, 15 failed to come for the required 2 visits prior to starting G/P. Lost to follow up occurred due to relapse of addiction (9), overdose death (1), lost communication and suspected relapse (4). 15 began and completed G/P. 15 were cured of their HCV infection. 17 patients receive one or more doses of XR-NTX. On average patients were on XR-NTX for 4.8 months. Sobriety was measured for patients on XR-NTX using Opiate Craving Scores using the Visual Analogue Scale (VAS) and UDS (Figure 1) demonstrating excellent control of craving and significant declines positive UDS. Toxicities were uncommon with no treatment limiting adverse events. Adverse effects of XR-NTX included mild injection site irritation. No ALT abnormalities were noted.

Conclusion

Young active PWIDS can successfully be cured of HCV. Their addiction can be concurrently managed with XR-NXT. Our findings suggest it is safe to treatment active users with active HCV with XR-NXT improving elimination goals.

Disclosures

Ronald G. Nahass, MD, Abbvie (Grant/Research Support, Speaker’s Bureau)Alkermes (Grant/Research Support)Gilead (Grant/Research Support, Speaker’s Bureau)Merck (Grant/Research Support, Speaker’s Bureau) Kathleen H. Seneca, MSN, Abbvie (Research Grant or Support)Alkermes (Research Grant or Support)Gilead (Speaker’s Bureau) Ruth A. Homer, MSW, Abbvie (Grant/Research Support)Alkermes (Grant/Research Support)
910. Evaluation of an Enzymatic Immunoassay System for Detection and Differentiation of Rat Hepatitis E Virus Infection in Humans
Authors: Sridhar Siddharth , Situ Jianwen , Lo Kelvin Hon Yin , Cai Jianpiao
Published: December 2021

Background

Previously, hepatitis E in humans was believed to be caused exclusively by species A variants of the Orthohepevirus genus (HEV-A) of the family Hepeviridae. However, we have previously demonstrated that Orthohepevirus species C (HEV-C), also known as rat hepatitis E virus, also causes hepatitis in humans. Due to high sequence divergence between HEV-A and HEV-C, serological tests based on HEV-A are often insensitive for HEV-C diagnosis. Therefore, we developed an enzymatic immunoassay (EIA) system for differentiating HEV-A and HEV-C antibody signatures in patient sera.

Methods

HEV-A and HEV-C peptide homologs spanning the entire immunogenic E2s region of HEV ORF2 capsid protein were expressed in E. coli. These peptides, HEV-A4 p239 and HEV-C p241, form virus-like particles (figure 1). Both peptides were coated in separate 96-well plates. Sera obtained from patients with RT-PCR confirmed acute HEV-A infection (n = 54), HEV-C infection (n = 15), and uninfected HEV seronegative controls (n = 126) were tested in parallel in HEV-A4 p239 and HEV-C p241 EIAs for respective IgG antibodies. Sample optical densities (ODs) were divided by mean OD + 3SD of the seronegative controls to generate signal/noise (S/N) ratios. S/Ns marking positivity in either assay were determined by ROC analysis. An algorithm for assay interpretation was developed (table 1) and the performance of this algorithm was measured against the RT-PCR gold standard.

HEV-A4 p239 and HEV-C1 p241 virus like particles

Transmission electron microscopy images of the two peptides used in this study

Diagnostic testing algorithm interpretation

Interpretation of results of testing using parallel enzymatic immunoassays

Results

Using cutoffs determined by ROC analysis (figure 2), HEV-A4 p239 and HEV-C p241 EIAs detected species-specific antibody responses well (sensitivity: 92.6% and 80% respectively) and were specific (92.9% and 98.3% respectively). The DC was 100% congruent with HEV-C RT-PCR and 88.9% congruent with HEV-A RT-PCR in RT-PCR positive samples. Incorporating all three cutoffs into the algorithm, we derived a 3×3 confusion matrix of RT-PCR sample assignation vs EIA algorithm classification (table 2). The Cohen’s κ value was 0.883 indicating excellent inter-rater reliability.

ROC analysis for determining S/N cutoffs

Curve for A/A represents analysis for HEV-A4 p239 EIA. Curve for C/¬C represents analysis for HEV-C p241 EIA. Curve for r(C/A) represents analysis for the differentiating ratio.

3×3 confusion matrix comparing sample assignations by RT-PCR vs. EIA algorithm

Conclusion

A parallel EIA system accurately differentiated HEV-A and HEV-C serological signatures in acute patient sera. This method can now be applied to seroprevalence studies to determine seroprevalence of rat hepatitis E in human populations.

Disclosures

Siddharth Sridhar, FRCPath, Abbott (Other Financial or Material Support, Speaker’s honoraria)
911. Rapid Hepatitis C Treatment Initiation in Young People Who Inject Drugs: Final Results from the HCV-Seek, Test and Rapid Treatment (HCV-ST&RT) Randomized Pilot Clinical Trial
Authors: Eckhardt Benjamin , Kapadia Shashi , Smith Melinda , Aponte-Melendez Yesenia , Fong Chunki , Davis La , Mateu-Gelabert Pedro , Marks Kristen , Marks Kristen
Published: December 2021

Background

Young people who inject drugs (PWID) have higher HCV incidence and lower treatment initiation rates compared to their older peers. Novel, simplified care models need to be developed to engage, treat and cure hard to reach patient populations, such as young PWID.

Methods

We present final data from the randomized pilot clinical trial HCV-Seek Test & Rapid Treatment (HCV-ST&RT) for curing HCV in young PWID. Eligible participants were 18-29 years of age, HCV Ab+, treatment naïve, and had injected drugs in the past 30 days. Participants were randomized 1:1 to the Rapid Treatment or Usual Care arm. Participants randomized to Rapid Treatment received a same-day medical evaluation, confirmatory and baseline lab testing, and 7-day starter pack of sofosbuvir/velpatasvir. Participants in Usual Care received same-day HCV confirmatory testing and, if positive, facilitated referral to local providers. The primary endpoint was sustained virologic response (SVR12) in RNA+ participant within 12 months of enrollment.

Results

Among 47 eligible participants, 38 were enrolled and randomized. 14/18 in the Rapid Treatment arm and 11/20 in the Usual Care arm were confirmed HCV RNA+ and included in the intention-to-treat analysis. Demographics of the RNA+ participants were similar in the two arms with a mean age of 26 years; 24% women; 36% Hispanic and 4% non-Hispanic black. At baseline 24% were homeless, 52% received medication for opioid use disorder in the prior 90 days, and participants injected a median of 20 of the last 30 days. In the intention-to-treat analysis, 9/14 (64%) of the Rapid Treatment arm and 2/11 (18%) of the Usual Care arm had confirmed SVR12 (p=0.042). Of the 5 participants in the Rapid Treatment arm who did not achieve SVR12, 1 had treatment failure, 1 never started DAA therapy, 1 had an on-treatment response with pending SVR12 confirmation, and 2 were lost to follow-up.

Conclusion

Among young HCV RNA+ PWID, significantly higher rates of cure were achieved using the Rapid Treatment model with same day, low-threshold, simplified HCV care compared to facilitated referral. Meeting young PWID where they’re at and initiating HCV treatment ‘in the moment’ without the need for repeat visits appears to be a promising strategy for treating this hard to reach population.

Disclosures

Benjamin Eckhardt, MD, MS, Gilead Sciences (Grant/Research Support) Shashi Kapadia, MD, Gilead Sciences Inc (Grant/Research Support) Kristen Marks, MD, Gilead Sciences (Grant/Research Support)
912. Expansion of Hepatitis C Treatment with New Medicaid Subscription Model in Louisiana
Authors: Richey Lauren E , Bennani Yussef , Frontini Maria
Published: December 2021

Background

It is estimated that nearly 80,000 people with hepatitis C are living in Louisiana, many with Medicaid coverage. Previously, only Medicaid patients free from drugs and alcohol with a fibrosis score of F3 or F4 were eligible for treatment, resulting in few patients receiving treatment. Beginning in July 2019, generic sofosbuvir/velpatasvir was made available through the Medicaid program in a subscription model, allowing unlimited hepatitis C treatment in Louisiana’s Medicaid program for 5 years at a set price to the program. This has dramatically expanded access to Hepatitis C treatment for people with Medicaid in Louisiana.

Methods

Patients with Hepatitis C seen in the Infectious Diseases Center at University Medical Center in New Orleans, in 2020 by the 5 main hepatitis C providers were included. Demographics and laboratory data were collected to determine outcomes.

Results

Most patients with a hepatitis C (HCV) viral load and insurance data had Medicaid (80%, N=275). Twenty-two (8%) were HIV co-infected. Most were men (75%) and African-American (77%). Among the mono-infected patients with Medicaid and an HCV viral load, 216 (85%) had an undetectable viral load by the beginning of June 2021. Of the remaining 37 patients, 30 patients were prescribed treatment; but did not take it (n=4), didn’t follow-up (n=23), or followed-up but never got labs (n=3). One was treated but had a treatment failure (n=1). Six of the 37 were not prescribed medications due to a short life expectancy or significant drug interactions. The percentage of patients with an undetectable viral load was similar by gender and race, however younger age groups had lower viral suppression. In those aged less than 35, only 47% had an undetectable viral load and among those aged 36 to 44, it was 66%. Using the previous criteria of requiring a fibrosis score of F3 or F4, only 20% (n=44) would have been eligible for medicine to treat hepatitis C.

Conclusion

The new hepatitis C treatment subscription model with resultant removal of previous barriers has dramatically expanded treatment for people with Medicaid in Louisiana. More than five times the number of Medicaid patients received treatment in 2020 in our academic medical clinic.

Disclosures

Yussef Bennani, MD, MPH, Gilead Sciences (Scientific Research Study Investigator)ViiV Healthcare (Scientific Research Study Investigator)
914. The Relationship Between Buprenorphine Maintenance Therapy and Hepatitis C Virus Infection, Testing, and Treatment in Southern Appalachian Ohio
Authors: Brook Daniel L , Schalkoff Christine , Piscalko Hannah M , Sibley Adams L , Kline David , Lancaster Kathryn , Go Vivian , Miller William
Published: December 2021

Background

The hepatitis C virus (HCV) epidemic in the United States is primarily among young people who use drugs (PWUD), especially in rural and Appalachian regions. Buprenorphine maintenance therapy (BMT) may indirectly prevent HCV infection by reducing injection drug use. We aim to assess the relationship between BMT and HCV infection, testing, and treatment among rural PWUD.

Methods

We conducted a cross-sectional respondent driven sampling survey of 243 PWUD adults in southern Appalachian Ohio from May to November 2019. Participants completed audio computer-assisted self-interview and were tested for HCV antibodies. We defined recent BMT use as self-reported BMT in the past 30 days and prior BMT use as self-reported BMT any time prior to the past 30 days. HCV antibody positive participants were incentivized to receive confirmatory HCV RNA testing. We fit log-binomial regression models to assess the relationship between BMT and HCV infection, testing, and treatment.

Results

72% of participants were HCV antibody positive (n=175). 31% (n=54) of antibody positive participants received an RNA test; of those, 96% (n=52) were HCV RNA positive. Compared to participants with no history of BMT, those with prior BMT were more likely to be HCV antibody positive (PR=1.3, 95% CI: 1.1-1.6) and to have been tested for HCV (PR=1.3 95% CI: 1.1-1.5); they were somewhat more likely to have been treated for HCV (PR=1.3 95% CI: 0.5-3.4). Compared to participants with no history of BMT, those reporting recent BMT had similar HCV antibody positivity (PR=1.1 95% CI: 0.9-1.5) but were more likely to have been tested (PR=1.3 95% CI: 1.1-1.6) and possibly more likely to have been treated for HCV (PR=2.0 95% CI: 0.6-5.9). Compared to those with a prior BMT, people with recent BMT use had slightly lower HCV antibody positivity (PR=0.8 95% CI: 0.7-1.1) and possibly higher prevalence of HCV treatment (PR=1.5 95% CI: 0.6-3.8) but had similar prevalence of HCV testing (PR=1.0 95% CI: 0.9-1.2).

Conclusion

Participants with a recent history of BMT were more likely to have been tested for HCV and possibly to have received prior treatment. Participants with prior BMT were more likely to be antibody positive and to have tested for HCV. Improved coordination between BMT and HCV care may increase HCV treatment among rural PWUD.

Disclosures

All Authors: No reported disclosures
916. Finding the Missing Millions and Addressing Health Disparities: Automated Hepatitis B Screening and Linkage to Care
Authors: Xu Binghong , Wang Su , Brogden Ruth P , Yango Jaymie , Adedeji Mary O
Published: December 2021

Background

Globally, HBV is the most common blood-borne infection. An estimated 1.2 million people in the US and 350 million worldwide lived with HBV, a primary driver of liver cancer. It is endemic in many parts of the world and is a major health disparity in immigrant communities, including the US, which has the largest immigrant population in the world. Asian American Pacific Islanders are 5% of the total population in the US, but represent 50% of people living with HBV. In 2016, WHO set a goal of hepatitis elimination by 2030 but with only 10% of those living with HBV diagnosed, screening must be scaled up.

Methods

Modifications were made in the electronic medical record (EMR) to automate screening, with HBV (HBsAg) orders triggered by a patient’s country of birth or race. The began in the Emergency Department and later expanded to the Inpatient setting. Automated notifications are sent to nurse for eligible patients and then to the patient navigator (PN) for positive tests. The PN contacts the patient to provide education and arrange linkage-to-care (LTC) for evaluation and care.

Results

From Mar 2018 to Mar 2021, we conducted 23,883 HBV screenings. The patients originated from 173 countries based on registration; top 5 countries of origin were Haiti, Jamaica, Ecuador, Guyana, and Portugal. We found 228 (1.0%) patients with HBV infection, 101 (47%) were newly diagnosed and 182 (85%) were linked to care. We examined race and insurance status for any association with those previously tested versus newly diagnosed. Blacks were more likely to be newly identified HBV versus Asians (61.6% vs. 28.9%, p< .001), as were self-pay (uninsured) versus insured patients (66.7% vs 47.2%, p=0.043). Compared to the approximately 0.4% HBV prevalence in the US, the HBV prevalence in several towns around our hospital in Essex County is two to four times higher.

Table 1. The HBV Prevalence in Towns of Essex County

Conclusion

Our community is diverse and social determinants of health, like race and insurance status, may contribute to provider behaviors of HBV screening with blacks receiving less screening than Asians. Automated testing programs can address health disparities and scale up screening. Such micro-elimination approaches are important for achieving global hepatitis elimination by 2030.

Disclosures

Su Wang, MD MPH, Gilead Sciences (Grant/Research Support)Gilead Sciences (Grant/Research Support)
918. 2019 Implementation of Universal Hepatitis C Screening at an Urban Federally Qualified Health Center: A Descriptive Analysis and Lessons Learned
Authors: Kahal Deborah A , Testa Karla A , Goldstein Neal
Published: December 2021

Background

Hepatitis C infection (HCV) is a curable disease that can be effectively managed by non-specialists. Delaware has high HCV rates but limited resources to care for individuals with HCV. Successful HCV micro-elimination starts with universal HCV screening and case identification.

Methods

ChristianaCare (CC) and Westside Family Healthcare (WFH), Delaware’s largest federally qualified health center (FQHC), created a multidisciplinary initiative to support comprehensive HCV care from July 2018-2020 (Figure 1). As part of this partnership, universal opt-out HCV screening in eligible (no prior HCV RNA result) adults ≥ 18 years was implemented at a pilot site in Wilmington in 2019. To characterize screening practices, pre- (risk-based screening) and post-intervention (universal screening) electronic health record data was collected following the first 6 months of the intervention (Jan-June 2019). An HCV dashboard was created and updated monthly to evaluate trends in 2019 screening rates. Collaboration was supported through a 2-year CC Harrington grant.

Figure 1. Components of Federally Qualified Health Center HCV Medical Care Model

Table 1. Pilot Site Patient Characteristics

Results

Pre- and post-intervention patient characteristics and screening data are presented in Table 1 and Figure 2 respectively. 39% of patients had screening ordered during the first 6 months of universal screening, a 4% increase from baseline. HCV seroprevalence [amongst resulted tests] remained unchanged from baseline at 5%. During the universal screening period, 2.5% (12/482) of individuals with resulted tests had HCV compared to 4.0% (29/795) tested during risk-based screening. HCV dashboard data demonstrated a trend of increased ordering and fulfillment of screening tests (Figure 3).

Figure 3. 2019 HCV Dashboard

Conclusion

The early adoption of universal HCV screening in adults (prior to 2020 USPSTF update) at an urban FQHC, together with an initiative to provide multidisciplinary HCV care at this FQHC (Figure 1), led to increasing rates of ordered screening. The presented 6-month data does not fully account for lag times between test ordering and fulfillment, resulting in under-reporting of universal HCV screening rates. Multidisciplinary care models to address HCV in patients’ medical homes are vital to HCV eradication with the robust implementation of universal HCV screening a vital first step in this continuum.

Disclosures

Deborah A. Kahal, MD,MPH, FACP, Gilead (Speaker’s Bureau)Viiv (Speaker’s Bureau)
919. Rates of False-Positive Hepatitis B Surface Antigen Is Low in Cancer Patients
Authors: Klingen Joseph , Yibirin Marcel , Hwang Jessica P , Torres Harrys A
Published: December 2021

Background

Accurate interpretation of hepatitis B virus (HBV) laboratory testing is paramount in avoiding inaccurate diagnosis and incorrect management that could lead to unnecessary and overtreatment. This is particularly relevant in patients with cancer where universal testing is recommended in order to avoid HBV reactivation. Hepatitis B surface antigen testing (HBsAg) positivity indicates chronic or acute HBV infection. The rates and outcomes of a false-positive HBsAg have not been established for patients with cancer.

Methods

Three hundred and ninety-seven patients with any type of cancer and positive HBsAg seen at MD Anderson Cancer Center from January 2016 – January 2021 were retrospectively reviewed in this study approved by the institutional review board. Cases of false-positive HBsAg were defined as those patients with a positive HBsAg but negative HBsAg quantitative, negative HBV core antibody (total Ig), and undetectable HBV DNA within 30 days of positive HBsAg testing. Serum samples from patients were tested for HBsAg using Vitros Enhanced Chemiluminescent Immunoassay (Ortho-Clinical Diagnostics, Raritan, NJ, USA). Data collection includes demographics, past medical history, underlying cancer and its stage, prior cancer treatment, risk factors for HBV, co-infections (hepatitis C, HIV), symptoms, liver function tests, anti-HBV treatment, and interruptions on cancer treatment.

Results

Out of 397 patients with a positive HBsAg, 33 were excluded as they did not meet the diagnostic criteria or have insufficient HBV data. Of them, 3 cases (0.8%) were identified as false positive HBsAg. All 3 patients were female, white, and had progressive malignancy (Table 1). No prior history of liver disease or liver function abnormalities were noted with these 3 patients. Initially, antiviral treatment was started on 1 patient which was discontinued shortly after confirmation of false-positive HBsAg. All 3 patients had additional workup and evaluation by an HBV specialist. In 2 patients, cancer treatment was canceled or delayed.

Conclusion

Although uncommon, cancer patients with false-positive HBsAg need further workup to avoid overtreatment and unnecessary interruptions in cancer care

Disclosures

Jessica P. Hwang, MD, MPH , Merck (Grant/Research Support)
920. Automated Hepatitis C Screening and Linkage to Care among Hospitalized Patients Born Between 1945-1965
Authors: Gasior Julia A , Russell Rebecca , Lo Re Vincent , Norris Anne , Bennett Schenevelyn , Aitcheson Nancy , Ferrante Nicole , Evans Chalanda , Patel Mitesh , Mehta Shivan , Torgersen jessie
Published: December 2021

Background

Hepatitis C virus (HCV) infects 4.1 million people in the United States, of whom 50% are unaware of their status. In 2016, Pennsylvania introduced a law mandating HCV screening for patients born between 1945-1965 in inpatient settings. However, HCV screening during hospital admissions has remained low in part due to limited knowledge on HCV testing requirements, interpretation of results, and treatment approaches. To overcome these barriers, we implemented a quality improvement initiative to automate HCV screening as part of hospital admission order sets, facilitate linkage to HCV treatment, and sought to evaluate its effectiveness.

Methods

Between September 2020 and May 2021, the automated inpatient HCV screening strategy was implemented at a single 328-bed academic hospital in Philadelphia, PA. Patients born between 1945-1965 without documentation of HCV screening or diagnosis in the electronic medical record had a HCV antibody with reflexive confirmatory RNA assay automatically populated in the admission order set. Admitting providers could opt out of the screening as appropriate. All patients with reactive HCV antibody were approached by the Hepatitis Linkage Team for result disclosure, counseling, and linkage to treatment for those with HCV viremia. Cascade of care was detailed for those linked to providers within the health system.

Results

During the initial 8 months of the program, 2,203 patients were screened for HCV, identifying 156 with reactive HCV antibody (7.1% seroprevalence). Among 147 with completed HCV RNA assay, 51 were viremic (34.7%). Fourteen viremic patients were not linked to care, including six with a terminal illness, two who declined linkage, and six who did not respond to linkage attempts. Nine were linked to care at other health systems. Among the 28 patients linked to providers in the health system, 50% completed initial visits, 42.8% were prescribed direct acting antivirals (DAA), and 21.4% completed therapy by May 2021. One person achieved sustained virologic response 12 weeks after treatment as of May 2021 (Figure 1).

Figure 1. Cascade of HCV Care Among Patients Screened During Hospital Admission from September 2020 to May 2021

Conclusion

Automated inpatient HCV screening is a viable strategy to identify people with HCV and facilitate linkage to care. Optimal strategies to ensure patients access and maintain care require further study.

Disclosures

All Authors: No reported disclosures