bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Cost-Effectiveness Analysis of an Adjuvanted Subunit Vaccine for the Prevention of Herpes Zoster and Post-Herpetic Neuralgia
Authors: Carpenter Christopher , Aljassem Annas , Stassinopoulos Jerry , Pisacreta Giovanni , Hutton David 
Published: October 2017

Abstract

Background
Herpes zoster (HZ) develops in up to 50% of unvaccinated individuals who live to 85 years of age, accounting for more than 1 million cases of HZ annually in the United States. A live attenuated vaccine (LAV) for HZ is U.S. FDA approved for persons 50 years or older, though CDC Advisory Committee on Immunization Practices (ACIP) recommendations are only for persons beginning at age 60 years. LAV efficacy at preventing HZ is ~70% for persons 50–59 years of age, with lower efficacy in older adults, and it is efficacious in preventing post-herpetic neuralgia (PHN) beyond the HZ prevention. The efficacy of LAV after vaccination wanes over time. A new adjuvanted HZ subunit vaccine (SUV), administered as a two-dose series, has greater than 95% efficacy against HZ in persons 50–69 years of age. SUV efficacy remains greater than 90% in persons vaccinated at age 70 years and older, including the subgroup older than 80 years of age. Overall efficacy of SUV against PHN approaches 90%. The waning rate of efficacy after SUV vaccination is unknown.

Methods
To estimate the relative cost-effectiveness of SUV, LAV and no vaccination (NV) strategies, a Markov model was developed based on published trials and data on vaccine efficacy persistence, quality of life, resource utilization, costs and disease epidemiology. The perspective was U.S. societal, and the cycle length was one year with a lifelong time horizon. SUV efficacy was estimated for the base case to wane at the same rate as LAV, all persons were assumed to receive both doses of SUV, and the cost of SUV included both doses.

Results
For individuals vaccinated at age 50 years the incremental cost-effectiveness ratio (ICER) for LAV vs. NV was $142,811 per quality-adjusted life-year (QALY); at age 60 years the ICER dropped to $59,482 per QALY. The cost-effectiveness ratio of SUV approached that of LAV when the SUV cost approached $500 for persons vaccinated at age 50 years and when the cost was $400 for those vaccinated at age 60 years. The SUV cost that would result in achieving an ICER target of $100,000 per QALY for SUV vaccination vs. NV at age 50 years was $316; at age 60 years the cost was $638.

Conclusion
Vaccination at age 60 years with SUV was more cost-effective than LAV when SUV cost was ~$450 or less. Vaccination with SUV at age 50 years appeared to be cost-effective if SUV cost was ~$315 or less.

Disclosures
All authors: No reported disclosures.
Vaccination Response to an Ongoing Meningitis Outbreak: Uptake and Attitudes among Men Who Have Sex with Men in Los Angeles, CA
Authors: Holloway Ian , Wu Elizabeth , Gildner Jennifer , Fenimore Vincent , Frew Paula 
Published: October 2017

Abstract

Background
Men who have sex with men (MSM) are at high risk for invasive meningococcal disease (IMD). Following a 2016 IMD outbreak in Southern California, public health officials issued an advisory that urged at-risk adult gay and bisexual men, and all people with HIV, to obtain immunizations. Despite public health efforts to increase MCV4 coverage, uptake and acceptance among MSM remains unknown. Thus, our study sought to: (1) estimate reported MCV4 immunization among MSM in Los Angeles, CA; and (2) document the facilitators and barriers to the newest vaccination recommendation following the recent outbreak.

Methods
From November 2016 through February 2017, we used venue-based sampling to recruit MSM in Los Angeles (N = 513). Eligible participants completed a 30-minute iPad survey that included items on MCV4 status, sexual behavior, vaccination knowledge and behaviors among other factors. Chi-square and independent sample t-tests were used to determine bivariate associations. Statistically significant variables from bivariate analyses were included in a multivariate logistic regression model predicting MCV4 uptake.

Results
Participants were young (M=33, SD=10) and racially/ethnically diverse: White (35.7%), Black/African American (14.6%), Hispanic (36.5%), Asian/Pacific Islander (4.1%), Other (9.2%). Reported MCV4 immunization among MSM (25.4%) and MSM living with HIV (37.7%) was low. Statistically significant correlates of MCV4 uptake in our multivariate model included: younger age (aOR=2.51), prior STI diagnosis (aOR=2.21), believing MCV4 vaccination was important (aOR=3.45), having confidence in the MCV4 vaccine (aOR=5.43), and knowing someone who had received the vaccination (aOR=5.79).

Conclusion
MSM’s perceived health risk, vaccine confidence, and knowledge of someone who received the MCV4 vaccine were important indicators of meningitis immunization in this outbreak context. Provider and public health education efforts may be enhanced by messages that emphasize personal health risks, the safety and efficacy of MCV4, and the importance of meningococcal vaccines for men’s health. Popular opinion leader programs facilitated by someone who had been vaccinated are warranted to enhance MCV4 uptake.

Disclosures
All authors: No reported disclosures.
Factors Associated with Elevated HIV RNA Levels in HIV-Infected Individuals
Authors: Degener Tyler , Allen Sara , Wilson Alicia , Baranoski Amy 
Published: October 2017

Abstract

Background
Virologic suppression is necessary to reduce the risk of complications from HIV infection and to prevent transmission to other individuals. Understanding factors associated with elevated HIV RNA levels in HIV-infected individuals could lead to interventions to improve engagement in care.

Methods
This retrospective, observational study assessed HIV-infected individuals engaged in care in an urban HIV clinic between April 1, 2015 and March 31, 2016. The electronic medical record was reviewed for demographic and HIV-related factors for all individuals with elevated HIV RNA PCR ≥200 copies/mL (EVL) during the study period. Demographic data were compared with individuals with decreased HIV RNA PCR (DVL) &lt;200 copies/mL. Patients with recent HIV diagnosis within 6 months of EVL were excluded due to the possibility of insufficient time to achieve viral suppression after engagement in care. Statistical analysis including Student T-test and Chi Square test was conducted in SPSS, version 24.

Results
There were 519 individuals with EVL with 72 (13.9%) excluded due to recent HIV infection. Of 1,789 patients included in this analysis, 447 (25.0%) had an EVL. The median HIV RNA PCR was 7,240 copies/mL (range 200 to 6,720,990) and median CD4 count was 411 cells/mm3(range 1 to 1,510) in the EVL group. Individuals with EVL were more likely to be younger (mean EVL group age 43.4 years ± S.D. 11.7, range 22–77 vs. 47.5 years ± S.D. 12.4, range 19–84 in DVL group) (P &lt; 0.0001). Individuals with EVL were more likely to be Black (82.1%) (with White 9.2% and Hispanic 8.7%) compared with those with DVL (74.8% Black, 12.4% White, 11.6% Hispanic, 1.6% other) (P = 0.004). The EVL group was 59.3% male, 39.8% female and 0.9% transgender vs. 64.8% male, 34.3% female, and 1.0% transgender in the DVL group. The main risk factors for HIV acquisition were heterosexual sex (46.3% of EVL vs. 43.4% DVL), men who have sex with men (31.8% vs. 36.4%) and injection drug use (14.3% vs. 14.6%). There were no significant differences in gender or risk factors for HIV acquisition between the two groups.

Conclusion
Decreased levels of HIV viremia is a major focus of quality HIV care. Younger age and Black race were associated with elevated HIV RNA levels in individuals engaged in care in a large urban HIV clinic.

Disclosures
All authors: No reported disclosures.
Electronic data sharing between public health department and clinical providers improves accuracy of HIV retention data
Authors: Ridgway Jessica P , Schmitt Jessica , Almirol Ellen , Millington Monique , Harding Erika , Pitrak David 
Published: October 2017

Abstract

Background
Retention in care is critical for treatment and prevention of HIV. Many HIV care clinics measure retention rate, but data are often incomplete for patients who are classified as lost to follow-up but may be actually in care elsewhere, moved, or died. The Data to Care (D2C) initiative supports data sharing between health departments and HIV providers to confirm patient care status and facilitate reengagement efforts for out of care HIV patients.

Methods
The University of Chicago Medicine (UCM) provided an electronic list to the Chicago Department of Public Health (CDPH) of adult HIV-positive patients whose retention status was not certain. Retention in care was defined as at least 2 visits &gt;90 days apart within the prior 12 months. CDPH matched this list of patients with data from the Chicago electronic HIV surveillance database. Matches were based on patient name, including alternative spellings and phonetics, and birth date. CDPH also cross-checked patient names with the CDC’s national enhanced HIV-AIDS Reporting System (eHARS) database. CDPH provided UCM with patient current care status, i.e., patient was in care elsewhere (as verified by lab data), moved out of state, or deceased.

Results
780 HIV-positive patients received care in the UCM adult HIV clinic from January 1, 2013 to March 31, 2017. Of these, 360 were retained in care as of March 2017. We shared data with CDPH for 492 patients. Of these, 294 (59.8%) were matched, and 168 (34.1%) had a date of last medical care provided. See Table 1 for patient dispositions, before and after data sharing. 24 (13.4%) of patients believed to be lost to follow up according to UCM records were confirmed either transferred care or deceased according to health department data.

Conclusion
Data sharing between the health department and HIV providers can improve data accuracy regarding retention in care among people living with HIV.

Disclosures
J. P. Ridgway, Gilead FOCUS: Grant Investigator, Grant recipient; D. Pitrak, Gilead Sciences FOCUS: Grant Investigator, Grant recipient
HIV Transmitted Drug Resistance in the Philippines: The Case for Baseline Genotyping and Drug Resistance Testing
Authors: Salvana Edsel Maurice , Schwem Brian , Penalosa Christine , Arevalo Geraldine , Dungca Nina , Lim Jodor , Leyritana Katerina , Destura Raul 
Published: October 2017

Abstract

Background
The Philippines has one of the fastest growing HIV epidemics in the world. Parallel to the increase is a shift in HIV subtype from B to CRF01_AE. No transmitted drug resistance (TDR) surveillance has ever been conducted. With the widespread rollout of antiretrovirals and the limited repertoire of 6 drugs (tenofovir, lamivudine, zidovudine, nevirapine, efavirenz, lopinavir/ritonavir) makes TDR monitoring imperative. In addition, a high rate of hepatitis B (HBV) co-infection (17%) in the general population raises the risk of TDR with prior NRTI monotherapy.

Methods
Following IRB approval, we performed TDR surveillance at the Philippine General Hospital, one of the largest tertiary referral centers in the country. Treatment-naïve patients had their HIV RT and PR genes sequenced using WHO approved-protocols for HIV genotyping. Generated sequences were analyzed using the Stanford Drug Resistance Database. Pertinent demographic and clinical data were collected. The current results represent year 1 of the study.

Results
95 treatment naïve patients were analyzed. Median age was 30 years (range 20–68). There were 88 males and 7 females. Median CD4 count was 90 cells/mL (range 0–936) and median viral load was 1792000 copies/mL. 18 patients were co-infected with HBV, but all denied previous HBV treatment.

Conclusion
The TDR rate for HIV in the Philippines is 6.3%. This is above the threshold for recommending baseline TDR genotyping for all local HIV patients. All HIV with TDR were subtype CRF01_AE, and this may signal a higher risk of TDR as the epidemic shifts further to a non-B subtype.

Disclosures
E. M. Salvana, Merck: Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium
Monitoring of HIV Drug Resistance Mutations in Newly Diagnosed Patients in Cyprus (2010–2012)
Authors: Demetriades Ioannis 
Published: October 2017

Abstract

Background
A molecular epidemiology study of HIV-1 infection was conducted in 100 HIV-1 diagnosed and untreated patients in Cyprus representing 65.4 percent of all the reported HIV-1 infections in Cyprus between 2010 and 2012.

Methods
Eighty-two patients were newly diagnosed (genotypic drug resistance testing within six months from diagnosis), and 18 patients were HIV-1 diagnosed for a longer period or the diagnosis date was unknown.

Results
Phylogenetic trees of the pol sequences obtained in this study with reference sequences indicated that subtypes B and A1 were the most common subtypes present and accounted for 41.0 and 19.0% respectively, followed by subtype C (7.0%), F1 (8.0%), CRF02_AG (4.0%), A2 (2.0%), other CRFs (7.0%) and unknown recombinant forms, URFs (12%). Most of newly-diagnosed study subjects were Cypriots (63%), males (78%) with median age 39 (Interquartile Range, IQR 33–48) reporting having sex with other men, MSM (51%).

Conclusion
A high rate of clustered transmission of subtype B drug-sensitive strains to reverse transcriptase and protease inhibitors was observed among MSM. Twenty-eight out of forty-one MSM study subjects (68.0%) infected were implicated in five transmission clusters, two of which are subtype A1 and three subtype B strains. The two largest MSM subtype B clusters included nine and eight Cypriot men, respectively, living in all major cities in Cyprus. There were only three newly diagnosed patients with transmitted drug resistant HIV-1 strains, one study subject from the United Kingdom infected with subtype B strain and one from Romania with subtype A2 strain, both with the PI drug resistance mutation M46L and one patient from Greece with subtype A1 strain with the NNRTI drug resistance mutation K103N.

Disclosures
All authors: No reported disclosures.
Drug Resistance After Failure of WHO Recommended First-Line Antiretroviral Regimen for Adult HIV-1 Infection in South Africa: A Modeling Analysis
Authors: Ding Yajun , Glaubius Robert , Abbas Ume 
Published: October 2017

Abstract

Background
Antiretroviral therapy (ART) is critical for ending the HIV epidemic. Tenofovir-containing ART is the first-line regimen in many countries including South Africa, with limited access to second-line ART. High levels of drug resistance have been reported among patients after virologic failure on tenofovir-containing first-line regimens (TenoRes Study, Lancet Infect Dis 2016). We assessed drug resistance at the population level using mathematical modeling.

Methods
We developed a stochastic individual-based model of the heterosexual HIV epidemic in KwaZulu-Natal South Africa, and compared drug resistance from scenarios of tenofovir-containing ART scale-up, either CD4-based (threshold &lt; 500 cells/mL) or Fast-track (80% coverage by 2020). The model represents details of HIV transmission and disease progression, demography, sexual behavior, condom use, circumcision, treatment interventions and drug resistance dynamics including key mutations (M184V, K65R and non-nucleoside reverse transcriptase inhibitor (NNRTI)). Using an initial population of 2.5 million, we performed 100 simulations from 1978 to 2030. We examined the prevalence of (majority) transmitted and acquired resistance by 2030.

Results
The total resistance (proportion of HIV-infected persons with drug resistance) reached 34% from CD4-based ART by 2030, with 30% relative contribution from transmitted resistance and 70% from acquired resistance. In contrast, Fast-track ART reduced the total resistance to 22%; though, there was an increased relative contribution from transmitted resistance (~ 50%). In both scenarios, NNRTI mutations were the most prevalent, followed by M184V and K65R mutations. About 48% of persons with acquired drug- resistance harbored dual drug mutations, 44.7% had triple mutations and 7.3% just single mutations, from CD4-based ART. The respective estimates from Fast-track ART were similar; 49% for dual, 44.1% for triple and 6.9% for single mutations. In both scenarios, NNRTI mutations comprised about 80% of prevalent transmitted resistance.

Conclusion
Current WHO-recommended first-line ART could lead to substantial drug resistance. Effective surveillance for resistance transmission and access to second-line regimens would be crucial.

Disclosures
All authors: No reported disclosures.
Routinization of HIV & HCV Testing in the Inpatient Setting: Involvement of Residents and Nurses
Authors: Buluku Gabriel , Bjornholm Sally , Brown Travis , Mignano Jamie , Schmalzle Sarah 
Published: October 2017

Abstract

Background
Approximately 1 in 5 and 1 in 2 of people infected with HIV and HCV respectively in the US are unaware of their infection. Risk based opt-in testing strategies result in missed or delayed diagnoses and may further stigmatize these illnesses. The use of routine opt-out testing increases test uptake and can identify patients with HIV or HCV early, resulting in improved outcomes and decreased transmission. This strategy has not yet been fully accepted or operationalized in many health care settings.

Methods
We implemented routine opt-out HIV and HCV testing for all inpatients using internal medicine resident and nurse driven screening models. Patients were eligible for each test if they had not been tested within 1 year and were not known to be infected. Residents were educated on rationale and protocols for routine opt out testing via one grand rounds lecture (January 2016) and one residency orientation lecture (August 2016). Between March and November 2016, residents were incentivized with gift cards awarded for most tests ordered. Nurses were educated through targeted forums. Instructions were distributed and placed in high traffic areas and HIV 1/2 fourth-generation Ag-Ab and HCV Ab orders were added to admission order sets. Patients were given a chance to decline after routine opt-out testing was offered and educational brochure provided, in accordance with Maryland law. Positive tests were confirmed using Western Blot initially, later changed to HIV 1/2 differentiation assay; HCV was confirmed with HCV RNA. Those with confirmed infection were linked to care.

Results
71% of 3814 and 83% of 2219 eligible patients were tested for HIV and HCV; 54 (2%) and 390 (21%) were diagnosed with HIV and HCV respectively (Figure 1). Testing activity averaged 32 HIV and 28 HCV tests per month from January to March 2016 and increased after the noted interventions to an average of 300 HIV and 247 HCV tests per month from January to March 2017.

Conclusion
A high disease burden was found within the studied population, highlighting the benefit of routine opt out testing for HIV and HCV. Empowering residents and nurses to offer screening at time of admission is a viable strategy to scale up testing in the inpatient setting.

Disclosures
All authors: No reported disclosures.
Can an HIVSmart! App-optimized Self-Testing Strategy be Operationalized in Canada?
Authors: Pai Nitika Pant , Smallwood Megan , Desjardins Laurence , Goyette Alexandre , Vassal Anne-Fanny , Thomas Réjean 
Published: October 2017

Abstract

Background
Although HIV self-tests are recommended by the WHO, they are not yet approved in Canada. Service delivery gaps such as linkages to counseling and care remain unachieved by offering self-tests without adequate support. In this first Canadian study, we evaluated the feasibility of operationalizing an innovative HIVSmart! app-optimized oral HIV self-testing strategy in men who have sex with men (MSM), presenting at a large sexual health clinic in Montreal.

Methods
Between July 2016 to February 2017, participants were offered the OraQuick In-Home HIV Test, and a tablet installed with the HIVSmart! app, at a private office in the clinic to simulate an unsupervised home environment. With the HIVSmart! app, participants independently performed and interpreted self-tests, and were linked to in-person post-test counseling and care. Self-test results were confirmed by laboratory tests (p24, Western Blot, RNA as needed).

Results
The mean age of the 451 participants was 34 years (18–73); 85% were well educated (beyond high school, n = 371/438); 53% (230/438) were frequent testers (past 6 months), and 13% were on PrEP (52/451). 99% (417/422) of participants found the HIVSmart! app helpful in guiding them through the self-testing procedure; 93% (418/451) of participants interpreted their tests accurately; and 94% (395/419) stated they would recommend the app-optimized self-testing strategy to their partners. Feasibility (completion rate of self-testing) was 93% (419/451), and acceptability of the strategy was high at 99% (451/458). All HIV self-test negative participants (448/451, 100%) were counseled following the self-test. Three participants self-tested positive, were confirmed HIV positive (0.7% prevalence), and were rapidly linked to care with a physician.

Conclusion
The HIVSmart! app-optimized strategy was feasible, and highly accepted by an educated, frequently testing, urban MSM population of Montréal. With the app, participants were able to interpret their test results accurately and were rapidly linked to care. Innovations like HIVSmart! which engage, aid, and facilitate linkages to care, can be adapted to suit the needs of many populations in Canada and internationally, maximizing global impact through reverse innovation.

Disclosures
All authors: No reported disclosures.
No Emergent Resistance in HIV-1 Infected Virologically-Suppressed Subjects Who Switched to R/F/TAF
Authors: Porter Danielle , Kulkarni Rima , Cao Huyen , Sengupta Devi , White Kirsten 
Published: October 2017

Abstract

Background
GS-US-366-1216 and GS-US-366-1160 are randomized, double-blind, phase 3b studies evaluating the safety and efficacy of switching to rilpivirine/emtricitabine/tenofovir alafenamide (R/F/TAF) from R/F/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/F/TDF, respectively, in HIV-1-infected virologically-suppressed subjects. At Week 48, switching to R/F/TAF was non-inferior to staying on R/F/TDF (94% vs. 94%, respectively) or EFV/F/TDF (90% vs. 92%) for HIV-1 RNA &lt;50 c/mL (virologic success) by FDA snapshot analysis. Here, we present integrated resistance analyses of these two studies through Week 48.

Methods
Historical genotypes were collected when available. Subjects in the resistance analysis population (subjects with HIV-1 RNA ≥400 c/mL at virologic failure, discontinuation, or Week 48) had genotypic/phenotypic analyses at failure for protease and reverse transcriptase (RT; PhenoSense GT, Monogram). Subjects with post-baseline resistance mutations detected had their baseline proviral DNA analyzed retrospectively (GenoSure Archive, Monogram).

Results
Of the 1504 randomized and treated subjects, resistance development was analyzed for 7 subjects (0.9%; 7/754) on R/F/TAF, 1 subject (0.3%; 1/313) on R/F/TDF, and 2 subjects (0.5%; 2/437) on EFV/F/TDF. No R/F/TAF (0%) or R/F/TDF (0%) subjects developed primary NNRTI or NRTI resistance mutations. One EFV/F/TDF subject (0.2%; 1/437) developed primary NNRTI and NRTI resistance mutations (NNRTI: Y188L; NRTI: M184V). Three subjects on R/F/TAF had virologic rebound with mutations also detected at baseline by proviral DNA analysis. Historical genotypes were available for 527 subjects; virologic success rates were high among subjects with pre-existing mutations (Table 1).

Conclusion
No emergent resistance to any of the components of R/F/TAF was detected through 48 weeks after switching. Virologic success rates were high among subjects with pre-existing mutations.

Disclosures
D. Porter, Gilead Sciences, Inc.: Employee and Shareholder, Salary; R. Kulkarni, Gilead Sciences, Inc.: Employee and Shareholder, Salary; H. Cao, Gilead Sciences, Inc.: Employee and Shareholder, Salary; D. Sengupta, Gilead Sciences Inc.: Employee and Shareholder, Salary; K. White, Gilead Sciences, Inc.: Employee and Shareholder, Salary