bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tigecycline Susceptibility Trends Among Pathogens Isolated from Complicated Skin and Soft-Tissue Infections in North and Latin America: 2012–2016
Authors: Hoban Daryl , Renteria Martha , Leister-Tebbe Heidi , Sahm Dan 
Published: October 2017

Abstract

Background
The Tigecycline Evaluation Surveillance Trial (TEST) monitors the activity of tigecycline and other antimicrobials against clinically-relevant pathogens collected globally. This study reports the activity of tigecycline (TGC) against Gram-positive and Gram-negative isolates collected in North and Latin America from patients with complicated skin and soft-tissue infections (CSSTI).

Methods
Hospital sites from North America (NA) and Latin America (LA) collected non-duplicate clinical Gram-positive and -negative isolates from various complicated skin and skin structure infection sources during 2012–2016. Organism identification and antibiotic susceptibility (S) testing was performed by the local laboratories. Susceptibility testing was determined using the broth microdilution method according to CLSI guidelines and categorical interpretation of results was done using CLSI or FDA (tigecycline) breakpoint criteria where appropriate. Cefoxitin disk testing was performed for all S. aureus to determine methicillin susceptibility (i.e., MRSA and MSSA).

Results
The table provides %S and MIC90 data for TGC against CSSTI isolates

Conclusion
Based on %S and MIC90 data TGC exhibited potent activity against isolates of all organism groups from complicated skin and soft-tissue infections, regardless of the geographic region. However, given the potential many of these organisms have for developing resistance, continued and careful surveillance monitoring is warranted.

Disclosures
M. Renteria, IHMA, Inc.: Employee, Salary. H. Leister-Tebbe, Pfizer: Employee, Salary
Efavirenz-metabolizing polymorphisms, viral suppression, and depression in HIV-infected individuals initiating antiretroviral therapy in southwestern Uganda
Authors: Chang Jonathan , Lee Sulggi , Hunt Peter , Kroetz Deanna , Siedner Mark 
Published: October 2017

Abstract

Background
Single-nucleotide polymorphisms (SNPs) in CYP2B6 have previously been associated with a 10-fold range in trough plasma efavirenz concentrations, but associations between these SNPs and efavirenz (EFV)-mediated viral suppression and tolerability remain unclear.

Methods
We evaluated three SNPs in CYP2B6 (rs3745274, rs28399499, and rs4803419, Illumina OmniExpress) among HIV-infected Ugandans observed in a cohort study every 3–4 months from 2005–2015. Genotypes from these SNPs were used to group participants into previously described pharmacokinetic strata: extensive (EXT), intermediate (INT), and slow metabolizers (Figure 1). The primary outcomes were viral suppression, defined by an undetectable viral load in the first measurement a minimum of three months after ART initiation, and incident depression in the first two years, defined by a mean score &gt;1.75 on the Hopkins Symptom Checklist. We fitted standard and generalized estimating equations (GEE) logistic regression models for viral suppression and depression, respectively. Models were adjusted for clinical and demographic covariates that reached a significance of P &lt; 0.25 in unadjusted models.

Results
Among 103 participants with genotyping, there were no differences in pre-ART viral load or depression by metabolism strata (P &gt; 0.5). Minor allele frequencies for rs3745274, rs28399499, and rs4803419 were 33%, 7%, and 4%, respectively. Approximately 79%, 78%, and 94% of participants were suppressed at their first viral load measurement in the extensive, intermediate, and slow metabolizer strata, respectively (Figure 2; P = 0.35). In adjusted models, metabolism strata were not associated with viral suppression (AORINT 0.81, 95% CI 0.26–2.56; AORSLOW 3.92, 95% CI 0.39–39.40) or with depression (AORINT 1.95, 95% CI 0.75–5.09; AORSLOW 0.72, 95% CI 0.17–3.02; Table).

Conclusion
We did not identify an association between efavirenz-metabolizing polymorphisms and viral suppression or depression in a cohort of HIV-infected individuals initiating ART in southwestern Uganda. Future work should reassess these relationships with larger samples and longer-term outcomes and explore additional polymorphisms that may be associated with efavirenz metabolism in this population.

Disclosures
P. Hunt, Merck: Consultant, Consulting fee; Gilead: Consultant, Consulting fee; Viiv: Consultant, Consulting fee
Darunavir and Dolutegravir Combination Therapy in ART experienced HIV-infected Patients: A Preliminary Report
Authors: Stang Alexandra , Perry Tracy , Fadul Nada 
Published: October 2017

Abstract

Background
Patients with HIV may require change in therapy for simplification, salvage, or to avoid side effects. There is limited data on the use of dolutegravir (DTG) and ritonavir- or cobicistat-boosted darunvair (DRV) combination therapy alone or with additional active agents in patients with HIV. The objectives of this study were to describe the current use and indications of DTG/DRV combination and to evaluate its effectiveness on viral load suppression (VLS).

Methods
A retrospective chart review of HIV-infected patients, 18 years or older, seen at our clinic between August 2013 and December 2015 who were on DRV/DTG combination alone or with additional active agents was conducted. Demographic, clinical, and laboratory information was collected. Descriptive statistics were used for data analysis.

Results
Eighty-seven patients were included in the study: 64 (74%) on DRV/DTG alone and 23 (26%) on DRV/DTG plus additional agents. Mean age was 49.3 (18–79); 29 (33.3%) were female; and 77 (89%) were black. Coronary artery disease (CAD) or CAD equivalent was present in 27 (31%), chronic kidney disease in 24 (28%), and chronic hepatitis B infection in 3 (3%) patients. The majority 86 (99%) of patients were treatment experienced; 60 (69%) had been treated with 3 or more antiretroviral drug classes; 57 (66%) were integrase experienced, including 6 (6.9%) with baseline integrase resistance. Baseline HIV viral load was &gt;200 copies/mL in 41 (47%); and CD4 count was &lt;200 in 29 (33%) patients. Reason for switch was reported as salvage in 42 patients (48%) simplification in 33 patients (38%), renal impairment in 11 patients (13%), and other in 6 patients (7%). VLS was achieved or maintained in 40 of 46 patients (87%) who presented for follow up at 6–8 weeks, 25 of 28 (89%) at 3–4 months, 35 of 41 (85%) at 5–6 months, and 55 of 61 (90%) at 7–12 months after starting therapy. Six patients were later switched off of DRV/DTG to another combination, of whom only two required switch due to intolerance (rash in 1 and large pill size in 1).

Conclusion
Our preliminary results suggest that darunavir/dolutegravir combination is a viable switch option in HIV patients with the majority of patients achieving or maintaining VLS at 1 year of follow up and only 2 patients required a regimen change due to intolerance.

Disclosures
All authors: No reported disclosures.
Comparison of Time to Viral Suppression Among Treatment-Naïve HIV-Infected Adults Initiating Combination Antiretroviral Therapy by Antiretroviral Regimen Class
Authors: Jacobson Karen , Ogbuagu Onyema 
Published: October 2017

Abstract

Background
Antiretroviral therapy (ART) regimens for the treatment of HIV that incorporate the integrase strand inhibitor (INSTI) class of antiretroviral medications have high efficacy and tolerability, and may result in faster time to virologic suppression compared with regimens that contain protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, differences in viral suppression are not well-defined in routine clinical settings.

Methods
We performed a retrospective single-center chart review of treatment-naïve HIV patients initiating ART between 2013 and 2016. Among patients on different ART regimen types, we compared rates of achievement of viral suppression (defined as viral load less than limit of detection or &lt;20 copies/uL) over time and median time to viral suppression using chi-square and independent samples median testing. Patients who were prescribed nonstandard regimens, were nonadherent, or discontinued or changed ART within 6 months were excluded.

Results
One hundred and fifty-five patients—45 (29.0%) female and 110 (71%) male—met study inclusion criteria. Mean age at ART initiation was 41.3 years (SD 12.5), and mean baseline viral load was 293,974 copies/uL. Twelve (7.7%) patients had an opportunistic infection diagnosed at time of ART initiation. Seventy-one (45.8%) initiated an INSTI-based ART regimen, 58 (37.4%) initiated a NNRTI-based regimen, and 26 (16.8%) initiated a PI-based regimen. Eighty-one (52.3%) patients had documented viral suppression, with median time to viral suppression 105 days (IQR 49–159). Patients on INSTI regimens were more likely to achieve viral suppression by 6 months (93.2% compared with 69.7% on NNRTIs and 30.8% on PIs), and had lower median time to suppression (62.6 days vs. 140.5 days on NNRTI regimens and 154.5 days on PI regimens, P = 0.002).

Conclusion
In this cohort, patients on INSTI-based ART regimens experienced higher rates of viral suppression at 6 months and shorter time from ART initiation to viral suppression. In HIV patients on INSTI-based ART regimens, virologic failure should be suspected prior to the current recommendation of 6 months.

Disclosures
All authors: No reported disclosures.
Weight Gain After Switch from Efavirenz-Based to Integrase Inhibitor-Based Regimens
Authors: Norwood Jamison , Turner Megan , Bofill Carmen , Jenkins Cathy , Bebawy Sally , Rebeiro Peter , Hulgan Todd , Raffanti Stephen , Haas David , Sterling Timothy R , Koethe John 
Published: October 2017

Abstract

Background
Integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) offers persons living with HIV a potent new treatment option. Recently, local HIV clinicians noted weight gain in patients who switched from daily, fixed-dose efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) to fixed-dose dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). To assess whether regimen switch was significantly associated with weight gain, we evaluated body weight over time among patients with sustained virologic suppression who switched from EFV/TDF/FTC to an INSTI-containing regimen, including DTG/ABC/3TC.

Methods
We analyzed data from adult patients on EFV/TDF/FTC for &gt;=2 years with consistent plasma HIV-1 RNA &lt;1000 copies/mL prior to date of switch (or date of sham switch for those who remained on EFV/TDF/FTC). All maintained HIV-1 RNA &lt;1000 copies/mL for &gt;=18 months post-switch. We assessed weight change over 18 months in patients switched to an INSTI-containing regimen or a protease inhibitor (PI)-containing regimen vs. those remaining on EFV/TDF/FTC over the same period. In a sub-group analysis, we compared patients switched to DTG/ABC/3TC vs. raltegravir- or elvitegravir-containing regimens. Linear mixed effects models assessed mean differences in weight over time, adjusting for baseline age, sex, race, CD4+ count and weight.

Results
Among 495 patients, 136 switched to an INSTI-containing regimen, 34 switched to a PI-containing regimen, and 325 remained on EFV/TDF/FTC. Patients switched to an INSTI-containing regimen gained an average of 2.9 kilograms (kg) at 18 months compared with 0.9 kg among those continued on EFV/TDF/FTC (P = 0.003, Figure a), while those switched to a PI regimen gained 0.7 kg (P = 0.81, Figure b). Among INSTI regimens, those switched to DTG/ABC/3TC gained 5.3 kg at 18 months, which was more than raltegravir or elvitegravir regimens (P = 0.19, Figure c) and significantly more than those continued on EFV/TDF/FTC (P = 0.001, Figure d).

Conclusion
Switching from daily, fixed-dose EFV/TDF/FTC to an INSTI-containing regimen among patients with virologic control was associated with weight gain at 18 months. This weight gain was particularly profound among those switching to DTG/ABC/3TC.

Disclosures
All authors: No reported disclosures.
A Prediction Model of Pretreatment HIV RNA Levels in Naïve Thai HIV-infected Patients: An Application for Resource-limited Settings
Authors: Pongpech Nisha , Avihingsanon Anchalee , Chaiwarith Romanee , Kantipong Pacharee , Boettiger David , Ross Jeremy , Kiertiburanakul Sasisopin 
Published: October 2017

Abstract

Background
The use of abacavir (ABC) and rilpivirine (RPV) in the first-line regimen for naïve HIV-infected patients with pretreatment HIV RNA &gt;100,000 copies/mL is not recommended due to a high rate of treatment failure. If a model could accurately predict pretreatment HIV RNA levels, it would be a useful tool for the selection ABC or RPV in the first-line regimen.

Methods
Thai HIV-infected adults enrolled in the TREAT Asia HIV Observational Database (TAHOD) and additional patients of Ramathibodi Hospital were eligible if they had an HIV RNA result at the time of antiretroviral therapy initiation. Factors associated with pretreatment HIV RNA &lt;100,000 copies/mL were determined by logistic regression. Based on the results of the final model, a prediction model was created.

Results
A total of 1,223 patients were included in the analysis. Among those in the derivation data set, median [interquartile range (IQR)] age was 36.3 (30.5–42.9) years, median (IQR) CD4 count was 122 (39–216) cells/mm3, and pretreatment HIV RNA was 100,000 (32,449–229,777) copies/mL. Factors associated with pretreatment HIV RNA &lt;100,000 copies/mL were anemia [odds ratio (OR) 2.05 vs. no anemia; 95% confidence interval (CI) 1.28–3.27], CD4 count &gt;200 cells/mm3 (OR 3.00 vs. CD4 count &lt;200 cells/mm3; 95% CI 2.08–4.33), and non-heterosexual HIV exposure (OR 1.61 vs. heterosexual HIV exposure; 95% CI 1.07–2.43). No AIDS-defining illness (11.5), no anemia (18.5), age &lt;35 years (11), CD4 count &gt;200 cells/mm3 (27), duration of HIV infection &gt;1 year (9), and weight &gt;50 years (11) were included in the clinical prediction tool scores. A score ≥45 yielded a sensitivity of 45.3%, specificity of 76.7%, positive predictive value of 68.1%, and negative predictive value of 56.1% among patients in the derivation. The area under the receiver-operator characteristic curve was 0.655 (95% CI 0.614- 0.696) and 0.600 (95% CI 0.533–0.667) in the derivation and validation patients, respectively.

Conclusion
Our final prediction model had poor sensitivity and specificity for predicting HIV RNA &lt;100,000 copies/mL. Further study on a larger population with a greater diversity of data variables available is necessary to improve the model. Pretreatment HIV RNA remains necessary before ABC or RPV initiation for naïve Thai HIV-infected patients.

Disclosures
All authors: No reported disclosures.
The Costs of Home-Based ART Initiation and Mobile Refill in Uganda
Authors: Roberts D Allen , Asiimwe Stephen , Turyamureeba Bosco , Barnabas Ruanne 
Published: October 2017

Abstract

Background
Antiretroviral therapy (ART) is effective at reducing HIV-associated morbidity, mortality, and transmission, but 20 million people who meet WHO eligibility criteria for ART are not in care. While decentralized care is a promising strategy to expand ART access, the costs of implementing a community-based model on a large scale remain unknown.

Methods
The DO-ART study is a randomized trial of community- vs. clinic-centered ART delivery in South Africa and Uganda using 12-month viral suppression as the primary outcome. We evaluated the costs of home-based ART initiation and refill in southwest Uganda using time-and-motion studies, staff interviews, and budgetary analysis. Costs categories included medications, supplies, personnel, building and utilities, start-up, vehicles, and community mobilization. We used a programmatic perspective with a 3% discount rate and removed research-associated costs.

Results
The largest cost categories included medications, supplies, and salaries, constituting 41%, 27%, and 17% of the total cost, respectively. Time-and-motion studies revealed that each outreach worker could serve an average of three patients per day in a fully decentralized model. In a scenario of providing home-based ART to 1400 patients aross seven sub-counties, the yearly per-patient cost was estimated to be $304 (2016 USD), which is similar to literature reports of the costs of facility-based ART provision.

Conclusion
These estimates suggest that home-based ART may be a realistic delivery option, especially if it is found to be effective at improving viral suppression. Further research is needed to evaluate how this intervention can most efficiently scale to provide widespread ART access over a large geographic area.

Disclosures
All authors: No reported disclosures.
Partnerships between a University-Affiliated Clinic and Community Based Organizations to Reach Black Men who have Sex with Men for PrEP Care
Authors: Clement Meredith , Okeke Nwora Lance , Munn Terry , Hunter Miguel , Alexis Kareem , Corneli Amy , Sena Arlene , McGee Kara , McKellar Mehri 
Published: October 2017

Abstract

Background
While pre-exposure prophylaxis (PrEP) is a promising strategy for reducing HIV transmission, persons at highest risk for infection are not being adequately reached, particularly Black Men who have Sex with Men (MSM).

Methods
In December 2015, a dedicated PrEP clinic was established at Duke University Medical Center in Durham, North Carolina (NC). We performed a retrospective review of patients evaluated at the PrEP clinic, abstracting the following routinely collected variables: age, race, ethnicity, sex at birth, self-identified gender, HIV risk factors and source of referral. Descriptive statistics are presented as medians and frequencies.

Results
Over 18 months, 91 patients were evaluated. Most were male (90%, n = 82), approximately half were non-Hispanic Black (46%, n = 42), and median age was 31 years (range 19–66). Most patients identified as MSM (78%, n = 71) and 3 (3%) were transgender women who have sex with men (TGW). Specifically, 30% (n = 27) were Black MSM or TGW. Risk factors for all patients included multiple sexual partners (65%), known HIV+ partner (19%), or a recent sexually transmitted infection (16%). One-quarter of patients (n = 23) were uninsured. Among all Black patients, the most common source of referral was a community-based organization (CBO) (40%, n = 17), and specifically, Black MSM and TGW were most commonly referred by a CBO (44%, n = 12). Among White patients, most were self-referrals (47%, n = 18). Demographic characteristics of our patient population relative to those newly diagnosed with HIV in NC in 2015 are shown in Table 1.

Conclusion
Although further efforts are needed to improve PrEP uptake in underserved populations in NC, the racial breakdown of our PrEP clinic is more representative of the national HIV epidemic as compared with all PrEP users in the US. Our study demonstrates that community partnerships can be a valuable avenue for patient recruitment and achieve success in reaching Black MSM with messages about PrEP.

Disclosures
All authors: No reported disclosures.
Correlating Isavuconazole Serum Levels with Efficacy and Adverse Effects (AE) Among Immunocompromised Patients
Authors: Kim Pauline , Tegtmeier Bernard , Dadwal Sanjeet , Ito James , Kriengkauykiat Jane 
Published: October 2017

Abstract

Background
Isavuconazole (ISV) is an antifungal approved for treatment of invasive aspergillosis and mucormycosis. Although data correlating response to serum levels is lacking, we found in a previous report a trend towards increased side effects with elevated serum trough levels. This study expands to a larger population to evaluate ISV trough levels in relation to clinical outcomes and side effects (AE).

Methods
Patients who received ISV &gt;/ = 7 days with serum trough levels from April 2015 to September 2016 were included in AE analysis. Patients with proven or probable invasive fungal infection (IFI) were evaluated for response. Demographics, ALT, total bilirubin, serum creatinine, QTc, 14-, 30-, and 90-day response (complete, partial or no response) were collected.

Results
94 patients were evaluated for response. At baseline, 39% were female, 70% had leukemia, 55% had hematopoietic cell transplant (87% were allogeneic), and 73% had active disease (relapsed, progressing, newly diagnosed). Of the IFIs, 64% were due to Aspergillus species, 12% Mucorales, and 4% Fusariumspecies. Response rates for patients by trough levels &lt;3 vs. 3 to 5 vs. &gt;5 mcg/mL are as follows: 14-day was 32% vs. 32% vs. 25%, 30-day was 48% vs. 52% vs. 44%, and 90-day was 39% vs. 50% vs. 33%, all P = NS.
205 patients were evaluated for AE in relation to trough levels. In comparing patients with trough levels &lt;5 vs. &gt;/ = 5 ug/mL, ALT levels 3 times upper limit was 18% vs. 36% (P = 0.032), total bilirubin 3 times upper limit was 22% vs. 32% (P = 0.79), serum creatinine 3 times upper limit was 7.8% vs. 12% (P = 0.47), and QTc interval was 1% vs. 2% mean decrease from baseline (P = 0.9).

Conclusion
Higher ISV levels were associated with increased ALT. ISV levels did not show apparent correlation with response rates, but there is a trend towards improved response rates with ISV levels between 3 - 5 ug/mL.

Disclosures
S. Dadwal, Merck: Investigator, Research support. GlaxoSmithKline: Investigator, Research support. Ansun Biopharma: Investigator, Research support. Oxford Immunotec: Investigator, Research support. Gilead Sciences: Investigator, Research support. J. Ito, Astellas: Speaker’s Bureau, Speaker honorarium.
Genetic Polymorphisms influencing Low Posaconazole Plasma Concentration in Patients with Hematologic malignancies
Authors: Suh Hyeon Jeong , Lee Eunyoung , Song Kyoung-Ho , Choe Pyeong-Gyun , Bang Ji Whan , Kim Eu Suk , Kim Hong Bin , Park Sang Won , Kim Nam Joong , Park Wan Beom , Oh Myoung-Don 
Published: October 2017

Abstract

Background
There are poor absorbers for posaconazole oral suspension who show low posaconazole plasma concentration (PPC) despite increased dosage. Posaconazole metabolism is mediated mainly by the UDP-glucuronosyltransferase (UGT) enzyme, especially the enzyme UGT1A4. The aim of this study was to investigate the effects of genetic polymorphisms on the PPC.

Methods
This prospective study was conducted from September 2014 to August 2016. We enrolled patients with acute myeloid leukemia or myelodysplastic syndrome who received a posaconazole oral suspension of 200 mg three times daily for fungal prophylaxis. The steady-state PPC on day 8 was measured by liquid chromatography-tandem mass spectrometry. The multi-drug resistance gene 1 C3435T and G2677T/A variations, and UGT1A4*3b were examined by direct sequencing of DNA from peripheral whole blood samples. We defined the poor absorbers as those with PPC &lt;200 ng/mL and the optimal PPC as ≥700 ng/mL. The associations between genetic polymorphisms and PPC were evaluated using multivariate logistic regression analysis including clinical variables.

Results
In the study period, 155 patients were enrolled. The median age of patients was 56 years (interquartile range, 44–64 years), and 54.2% were man. Six patients (3.9%) were defined as poor absorbers and 57 patients (36.8%) did not reach the optimal PPC on day 8. In multivariate analysis, the independent risk factors for poor absorber were at least 1 UGT1A4*3b allele (adjusted odds ratio [aOR], 7.756; 95% confidence interval [CI], 1.034–58.152; P = 0.046) and poor oral intake (aOR per 100 kcal, 0.727; 95% CI, 0.555–0.953; P = 0.021). There was no statistically significant association between the genetic polymorphisms and the optimal PPC on day 8.

Conclusion
The UGT1A14*3b polymorphism is an independent risk factor for poor absorbers for posaconazole oral suspension in patients with hematologic malignancies.

Disclosures
All authors: No reported disclosures.