bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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 >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

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

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

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 < 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

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

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

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 <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
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

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

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 >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 < 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 > 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

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 >200 copies/mL in 41 (47%); and CD4 count was <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

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 <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

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 >=2 years with consistent plasma HIV-1 RNA <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 <1000 copies/mL for >=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

Background

The use of abacavir (ABC) and rilpivirine (RPV) in the first-line regimen for naïve HIV-infected patients with pretreatment HIV RNA >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 <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 <100,000 copies/mL were anemia [odds ratio (OR) 2.05 vs. no anemia; 95% confidence interval (CI) 1.28–3.27], CD4 count >200 cells/mm3 (OR 3.00 vs. CD4 count <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 <35 years (11), CD4 count >200 cells/mm3 (27), duration of HIV infection >1 year (9), and weight >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 <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

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

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

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 >/ = 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 <3 vs. 3 to 5 vs. >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 <5 vs. >/ = 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

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 <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.
Real-world Evaluation of Ceftolozane/Tazobactam (C/T) Use and Clinical Outcomes at an Academic Medical Center in Las Vegas
Authors: Leuthner Kimberly D , Kullar Ravina , Jayakumar Becky , Hewlett David A , Nguyen Truong , Puzniak Laura
Published: October 2017

Background

There is a global increase in Gram-negative (GN) pathogens, with Enterobacteriaceae and Pseudomonas aeruginosa(PSA) being the major threats in clinical practice. C/T is a novel antipseudomonal cephalosporin combined with an established β-lactamase inhibitor, approved for the treatment of complicated intra-abdominal and urinary tract infections. The objective was to describe the real-world clinical use and outcomes associated with C/T.

Methods

This retrospective descriptive study included adult patients treated with C/T > 48 hours from July 1, 2015–February 28, 2017 at University Medical Center of Southern Nevada. Treatment was considered empiric when antibiotic was given prior to culture results. Escalation was the additional of an aminoglycoside or colistin after the start of C/T.

Results

There were 30 patients in the study. Average age was 57 (SD = 16) and most 19 (63%) were male, Caucasian 22 (73%) and were admitted from the community or home 18 (60%). The most frequent comorbidities were diabetes 13 (43%), heart disease 12 (40%) and chronic pulmonary disease 10 (33%). Previous medical history within 90 days included 15 (50%) hospitalizations, 13 (43%) infections, 6 (20%) Intensive Care Unit stays and 7 (23%) surgeries. All patients received a GN antimicrobial within 30 days prior to C/T. Ninety-three percent of infections were due to PSA and 17 (57%) were polymicrobial. All but 4 patients had multidrug-resistant PSA. The most frequent source of infection (some multiple sources) was respiratory 20 (67%), cUTI 8(27%) and sepsis 5 (17%). Empiric C/T therapy was given to 7 (23%) patients. One patient required escalation of therapy after C/T. Average duration of C/T was 10 (SD = 5.4) days. 23 (77%) patients were discharged within 30 days of last dose of therapy. Microbiological eradication was documented for 12 patients. There were 5 (17%) readmissions, but none associated with a GN infection. Six patients died (1 bilateral stroke, 1 cancer, 2 septic shock, 1 pneumonia and 1 complications of burn).

Conclusion

In this study, C/T was used in patients with serious infections primarily due to PSA, with most patients discharged within 30 days and no patients readmitted due to GN infection. This study provides important insights on how C/T is used in clinical practice.

Disclosures

R. Kullar, Merck & Co., Inc.: Employee, Salary. B. Jayakumar, Merck: Grant Investigator, Research grant. L. Puzniak, Merck: Employee, Salary.
Breaking New Ground: An Evaluation of Susceptibility Breakpoints for Echinocandins against Candida Species
Authors: Bader Justin C , Andes David R , Castanheira Mariana , Ambrose Paul G , Bhavnani Sujata
Published: October 2017

Background

The increasing prevalence of resistant Candida species has led to renewed interest in evaluating the utility of echinocandins. PK-PD target attainment analyses are increasingly used to inform decisions about susceptibility breakpoints. We carried out such analyses to evaluate anidulafungin, micafungin, and caspofungin Clinical and Laboratory Standards Institute (CLSI) susceptibility breakpoints for C. Albicans, C. glabrata, and C. parapsilosis.

Methods

Monte Carlo simulations (n = 2000) were conducted using published population PK models [J Clin Pharmacol 2004; 44:590–598, ICAAC 2008; Abstr A-011, AAC 2013; 57:1664–1671]. The following labeled intravenous dosing regimens for the treatment of candidemia were evaluated: anidulafungin 200 mg followed by 100 mg daily, micafungin 100 mg daily, and caspofungin 70 mg followed by 50 mg daily. Day 1 free-drug plasma AUC values were calculated for simulated patients after administration of each agent. Free-drug plasma AUC:MIC ratio targets associated with 1-log10 CFU reductions from baseline of C. Albicans and C. glabrata for anidulafungin, micafungin, and caspofungin, derived from neutropenic murine disseminated candidiasis models, were used [AAC 2007; 52:539–550, AAC 2010; 54:2497–2506]. Similar such targets for C. parapsilosis were utilized to evaluate caspofungin and micafungin. Percent probabilities of PK-PD target attainment were computed by MIC. The results were evaluated in the context of MIC distributions for each pathogen from a collection of isolates obtained worldwide from 2014 to 2015 [ECCMID 2017; Abstr P1748].

Results

Among the CLSI susceptibility breakpoints evaluated, only one was supported by the analysis results shown in Figure 1 (caspofungin vs. C. glabrata), and only one other susceptibility breakpoint was within one dilution of the highest MIC at which the percent probability of PK-PD target attainment was ≥90% (anidulafungin vs. C. glabrata). All other susceptibility breakpoints were ≥2 dilutions above this MIC.

Conclusion

These results demonstrate the need to re-evaluate the echinocandin susceptibility breakpoints for Candida spp. Establishing appropriate susceptibility breakpoints will ensure appropriate prescribing and optimal patient outcomes.

Disclosures

All authors: No reported disclosures.
Impact of an Extended Infusion Β-lactam Strategy on Outcomes in Critically Ill Patients with Pseudomonas Infections
Authors: Klinker Kenneth , Venugopalan Veena , Carnley Andrea , Voils Stacy , Cope Jessica , Cherabuddi Kartikeya
Published: October 2017

Background

Pseudomonas aeruginosa (PSA) is frequently associated with nosocomial infections resulting in significant morbidity and mortality. High MICs in MDR strains highlights the need to maximize antibiotic exposure with the goal of improving patient outcomes. For β-lactams, optimal efficacy is achieved when free drug concentrations are above the MIC for ~ 40–60% of the dosing interval. Unfortunately, due to significant pharmacokinetic variability in the critically ill, achieving this target with standard intermittent infusions (II) is challenging, resulting in preference for extended (EI) or continuous infusion strategies. Additional data in patients with PSA infections are needed to understand the association between infusion strategy and clinical outcome.

Methods

A single-center, retrospective chart review. Adult patients with positive respiratory or blood cultures for PSA treated with cefepime or piperacillin/tazobactam managed in an ICU from January 2012 to May 2016 were included. Primary endpoint was clinical cure (CC) at end of therapy (EOT) between patients receiving EI or II. Secondary endpoints included microbiologic eradication (ME), 28-day mortality, length of ICU and hospital stay, and effect of baseline kidney function on clinical cure.

Results

Eighty-three patients were included in the analysis. Patient characteristics were well matched except for a higher frequency of malignancy in the EI arm (P = 0.02). CC was achieved in an overwhelming majority of EI patients compared with II (89.2% vs. 69.6%, P = 0.031). Further, patients with normal renal function (CrCL ≥ 60; P = 0.02) or APACHE II ≥ 17 (P = 0.04) receiving II experienced higher failure rates. In multivariate analysis, use of II associated with 4-fold higher incidence of clinical failure (OR 4.5 [1.3–16.3]). For other secondary endpoints, ME was observed in 73% of EI vs. 65% of II (P = 0.44) and 28-day mortality was observed in 13% of patients in both arms (P = 0.94). No significant differences were observed with other secondary variables.

Conclusion

Use of an EI strategy in critically ill patients with PSA infections improves CC. Further, EI benefitted those patients with normal to augmented renal clearance suggesting that improved exposure may play a role in clinical outcomes.

Disclosures

K. Klinker, The Medicines Company: Scientific Advisor, Consulting fee.