bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transmitted Drug Resistance in Treatment-naïve HIV-Infected VCT clients in Taiwan, 2007–2016
Authors: Tsai Hung-Chin , Chen I-Tzu , Lee Susan Shin-Jung , Chen Yao-Shen 
Published: October 2017

Abstract

Background
The transmission of drug-resistant HIV-1 strains might compromise the efficacy of antiretroviral treatment. The aim of this study was to monitor the prevalence of transmitted drug resistance (TDR) in Taiwan, where free highly active antiretroviral therapy (HAART) was provided since 1997.

Methods
A cohort study on TDR was conducted in antiretroviral therapy -naïve HIV-1 ¡Vinfected voluntary counseling and testing (VCT) clients from 2007 to 2016 in southern Taiwan. Genotypic drug resistance testing to PR/RT (pol gene) were determined by ViroSeqTM system and drug resistance testing to integrase inhibitors (INSTI) was done by in house PCR. Antiretroviral resistance was interpreted using the HIVdb program of the Stanford University HIV Drug Resistance Database. The patients classified as having low-level resistance, intermediate resistance and high-level resistance were defined as having drug resistance. Resistance-associated mutations were defined by the presence of at least one mutation included in the 2017 drug resistance mutation list of the International AIDS Society-USA consensus guidelines.

Results
A total of 29384 individuals received a free HIV anonymously screening test during 2007 to 2016. The positive rate for HIV-1 infection was 2%. Sequences were obtained from 407 individuals, of whom 90% were infected by MSM, and 10% were infected by heterosexually. Subtype B HIV-1 strains were found in 97%, subtype C in 0.3% and subtype CRF01_AE in 2.7%. A total of 6% was found to harbor drug resistance strains. The most common NRTI resistance associated mutation was D67N, M184V, K219N, Y118I and T215S/P. The most common NNRTI resistance associated mutation was Y181C, K103N, V179D and Y318F. No any one harbored resistance to INSTI inhibitors (n = 188).

Conclusion
The resistance prevalence (6%) in this study supported the WHO guideline to prescribe pol resistance testing before initiation of HAART therapy in the treatment naïve patients.

Disclosures
All authors: No reported disclosures.
High Tenofovir Failure Rates in an Emerging, Non-B Subtype HIV Epidemic
Authors: Salvana Edsel Maurice , Schwem Brian , Samonte Genesis , Telan Elizabeth , Tactacan-Abrenica Rosario , Ching Patrick , Mendoza Kevin , Arevalo Geraldine , Alejandria Marissa , Leyritana Katerina , Trinidad Lyka , Penalosa Christine , Lim Jodor 
Published: October 2017

Abstract

Background
The WHO-recommended regimen for antiretrovirals (ARVs) is tenofovir (TDF) + lamivudine/emtricitabine (3TC/FTC) + efavirenz (EFV), based on demonstrated superiority of TDF+FTC+EFV over zidovudine (AZT) +FTC+ EFV in clinical trials. However, there are reports of increasing TDF resistance in non-B subtypes. We have previously shown that HIV genotypes in the Philippines have shifted (https://idsa.confex.com/idsa/2014/webprogram/Paper45090.html) from B to CRF01_AE. We compared failure rates for ARVs during an acquired drug-resistance surveillance study.

Methods
We analyzed ARV data from a study with the Department of Health on treatment failure in Filipinos after one year of treatment. Institutional Board Review approval and informed consent were obtained.

Results
513 adult patients from 3 national treatment hubs (Philippine General Hospital, San Lazaro Hospital, Vicente Sotto Memorial Medical Center) were enrolled and analyzed. Treatment failure (viral load&gt;1000 copies/mL) at one year for specific regimens are summarized in Table 1. No baseline genotyping was available. 53 (10.3%) patients failed treatment. Genotypes among these were CRF01_AE (87%), B (11%) and C (2%). TDF-containing regimens had significantly higher failure rates (43/303;14.2%) than AZT-containing regimens (10/209;4.5%) (P &lt; 0.001). Failure rates for NVP-based regimens (13/85;15.3%) vs. EFV-based regimens (40/424; 9.4%) were not significantly different (P = 0.1064). The most durable regimen (with &gt;3 patients) was AZT+3TC+EFV, and the worst regimen was TDF+3TC+NVP (P &lt; 0.001). Failure rates for TDF+3TC+EFV were significantly higher than for AZT+3TC+EFV (P = 0.0029). There was no significant difference in adherence (P = 0.5531). 53% of unsuppressed patients had a TDF-resistance mutation, compared with 8% for AZT (P &lt; 0.001).

Conclusion
TDF-containing regimens were associated with higher treatment failure rates in our CRF01_AE-predominant HIV epidemic. WHO recommendations for treatment may need be revisited for non-B subtypes.

Disclosures
E. M. Salvana, Merck: Scientific Advisor and Speaker’s Bureau, Consulting fee and Speaker honorarium
Impact of Tablet Burden and Antiretroviral Therapy (ART) Choice on Virologic Outcomes in Treatment Naive HIV+ Individuals Attending an Inner City Clinic
Authors: Markowitz Norman , Tidwell Beni , Lamerato Lois , Zelt Susan , D’Amico Ronald , Schulman Kathy 
Published: October 2017

Abstract

Background
The durability and effectiveness of single tablet regimens (STR) in treating ART naïve patients in real world, inner city settings, has not been well established.

Methods
Data was abstracted from administrative/medical records at Henry Ford Health System, serving metropolitan Detroit, for HIV+ patients initiating ART (1/1/2007–9/30/2015), who were enrolled in the Health Alliance Plan (HAP) or had ≥1 clinician contact per year and ≥1 viral load (VL)/CD4 test result ≤90 days prior to ART initiation. Patients were followed from initiation to first of: change in ART, death, HAP disenrollment, study end (03/31/2016), or lost to follow-up. Cox regression estimated impact of tablet burden on ART regimen duration, achievement of viral suppression (VS) and viral failure—(VF) failure to suppress plasma HIV RNA to &lt;50 copies/mL or rebound after VS.

Results
Among 390 eligible patients, 79% were male, 74% African-American. Median (IQR) age was 37 years (27–47), 49% MSM and 22% presented with AIDS. The majority (65%) initiated on an STR; 35% on multiple tablet regimens (MTR). The majority of STR initiators (63%) began with EFV/FTC/TDF; 24% with EVG/c/FTC/TDF; and 8% with DTG/ABC/3TC. The most frequent MTR were DRV+RTV+TDF/FTC (26%) and ATV+RTV+TDF/FTC (20%). Median (IQR) log10 VL at baseline was 4.8 (4.3–5.2) in STR; 4.8 (4.4–5.4) in MTR cohorts. Median CD4 cells/µL (IQR) was 277 (115–407) in STR; 231 (37–371) in MTR. VL suppression occurred in 81% (85% STR, 74% MTR, P &lt; 0.01) of patients and in 91% of INSTI regimens (91% STR, 90% MTR, P = 0.757).VF occurred in 19% (15% STR, 25% MTR, P = 0.015) and in 10% of INSTI regimens (9% STR, 13% MTR, &#x2028;P = 0.459). Resistance occurred in 15% of VF patients, predominantly with NNRTI mutations. A total of 22% of STR and 60% of MTR initiators experienced a change in their initial ART regimen (P &lt; 0.0001). Cox model results suggest STR initiators were 59% less likely to experience regimen change (P &lt; 0.0001), 46% less likely to experience VF (P &lt; 0.05) and 30% more likely to achieve viral suppression (P &lt; 0.05) compared with MTR initiators.

Conclusion
Inner city, HIV treatment naïve patients, initiating ART with a STR are significantly more likely to achieve viral suppression and less likely to experience a change in ART regimen.

Disclosures
B. Tidwell, ViiV Healthcare: Research Contractor, Research support; L. Lamerato, ViiV Healthcare: Collaborator, Research support; S. Zelt, ViiV Healthcare: Employee and Shareholder, Salary and Stock; R. D’Amico, ViiV Healthcare: Employee and Shareholder, Salary and Stock; K. Schulman, ViiV Healthcare: Research Contractor, Research support
Pharmacokinetics of Cabotegravir in Subjects with Moderate Hepatic Impairment
Authors: Shaik Jafar Sadik , Ford Susan , Lou Yu , Zhang Zhiping , Bakshi Kalpana , Tenorio Allan , Trezza Christine , Spreen William , Patel Parul 
Published: October 2017

Abstract

Background
Cabotegravir (CAB) is an integrase inhibitor in phase 3 clinical trials for the treatment and prevention of HIV. CAB undergoes hepatic metabolism primarily via UGT1A1; thus hepatic impairment has the potential to affect CAB exposure.

Methods
This was a multi-center, single-dose, open-label, parallel group study to evaluate the effect of moderate hepatic impairment on the pharmacokinetics (PK) and safety of CAB. Adults with moderate hepatic impairment as determined by Child-Pugh classification score of 7–9 (n = 8) and matched healthy control subjects (n = 8) were enrolled. Control subjects were matched for gender, age (±10 years), and body mass index (BMI) (±25%). Subjects received oral CAB 30 mg as a single dose in the fasted state followed by serial PK sampling for 168 hours. CAB unbound concentrations at 2 and 24 hours after dosing were determined by equilibrium dialysis. Non-compartmental PK analysis was performed; geometric least squares (GLS) mean ratios (hepatic impaired group/control group) and 90% confidence intervals (CI) were generated.

Results
Sixteen subjects completed study; 12 (75%) male, mean age 59 years (range: 51–67), mean BMI 29 kg/m2 (range: 21–37), and total Child Pugh score in range of 7–9. CAB PK parameters were similar between subjects with moderate hepatic impairment and matched healthy subjects. The GLS mean ratios (90% CI) for AUC(0-∞), Cmax, C24, CL/F, and t1/2 were 0.73 (0.50, 1.06), 0.69 (0.51, 0.93), 0.73 (0.53, 1.02), 1.38 (0.95, 2.01), and 0.82 (0.65, 1.04), respectively. Although highly protein bound, the unbound fraction of CAB was increased in subjects with moderate hepatic impairment relative to healthy subjects with GLS mean ratio (90%CI) of 2.14 (1.57, 2.90) at 2 hours post dose and 1.90 (1.14, 3.18) at 24 hours post dose; this was associated with lower serum albumin concentrations and was not considered clinically significant. All adverse events (AE) were reported as mild (Grade 1) to moderate (Grade 2) in severity and no serious AEs were reported.

Conclusion
Plasma exposures of CAB in subjects with moderate hepatic impairment were similar to those in healthy subjects. No dose adjustment of CAB is required for subjects with mild to moderate hepatic impairment.

Disclosures
J. S. Shaik, GlaxoSmithKline: Employee and Shareholder, Salary; S. Ford, PAREXEL International: Employee, Salary; Y. Lou, PAREXEL International: Employee, Salary; Z. Zhang, PAREXEL International: Employee, Salary; K. Bakshi, GlaxoSmithKline: Employee and Shareholder, Salary; A. Tenorio, ViiV Healthcare: Employee and Shareholder, Salary; C. Trezza, ViiV Healthcare: Employee and Shareholder, Salary; W. Spreen, ViiV Healthcare: Employee and Shareholder, Salary; P. Patel, ViiV Healthcare: Employee and Shareholder, Salary
Pharmacokinetics of Cabotegravir in Subjects with Severe Renal Impairment
Authors: Parasrampuria Ridhi , Ford Susan , Lou Yu , Fu Caifeng , Bakshi Kalpana , Tenorio Allan , Trezza Christine , Spreen William , Patel Parul 
Published: October 2017

Abstract

Background
Cabotegravir (CAB) is an integrase inhibitor in phase 3 clinical trials for the treatment and prevention of HIV. CAB undergoes glucuronidation via UGT1A1 with &lt;1% renal elimination of unchanged CAB. Renal impairment may affect PK of drugs that are primarily metabolized or secreted in bile; thus impact of renal impairment on CAB pharmacokinetics was evaluated.

Methods
This was a multi-center, single-dose study of oral CAB 30mg administered to subjects with severe renal impairment (creatinine clearance [CLcr] &lt;30 mL/minute; not on renal replacement therapy) and to healthy controls (CLcr ≥90 mL/minute) matched for gender, age (±10 years), and body mass index (BMI) (±25%) (8 per group). Serial PK for plasma CAB concentrations were collected through 168 hours post dose and unbound CAB concentrations determined at 2 and 24 hours post dose. Non-compartmental PK analysis was performed; geometric least squares (GLS) mean ratios and 90% confidence intervals (CI) were generated.

Results
Sixteen subjects completed study; 12 (75%) male, mean age 54 years (range:35–69), mean BMI 28 kg/m2 (range: 24–35), and mean CLcr 22 mL/minute (range: 17–29) and 121 mL/minute (range: 95–162) for renal impaired and healthy subjects, respectively. CAB PK parameters were similar between severe renal impairment and healthy subjects. Based on preliminary PK, GLS mean ratios (90% CI) for AUC(0-¥), Cmax, C24, CL/F, and t1/2 were 0.97 (0.835, 1.14), 1.01 (0.865, 1.17), 1.02 (0.868, 1.20), 1.03 (0.881, 1.20) and 0.93 (0.831, 1.04), respectively. Although highly protein bound, the unbound fraction was higher in subjects with severe renal impairment with GLS mean ratio (90%CI) of 1.31 (0.843, 2.03) at 2 hours and 1.51 (1.19, 1.92) at 24 hours post dose. One renal impairment subject developed grade 3 lipase elevation considered drug-related by investigator, otherwise all reported adverse events (AE) were Grade 1 in severity with no serious AEs reported.

Conclusion
Plasma CAB exposures in subjects with severe renal impairment were similar to healthy subjects; therefore, no dose adjustment of CAB is required in renal impairment. Although no data are available, CAB PK is not expected to be affected in subjects undergoing dialysis given CAB’s non-renal clearance and high plasma protein binding (~99%).

Disclosures
R. Parasrampuria, GlaxoSmithKline: Employee and Shareholder, Salary; S. Ford, PAREXEL International: Employee, Salary; Y. Lou, PAREXEL International: Employee, Salary; C. Fu, PAREXEL International: Employee, Salary; K. Bakshi, GlaxoSmithKline: Employee and Shareholder, Salary; A. Tenorio, ViiV Healthcare: Employee and Shareholder, Salary; C. Trezza, ViiV Healthcare: Employee and Shareholder, Salary; W. Spreen, ViiV Healthcare: Employee and Shareholder, Salary; P. Patel, ViiV Healthcare: Employee and Shareholder, Salary
Risk Factors for Pseudomonas aeruginosa in Diabetic Foot Infections
Authors: Farhat Nada , McClung Daniel , Nagel Jerod 
Published: October 2017

Abstract

Background
Infectious Diseases Society of America guidelines for the management of diabetic foot infections (DFIs) suggest 15 different antibiotic treatment options for moderate-to-severe infections. All treatment options provide coverage for Gram-positive cocci, and some provide coverage for Gram-negative pathogens, including Pseudomonas aeruginosa (PSA). However, there is minimal guidance in determining which patients require anti-PSA therapy.

Methods
This single-center retrospective case–control study included patients hospitalized between October 2013 and September 2015. Adult patients admitted with a DFI were identified using a combination of ICD-9 codes for diabetes with complications and cellulitis. The primary outcome was identification of risk factors associated with PSA DFIs. A multivariable model using logistic regression was constructed, and a receiver operator characteristic (ROC) curve was generated to assess the sensitivity and specificity of the model.

Results
262 patients were included and 12 (4.6%) patients had cultures with PSA. Multivariable analysis yielded six risk factors for PSA DFIs (see Table). ROC construction yielded an area under the curve of 0.895.

Conclusion
The incidence of PSA from DFIs is low. A model with excellent performance characteristics demonstrated that risk factors for PSA DFIs include age &gt; 65, BMI ≥ 35, former or current smoker, history of lower extremity bypass procedure, and cardiovascular disease. Future validation of these factors could help stewardship programs reduce unnecessary antibiotic utilization.

Disclosures
All authors: No reported disclosures.
Clinical outcomes associated with once daily ritonavir-boosted darunavir in HIV infected patients harboring single or multi-class resistant virus
Authors: Duggan Joan , Sahloff Eric 
Published: October 2017

Abstract

Background
Limited data exist on the use of a potent boosted protease inhibitor plus &lt;2 active nucleotide reverse transcriptase inhibitors without use of additional classes of ART in treatment experienced patients with background resistance. We evaluated the clinical outcomes in HIV-infected patients harboring single or multi-class resistant virus (NRTI ± PI and/or NNRTI) treated with once daily darunavir/ritonavir (DRV/r) plus tenofovir/emtracitabine (TDF/FTC).

Methods
This was a single-center, retrospective chart review of HIV-1 infected patients harboring single or multi-class resistant virus and receiving an ART regimen of TDF/FTC plus DRV/r administered as a once daily regimen &gt; 24 weeks. The primary outcome was HIV viral load (VL) &lt; 200 copies/mL (cp/mL) at last measurement. Additional endpoints included virologic rebound, re-suppression, and/or failure; VL &lt; 40 cp/mL at last measurement; development of additional mutations. Virologic failure (VF) was defined as failure to achieve a VL &lt; 200 cp/mL or achievement of VL &lt; 200 cp/mL but with rebound to &gt; 200 cp/mL on all successive VLs.

Results
34 of 387 patients meet criteria for inclusion in the study and were receiving DRV 800 mg daily/r 100 mg daily with fixed combination TDF/FTC. All patients had baseline resistance to FTC (M184V/I), 12 (35.3%) had resistance to TDF, and none had high level DRV resistance. 27 (79%) achieved a VL &lt; 200 cp/mL and 25 (74%) had a VL &lt; 200 cp/mL at the last reading. 23 (68%) achieved a VL of &lt; 40 cp/mL. VF occurred in 8/34 patients (24%) with the following baseline parameters: TDF resistance (2/8), low/ intermediate DRV resistance (2/8), and VL &gt; 100,000 cp/mL (3/8). Both patients with baseline DRV resistance and VF demonstrated high level resistance to DRV on repeat genotype testing. Adherence was considered a major contributor to VF.

Conclusion
The use of once daily DRV/r plus TDF/FTC in treatment experienced patients with single/multi-class resistant virus resulted in virologic suppression in over two-thirds of patients. VF was seen in nearly 25% of patients including development of high level DRV resistance. This combination is a potentially viable option in a patient population seeking a once-daily option to improve adherence.

Disclosures
All authors: No reported disclosures.
Application of The Change Point Analysis to The Long-Term Restoration of CD4 Count Among Well-Controlled HIV-1 Infected Patients Who Started Antiretroviral Therapy
Authors: Yoshikazu Mutoh , Nishijima Takeshi , Tanaka Noriko , Inaba Yosuke , Kikuchi Yoshimi , Gatanaga Hiroyuki , Oka Shinichi 
Published: October 2017

Abstract

Background
Although CD4 count is an important marker for prognosis of patients infected with HIV-1, how long and how much CD4 count will increase after initiation of cART are still unknown. Hence, the aim of this study is, using change point analysis, to examine the long-term CD4 count restoration among well-controlled HIV-1 patients.

Methods
In this single-center cohort study at AIDS Clinical Center, Tokyo, we examined HIV-1 infected patients who initiated cART between January 2004 and January 2012 and achieved HIV viral load of &lt;200 copies/mL within first 48 weeks of treatment and maintained viral suppression (VL &lt;200 copies/mL) for at least 4 years. cART was defined as combination regimen which consisted of NNRTI, PI, or INSTI, plus two NRTIs. All patients were followed until censoring (defined by VL &gt;200 copies/mL, discontinuation of cART for &gt;30 days, lost to follow-up for &gt;1 year, initiating chemotherapy for malignancy, or death), or at end of the observation period (September 30, 2015). Change point analysis was performed to determine the time point where the restoration of CD4 count becomes plateau.

Results
Of 752 patients, 708 (94.2%) were male and 89.9% was MSM. The median age was 39.3 years [IQR, 32–45] and the median baseline CD4 count and %CD4 were 172 cells/mm3 [IQR, 61–254], and 13.8% [IQR, 7.7–18.5], respectively. The median follow-up period was 87.0 months [IQR, 65.2–109.2] and 134 were followed over ten years. With change point analysis, both longitudinal increase of CD4 count and %CD4 increased linearly until 78.6 and 62.2 months, respectively. Stratified by baseline CD4 count (&lt;200 cells/mm3, 200–350 cells/mm3, and &gt;350 cells/mm3), CD4 count increased linearly until 76.2, 62.4, and 58.6 months, respectively. Moreover, the percentage of patient who achieved 500 cells/mm3 during study period was 63.5%, 87.2%, and 92.0%, respectively.

Conclusion
With change point analysis, restoration of CD4 count and %CD4 continued increasing linearly until 6.5 and 5 years of cART, respectively. Patients with lower baseline CD4 count showed longer CD4 count recovery than those with higher baseline CD4; however, their CD4 count did not recover as high as those with higher baseline CD4 count.

Disclosures
All authors: No reported disclosures.
Treatment of HIV and Use of HAART in HIV Infected Patients with Acute Septic Shock
Authors: Polk Christopher , Webb Samuel , Rozario Nigel , Moore Charity , Leonard Michael 
Published: October 2017

Abstract

Background
For HIV patients admitted with sepsis, ARVs are often stopped or held due to myriad concerns including drug interactions, acute renal failure, gastrointestinal dysfunction, or inability to administer crushed medications down feeding tubes. We seek to examine prescription patterns of HAART for HIV positive patients admitted for sepsis in our healthcare system and the impact of HAART prescription on patient outcomes.

Methods
We identified HIV positive patients from an institutional database of patients admitted for sepsis within our multi-hospital healthcare system and retrospectively extracted further clinical patient and laboratory information as well as information on HAART prescription by chart review. The impact of HAART prescription and immunologic and virologic parameters of HIV infection on mortality was examined.

Results
Inpatient mortality was 35% in HIV patients admitted for sepsis, compared with 17% for all patients with sepsis in our healthcare system. Opportunistic infections were identified in only 25% of patients while 56% had other infections identified. Only 55% of patients had HAART prescribed while inpatient. CD4 count, virologic suppression, APACHE score, presence of an opportunistic infection, admission to a tertiary care hospital, and inpatient prescription of HAART were all predictors of survival.

Conclusion
Immunologic and virologic status at time of admission predicted survival in HIV patients admitted for sepsis but prescription of HAART to HIV patients admitted for sepsis may increase survival.

Disclosures
C. Polk, Gilead Sciences: Investigator, Research support; Viiv Healthcare: Investigator, Research support