Characteristics of 2-drug regimen users living with HIV-1 in a real-world setting: A large-scale medical claim database analysis in Japan.

BACKGROUND: Regimen simplification to 2-drug antiretroviral therapy (2-ART) may address potential tolerability issues, increase adherence, and reduce toxicity and potential drug-drug-interactions among people living with HIV-1 (PLWH). However, real-world treatment patterns and characteristics of 2-ART users are unclear. METHODS: This retrospective observational cohort study employed a large-scale medical claim database of Japanese hospitals to extract data on 4,293 PLWH aged ≥18 years with diagnosis of HIV and treated with any ART regimens between April 2008 and April 2019. A 2-ART cohort was compared with a 3-drug antiretroviral therapy (3-ART) cohort in terms of population characteristics, comorbid conditions, and treatment patterns. Treatment switching rates were calculated for each cohort followed by sensitivity analysis to confirm the robustness of the findings. RESULTS: There were 94 individuals identified in the 2-ART cohort. Compared to the standard 3-ART cohort (n = 3,993), the 2-ART cohort was older (median age 53 [IQR 44-64] vs 42 years [IQR 35-50]), with a lower proportion of males (87.2% vs 93.8%), higher Charlson Comorbidity Index (CCI) (median score 6 [IQR 5-8] vs 5 [IQR 4-6]), more co-medications (median 6 [IQR 4-11] vs 3 [IQR 2-7]), and a higher percentage of AIDS-defining conditions (66.0% vs 42.8%). The most common 2-ART were protease inhibitor (PI) + integrase strand transfer inhibitor (INSTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) + INSTI (33.0% and 31.9%, respectively). Overall, most of the regimens were nucleoside reverse transcriptase inhibitor (NRTI)-sparing (71.3%), with a decreasing trend over time (76.2% to 70.2%). ART regimen switch occurred more often in the 2-ART cohort than in the 3-ART cohort (33.0% vs 21.2%). CONCLUSION: The profiles of individuals on 2-ART in Japan were demonstrated to be complex. Most were treated with NRTI-sparing regimens which may reflect an effort to reduce treatment-related toxicities.

Incidence of and risk factors for recurrent Clostridioidesdifficile infection in Japan using a claims database: A retrospective cohort study.

This retrospective cohort study aimed to determine the incidence rates of and risk factors for recurrent Clostridioides difficile infection (rCDI) in Japan using a claims database. Inpatients of any age with ≥1 record of C. difficile infection (CDI) during the study period (January 2012-September 2016) were analyzed. We estimated the incidence rate of health care onset, health care facility associated (HO-HCFA) primary CDI and HO-HCFA rCDI for each of the first to fifth recurrences. Risk factors for the first recurrence were investigated using a univariate, and subsequently, a multivariable Cox regression model. The incidence rates (95% confidence interval [CI]) of CDI and HO-HCFA CDI were 2.43 (2.40-2.46) and 1.26 (1.24-1.28) cases per 10,000 inpatient-days, respectively. Among the 11,287 inpatients with ≥1 HO-HCFA CDI, 1424 patients had ≥1 recurrent episode (12.6% [95% CI 12.0-13.2]). The rCDI incidence rates consistently increased, with the number of recurrences ranging from 29.2 to 181.8 cases per 10,000 inpatient-days. The multivariable analysis revealed five risk factors (hazard ratio [95% CI]): age ≥65 years (vs. <65 years; 65-74 years, 1.275 [1.048-1.551]; 75-79 years, 1.612 [1.315-1.975]; ≥80 years, 2.110 [1.776-2.507]); cephalosporin use both before (vs. without cephalosporin; 1.241 [1.098-1.402]) and during the primary CDI (vs. without cephalosporin; 1.137 [1.011-1.279]); higher number of comorbidities (vs. ≤10 comorbidities; 11-14 comorbidities: 1.336 [1.131-1.580]; 15-20 comorbidities: 1.433 [1.219-1.685]; ≥21 comorbidities: 1.310 [1.099-1.561]); and gastrointestinal surgery (vs. without surgery; 0.823 [0.701-0.965]). In conclusion, CDI recurred in some Japanese patients, and the incidence rates increased with the number of recurrences. Special care is needed in patients aged ≥65 years, those with a higher number (>10) of comorbidities, and those who have received cephalosporin before or during the primary CDI.

Switch rates, time-to-switch, and switch patterns of antiretroviral therapy in people living with human immunodeficiency virus in Japan, in a hospital-claim database.

BACKGROUND: Regardless of chronic treatment with antiretroviral therapy (ART), the switching rate for ART regarding anchor drugs has not been articulated in real-world clinical-settings in Japan. We assessed switch rates and time-to-switch of ART regimens according to anchor drug classes (integrase strand transfer inhibitors (INSTI), non-nucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI)) and common switching patterns of anchor drug classes in people living with human immunodeficiency virus (HIV) (PLWH) from 2008 to 2016. METHODS: This retrospective, observational study used data of 1694 PLWH drawn from a large-scale medical claims database. The median time-to-switch and switch rates of anchor drug class were estimated by Kaplan-Meier analysis. To estimate 95% confidence intervals for switch rates and median days, the Brookmeyer and Crowley method and Greenwood method were used respectively. The switching patterns were summarized based on the time of switching. The switch rates were compared between two anchor drug classes for each year using log-rank tests. RESULTS: We focused our results on 2011-2016 (n = 1613), during which most ART prescriptions were observed. A total of 268 patients switched anchor drug class from the first to a second regimen. The switch rate constantly increased over four years for NNRTIs (17.8-45.2%) and PIs (16.2-47.6%), with median time-to-switch of 1507 and 1567 days, respectively, while INSTI maintained a low switch rate (2.3-7.6%), precluding median-days calculation. The majority originally treated with NNRTI and PI switched to INSTI regardless of the switching timing after starting the first regimen (< 1 year: 91.7 and 97.5%, respectively, and ≥ 1 year: 100.0 and 97.5%, respectively). The risk of switching anchor drug classes was lower for INSTI than for other anchor drug classes in the first regimen even after adjusting for potential confounding factors. CONCLUSIONS: Patients with an ART regimen including INSTI as an anchor drug class maintained a low switch rate for long durations. The major switching strategies of anchor drug class for secondary treatment were from NNRTI or PI to INSTI. These results suggest that INSTI may be a durable anchor drug class for PLWH on ART although there are limitations inherent to the database.

Long-term tolerability and effectiveness of raltegravir in Japanese patients: Results from post-marketing surveillance.

Antiretroviral agents are approved in Japan based on non-clinical and clinical data reported from overseas. Neither the long-term tolerability nor the effectiveness of raltegravir or other integrase strand transfer inhibitors in Japan is known. This study reports on the long-term tolerability and effectiveness of raltegravir in Japanese clinical practice using data collected through approximately 9 years of post-marketing surveillance. This observational survey used data on human immunodeficiency virus (HIV) infected patients initiated treatment with raltegravir between 2008 and 2017 in the HIV-related drug (HRD) cooperative survey to assess the safety and effectiveness of raltegravir in real world clinical practice. There were totally 1,303 patients prescribed raltegravir across 30 institutions; 1,293 patients and 1,178 patients were included for the safety and effectiveness analyses, respectively. The overall risk of adverse drug reaction was 17.25%, with abnormal hepatic function and hyperlipidaemia (<1.5%) having the highest proportion. Median HIV-1 RNA viral loads rapidly decreased below 40 copies/mL after 3 months of raltegravir use in treatment-naïve patients, and consistently sustained below 40 copies/mL after the start of raltegravir use in treatment-experienced patients. Among the patients who were treated for 7 years, 92.00% (95% CI: 73.97-99.02) maintained HIV-1 RNA viral load below 50 copies/mL. Additionally, CD4+ cell counts exceeded >500 cells/µL in treatment-naïve and treatment-experienced patients after 3 years and 4 years of treatment, respectively. In Japanese HIV patients, long-term treatment with raltegravir is well-tolerated and effective at viral suppression as measured by HIV-1 RNA levels and subsequent change in CD4+ cell counts. Such benefits can be expected for not only treatment-naïve but also treatment-experienced patients.

Greater burden of chronic comorbidities and co-medications among people living with HIV versus people without HIV in Japan: A hospital claims database study.

OBJECTIVE: This study examined the prevalence of chronic comorbidities and the use of co-medications among people living with HIV (PLWH) on antiretrovirals in Japan, compared with age-matched controls without HIV. METHODS: This was an observational, retrospective, cross-sectional study using a hospital claims database of Japanese hospitals with advanced medical capabilities (i.e., advanced treatment hospitals, general hospitals, acute care hospitals). We extracted data for PLWH aged ≥18 years with a prescription record of antiretrovirals between January 2010 and December 2015, and for age-, sex-, and hospital-matched people without HIV. For each group, chronic comorbidities (diabetes, hypertension, lipid disorders, vascular diseases, chronic kidney failure, cancers, psychiatric disorders, osteoporosis, and hepatitis B/C co-infection), and co-medications were examined by age group. RESULTS: We analyzed data for 1445 PLWH and 14,450 people without HIV. The proportion of patients with multiple comorbidities was much greater among PLWH than controls of the same age group. Lipid disorders and diabetes were more prevalent in PLWH than controls (31.6% vs. 10.3% and 26.8% vs. 13.2%, respectively), both of which were more common in PLWH at earlier ages. Cancer was present in 8.1% of PLWH and 8.9% of controls. A greater proportion of PLWH used multiple co-medications other than antiretrovirals at earlier ages than controls. CONCLUSION: PLWH taking antiretrovirals in Japan had a greater burden of comorbidities and co-medications with increasing age than people without HIV. In addition to appropriate management of comorbidities, medication reconciliation according to patients' co-medication profiles is important for successful management of this patient population.

Comorbidities and the use of comedications in people living with HIV on antiretroviral therapy in Japan: a cross-sectional study using a hospital claims database.

OBJECTIVES: To investigate the prevalence of chronic comorbidities and the use of comedications in people living with HIV (PLWH) and on antiretrovirals in Japan, by using a hospital claims database. DESIGN: Observational, retrospective, cross-sectional study. SETTING: A hospital claims database of Japanese hospitals that have advanced medical treatment capabilities (ie, advanced treatment hospitals, general hospitals, acute care hospitals), which include those providing acute and chronic care (excluding nursing homes or hospices). PARTICIPANTS: A total of 1445 PLWH aged ≥18 years and with a prescription record of antiretrovirals between January 2010 and December 2015 were identified from the database. OUTCOME MEASURES: The number and types of chronic comorbidities, as well as the number and types of comedications, in different age groups of the PLWH. RESULTS: The median (range) age of patients was 45 (18-90) years, and 90.4% were men. Of the 1445 patients, 972 (67.3%) had at least one chronic comorbidity. Common chronic comorbidities included lipid disorders (31.6%), diabetes (26.8%), hypertension (18.2%) and hepatitis B/C coinfection (18.2%). Patients in the older age groups had greater numbers of chronic comorbidities. The most common chronic comorbidities in the older age groups were hypertension, diabetes and lipid disorders. The majority of patients used at least one comedication, and those in the older age groups used greater numbers of comedications. The most common therapeutic category of comedication included antacids, antiflatulents and antiulcerants (31.7%). Of 151 malignancies reported in 117 patients, 84 were AIDS-defining cancers and 67 were non-AIDS-defining cancers. CONCLUSIONS: Chronic comorbidities and comedications were common among PLWH in Japan taking antiretrovirals; particularly among older patients, who more frequently used comedications. This suggests the need for giving special attention to the appropriate management of this patient population.

Comorbidities and co-medications in populations with and without chronic hepatitis C virus infection in Japan between 2015 and 2016.

BACKGROUND: Direct-acting anti-viral agents have improved the treatment of chronic hepatitis C virus (HCV) infection, but this treatment is challenging for patients using co-medications because of potential drug-drug interactions. This study aimed to examine the comorbidities and co-medications of Japanese chronic HCV patients by age group, compared with a non-HCV patient population. METHODS: This was a retrospective observational study using a hospital-based medical claims database. We extracted data of patients with chronic HCV aged ≥18 years, and age-, sex-, and hospital-matched patients without HCV, for the period from January 2015 to November 2016, and then examined chronic comorbidities, long-term co-medications, and medications prescribed at least once during the study period. RESULTS: We analysed data from 128,967 chronic HCV patients and 515,868 non-HCV patients. The median age was 70 years, and 51.0% of patients were male. More chronic HCV patients than non-HCV patients (70.5% vs. 47.1%) had at least one comorbidity, and older patients had more comorbidities than younger patients. The most common comorbidities in chronic HCV patients were diseases of oesophagus, stomach and duodenum (41.7%), followed by hypertensive diseases (31.4%). Chronic HCV patients used co-medications more commonly than non-HCV patients, and older patients used more co-medications. The most common long-term co-medications in chronic HCV patients were proton pump inhibitors (14.0%), which were prescribed to 31.9% of chronic HCV patients at least once during the study period. CONCLUSIONS: Patients with chronic HCV in Japan had more comorbidities than patients without chronic HCV regardless of age. Particularly older patients, who constitute the majority of the HCV patient population in Japan, commonly had multiple comorbidities and used co-medications. To optimise HCV treatment, physicians need to know the exact medication profiles of patients and take appropriate action to manage drug-drug interactions.

The complete supraannular concept: in vivo hemodynamics of bovine and porcine aortic bioprostheses.

BACKGROUND: Complete supraannular placement of an aortic bioprosthesis is one approach to optimize the hemodynamic result of an aortic valve replacement. It is achieved with the combination of a special valve design and the supraannular sewing technique with noneverted mattress sutures. We evaluated 5 bioprostheses designed for complete supraannular placement to assess potential hemodynamic differences caused by factors (eg, valve material) other than implantation position. METHODS AND RESULTS: In 336 patients (mean age, 72.0+/-7.1 years; 143 women), hemodynamics including mean pressure gradients, effective orifice areas, and indices and incidence of patient-prosthesis mismatch were evaluated 6 months after surgery. Annulus diameter was measured during surgery. Patients received the Carpentier Edwards Perimount Magna (Magna, n=169), the Medtronic Mosaic (Mosaic, n=46), the Mosaic Ultra (Ultra, n=17), the SJM Epic Supra (Epic, n=46), and the Sorin Soprano (Soprano, n=58). For small annulus sizes (<23 mm), the mean pressure gradients of the Magna (11.82+/-4.8 mm Hg) were significantly lower than the Mosaic (16.04+/-6.1 mm Hg) and the Ultra (22.0+/-4.1 mm Hg), and the Soprano (13.3+/-5.2 mm Hg) was hemodynamically superior to the Ultra. For medium (23 to 24 mm) and large (>24 mm) annulus sizes, the mean pressure gradients of the Magna were lower than the Epic (10.0+/-3.5 mm Hg versus 14.9+/-6.4 mm Hg; 9.9+/-4.0 mm Hg versus 18.6+/-12.7 mm Hg). Furthermore, in patients with large annulus size, the mean pressure gradients of the Soprano (11.4+/-3.8 mm Hg) were lower compared with the Epic (18.5+/-12.7 mm Hg). Severe patient-prosthesis mismatch was observed more frequently in patients with the Mosaic (12/46; 26.1%) and the Ultra (3/17; 17.6%) prostheses. CONCLUSIONS: Complete supraannular placement cannot prevent high pressure gradients or patient-prosthesis mismatch thoroughly, but the choice of a bovine prosthesis can optimize hemodynamic performance.

Twenty-year experience with the St. Jude medical Biocor bioprosthesis in the aortic position.

BACKGROUND: The purpose of this study was to evaluate the long-term performance of the St. Jude Medical Biocor stented porcine prosthesis in the aortic position. METHODS: From January 1985 to December 1996, 455 patients admitted for aortic valve replacement were consecutively enrolled in this study. The mean age was 72.5 +/- 9 years, 18 patients (3.5%) had had previous cardiac surgery, and coronary artery bypass grafting was performed in 171 patients (37.6%). Follow-up was complete in 99.6%; up to 21 years were covered. Actuarial event-free rates are given as mean +/- standard error and adverse events were classified according to the guidelines for reporting morbidity and mortality after cardiac valvular operations. RESULTS: Cumulative follow-up time was 3,321 patient-years with a mean follow-up of 8.2 years. The actuarial survival rate after 20 years was 9.4% +/- 2.8%. The actuarial rates for freedom from structural valve deterioration were 93.1% +/- 1.7% at 10 years, 88.4% +/- 3.5% at 15 years, and 70.3% +/- 10.9% at 20 years. The actuarial rates for freedom from reoperation due to structural valve deterioration were 91.9% +/- 1.6% at 10 years, 90.6% +/- 2.1% at 15 years, and 86.5% +/- 4.5% at 20 years. CONCLUSIONS: This study presents one of the largest series of St. Jude Medical Biocor aortic valves in the world. Results indicate an age-dependent risk of structural valve degeneration beginning as soon as 7 years postoperatively for patients below the age of 65 years, but show a low overall incidence of valve-related complications and excellent durability.

Hemodynamic performance of the new St. Jude Medical Epic Supra porcine bioprosthesis in comparison to the Medtronic Mosaic on the basis of patient annulus diameter.

BACKGROUND AND AIM OF THE STUDY: The St. Jude Medical Epic Supra (ES) valve is a new porcine bioprosthesis designed for complete supra-annular implantation. To date, no in-vivo data regarding the hemodynamic and clinical performance of this valve are available. The study aim was to compare the hemodynamic performance of the ES valve with the completely supra-annular Medtronic Mosaic (MM) porcine valve. METHODS: Between July 2000 and April 2006, 83 patients (39 males, 44 females) underwent aortic valve replacement with either the ES (n = 44) or MM (n = 39) bioprosthesis. Hemodynamic performance was evaluated echocardiographically at six months postoperatively. Comparison between the valves was performed by dividing the patient groups according to their intraoperatively measured tissue annulus diameter rather than the labeled valve size. RESULTS: The internal diameter and sewing ring diameter differed in ES and MM valves with the same labeled size. For example, in valves labeled '23' the internal diameter/sewing ring diameters were 21.5 and 29.3 mm in the ES valve versus 20.5 and 30 mm in the MM. The mean pressure gradients (MPG) for patients with ES or MM valves were 15.5 +/- 4.5 or 14.8 +/- 5.1 mmHg for annulus diameter < or =22 mm, 14.6 +/- 6.4 or 13.9 +/- 3.6 for annulus diameter 23-24 mm, and 15.3 +/- 3.8 or 13.4 +/- 4.2 mmHg for annulus diameter > or =25 mm. No significant differences were identified in the hemodynamic data, including MPG, effective orifice area (EOA) and effective orifice area index (EOAI). The incidence of moderate or severe patient-prosthesis mismatch (PPM) was 40% (n = 18) and 5% (n = 1) in patients with ES valves, and 26% (n = 10) or 23% (n = 9) in patients with MM valves (p = 0.01). In patients with an annulus size < or =22 mm, severe PPM occurred in 29% (n =5) of patients with MM valves but in none of those with ES valves. CONCLUSION: The hemodynamic performance of the ES valve was comparable to that of the well-established MM valve. The incidence of severe PPM was lower in patients with ES valves than MM valves, presumably due to the somewhat larger EOA values in patients with a small aortic annulus (<25 mm).

Occasional single beat regurgitation observed with the medtronic advantage bileaflet heart valve.

BACKGROUND: The purpose of this clinical study was to obtain further evidence of the underlying mechanism causing the echocardiographically detected phenomenon of single beat regurgitation in a new bileaflet heart valve. As part of a prospective multicenter trial at our institution, 63 patients received the Advantage bileaflet mechanical heart valve (Medtronic, Minneapolis, Minnesota) in aortic position. During routine follow-up performed at discharge and annually after the operation, intermittent moderate transvalvular regurgitation was detected by echocardiography in 5 patients. METHODS: Fluoroscopy of leaflet motion (n = 4), invasive blood pressure measurements in the ascending aorta (n = 3) and digital phonocardiography (n = 5) was obtained in the patients showing an intermittent regurgitation during echocardiography. RESULTS: Valve thrombosis, sutures, or pannus ingrowth impairing valve closure was not detected. Fluoroscopy of leaflet motion showed intermittent incomplete closure of either one of the two leaflets in the same prosthesis. This could be correlated with a distinct diastolic blood pressure drop in the same cardiac cycle. Digital phonocardiography showed pathologic closure sounds in those cycles in which echocardiographically the intermittent regurgitation was observed. CONCLUSIONS: Some patients with the Medtronic Advantage prosthesis in the aortic position show an intermittent inability of complete valve closure that leads to a single beat transvalvular regurgitation. As thrombotic or other material that might cause a disturbance of leaflet motion could not be detected, and the patients seem not to be exposed to any risk except for some chronic regurgitant volume, we decided not to replace the prostheses.

Hemodynamic evaluation of the Sorin Soprano bioprosthesis in the completely supra-annular aortic position.

BACKGROUND AND AIM OF THE STUDY: The study aim was to evaluate the clinical and hemodynamic performance of the Sorin Soprano bioprosthesis in the aortic position. METHODS: Rest and stress echocardiography were performed at six months after surgery in 57 patients who underwent aortic valve replacement with the stented Soprano bioprosthesis. The exercise protocol included workloads of 25, 50, 75 and 100 W, each of 2 min duration. RESULTS: Thirty-day mortality was 1.8% (n = 1). Due to malperfusion of the coronary arteries, two Soprano prostheses had to be replaced by a different prosthesis, and one patient received coronary artery bypass grafts. One patient developed bacterial endocarditis of his prosthesis at seven months postoperatively and died as a result of a fulminant sepsis. There were no other prosthesis-related adverse events. Mean pressure gradients (MPG) ranged from 7.8 to 15.9 mmHg, effective orifice areas (EOA) from 1.25 to 2.98 cm2, EOA index (EOAI) from 0.79 to 1.43 cm2/m2, and EOA fraction from 34 to 45%. Stress echocardiography showed no significant increase in MPG up to 50 W, and MPGs did not exceed 35 mmHg at 75 and 100 W. CONCLUSION: Initial hemodynamic results showed low MPGs during rest and exercise. The EOAI was large due to completely supra-annular placement of the Soprano valve. The difficulty of complete supraannular placement is that the prosthesis is positioned relatively high, especially in narrow aortic roots, and this may handicap coronary artery perfusion. Patient selection with suitable aortic root anatomy is crucial to achieve the benefit of completely supra-annular implantation without coronary ostium deterioration.