Clinical characteristics and COVID-19-related outcomes of immunocompromised patients receiving tixagevimab/cilgavimab pre-exposure prophylaxis in Japan.

OBJECTIVE: Tixagevimab/cilgavimab is a cocktail of two long-acting monoclonal antibodies approved for pre-exposure prophylaxis (PrEP) of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (cause of coronavirus disease 2019 [COVID-19]) in immunocompromised (IC) or high-risk patients. We investigated the patient characteristics and clinical outcomes of IC patients administered tixagevimab/cilgavimab for PrEP in real-world use in Japan. METHODS: This observational study used anonymous secondary data from Real-World Data Co., Ltd. for IC patients aged ≥12 years administered tixagevimab/cilgavimab between September 2022 and September 2023. We analyzed the baseline characteristics and event-rates of COVID-19-related clinical outcomes within 6 months of administration. RESULTS: Data were analyzed for 397 IC patients. About half (53.4%) were male and the median age was 71.0 (interquartile range 61.0, 77.0) years. Malignancy (97.2%), cardiovascular disease (71.3%), and diabetes (66.5%) were frequent comorbidities. Systemic corticosteroids and immunosuppressants were prescribed to 87.4% and 24.9%, respectively. The two most common target clinical conditions were active therapy for hematologic malignancies (88.2%) and treatment with B cell-depleting therapies (57.4%). The event-rates per 100 person-months (95% confidence interval; number) for medically attended COVID-19, COVID-19 hospitalization, in-hospital mortality due to COVID-19, and all-cause death were 4.14 (3.06-5.48; n=49), 1.74 (1.09-2.64; n=22), 0.07 (0.00-0.42; n=1), and 0.60 (0.26-1.17; n=8), respectively. CONCLUSION: This is the first report using a multicenter database to describe the clinical characteristics and COVID-19-related outcomes of IC patients administered with tixagevimab/cilgavimab in real-world settings in Japan. This cohort of IC patients who received tixagevimab/cilgavimab included many elderly patients with comorbidities.

Exploring Current Practice, Knowledge, and Challenges of Sexually Transmitted Infection/HIV Management and Pre-Exposure Prophylaxis Among Japanese Health Care Professionals: A Cross-Sectional Web Survey.

We conducted a web-based survey targeting physicians in specialties of treating sexually transmitted infection (STI) and/or human immunodeficiency virus (HIV) patients to understand the current STI/HIV care practices and their acceptability of and barriers to the prescription of pre-exposure prophylaxis (PrEP) in Japan. A descriptive analysis was used to summarize survey responses. Univariate and multivariable logistic regression were performed to identify factors associated with willingness to prescribe PrEP. Of 316 survey respondents, 57 were specialized in HIV, 90 STI/Urology/Proctology, 55 Obstetrics/Gynecology, and 114 General Practice/Internal Medicine/Dermatology. Proportion of HIV-specialized physicians who interview the patients about risk behaviors tended to be higher than other physician groups (84.2% vs. 54.8%, 47.3%, and 50.9%, respectively), and 53 - 75% of non-HIV-specialized physicians reported that they were incapable of making decisions on HIV medications. Higher PrEP knowledge enhanced the willingness to recommend and prescribe PrEP drugs (odds ratio: 2.31, 95% confidence interval: 1.30-4.10, p = 0.0044), and 45.4% physicians with no PrEP knowledge raised the concern of incapability to respond and manage when an individual is infected with HIV. Educational opportunities on management and prevention measures for both STI and HIV may encourage non-HIV-specialized physicians to be involved in HIV care and to enhance initiation of HIV tests and adoption of PrEP.

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.

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.