Analysis of antiretroviral therapy switch rate and switching pattern for people living with HIV from a national database in Japan.

To report the status of switch rates and time-to-switch of antiretroviral therapy (ART) regimens by evaluating anchor drug classes and common switching patterns in Japanese people living with human immunodeficiency virus (HIV, PLWH). This cross-sectional cohort study extracted data of 28,089 PLWH from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), which contains data representing the entire population of Japan. PLWH with first prescription records of ART administered between January 2011 and March 2019 were identified (n = 16,069). The median time-to-switch and switch rates of anchor drug classes were estimated by Kaplan-Meier analysis. Brookmeyer-Crowley and Greenwood methods were used to estimate 95% confidence intervals for switch rates and median days, respectively. Switch rates were compared between anchor drug classes by year using log-rank tests. A total of 3108 (19.3%) PLWH switched anchor drug classes from first to second regimens. Switch rates increased continuously over 8 years for non-nucleoside reverse transcriptase inhibitors (NNRTIs) (14.9-65.5%) and protease inhibitors (PIs) (13.2-67.7%), with median time-to-switch of 1826 and 1583 days, respectively. Integrase strand transfer inhibitors (INSTIs) maintained a low switch rate (3.0-7.6%), precluding median-days calculation. Overall, the majority of patients treated initially with NNRTIs and PIs switched to INSTIs regardless of switching times (< 1 year: 67.3% and 85.9%, respectively; ≥ 1 year: 95.5% and 93.6%, respectively). The foremost switching strategies for first-to-second ART regimens are from NNRTIs or PIs to INSTIs regimens that maintain low switch rates long term. There was no observable difference in trend between sex, age and status of AIDS disease at first ART regimen. INSTIs HIV agents may be the most durable anchor drug class for PLWH receiving ART.

Comorbidities and co-medications among 28 089 people living with HIV: A nationwide cohort study from 2009 to 2019 in Japan.

OBJECTIVES: Comorbidities are associated with a high burden of disease in people living with HIV (PLWH). The objective was to investigate the prevalence of chronic comorbidities and use of co-medications in PLWH in Japan. METHODS: This study retrospectively analysed clinical information from PLWH receiving antiretroviral therapy (ART) between April 2009 and March 2019. Demographic characteristics, numbers and types of chronic comorbidities, and numbers and types of non-ART co-medications, were described by age groups. The source of data was the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). RESULTS: Overall, 28 089 PLWH (male 91.9%) who used ART were identified. Out of 28 089 PLWH, 81.5% had at least one chronic comorbidity. The numbers of AIDS-defining cancers and non-AIDS-defining cancers in this Japanese cohort were 2432 (8.7%) and 2485 (8.8%), respectively. The cumulative burden of comorbidities including non-AIDS-defining cancer increased with age. Changes in trend between 2009 and 2019 were observed, including a higher proportion of PLWH diagnosed at ≥ 70 years old [2019 (4.7%) vs. 2009 (2.4%)] and a decreasing percentage of patients with AIDS-defining cancers (down from 6.3% to 4.8% between 2009 and 2019). The most common co-medications during the most recent 3-month period were lipid-regulating/anti-atheroma preparations (11.3%), antacids, antiflatulents and anti-ulcerants (9.6%), and agents acting on the renin-angiotensin system (8.1%). The three most common therapeutic categories of co-medications during the study period were antacids, antiflatulents and anti-ulcerants (35.0%), systemic antihistamines (33.7%) and psycholeptics (27.1%). More than 30% of PLWH aged > 40 years used at least one co-medication in a 3-month period, while more than half of PLWH aged > 30 years had at least one co-medication prescribed concomitantly for a total of ≥ 90 days during the study period, and the numbers of co-medications used were greater in the older age groups. CONCLUSIONS: The burden of chronic comorbidities and co-medication were found to be greater in older, as compared to younger patients, among 28 089 PLWH in a nationwide study in Japan. This finding suggests the need to identify elderly PLWH and to appropriately manage their HIV and comorbidities.

Delayed diagnosis of human immunodeficiency virus infection in people diagnosed with syphilis: A nationwide cohort study from 2011 to 2018 in Japan.

Early treatment of HIV infection depends on timely diagnosis, but many persons living with HIV/AIDS (PLWHA) are unaware of their infection. Though many patients seeking medical attention for sexually transmitted diseases have HIV, many patients' HIV co-infection is undiagnosed in Japan. This is the first report to analyze the timing of syphilis infection in PLWHA of all ages through the use of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), containing clinical data of the largest group of HIV-positive patients available in Japan. Overall, 1521 PLWHA (male 93.2%) newly diagnosed and started on antiretroviral therapy were identified in 2016, and 646 (42.5%) patients had a diagnosis of syphilis between 2011 and 2018. Although 100 patients were diagnosed with syphilis before their HIV diagnosis, only 17 (17.0%) had been tested for HIV. Over 50 patients per year became infected with syphilis even after their HIV diagnosis (2017, n = 65 (4.3%); 2018, n = 58 (3.8%)). Although early diagnosis of HIV infection is important, most syphilis patients in Japan had not been properly tested for HIV infection. Since a certain number of HIV patients developed syphilis after HIV diagnosis, education for newly diagnosed HIV patients is important.

Study of effects of ifenprodil in patients with methamphetamine dependence: Protocol for an exploratory, randomized, double-blind, placebo-controlled trial.

AIMS: Pharmacotherapy for methamphetamine dependence has not yet been developed in Japan or elsewhere in the world. Ifenprodil is a blocker of G protein-activated inwardly rectifying potassium channels that play a key role in the mechanism of action of addictive substances. Our aim is to examine the safety, efficacy, and outcomes of ifenprodil for the treatment of methamphetamine dependence in a randomized, double-blind, placebo-controlled trial. METHODS: The recruitment of outpatients with methamphetamine dependence began in January 2018. The patients will be randomized into three arms: placebo, 60 mg/d ifenprodil, or 120 mg/d ifenprodil. Placebo or ifenprodil will be taken for 84 days. We will use Cerocral fine granule 4%® (ifenprodil tartrate). Follow-up assessments will be conducted for 84 d after the drug administration period. All of the patients will be assessed by self-administered questionnaires and urine tests. The primary outcome will be the presence or absence of methamphetamine use during the 84-day administration period in the 120 mg/d ifenprodil and placebo groups. Secondary outcomes will include the number of days and percentage of days of abstinence from methamphetamine use, positive urine for methamphetamine, relapse risk, and drug craving. DISCUSSION: This study is the first clinical trial of ifenprodil treatment for methamphetamine dependence and is designed as an intervention test with off-label drug use. The present study is expected to provide evidence of the effects of ifenprodil treatment on methamphetamine dependence. TRIAL REGISTRY: This trial was registered in the UMIN clinical trial registry (UMIN000030849; date of registration: January 17, 2018).