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IMSUT Hospital

Department of Infectious Diseases andApplied Immunology
感染免疫内科

Professor
Hiroshi Yotsuyanagi, M.D., D.M.Sc.
Senior Assistant Professor
Eisuke Adachi, M.D., D.M.Sc.
Project Senior Assistant Professor Michiko Koga, M.D., D.M.Sc.
Assistant Professor
Makoto Saito, M.D., D.Phil.
Assistant Professor
Yoshiaki Kannno, M.D., D.M.Sc.
Assistant Professor
Kazuhiko Ikeuchi, M.D., D.M.Sc.

教 授
講 師
特任講師
助 教助 教助 教博士（医学）
博士（医学）
博士（医学）
博士（医学）
博士（医学）
博士（医学）

四安古齋
菅池柳達賀藤野内英道芳和宏輔
子真明彦

Founded in 1981, IMSUT Hospital started its HIV clinic in 1986, and as of 2023,
1328 HIV-infected patients have visited us. Currently, a total of 572 patients areactively under our clinical management. In addition to HIV infection, we also provide
treatment for other infections such as hepatitis and malaria. Furthermore, we haveaddressed cases of mpox, an emerging and re-emerging infection prevalent among
HIV-MSM.

1.  Treatment of HIV/AIDS and sexually-transmitted diseases in IMSUT hospital
Statistical characteristics of HIV/AIDS at IMSUTHospital show that fourteen new patients with HIV
infection visited to our hospital this year (from January 1 to December 31, 2022), and 572 patients in total
are under medical management in our outpatient
clinic. Five hundred fifty-seven people living withHIV (PLWH) are receiving antiretroviral therapy [1]at the hospital, and most of their plasma HIV viralloads have been well controlled. This is due to the factthat the medication adherence of PLWH visiting ourclinic is at an adequate level for HIV suppression. Figure 1 shows the number of PLWH attending IMSUT
hospital since 1995.
This year, the results of the SOLAR study, Studyto Evaluate Efficacy and Safety of Cabotegravir (CAB)Long Acting [1] Plus (+) Rilpivirine (RPV) LA Versus
BIKTARVY® (BIK) in Participants With Human Immunodeficiency Virus (HIV)-1 Who Are VirologicallySuppressed were presented at national and interna-tional conferences, and real-world data from our hospital on CAB plus RPV were presented at conferences
and in papers. We also published a paper on the treatment and clinical findings of mpox, an emerging infectious disease of HIV-MSM.
2. Changes in inflammatory biomarkers and lipid
profiles after switching to long-acting cabotegravir plus rilpivirine
Eisuke Adachi, Makoto Saito, Amato Otani, Michiko Koga, Hiroshi Yotsuyanagi
We assessed whether the impact of cabotegravir
plus rilpivirine on inflammation reduction differsfrom that of oral antiretrovirals, using real-world
data. Inflammatory biomarkers and lipid profiles
were followed from baseline to 8 months after switching. Seventy-eight participants were analyzed. TheCD4/CD8 ratio and C-reactive protein did not change.
There were transient decreases in CD8 and CD4
counts in the group that switched from the dolutegra-

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Figure 1. Number of PLWH attending IMSUT Hospitalvir-based regimen, but not in the tenofovir alafenamide-based regimen group. High-density lipoprotein(HDL) cholesterol increased, resulting in a decrease in
the total-cholesterol to HDL cholesterol ratio, whereas there was no significant change in low-density lipoprotein cholesterol.
3.  Mpox associated with Panton-Valentin leucocidin-producing methicillin-resistant Staphylococcus aureus among people with HIV
Eisuke Adachi, Kazuhiko Ikeuchi, Amato Otani,
Makoto Saito, Michiko Koga, Hiroshi Yotsuyanagi
We report three cases of mpox (disease caused bythe monkeypox virus) that developed in people withHIV co-infected with Panton-Valentin leucocidin-producing methicillin-resistant Staphylococcus aureus(PVL-MRSA), diagnosed in mid-February 2023. All
three cases had preserved HIV immune status, andtheir mpox was mild and resolved without antiviral
medications, but the trigger for their visit was thepresence and history of skin and soft tissue infections.
Our cases suggest that mpox is already prevalent
among sexually active MSM in Tokyo, Japan.
PVL-MRSA has been extremely rare in the general
population of Japan, but several literatures reported
widespread prevalence of PVL-MRSA among sexually active MSM-HIV. Mpox will become prevalent in
the future in a population of sexually active MSM athigh risk for PVL-MRSA infection, requiring an understanding of the interaction and pathogenesis of thetwo diseases.
4.  Treatment of COVID-19 in IMSUT hospital
We started to treat COVID-19 patients at the IMSUT Hospital in February, 2020. To date, the numberof patients hospitalized at the request of public healthcenters, etc., is the second largest among all public

university hospitals in Japan. We participated in several international clinical trials. (e.g., S-217622) andconducted a phase I trial to evaluate the safety, tolerability, and immunogenicity of KM-414 (KM Biologics, Kumamoto, Japan), an inactivated vaccine against
SARS-CoV-2 developed by KM biologics and IMSUT(The investigator-initiated clinical trial, phase I trial,investigating the safety and immunogenicity of booster vaccination against COVID-19, jRCT2031210503).
5.  Bioterrorism-related information website management and crisis management“バイオテロ対応ホームページ” (a website providing information on bio-terrorism in Japanese), which
was developed in 2008 to provide information onclinical diagnosis and testing procedures for bioterrorism-related diseases for medical institutions, andwas opened to the public in 2016 in anticipation ofinternational situations and mass gathering events inJapan.
6.  Crisis management for the future: Building aplatform to provide information on emerging
and re-emerging infectious diseases from normal times in JapanEisuke Adachi, Amato Otani, Hiroshi Yotsuyanagi,
Masayuki Saijo1, Tomoya Saito2
Public Health Office, Health and Welfare Bureau, City of Sapporo, *2 Center for Emergency Preparedness and Response, National Institute of Infectious Diseases
At the beginning of the mpox (disease caused bymonkey pox) epidemic, there was no platform in Japan to provide appropriate information on emerging
and reemerging infectious diseases, and the numberof accesses to bioterrorism-related information sites
increased rapidly. Even though the interest in mpox
*1

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was much smaller than in coronavirus infectious disease, emerged in late 2019 (COVID-19), the increase in
the number of views were much greater than during
the COVID-19 epidemic. This may not be because
mpox is bioterrorism-related as an analog of smallpox, but rather because there were no other websites
providing information on mpox. For future crisis
management, there should be a platform for providing information on emerging and reemerging infectious diseases from normal times.
7. Pre- and post-travel treatment of imported infectious diseases and tropical diseases at IMSUT Hospital
The pandemic of COVID-19 had unprecedented
impact of our life; global transport and travelling was
one of the most affected areas. In mid 2022, the number of returnees and travelers consulted gradually increased, and two cases of malaria patients visited thehospital. For the tropical and parasitic diseases, dozens of important medicines essential for treatment ofthem are not licensed in Japan. Research Group on
Chemotherapy of Tropical Diseases, Research on
Publicly Essential Drugs and Medical Devices, Grant
from Japan Agency for Medical Research and Development had been established to cope with this situation. We are the medical institution of the researchgroup using these orphan drugs if needed, and colleting clinical data.
8.  Treatment of hepatitis in IMSUT hospital:
About 300 HIV-non-infected patients with liverdiseases such as viral hepatitis and NAFLD are under
medical management in our outpatient clinic. Several
patients were introduced from outside for the treatment of chronic hepatitis C with direct acting anti-vi-rals (DAA) and successfully achieved the sustained
viral response (SVR). In addition, we treated HIV-infected patients who developed acute hepatitis C withDAAs, who achieved SVR.
9.  Incidence of sexually transmitted hepatitis Cvirus infection among men who have sex withmen in Japan from 2009 to 2023
Eisuke Adachi, Makoto Saito, Tadashi Kikuchi, Kazuhiko Ikeuchi, Michiko Koga, Takeya Tsutsumi,
Hiroshi Yotsuyanagi
Although the prevalence of hepatitis C virus(HCV) infection has decreased significantly with theadvent of direct-acting antiviral agents, HCV is
known to spread as a sexually transmitted disease
among men who have sex with men (MSM), and thisstudy aims to provide a perspective on the future
prevalence of HCV in Japan. We examined incidence
in two groups of MSM with HIV attending our institution in this retrospective cohort study, from 2009 to2019 and from 2020 to May 2023 and investigatedtheir background factors. Twenty-two cases were
newly confirmed to be HCV infection in 2009-2019
and a total of 9 cases in 2020-2023, with an incidence
rate of 5.04 per 1000 person-years in 2009-2019 and5.55 per 1000 person-years in 2020-2023. All of themwere diagnosed at routine outpatient visits for HIV,and few cases were considered to have symptoms ofsuspected hepatitis that led to a visit to the hospitaland a diagnosis of HCV. Although HCV is still prevalent among MSM in Japan, it is possible that it would
not have been diagnosed without testing at regularvisits as in the case of people with HIV, and that thetrue prevalence rate among MSM, including
non-HIV-infected persons, may be much higher.

Publications
1.		Adachi E, Saito M, , Otani A, Koga M and Yotsuyanagi H Changes in inflammatory biomarkers andlipid profiles after switching to long-acting cabotegravir plus rilpivirine. AIDS Res Treat 2023 inpress.
2.		Adachi E, Otani A, Yotsuyanagi H, Saijo M andSaito T. Crisis management for the future: Building a platform to provide information on emerging and re-emerging infectious diseases from normal times in Japan, Global Health & Medicine
2023, DOI: 10.35772/ghm.2023.01089
3.		Adachi E, Ikeuchi K, Otani A, Saito M, Koga M
and Yotsuyanagi H. Mpox associated with panton-valentin leucocidin-producing methicillin-resistant staphylococcus aureus among people withHIV. J Infect Chemother.29:710-12.2023
4.		Adachi E, Owada R, Sato S, Kono M and Yotsuy-anagi H. Febrile gluteal inflammation evident on
imaging findings after long-acting cabotegravir
administration. Clin Infect Dis, doi 10.1093/cid/ciad705.2023
5.		Adachi E, Saito M, Kikuchi T, Ikeuchi K, Koga M,Tsutsumi T and Yotsuyanagi H. Incidence of sexually transmitted hepatitis c virus infection among
men who have sex with men in japan from 2009 to2023. J Med Virol.95:e29039.2023
6.		Adachi E, Saito M, Otani A, Koga M and Yotsuyanagi H. Transient decrease in t cells and atypicallymphocyte proliferation after the onset of mpox.
J Med Virol.95:e29021.2023
7.		Ikeuchi K, Saito M, Adachi E, Koga M, Okushin K,
Tsutsumi T and Yotsuyanagi H. Injection drug use
and sexually transmitted infections among men
who have sex with men: A retrospective cohort

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study at an hiv/aids referral hospital in tokyo,
2013-2022. Epidemiol Infect.151:e195.2023
8.		Mori N, Mikamo H, Mukae H, Yanagihara K, Kunishima H, Sasaki J and Yotsuyanagi H. Influence ofthe coronavirus infectious disease 2019 pandemic
on infectious disease practice and infection control
in japan: A web questionnaire survey. J InfectChemother.30:1-6.2024
9.		Mukae H, Yotsuyanagi H, Ohmagari N, Doi Y,
Sakaguchi H, Sonoyama T, Ichihashi G, Sanaki T,
Baba K, Tsuge Y and Uehara T. Efficacy and safetyof ensitrelvir in patients with mild-to-moderatecoronavirus disease 2019: The phase 2b part of arandomized, placebo-controlled, phase 2/3 study.
Clin Infect Dis.76:1403-11.2023
10.	Soga T, Duong C, Pattinson D, Sakai-Tagawa Y,Tokita A, Izumida N, Nishino T, Hagiwara H,Wada N, Miyamoto Y, Kuroki H, Hayashi Y, Seki
M, Kasuya N, Koga M, Adachi E, Iwatsuki-Horimoto K, Yotsuyanagi H, Yamayoshi S and Kawaoka Y. Characterization of influenza a(h1n1)pdm09
viruses isolated in the 2018-2019 and 2019-2020
influenza seasons in japan. Viruses.15.2023
11.	Takahashi R, Matsubara Y, Takahashi S, Yokoyama
K, Ahyoung LL, Koga M, Sakamoto H, Boku N,Shida D and Yotsuyanagi H. Refractory intestinal
behçet-like disease associated with trisomy 8 myelodysplastic syndrome resolved by parenteral nutrition. Case Rep Gastroenterol.17:287-93.2023
12.	Uraki R, Ito M, Furusawa Y, Yamayoshi S, Iwatsuki-Horimoto K, Adachi E, Saito M, Koga M,
Tsutsumi T, Yamamoto S, Otani A, Kiso M,Sakai-Tagawa Y, Ueki H, Yotsuyanagi H, Imai M
and Kawaoka Y. Humoral immune evasion of theomicron subvariants bq.1.1 and xbb. Lancet InfectDis.23:30-32.2023
13.	Uraki R, Ito M, Kiso M, Yamayoshi S, Iwatsuki-Horimoto K, Furusawa Y, Sakai-Tagawa Y,Imai M, Koga M, Yamamoto S, Adachi E, Saito M,
Tsutsumi T, Otani A, Kikuchi T, Yotsuyanagi H,Halfmann PJ, Pekosz A and Kawaoka Y. Antiviraland bivalent vaccine efficacy against an omicron
xbb.1.5 isolate. Lancet Infect Dis.23:402-03.2023
14.	Uraki R, Ito M, Kiso M, Yamayoshi S, Iwatsuki-Horimoto K, Sakai-Tagawa Y, Furusawa Y,
Imai M, Koga M, Yamamoto S, Adachi E, Saito M,Tsutsumi T, Otani A, Kashima Y, Kikuchi T, Yotsuyanagi H, Suzuki Y and Kawaoka Y. Efficacy ofantivirals and bivalent mrna vaccines against sarscov-2 isolate ch.1.1. Lancet Infect Dis.23:52526.2023
15.	Uraki R, Ito M, Kiso M, Yamayoshi S, Iwatsuki-Horimoto K, Sakai-Tagawa Y, Imai M, Koga

M, Yamamoto S, Adachi E, Saito M, Tsutsumi T,Otani A, Fukushi S, Watanabe S, Suzuki T, Kikuchi
T, Yotsuyanagi H, Maeda K and Kawaoka Y. Antiviral efficacy against and replicative fitness of anxbb.1.9.1 clinical isolate. iScience.26:108147.2023
16.	Uraki R, Ito M, Kiso M, Yamayoshi S, Iwatsuki-Horimoto K, Sakai-Tagawa Y, Imai M, Koga
M, Yamamoto S, Adachi E, Saito M, Tsutsumi T,Otani A, Kashima Y, Kikuchi T, Theiler J, Yotsuyanagi H, Suzuki Y, Korber B and Kawaoka Y. Efficacy of antivirals and mrna vaccination against an
xbf clinical isolate. Lancet Reg Health West
Pac.34:100777.2023
17.	Yamamoto S, Yamayoshi S, Ito M, Sakai-Tagawa Y,Nakachi I, Baba R, Kamimoto S, Ogura T, Hagiwara S, Kato H, Nakajima H, Uwamino Y, Yagi K,Sugaya N, Nagai H, Saito M, Adachi E, Koga M,Tsutsumi T, Duong C, Okuda M, Murakami J, Furusawa Y, Ujie M, Iwatsuki-Horimoto K, Yotsuyanagi H and Kawaoka Y. Differences among
epitopes recognized by neutralizing antibodies
induced by sars-cov-2 infection or covid-19 vaccination. iScience.26:107208.2023
18.	Yotsuyanagi H, Ohmagari N, Doi Y, Imamura T,Sonoyama T, Ichihashi G, Sanaki T, Tsuge Y, Uehara T and Mukae H. A phase 2/3 study of s-217622
in participants with sars-cov-2 infection (phase 3part). Medicine (Baltimore).102:e33024.2023
19.	Karver TS, Pascual-Bernaldez M, Berni A, HnooshA, Castagna A, Messiaen P, Puerto MJG, Bloch M,
Adachi E, Sinclair G, Felizarta F, Angel JB, Sutton
K, Sutherland-Phillips D, D’Amico R and Kerrigan
D. Factors associated with health care providers’preference for forgoing an oral lead-in phase when
initiating long-acting injectable cabotegravir andrilpivirine in the solar clinical trial. AIDS Patient
Care STDS.37:53-59.2023
20.	Nakagama Y, Candray K, Kaku N, Komase Y,
Rodriguez-Funes MV, Dominguez R, Tsuchida T,Kunishima H, Nagai E, Adachi E, Ngoyi DM,Yamasue M, Komiya K, Hiramatsu K, Uemura N,Sugiura Y, Yasugi M, Yamagishi Y, Mikamo H,
Shiraishi S, Izumo T, Nakagama S, Watanabe C,Nitahara Y, Tshibangu-Kabamba E, Kakeya H andKido Y. Antibody avidity maturation following recovery from infection or the booster vaccination
grants breadth of sars-cov-2 neutralizing capacity.
J Infect Dis.227:780-787.2023
21.	Adachi E, Ikeuchi K, Koga M and Yotsuyanagi H.
Background factors in people living with hiv injapan who switch to cabotegravir plus rilpivirine:
A pilot study. J Infect Chemother.29:109-111.2023