Virological outcomes of various first-line ART regimens in patients harbouring HIV-1 E157Q integrase polymorphism: a multicentre retrospective study.

Shunsuke Uno, Hiroyuki Gatanaga, Tsunefusa Hayashida, Mayumi Imahashi, Rumi Minami, Michiko Koga, Sei Samukawa, Dai Watanabe, Teruhisa Fujii, Masao Tateyama, Hideta Nakamura, Shuzo Matsushita, Yusuke Yoshino, Tomoyuki Endo, Masahide Horiba, Toshibumi Taniguchi, Hiroshi Moro, Hidetoshi Igari, Shigeru Yoshida, Takanori Teshima, Hideaki Nakajima, Masako Nishizawa, Yoshiyuki Yokomaku, Yasumasa Iwatani, Atsuko Hachiya, Shingo Kato, Naoki Hasegawa, Kazuhisa Yoshimura, Wataru Sugiura, Tadashi Kikuchi

Journal: The Journal of antimicrobial chemotherapy 2023;78(12):2859-2868

PMID: 37856677

Full Text on Ovid Technologies, Inc. View on PubMed

Abstract

BACKGROUND

Integrase strand transfer inhibitors (INSTIs) are recommended as first-line ART for people living with HIV (PLWH) in most guidelines. The INSTI-resistance-associated mutation E157Q, a highly prevalent (2%-5%) polymorphism of the HIV-1 (human immunodeficiency virus type 1) integrase gene, has limited data on optimal first-line ART regimens. We assessed the virological outcomes of various first-line ART regimens in PLWH with E157Q in real-world settings.

METHODS

A multicentre retrospective observational study was conducted on PLWH who underwent integrase genotypic drug-resistance testing before ART initiation between 2008 and 2019 and were found to have E157Q. Viral suppression (<50 copies/mL) rate at 24 and 48 weeks, time to viral suppression and time to viral rebound (≥100 copies/mL) were compared among the first-line ART regimens.

RESULTS

E157Q was detected in 167 (4.1%) of 4043 ART-naïve PLWH. Among them, 144 had available clinical data after ART initiation with a median follow-up of 1888 days. Forty-five started protease inhibitors + 2 NRTIs (PI group), 33 started first-generation INSTI (raltegravir or elvitegravir/cobicistat) + 2 NRTIs (INSTI-1 group), 58 started once-daily second-generation INSTI (dolutegravir or bictegravir) + 2 NRTIs (INSTI-2 group) and eight started other regimens. In the multivariate analysis, the INSTI-2 group showed similar or favourable outcomes compared with the PI group for viral suppression rates, time to viral suppression and time to viral rebound. Two cases in the INSTI-1 group experienced virological failure.

CONCLUSIONS

The general guideline recommendation of second-generation INSTI-based first-line ART for most PLWH is also applicable to PLWH harbouring E157Q.

Address: Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan.; AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.; Clinical Research Center, National Hospital Organization Nagoya Medical Center, Aichi, Japan.; Department of Internal Medicine, Immunology and Infectious diseases, Clinical Research Center, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan.; Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.; Department of Hematology and Clinical Immunology, Yokohama City University School of Medicine, Kanagawa, Japan.; AIDS Medical Center, National Hospital Organization Osaka National Hospital, Osaka, Japan.; Division of Transfusion Medicine, Hiroshima University Hospital, Hiroshima, Japan.; Department of Infectious, Respiratory and Digestive Medicine, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.; First Department of Internal Medicine, Division of Infectious, Respiratory, and Digestive Medicine, University of the Ryukyus Graduate School of Medicine, Okinawa, Japan.; Clinical Retrovirology, Joint Research Center for Human Retrovirus Infection, Kumamoto University, Kumamoto, Japan.; Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.; Department of Hematology, Hokkaido University Hospital, Sapporo, Japan.; Department of Respiratory Medicine, NHO Higashisaitama National Hospital, Saitama, Japan.; Department of Infectious Diseases, Chiba University Hospital, Chiba, Japan.; Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.; School of Medical Technology, Health Science University of Hokkaido, Hokkaido, Japan.; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.; Hanah MediTech, Co. Ltd., Tokyo, Japan.; Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.; Tokyo Metropolitan Institute of Public Health, Tokyo, Japan.; Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan.; Division of Infectious Diseases, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan.; AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.

DOI: 10.1093/jac/dkad319

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MeSH Terms: Humans, HIV-1, Retrospective Studies, HIV Infections, HIV Integrase Inhibitors, Raltegravir Potassium, HIV Integrase, Heterocyclic Compounds, 3-Ring, Drug Resistance, Viral