Hattori Junko, Shiino Teiichiro, Gatanaga Hiroyuki, Mori Haruyo, Minami Rumi, Uchida Kazue, Sadamasu Kenji, Kondo Makiko, Sugiura Wataru
*Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan; †Currently, HIV Dynamics and Replication Program, National Cancer Institute, National Institutes of Health, MD; ‡Infectious Disease Surveillance Center, National Institute of Infectious Diseases, Tokyo, Japan; §National Center for Global Health and Medicine, Tokyo, Japan; ‖Osaka Prefectural Institute of Public Health, Osaka, Japan; ¶National Hospital Organization Kyushu Medical Center, Fukuoka, Japan; #Saitama Institute of Public Health; **Tokyo Metropolitan Institute of Public Health, Tokyo, Japan; ††Kanagawa Prefectural Institute of Public Health, Chigasaki, Japan; ‡‡Division of Basic Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan; and §§Currently, GlaxoSmithKline KK, Tokyo, Japan.
J Acquir Immune Defic Syndr. 2016 Apr 1;71(4):367-73. doi: 10.1097/QAI.0000000000000861.
Progress in antiretroviral treatment has led to fewer virological failure cases, but 10%-20% of treatment-naive HIV/AIDS cases are reported to harbor drug-resistant strains, suggesting transmission of drug-resistant HIV. We aimed to determine the trend in prevalence of transmitted drug-resistant (TDR) HIV in Japan, particularly in recently infected patients.
Drug-resistance test was performed on 3904 HIV-1-infected cases newly diagnosed between 2007 and 2012. The number of cases infected within 6 months [recent seroconverters (RS)] was estimated by BED assay of 2700 plasma samples. Characteristics of RS cases were further analyzed.
The overall prevalence of TDR was 9.1%, ranging from 7.3% in 2008% to 12.5% in 2010. Among 1403 subtype B/E/D cases with >50 CD4 T cell counts and >1000 HIV copies per milliliter, 468 (33.4%) were estimated to be RS. The prevalence of RS was significantly higher among cases who were male, Japanese, and men who have sex with men. The prevalence of TDR did not differ significantly between recent and long-term seroconverters (8.5% vs. 9.2%, respectively, P = 0.68). Common mutations in both groups were M46I/L and T215 revertants. Furthermore, sequences with these mutations, K103N and D30N/N88D formed clusters on phylogenetic trees.
Our study clarified an increase in prevalence of TDR in Japan from 2007 to 2012. The phylogenetic clustering of cases with M46I/L or T215 revertants suggests that HIV with these mutations have become circulating strains. Furthermore, detailed analyses showed that Japanese men who have sex with men are more aware of their risk of HIV infection.
抗逆转录病毒治疗的进展已使病毒学失败病例减少，但据报告，10%-20%未经治疗的艾滋病毒/艾滋病病例携带耐药菌株，提示耐药艾滋病毒的传播。我们旨在确定日本传播性耐药（TDR）艾滋病毒的流行趋势，特别是在近期感染的患者中。
对2007年至2012年新诊断的3904例艾滋病毒-1感染病例进行耐药性检测。通过对2700份血浆样本进行BED检测，估计6个月内感染的病例数[近期血清转化者（RS）]。进一步分析RS病例的特征。
TDR的总体流行率为9.1%，范围从2008年的7.3%到2010年的12.5%。在1403例CD4 T细胞计数>50且每毫升艾滋病毒拷贝数>1000的B/E/D亚型病例中，估计有468例（33.4%）为RS。在男性、日本人以及男男性行为者中，RS的流行率显著更高。近期和长期血清转化者之间的TDR流行率无显著差异（分别为8.5%和9.2%，P = 0.68）。两组常见的突变是M46I/L和T215回复突变。此外，具有这些突变、K103N和D30N/N88D的序列在系统发育树上形成簇。
我们的研究阐明了2007年至2012年日本TDR流行率的上升。具有M46I/L或T215回复突变的病例的系统发育聚类表明，具有这些突变的艾滋病毒已成为流行毒株。此外，详细分析表明，日本男男性行为者对艾滋病毒感染风险的认识更高。
