当院におけるTDF関連高CK血症の検討
TDF 㛵㐃㧗 CK ⾑ ཎⴭㄽᩥ ᙜ㝔࠾ࡅࡿ TDF 㛵㐃㧗 CK ⾑ࡢ᳨ウ 㜿㒊᠇ 1)ࠊబ⸨㯞ᕼ 1)ࠊ⚄ᑿဏ␃ᮍ 1)ࠊᑠᒣ⏣ගᏕ 1)ࠊሯᮏ⌶ஓ 2),3)ࠊబࠎᮌᏊ 4)ࠊఀ⸨ࡦࡳ 4)ࠊబ⸨ຌ 2),5)ࠊఀ⸨ಇᗈ 2) 1) ྎ་⒪ࢭࣥࢱ࣮ ⸆⛉ࠊ2) ྎ་⒪ࢭࣥࢱ࣮ ឤᰁෆ⛉ࠊබ┈㈈ᅋἲே࢚ࢬண㜵㈈ᅋ ྎ་⒪ࢭࣥࢱ࣮ ┳ㆤ㒊ࠊ5) ་⒪ἲே་ᚨ┿ቨ㝔 Ӑᢒ㘓ӑ 㸧40 ṓࠊMen who have sex with men (MSM)ࠋ➽⫗ࢺ࣮ࣞࢽࣥࢢṔ࠶ࡾࠋࢽ࣮ࣗࣔࢩࢫࢳࢫ⫵⅖Ⓨ ࡼࡾᙜ㝔ࢆึデࡋࠊࢪࢻࣈࢪࣥ (AZT) + ࣑ࣛࣈࢪࣥ (3TC) + ࣟࣆࢼࣅࣝ (LPV/r)࡛㛤ጞࡋࡓࡀࠊస ⏝㸦㈋⾑ࠊἾ≧౽㸧ࡼࡾ RAL + TDF/FTC ኚ᭦ࡋࡓࠋ42 ᪥ᚋ↓≧ࡢ㧗 CK ⾑㸦CK:43380IU/L㸧 ࢆ࿊ࡋࠊTDF ࡢస⏝ࢆ࠸ࣛࣝࢸࢢࣛࣅࣝ (RAL) + ABC/3TC ኚ᭦ᚋࠊᨵၿࡋࡓࠋ TDF ⏝࠾ࡅࡿ CK 㛵ࡍࡿ᳨ウ ┠ⓗ㸧ࢡࣞࢳࣥ࢟ࢼ࣮ࢮ (CK) ࡣ➽⣽⬊ෆᏑᅾࡋࠊ➽⧄⥔㞀ᐖࡸ㐠ືࠊࡉࡽࡣࠊ⸆ࡸ⏥≧⭢ᶵ⬟ పୗࡼࡿ CK ್ࡢୖ᪼ࡀ▱ࡽࢀ࡚࠸ࡿࠋᅇࠊᢠ HIV ⸆࡛࠶ࡿࢸࣀ࣍ࣅ࣭ࣝࢪࢯࣉࣟ࢟ࢩࣝࣇ࣐ࣝ㓟 ሷ (TDF) ࡼࡿᛮࢃࢀࡿ CK 㧗್ࢆ⤒㦂ࡋࠊຍ࠼࡚ᙜ㝔 TDF ⏝࡛ࡢ᳨ウࢆ⾜ࡗࡓࠋ ᪉ἲ㸧TDF ⏝ 109 ࠋCK ᇶ‽್ࢆ 60~270IU/L (JSCC ᶆ‽ᑐᛂ⾲)ࡋࠊᚋ᪉どⓗ CK ୖ᪼ࡢ ᭷↓ࢆㄪᰝࡋࡓࠋ ⤖ᯝ㸧CK ࢆ ᐃࡋ࡚࠸ࡓ 93 ୰ 16 (17.2%)࡛㧗್ࢆ࿊ࡋࡓࠋ ⤖ㄒ㸧ᢠ HIV ⸆ࡼࡿ㧗 CK ⾑ࡣࠊTDFࠊRAL ࡼࡿࡶࡢࡀ࠶ࡿࠋRAL ࡛ࡣࠊᶓ⣠➽⼥ゎࢆ♧ࡍࡓ ࡵࠊᮏࡢ㧗 CK ⾑ࡣ TDF ⪃࠼ࠊ⸆ኚ᭦ࡋᨵၿࡋࡓࠋ➽⫗ࢺ࣮ࣞࢽࣥࢢ㛤ᚋࡶ⇞ࡣ࡞ࡃࠊ㐠ື ㈇Ⲵࡼࡿྍ⬟ᛶࡶప࠸ࠋ ᙜ㝔࠾ࡅࡿ TDF 㛵㐃㧗 CK ⾑ࡣ 17.2%࡛⏕ࡌࠊሗ࿌㢖ᗘྠ⛬ᗘ࡛࠶ࡗࡓࠋ TDF ᭹⏝࡛ CK 㧗್ࢆ♧ࡋࡓሙྜࠊ➽⫗ࢺ࣮ࣞࢽࣥࢢࡢ㛵ಀᛶࡶ᳨ウࡋࡘࡘࠊCK ࡢࣔࢽࢱࣜࣥࢢ⥅ ⥆ࡀᚲせ࡛࠶ࡿࠋ ࣮࣮࢟࣡ࢻ㸸ࢸࣀ࣍ࣅࣝࠊCKࠊ㧗 CK ⾑ࠊ➽⫗ࢺ࣮ࣞࢽࣥࢢࠊࣛࣝࢸࢢࣛࣅࣝ 㸦ᖹᡂ 26 ᖺ 3 ᭶ 28 ᪥ཷ㡿ࠊᖹᡂ 26 ᖺ 5 ᭶ 9 ᪥᥇⏝㸧 㸯 ࡣࡌࡵ ᱾ሰࠊ➽ࢪࢫࢺࣟࣇ࣮ࠊᚰ➽⅖ࠊከⓎᛶ➽⅖ࠊ⏥ ࢡࣞࢳࣥ࢟ࢼ࣮ࢮ (CK) ࡣࠊ㦵᱁➽ࡸᚰ➽ࠊᖹ ≧⭢ᶵ⬟పୗ࡞ࡢᝈࡢࠊ⸆ࠊ➽⫗ෆὀ ➽࡞ࡢ➽⣽⬊ෆᏑᅾࡍࡿ㓝⣲࡛࠶ࡿࡀࠊఱࡽ ᑕࠊ➽⫗ࢺ࣮ࣞࢽࣥࢢࡸࣛࣥࢽࣥࢢ࠸ࡗࡓ㐠ື ࡢ㈇Ⲵࡼࡾ➽⣽⬊㞀ᐖࡀ㉳ࡁࡿ⾑ᾮ୰ ࡼࡿ㈇Ⲵࡢ㛵➼ࡶ⪃៖ࡍࡿᚲせࡀ࠶ࡿࠋࡲࡓࠊ⸆ ὶฟࡋࠊ㧗 CK ⾑ࢆ⏕ࡌࡿࡇࡀ▱ࡽࢀ࡚࠸ࡿࠋ ࠾࠸࡚௦⾲ⓗ࡞ࡶࡢࠊᢠ࡚ࢇࢇ⸆ࡢ࢝ࣝࣂ ⾑Ύ CK άᛶࡀ㧗್ࢆ♧ࡍཎᅉࡋ࡚ࡣࠊᛴᛶᚰ➽ ࣐ࢮࣆࣥࡸᢠࣃ࣮࢟ࣥࢯࣥ⸆ࡢࢻࣟ࢟ࢩࢻࣃࠊࣉࣟ 20 ྎ་⒪ࢭࣥࢱ࣮་Ꮫ㞧ㄅ Vol 4, 2014 ࣇ࢙ࢼ࣑ࣥ࡞ࠊ㌟㯞㓉⸆ࡢࢻࣟ࣌ࣜࢻ࣮ࣝࠊᙉ ᚰ⸆ࡢ࣑ࣀࣇࣜࣥࠊᒀ⸆ࡢࢺࣛࢭ࣑ࢻࠊࢫࢱ ࢳࣥ⣔ࡸࣇࣈ࣮ࣛࢺ⣔ࡢ⬡㉁␗ᖖ⒪⸆ࠊ⏥≧ ⭢ᝈ⒪⸆ࡢࢳ࣐ࢰ࣮ࣝ࡞ࡀ▱ࡽࢀ࡚࠸ࡿ 1)ࠋ ᅇࠊᅜ❧㝔ᶵᵓྎ་⒪ࢭࣥࢱ࣮ (௨ୗࠊᙜ㝔) ࠾࠸࡚ࠊࢸࣀ࣍ࣅ࣭ࣝࢪࢯࣉࣟ࢟ࢩࣝࣇ࣐ࣝ㓟ሷ (TDF) ࡼࡿ⪃࠼ࡽࢀࡿ CK 㧗್ࢆ⤒㦂ࡋࡓࠋ ࡢሗ࿌ࡶࠊᙜ㝔ࡢ TDF ⏝࠾ࡅࡿ CK ್ࡢኚືࡘ࠸᳨࡚ウࡋࡓࡢ࡛ሗ࿌ࡍࡿࠋ ⾲㸯 ࣞࢪ࣓ࣥኚ᭦๓᳨ᰝᡤぢ㸦20XX+6.8㸧 㸰 ₯⾑ࠊ㉥⾑⌫ࡀ᳨ฟࡉࢀࡓ㸦⾲ 2)ࠋ⸆ኚ᭦ࡼ 40 ṓࠊMSM (Men who have sex with men)ࠋ⏕ ࡿ ASTࠊALTࠊLDHࠊCK ࡢ᥎⛣ࢆᅗ 1 ♧ࡍࠋ ά⩦័ࡋ࡚ࡣࠊ➽⫗ࢺ࣮ࣞࢽࣥࢢ࡞ࡢ㐠ືࢆ㐌 2~3 ᅇ⾜ࡗ࡚࠸ࡓࠋ20XX ᖺ 1 ᭶ࠊ⊩⾑࡛ HIV 㝧 ᛶࢆᣦࡉࢀࠊປసࡢᜥษࢀࢆッᙜ㝔ࢆ⤂ ࡉࢀࡓࠋᮎᲈ⾑ CD4 㝧ᛶ T ࣜࣥࣃ⌫ࡣ 87/ȣLࠊ HIV-1-RNA ࡣ 9.3104 copies/mLࠊș-D-ࢢࣝ࢝ࣥ ࡣ 300pg/mL ࡛ AIDS㸦ᣦᶆᝈ㸸ࢽ࣮ࣗࣔࢩࢫࢳ ࢫ⫵⅖㸧デ᩿ࡉࢀࡓࠋྜే⒪ᚋࡢ 20XX ᖺ 10 ᭶ࡽࢪࢻࣈࢪࣥ (AZT)ࠊ࣑ࣛࣈࢪࣥ (3TC)ࠊ ࣜࢺࢼࣅࣝࣈ࣮ࢫࢺࡉࢀࡓࣟࣆࢼࣅࣝ (LPV/r) ࡚ᢠ HIV ⒪ἲ (ART)ࢆ㛤ጞࡋࡓࠋART ⥅⥆࡚࢘ ࣝࢫࡢࢥࣥࢺ࣮ࣟࣝࡣⰋዲ࡛࠶ࡗࡓࡀࠊ㛤ጞᚋ ⾲㸰 ࣞࢪ࣓ࣥኚ᭦ᚋ᳨ᰝᡤぢ㸦20XX+6.12㸧 ࡽᚎࠎ㉥⾑⌫ (RBC) ࡀῶᑡࡋࠊ៏ᛶⓗ࡞㈋⾑≧ ែࡸἾ≧౽ࡀ⥆࠸࡚࠸ࡓࡓࡵࠊ20XX+6 ᖺ 10 ᭶ࠊ ࣛࣝࢸࢢࣛࣅࣝ (RAL) + TDF/࢚࣒ࢺࣜࢩࢱࣅࣥ (FTC)(ࢶࣝࣂࢲ®㓄ྜ㘄ࠊTVD) ࣞࢪ࣓ࣥࢆኚ᭦ ࡋࡓ 2)ࠋ20XX+6 ᖺ 12 ᭶㸦42 ᪥ᚋ㸧ࡢࣇ࢛࣮ࣟ ࢵࣉ᳨ᰝ࡚ࠊCK ࡀ␗ᖖ㧗್ࢆ࿊ࡋࡓࠋTDF ࡀཎ ᅉࡢ㧗 CK ⾑⪃࠼ࠊTDF/FTC (TVD) ࢆࣂ࢝ ࣅࣝ (ABC) /3TC (࢚ࣉࢪࢥ࣒®㓄ྜ㘄ࠊEZC) ኚ ᭦ࡍࡿࡇࡼࡾࠊCK ࡣṇᖖࡋࡓࠋ 㸱 CK ␗ᖖ㧗್ࡘ࠸࡚ࡢ⪃ᐹ ௨๓ࡽ CK ࡣ➽⫗ࢺ࣮ࣞࢽࣥࢢࡼࡿࡶࡢ ᅗ㸯 CK, LDH, AST, ALT ࡢ᥎⛣ ⪃࠼ࡽࢀࡿ⛬ᗘࡢୖ᪼ࢆ♧ࡋ࡚࠸ࡓࡀ㸦⾲ 1)ࠊ RAL+TDF/FTC (TVD) ኚ᭦ᚋࠊWBC ࡣ 7,600/ ࣞࢪ࣓ࣥኚ᭦ᚋࡢ␗ᖖ㧗್ฟ⌧࡛࠶ࡿࡇࡽࠊ ȣLࠊRBC ࡣ 447104/ȣL ṇᖖࡋࡓ୍᪉ࠊASTࠊ ART ࡢ⸆ࡀᙳ㡪ࡋ࡚࠸ࡿྍ⬟ᛶࢆ⪃៖ࡋࠊྛ⸆ ALTࠊLDHࠊCK ࡀⴭቑࠊ≉ CK ࡣ 43,380IU/L ࡢῧᩥ᭩ࡸࣥࢱࣅ࣮ࣗࣇ࢛࣮࣒ࢆࡶ ␗ᖖ㧗್ࢆ࿊ࡋࠊࡲࡓࠊ᳨ᒀ࠾࠸࡚ࡶ⺮ⓑࠊ స⏝ࡘ࠸᳨࡚ウࡋࡓ(⾲ 3)ࠋRAL ࡛ࡣⓎ⌧㢖ᗘ 21 TDF 㛵㐃㧗 CK ⾑ ࡛᫂ࡣ࠶ࡿࡀࠊ➽⫗③ࡸ⬺ຊឤࢆక࠺ᶓ⣠➽⼥ゎ ࡸ࣑࢜ࣃࢳ࣮࡞ࡀస⏝ࡋ࡚ሗ࿌ࡉࢀ࡚࠸ࡿ 3)ࠋ ࡲࡓࠊTDF ࡛ࡣ➽③(Ⓨ⌧㢖ᗘ:2%ᮍ‶)ࡸ࣑࢜ࣃࢳ ࣮ (Ⓨ⌧㢖ᗘ᫂) ࡢࠊCK ቑຍ (Ⓨ⌧㢖 ᗘ:12.3%)ࠊAST ቑຍ (5.1%)ࠊALT ቑຍ (4.3%)ࠊ ங㓟ࢩࢻ࣮ࢩࢫ (1%ᮍ‶)ࠊȚ-GTP ቑຍࠊ⺮ⓑ ⾲㸲 ࣞࢪ࣓ࣥኚ᭦ᚋ᳨ᰝᡤぢ㸦20XX+7.1㸧 ᮏࡢ⤒㦂ࢆ㋃ࡲ࠼ࠊᙜ㝔ࡢ TDF ⏝࠾ ࡅࡿ㧗 CK ⾑ࡘ࠸᳨࡚ウࡋࡓࠋ ⾲㸱 TAL, TDF ࠾ࡼࡧ FTC ࡢ࡞స⏝㸧ῧᩥ᭩ࡼࡾࠊ 㸳 ᪉ἲ ࢝ࢵࢥෆࡣస⏝Ⓨ⌧㢖ᗘ㸧 ᚋ᪉どⓗ CK ್ࢆㄪᰝࡋࡓࠋCK ࡢᇶ‽್ࡣ᪥ᮏ ⮫ᗋᏛ (JSCC) ᶆ‽ᑐᛂ⾲ᇶ࡙ࡁࠊ60ࠥ ᒀࠊ⾑ᒀ (Ⓨ⌧㢖ᗘ᫂)ࡢሗ࿌ 4)ࡀ࠶ࡾࠊFTC 270IU/L ࡋࡓࠋ ࡛ ࡶ TDF ྠᵝࠊ➽③ (2%ᮍ‶) ࡸ CK ቑຍ (2.2%)ࠊAST ቑຍ (3.1%)ࠊALT ቑຍ (2.9%)ࠊங㓟 㸴 ⤖ᯝ ࢩࢻ࣮ࢩࢫ (1%ᮍ‶) ࡀሗ࿌ 5)ࡉࢀ࡚࠸ࡿࠋᮏ TDF ⏝ 109 ୰ࠊCK ࢆ ᐃࡋ࡚࠸ࡓ ࡛ࡣࠊCKࠊASTࠊALTࠊLDHࠊȚ-GTP ࡀ㧗್ ࡣ 93 ࡛࠶ࡗࡓ㸦⾲ 5)ࠋࡑࡢ࠺ࡕ 77 (82.8%)࡛ ࢆ♧ࡋࠊᒀ⺮ⓑࠊ₯⾑ࠊ㉥⾑⌫ࡀ᳨ฟࡉࢀࡓ୍᪉࡛ࠊ ᅄ⫥ࡢ⬺ຊឤࡸ➽③࠸ࡗࡓ⮬ぬ≧ࡣࡃ࡞ࡃࠊ ⬡㉁␗ᖖ⒪⸆࡞ࡢ᭹⏝ࡸ⏥≧⭢ᶵ⬟ప ୗࡶ࡞ࡗࡓࠋ ࡇࢀࡽࡢⅬࡽྛ⸆ࡢస⏝ࢆ⪃៖ࡍࡿࠊࣞࢪ ࣓ࣥኚ᭦ᚋࡢ᳨ᰝ್␗ᖖࡢཎᅉࡋ࡚ࠊ➨୍ TDF ࡢᙳ㡪ࡀࢃࢀࡓࠋ ࡑࡇ࡛ࠊ20XX+6 ᖺ 12 ᭶ࠊ RAL + TDF/FTC (TVD)ࡽ RAL + ABC/3TC (EZC)ᗘࣞࢪ࣓ࣥኚ᭦ࢆ⾜ࡗࡓࠋࣞࢪ࣓ࣥኚ ᭦ᚋࠊ㧗್ࢆ♧ࡋ࡚࠸ࡓ ASTࠊALTࠊLDHࠊȚ-GTPࠊ ⾲㸳 TDF ⏝࠾ࡅࡿ CK ್ CK ࡣࡰṇᖖᅇࡋࠊCD4 㝧ᛶ T ࣜࣥࣃ⌫ᩘࡣ 486/ȣLࠊHIV-1-RNA ࡣ᳨ฟ㝈⏺௨ୗ⥔ᣢࡉࢀࠊ ࡣᇶ‽್ (270IU/L ௨ୗ)ࢆ㉸࠼ࡿ CK ࡢୖ᪼ࡣ୍ ⤒㐣Ⰻዲ࡛࠶ࡿ㸦⾲ 4㸧ࠋ ᗘࡶㄆࡵࡽࢀ࡞ࡗࡓࠋ୍᪉ࠊCK ࡀ୍ᗘ࡛ࡶ 270IU/L ࢆ㉸࠼ࡓࡀ 16 (17.2%)࠶ࡾࠊࡑࡢ 㸲 ᑐ㇟ ෆศࡅࡣࠊ270ࠥ1,000IU/L ୖ᪼ࡋࡓࡀ 10 2007 ᖺ 1 ᭶ࡽ 2012 ᖺ 6 ᭶ࡅ࡚ᙜ㝔࡛ TDF (10.8%)ࠊ1,001ࠥ2,000IU/L ୖ᪼ࡋࡓࡀ 2 ࢆྵࡴ ART ࢆ⾜ࡗࡓ 109 ࠋ (2.1%)ࠊ2,000IU/L ࢆ㉸࠼ࡿୖ᪼ࢆ♧ࡋࡓ 22 ྎ་⒪ࢭࣥࢱ࣮་Ꮫ㞧ㄅ Vol 4, 2014 ࡀ 4 (4.3%)࡛࠶ࡗࡓࠋCK ࡀ 2,000IU/L ࢆ㉸࠼ ṇᖖ್ᅇࡍࡿࡢࠊ㐠ືᚋ 3ࠥ5 ᪥㛫ࡗࡓ ࡓ 4 ୰ᅇࡢࡶྵࡵ 3 (ᖹᆒᖺ㱋 37 ṓ) ࡣ ሗ࿌ࡋࡓࠋᙜ㝔࡛ࡳࡽࢀࡓ TDF ⏝ࡢ ➽⫗ࢺ࣮ࣞࢽࣥࢢࢆ⾜ࡗ࡚࠸ࡓࡀࠊ࠸ࡎࢀࡢࡶ 2,000IU/L ࢆ㉸࠼ࡿ CK ␗ᖖୖ᪼⩌ 4 ࡢ୰࡛ࠊ➽ ➽⫗③ࡸ⬺ຊឤ࠸ࡗࡓッ࠼ࡣ࡞ࡗࡓࠋ ⫗ࢺ࣮ࣞࢽࣥࢢࢆ⾜ࡗ࡚࠸ࡓࡢࡣࠊ3 ࡛࠶ࡾࠊ ࡲࡓࠊࡇࡢ 4 ࡢ ART ࣞࢪ࣓࡛ࣥࡣࠊᮏࡣ ࡑࡢ࠸ࡎࢀࡶ➽⫗ࢺ࣮ࣞࢽࣥࢢࡼࡿ➽⫗⑂ປࢆ RAL + TDF/FTC (TVD) ࡛࠶ࡗࡓࡀࠊࡢ 3 ッ࠼࡚࠾ࡽࡎࠊ᳨ᰝ್ࡢࡳࡢ␗ᖖ࡛࠶ࡗࡓࠋ 㛵ࡋ࡚ࡣࠊࣜࢺࢼࣅࣝࣈ࣮ࢫࢺࡉࢀࡓࢱࢨࢼࣅࣝ TDF ࡣࢹࣀࢩ୍ࣥࣜࣥ㓟ࡢ㠀⎔≧ࢾࢡࣞ࢜ࢩ (ATV/r) + TDF/FTC (TVD) ࡛࠶ࡗࡓࠋࡉࡽࠊᮏ ࢻ࣭࣍ࢫ࣍ࣥ㓟ࢪ࢚ࢫࢸࣝㄏᑟయ࡛࠶ࡿࠋᚑࡗ࡚ࠊ ࡢࡳ TDF/FTC (TVD) ࡽ ABC/3TC (EZC) TDF ࡽࢸࣀ࣍ࣅࣝࡢኚࡣࢪ࢚ࢫࢸࣝࡢຍ ኚ᭦ࡋࡓࡀࠊࡑࢀ௨እ㛵ࡋ࡚ࡣࠊ᩿⥆ⓗ࡞ CK Ỉศゎࡀᚲせ࡛࠶ࡿࠋࡑࡋ࡚ࠊࢸࣀ࣍ࣅࣝࡣ⣽⬊ෆ ୖ᪼ࢆ♧ࡍࡓࡵࠊࣞࢪ࣓ࣥኚ᭦ࡏࡎ⤒㐣ほᐹ୰࡛࠶ 㓝⣲ࡼࡾࣜࣥ㓟ࢆཷࡅࠊࢸࣀ࣍ࣅࣝࣜࣥ㓟 ࡿࠋ ࡞ࡿࠋࢸࣀ࣍ࣅࣝࣜࣥ㓟ࡣࠊHIV-1 ㏫㌿㓝⣲ࡢ ᇶ㉁࡛࠶ࡿࢹ࢜࢟ࢩࢹࣀࢩࣥ 5'-୕ࣜࣥ㓟➇ྜ ࡍࡿࡇཬࡧ DNA ྲྀࡾ㎸ࡲࢀࡓᚋ DNA 㙐ఙ 㸵 ⪃ᐹ ART ࡼࡿ➽⣽⬊ࡢస⏝ࡋ࡚ࠊTDF ࡸ 㛗ࢆṆࡉࡏࡿࡇࡼࡾࠊHIV-1 ㏫㌿㓝⣲ࡢά FTCࠊRAL ࡞ࡼࡿ㧗 CK ⾑ࡀ▱ࡽࢀ࡚࠾ࡾ ᛶࢆ㜼ᐖࡋࠊ⸆ຠࢆ♧ࡍ 4)ࠋVarga ࡽ 12)ࡼࢀࡤࠊ 3- 6)ࠊTDF ࡼࡿ㧗 CK ⾑ࡢ㢖ᗘࡣ 12.3㸣ሗ࿌ ࡇࡢస⏝ᶵᗎࡢ㏵୰࠶ࡿࣜࣥ㓟࠾࠸࡚ࠊ့ங ࡉࢀ࡚࠸ࡿࠋࡲࡓࠊTDF RAL 㛵ࡋ࡚ࡣࠊⓎ⌧ 㢮ࡢ⤌ࡳ࠼ᆺࢾࢡࣞ࢜ࢩࢻࣜࣥ㓟࢟ࢼ࣮ࢮ 㢖ᗘ᫂࡞ࡀࡽ➽ຊపୗࡸ➽③࠸ࡗࡓ࣑࢜ࣃࢳ (NDPK)ࠊ3-࣍ࢫ࣍ࢢࣜࢭࣜࣥ㓟࢟ࢼ࣮ࢮ (PGK)ࠊ ࣮ࡶሗ࿌ 3),4)ࡉࢀ࡚࠸ࡿࠋࡉࡽࠊRAL 㛵ࡋ࡚ࡣࠊ CKࠊࡑࡋ࡚ࣆࣝࣅࣥ㓟࢟ࢼ࣮ࢮ(PK)ࢆ⏝࠸ࠊࡢ ➽⫗③ࡸ⬺ຊឤࢆకࡗࡓᶓ⣠➽⼥ゎ㛵ࡋ࡚ࡶ 㓝⣲ࡀ᭱ࡶάᛶࢆ♧ࡍᐇ㦂ࡋࡓ⤖ᯝࠊࢸࣀ࣍ࣅࣝ ሗ࿌ࡉࢀ࡚࠸ࡿ 3,6-10)ࠋࡑࡢ୰ࡢ୍࡛ࡣࠊRAL + ୍ࣜࣥ㓟ᑐࡋࠊNDPKࠊPGK ࡣࡃάᛶࢆ♧ࡉ TDF/FTC (TVD)ࡢࣞࢪ࣓࡛ࣥ᭹⏝㛤ጞᚋࠊ10 ᪥ ࡎࠊCK ࡀࢹࣀࢩࣥࣜࣥ㓟 (ADP)ࡢ 1/45 ⛬ᗘࠊ ࡛➽③ࠊ➽⫗ࡢ⾶࠼ࠊከᒀࠊCK ್ୖ᪼ PK ࡣ ADP ࡢ 1/1000 ⛬ᗘࡢࣜࣥ㓟άᛶࢆ♧ࡋ࡚ (14,260IU/L) ࡞ࡀ⏕ࡌࡓࡓࡵࠊRAL ࢆࢿࣝࣇ ࠸ࡓࠋᚑࡗ࡚ࠊࢸࣀ࣍ࣅ୍ࣝࣜࣥ㓟ࡀࢸࣀ࣍ࣅࣝ ࢼࣅࣝ (NFV) ኚ᭦ࡋࡓࡇࢁࠊ⮫ᗋ≧ࡢᨵၿ ࣜࣥ㓟ࣜࣥ㓟ࡉࢀࡿ㝿ࠊCK ࡀ≉␗ⓗࣜࣥ ࡶ CK ್ࡣ 2 ࣨ᭶ᚋ 284IU/L ࡞ࡗࡓ 9)ࠋ 㓟άᛶ㛵ࢃࡾࠊCK ୖ᪼⧅ࡀࡗ࡚࠸ࡿྍ⬟ᛶ ᡃࠎࡢሗ࿌࡛ࡣࠊᶓ⣠➽⼥ゎࢆᛮࢃࡏࡿ⮫ ࡀ⪃࠼ࡽࢀࡿࠋ ᗋ≧ࡣࡃ࡞ࡗࡓࡓࡵࠊTDF ࢆ࠸ࠊ⸆ኚ ᚋࡢㄢ㢟ࡋ࡚ࡣࠊୖグࡢ CK ୖ᪼ࡢᶵᗎࡘ ᭦ࡋࠊᨵၿࡋࡓࠋWatanabe ࡽ 11)ࡣࠊTDF ࡼࡾ ࠸࡚ࡼࡾ⪃ᐹࢆ῝ࡵ࡞ࡅࢀࡤ࡞ࡽ࡞࠸ࠋࡋࡋࠊ⌧ 75%ࡢᝈ⪅࠾࠸࡚ࠊ≉␗ⓗ⾑୰࣑ࢺࢥࣥࢻࣜ Ⅼ࡛ࡣࠊCK ࡀ㧗್ࢆ♧ࡋࡓሙྜࠊᝈࡸ⸆ࡔ CK άᛶࡀୖ᪼ࡋ࡚࠸ࡿሗ࿌ࡋ࡚࠸ࡿࡀࠊ㧗 CK ࡅ࡛ࡣ࡞ࡃࠊ➽⫗ࢺ࣮ࣞࢽࣥࢢࡸࣛࣥࢽࣥࢢ࡞ࡢ ⾑ᑐࡍࡿ࣑ࢺࢥࣥࢻࣜ CK ࡢ✚ᴟⓗ㛵ࢆ 㐠ືࡢ㛵㐃ᛶࡘ࠸࡚ࡶ᳨ウࡋࠊCK ࡢࣔࢽࢱࣜ ♧၀ࡍࡿࡣࢇ࡞࠸ࡓࡵࠊᚋࡶ᳨ウࡋ࡞ ࣥࢢࢆ⥅⥆ࡍࡿᚲせࡀ࠶ࡿ⪃࠼ࡽࢀࡿࠋ ࡅࢀࡤ࡞ࡽ࡞࠸ࠋ 㸶 ⤖ㄒ ୍᪉࡛ࠊCK ࡣ➽⫗ࢺ࣮ࣞࢽࣥࢢࡸࣛࣥࢽࣥࢢ ࠸ࡗࡓ㐠ື㈇Ⲵࡼࡿ➽⫗⑂ປࡼࡾୖ᪼ࡍࡿ 1,13)ࠋ ᅇࠊTDF ࡼࡿ⪃࠼ࡽࢀࡿ㧗 CK ⾑ࢆ ྜྷ⏣ 14)ࡣ 3 ᪥㛫ࡢࢺࣞࢵ࢟ࣥࢢ࠾࠸࡚ࠊ1 ᪥ᚋ ሗ࿌ࡍࡿࡶࠊᙜ㝔 TDF ⏝࠾ࡅࡿ CK 20 ṓ௦⏨ᛶ࡛ 300IU/Lࠊ30 ṓ௦⏨ᛶ࡛ 1,600IU/Lࠊ ⾑ࡘ࠸᳨࡚ウࡋࡓࠋ17.2% (16 /93 ) 㧗 60 ṓ௦⏨ᛶ࡛ 2,500IU/L ⛬ᗘࡲ࡛ CK ࡀୖ᪼ࡋࠊ CK ⾑ࡀㄆࡵࡽࢀࠊ᪤ሗ (12.3%㸸ῧᩥ᭩) 23 TDF 㛵㐃㧗 CK ⾑ 12) Varga A, Gráczer E, Chaloin L, et. al. ࡰྠ⛬ᗘ࡛࠶ࡗࡓࠋᶓ⣠➽⼥ゎࢆ♧၀ࡍࡿ≧ࡣ Selectivity of kinases on the activation of ㄆࡵࡽࢀ࡞ࡗࡓࠋ tenofovir, an anti-HIV agent. Eur J Pharm Sci. 2013,23;48:307-15 㸷 ᩥ⊩ 1) 㝰༤அࠊ℈㷂┤Ꮥ㸸ㄪሗ 2011;17:775-777 13) ᪂⏿ⱱࠊᐑཎ‶⏨ࠊୖ⏣୍༤㸸㛗㊥㞳ࣛࣥࢼ 2) HIV ឤᰁཬࡧࡑࡢྜేࡢㄢ㢟ࢆඞ᭹ࡍࡿ ࣮ࡢࢺ࣮ࣞࢽࣥࢢᙉᗘࠊ➽③ࠊ➽⑂ປឤ⾑Ύ ◊✲⌜㸸ᢠ HIV ⒪࢞ࢻࣛࣥ ᖹᡂ 24 ᖺ CPK ್ࡢ㛵ಀࡘ࠸࡚ ᗈᓥᏛ⥲ྜ⛉Ꮫ㒊⣖ ᗘཌ⏕ປാ⛉Ꮫ◊✲㈝⿵ຓ㔠࢚ࢬᑐ⟇◊✲ せ ϭࠊಖయ⫱Ꮫ◊✲ 1986;6:17-23 ᴗ(2013 ᖺ 3 ᭶) 14) ྜྷ⏣ᾈ㸸⮫ᗋ᳨ᰝ 2006;50:261-266 3) ࢭࣥࢺࣞࢫ®㘄 400mg ་⸆ရࣥࢱࣅ࣮ࣗ ࣇ࢛࣮࣒(2013 ᖺ 10 ᭶) 4) ࣅ࣮ࣜࢻ®㘄 300mg ་⸆ရࣥࢱࣅ࣮ࣗࣇ࢛ ࣮࣒(2013 ᖺ 1 ᭶) 5) ࢚࣒ࢺࣜࣂ®࢝ࣉࢭࣝ 200mg ་⸆ရࣥࢱࣅࣗ ࣮ࣇ࢛࣮࣒(2010 ᖺ 9 ᭶) 6) Teppler H, Brown DD, Leavitt RY, et. al. Long-Term Safety from the Raltegravir Clinical Development Program. Current HIV Research, 2011;9:40-53 7) Zembower TR, Gerzenshtein L, Coleman K, et. al. Severe rhabdomyolysis associated with raltegravir use. AIDS 2008;22:1382-1384 8) Dori L, Buonomini AR, Viscione M, et. al. A case of rhabdomyolysis associated with raltegravir use. AIDS 2010;24:473-476 9) Croce F, Vitello P, Pria AD, et. al. Severe raltegravir-associated rhabdomyolysis: a case report and review of the literature. International Journal of STD & AIDS 2010;21:783-785 10) Masia M, Enriquez R, Sirvent A, et. al. Severe acute renal failure associated with rhabdomylysis during treatment with raltegravir. Journal of infection 2010;61:189-190 11) Watanabe D, Yoshino M, Yagura H, et.al. Increase in serum mitochondrial creatine kinase levels induced by tenofovir administration. J Infect Chemother, 2012;18:675-682 24
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