대한에이즈학회 HIV 감염치료지침 HIV/AIDS. HIV. 2. 범위 ,,, B /C (HBV/HCV),.. 3. 임상진료지침위원회구성 HIV/AIDS 문헌검색방법 PubMed (w

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1 Supplementary Infection & Chemotherapy 국내 HIV 감염인의 HIV/AIDS 진단및치료에관한임상진료지침권고안 : 2015 년개정판 대한에이즈학회 The Committee for Clinical Guidelines for the Diagnosis and Treatment of HIV/AIDS of the Korean Society for AIDS was founded in The first edition of the Korean guidelines was published in 2011, and revised in The recommendations in the guideline contain important information for physicians working with HIV/AIDS in the clinical field. However, due to the rapid discovery of new data in the field of HIV and the evolution of the clinical environment in Korea, it has become necessary to revise the guideline again. This guideline aims to provide up-to-date comprehensive information regarding the diagnosis and management of HIV/AIDS in Korea. This guideline deals with issues regarding the initial assessment of newly diagnosed patients, timing of antiretroviral treatment (ART) initiation, preferred ART regimens in treatment-naïve as well as treatment-experienced patients and special populations such as HBV/HCV co-infected patients, or pregnant women. A brief summary of the revised guidelines and key changes to the original version of the guidelines are summarized below. Key Words: HIV/AIDS; Diagnosis; Antiretroviral treatment; Guidelines 머리말 1. 배경및목적 1981 (Centers for Disease Control and Prevention, CDC). CD4+ T.,,.,, * 대한에이즈학회 HIV/AIDS 진단및치료임상진료지침제정위원회위원장 : 위성헌 ( 가톡릭대학교성빈센트병원감염내과 ) 위원원 : 김남중 ( 서울대학교서울대학교병원감염내과 ), 방지환 ( 서울대학교서울시립보라매병원감염내과 ), 김낙현 ( 서울대학교서울대학교병원감염내과 ), 최준용 ( 연세대학교세브란스병원감염내과 ), 신형식 ( 국립중앙의료원감염내과 ), 신소연 ( 가톨릭관동대학교국제성모병원감염내과 ), 송준영 ( 고려대학교구로병원감염내과 ) * 본권고안은 2014년 11월현재국내실정에적합한 HIV 감염인의 HIV/AIDS 진단및치료에대한기본적인원칙을제시하는것으로서, 모든환자에대해서본진료지침을일률적으로적용하는것보다는기본적으로참고하되각환자의여러임상상황들을고려한의사의최종적인판단에의한진료가중요함. * 본권고안은개인적인진료및교육목적으로활용될수있지만상업적인목적이나진료심사목적등으로사용될수없으며, 어떠한형태로든다른목적으로사용하고자하는경우에는제정위원회에서면요구서를제출하여서면동의를얻어야함. Received: June 30, 2015 Corresponding Author : The Committee for Clinical Guidelines for the Diagnosis and Treatment of HIV/AIDS of the Korean Society for AIDS. The Korean Society for AIDS, 309 Gangnam-daero, Seocho-gu, Korea Business Center Room 512, Seoul 06628, Korea Tel: , Fax: , kosa@kosaids.or.kr

2 대한에이즈학회 HIV 감염치료지침 HIV/AIDS. HIV. 2. 범위 ,,, B /C (HBV/HCV),.. 3. 임상진료지침위원회구성 HIV/AIDS 문헌검색방법 PubMed ( KoreaMed ( ( kstudy.com)., / (International AIDS Society Conference, International AIDS Conference, Conference on Retroviruses and Opportunistic Infections ) 핵심질문 (Key Question) 설정및합의도출과정 HIV/AIDS, (highly active antiretroviral therapy, HAART),,, HIV/HBV HIV/HCV,,.,,.. 6. 권고의강도및근거수준 (Table 1) DHHS (Department of Health and Human Services) 1 A, B, C 3, I, II, III 3 (Table 1). 1) 권고의강도 A ~. B ~. C ~. 2) 근거수준 I ~ II ~ III ~ 7. 외부전문가평가 ,,,.. Table 1. Strength of recommendation and quality of evidence for recommendation Strength of recommendation A: Strong recommendation for the statement B: Moderate recommendation for the statement C: Optional recommendation for the statement Quality of evidence for recommendation I: One or more randomized trials with clinical outcomes and/or validated laboratory endpoints II: One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes III: Expert opinion

3 HIV 감염치료지침 대한에이즈학회 8. 용어및약어정리 5 (, ),.,,. (treatment-naive patient), (treatment-experienced patient).. ABC, abacavir; ATV, atazanavir; d4t, stavudine; ddi, didanosine; DRV, darunavir; EFV, efavirenz; FTC, emtricitabine; HBV, hepatitis B virus; HCV, hepatitis C virus; LPV, Lopinavir; MVC, maraviroc; NFV, nelfinavir; NVP, nevirapine; PI/r, protease inhibitors boosted with ritonavir; RAL, raltegravir; RPV, ripivirine; RTV, ritonavir; SQV, saquinavir; TDF, tenofovir; TPV, tipranavir; ZDV, zidovudine; 3TC, lamivudine. immunodeficiency virus, Diagnosis, Screening, Monitoring, Laboratory, Assay Assessment, Drug resistance, Hypersensitivity reaction,. (3) -? -? -? -? -? 항목별임상진료지침 1. 초기평가및추적검사 1) 서론 (1),,.,,,,,. [1-4]. (2) DHHS panel, European AIDS Clinical Society (EACS), IAS-USA panel, PubMed ( KoreaMed ( ( HIV Human 2) 사람면역결핍바이러스감염인이초기방문하였을때시행해야할실험실검사와영상학적검사는?,,, (Table 2). 1. CD4+ T, HIV RNA (A-I). CD4+ T, HIV RNA (A-II). 2. (differential count) (complete blood count, CBC),,,,, (A-III). 3. A (B-III), B (A-III), C (A-III). 4. (A-II) (B-III). 5. (tuberculin skin test, TST) interfereon (IFN)-γ release assay (A- I), (A-III). TST CD4+ T 200/mm 3 (A-III). 6., (B-II). 7. (genotypic test) (A-III).

4 대한에이즈학회 HIV 감염치료지침 Table 2. Initial assessment in HIV-infected subjects HIV antibody test CD4+T-cell count, plasma HIV RNA (viral load) Genotypic resistance test (in patients with HIV RNA level 1,000 copies/ml) Complete blood count with differentials Basic chemistry, liver function test, fasting lipid profile Chest X-ray Serologic tests for hepatitis A, B and C viruses Toxoplasma antibody, Pap smear Screening test for syphilis (VDRL) Screening tests for other sexually transmitted diseases Tuberculin skin test (TST) or IFN-γ release assay 8. 50,,, (B-III). (A-III). (B-III). (1) HIV RNA (A-III). CD4+ T HIV RNA,. (2) CD4+ T CD4+ T (A-I). CD4+ T, [4, 5]. CD4+ T, CD4+ T. CD4+ T /mm 3 CD4+ T 14-29% [1]. CD4+ T 1 2 (C-III). (3) HIV RNA HIV RNA (A-I)., [3, 6, 7].,. HIV RNA copies/ml, copies/ml. (4) (5) 30-40%,, 75% [8]. (differential count) (complete blood count, CBC) (basic chemistry) (AIII).,,,,,, [9]. (6) (tuberculin skin test, TST) IFN-γ release assay (IGRA) (A-I). (induration) 5 mm,. (A-I). TST CD4+ T 200 /mm 3 (A-III). (A- II). 48., (acid-fast bacilli, AFB) [10] (A-II). (7) B (HBsAg, anti-hbs Ab) (A-III). B (hepatitis B virus, HBV)

5 HIV 감염치료지침 대한에이즈학회 [11] (B-II). HBsAg HBcAg HBV DNA (polymerase chain reaction, PCR) B (C-III)., C (hepatitis C virus, HCV) (A-III). HCV HCV RNA (A-II). A 30%, [1] (B-III). (B-II).,,.,,, PCR ( ) (Neisseria gonorrhea ), (Chlamydia trachomatis ), (Trichomonas vaginalis), Mycoplasma genitalium, Ureaplasma urealyticum, Gardnerella vaginalis, (Haemophilus ducreyi), (Herpes simplex virus, HSV). (8) (B-III), CD4+ T 100 /mm 3 (C-III). (9).,,, (computed tomography, CT), (, ), (Cytomegalovirus, Toxoplasma gondii, Cryptococcus neoformans ) (Pneumocystis jirovecii, Mycobacteria spp. ) [12-15] (A-II). CD4+ T 100 /mm 3 (B-II). (10), [12] (A-II). 48 (Table 3),, (11) (Human papilloma virus, HPV) (men who have sex with men, MSM), (Pap test), HPV (C-III). (12) (trichomoniasis), 25 (Chlamydia) (A-II). 3) 고강도항레트로바이러스요법이필요하다고판단된환자에서항레트로바이러스약제를투여하기전에확인해야하는실험실검사는? 9. CD4+ T (A-II), 4 HIV RNA (B-I). 10. efavirenz (A-III). 11. Abacavir HLA-B*5701 (A-I), (B-III). 12. (A-III). (1) ( ) CD4+ T ( ). HIV RNA HIV RNA (B-I).,,,,,. (2) Abacavir HLA-B*5701 Abacavir abacavir 6.. abacavir 5-8% 534 HLA-B*5701 0% (95% 0-0.7%), ( %)

6 대한에이즈학회 HIV 감염치료지침. (0%), (0.003%) [16, 17]. HLA-B* % HLA-B*5701, HLA-B* % [18, 19]. abacavir HLA-B*5701 (A-I). abacavir HLA-B*5701 (B-III). (3) IAS-USA panel 5% [20]. 5% ( 2.5%; 4.8%; 8.8%)[21-23]. (A-III). (4) Efavirenz Efavirenz, 1 [24, 25]. Efavirenz (A-III). 4) 고강도항레트로바이러스요법을받고있는사람면역결핍바이러스감염인에서약제독성이나기회감염과관련된실험실검사의시행주기는? 13. CD4+ T (A-I), 2 24 (B-II), CD4+ T 500 /mm 3 CD4+ T (C-III). 14. HIV RNA (A-III) (A-III) , 2 24 (A-III). 16. Zidovudine , 2-4, , , (B-II) (A-III). (1) CD4+ T CD4+ T (A-I) (B-II). (2) HIV RNA HIV RNA (A-III) (A-III). (3) zidovudine 2-4., 2-4, , , , tenofovir 24,.

7 HIV 감염치료지침 대한에이즈학회 (4) 12 [26-28] (B-II).,,,, (A, B, C ) 48 (A-III). 5) 초기평가후에고강도항레트로바이러스요법을시행하지않고관찰중인사람면역결핍바이러스감염인에서질병진행상태및기회감염과관련된실험실검사의시행주기는? (Table 3) 20. CD4+ T HIV RNA (A-I)., Table 3. Monitoring schedule for HIV-infected patients CD4+T-cell count HAART-naive patients Initial visit follow-up HAART initiation/ modification 2-4 weeks post HAART initiation/ modification HAART-experienced patients every weeks every 24 weeks every 48 weeks Treatment failure Every weeks a a HIV RNA Every weeks Resistance test HLA-B*5701 test CBC with differential Basic chemistryb Liver function test (if considering ABC) Every weeks (if on AZT) Every weeks Every weeks Fasting glucose Every weeks (if abnormal previously) Fasting lipid profile (if normal previously) Every 48 weeks (if abnormal previously) Urinalysis (if on TDF) (if normal previously) Chest X-ray Every 48 weeks Tests for OI Every 48 weeks Serology for hepatitis virus Every 48 weeks STD screening (VDRL) Pregnancy test (if considering EFV) a 24. b Basic chemistry includes serum Na, K, Cl, HCO3, BUN, creatinine, Ca, P and glucose. CBC, complete blood count; OI, opportunistic infection; STD, sexually transmitted diseases.

8 대한에이즈학회 HIV 감염치료지침 21.,,,, (A, B, C ) 48 (A-III) , (1) CD4+ T HIV RNA CD4+ T HIV RNA (A-I)., CD4+ T HIV RNA., CD4+ T HIV RNA [10, 29] (A-II). (2),,,, (A, B, C ) 48 (A-III). (3) (, ) , (Table 3). 6) 항레트로바이러스제약제내성검사는언제시행해야하는가? (A-II). (C-III). HIV RNA 1,000 copies/ml (A-I). HIV RNA 500-1,000 copies/ml (B-II). (A-III). HIV RNA 1,000 copies/ml (A-I). (1) (genotypic assay) (phenotypic assay), (Table 4) ,000 copies/ml, 500-1,000 copies/ml %., [30-32] (A-II). (A-III). (C-III). HIV RNA 1,000 copies/ml (A-I). HIV RNA 500-1,000 copies/ml (B-II). (A-III). Table 4. Comparison of antiretroviral resistance tests: genotypic assay vs. phenotypic assay Type of assay Advantages Disadvantages genotypic assay phenotypic assay - wide availability - rapid turn-around time (1-2 weeks) - less expensive - earlier detection of resistance - direct measure of drug susceptibility - ability to assess net effect of mutational interactions and cross-resistance patterns - possible for new drugs - require expert interpretation - unable to assess mutational interactions - possible failure to detect minor variant - impossible for new drugs - longer turn-around time (3-4 weeks) - more expensive - appropriate cutoffs are not defined for all drugs - possible failure to detect minor variant

9 HIV 감염치료지침 대한에이즈학회 HIV RNA 1,000 copies/ml (A-I). (A-III). (B-III). (C-III)., (B-III). 2. 고강도항레트로바이러스요법시작시기 1) 서론 (1) HIV RNA,..,. CD4+ T -.,,, [33-38].. (2) PubMed ( KoreaMed ( ( Kiss.kstudy.com)., (International AIDS Society Conference, International AIDS Conference, Conference on Retroviruses and Opportunistic Infections ). HIV Human immunodeficiency virus, therapy treatment management antiretroviral therapy highly active antiretroviral therapy, start timing. (3) - HIV? - CD4+ T? -? 2) 모든 HIV 감염인에서고강도항레트로바이러스요법을시행하는것이권고되는가? 1. HIV. CD4+ T. 1) CD4+ T <350 /mm 3 (A-I) 2) CD4+ T /mm 3 (A-II) 3) CD4+ T >500 /mm 3 (B-III) CD4+ T 200 /mm 3. CD4+ T 200 /mm 3 [39-41]., CD4+ T 200 /mm /mm 3 [39-43]. (A-I). CD4+ T 200 /mm 3,. CIPRA HT-001

10 대한에이즈학회 HIV 감염치료지침 CD4+ T /mm 3 CD4+ T 200 /mm 3. CD4+ T /mm /mm 3 ( =4.0, P=0.0011) ( =2.0, P=0.0125) [44]. SMART (the Strategic Management of Antiretroviral therapy) CD4+ T 350 /mm 3 5,400 CD4+ T 250 /mm CD4+ T 250 /mm 3 (P=0.06)[45]. CD4+ T 350 /mm 3 (A-I). CD4+ T /mm 3... ART Cohort Collaboration (ART-CC) 18 46,691, CD4+ T /mm / mm 3 ( 1.28, 95% CI ) [43]. (NA-AC- CORD) CD4+ T 350 /mm /mm 3 ( 1.60, 95% CI ) [46]. CD4+ T /mm 3 5,527,, (CASCADE Collaboration) 350 /mm 3 [47]. HPTN052,, HIV [48]. CD4+ T /mm 3 1,763 HIV, 250 /mm 3 HIV. 2 HIV,. CD4+ T /mm 3 HIV,. CD4+ T /mm 3 (A-II)., HPTN 052 HIV HIV [48]. CD4+ T 500 /mm 3 HIV. NA-ACCORD CD4+ T 500 /mm 3 [46]. CD4+ T 500 /mm 3 2, /mm 3 6,935 ( : 1.64, 95% : ) [46].. NA-ACCORD 18 24,444 ART-CC CD4+ T 450 /mm 3 [43]. CD4+ T /mm /mm 3, ( : 0.99, 95% : )., CD4+ T 550 /mm 3 [43]. CASCADE CD4+ T /mm 3 5,162, [47]. Setpoint 6, 57% 500 /mm 3 CD4+ T [49].,.

11 HIV 감염치료지침 대한에이즈학회 CD4+ T 500 /mm 3. CD4+ T HIV HIV. -, CD4+ T 500 /mm /mm 3 CD4+ T (B-III).,, CD4+ T,,. 3) CD4+ T 세포수와무관하게고강도항레트로바이러스요법이더욱필요한경우는? 2. CD4+ T. 1) (A-I) 2) (A-I) 3) (HIV-associated nephropathy) (A-II) 4) HBV (A-II) 5) HCV (B-II) 6) CD4+ T 100 /mm 3 (A-III) 7) HIV RNA 10 5 copies/ml (B-II) 8) HIV (B-II) (1) HIV RNA., (A-I). 2, [50]. (2) (HIV-associated nephropathy) [51]. CD4+ T,, HIV [52, 53]. [54-56]., (A-II). (3) HBV,, [57, 58]., HBV [59-61]. HBV (, tenofovir, lamivudine, emtricitabine) HBV [62, 63]., (, ) [64]. HBV. HBV HBV HBV (A-II). (4) HCV,, [57, 58]., HCV [60, 61]. HCV, CD4+ T HCV

12 대한에이즈학회 HIV 감염치료지침 [65]., (, ) [64]. HCV (B-II). (5) HIV RNA CD4 + T 100 /mm 3 CD4+ T [66] (A-III). HIV RNA 10 5 copies/ml 10 5 copies/ml [2] (B-II). (6) HIV HIV.,,,, (viral set point) [67-69]., HIV, CD4+ T [49, 70]., HIV,. 4) 고강도항레트로바이러스요법을시행하기전약제순응도를위하여고려해야할사항은무엇인가? 3., (A-III)., (A-III). ( ),,,.,,,. D:A:D [36]. SMART [71]..,. 3. 치료경험이없는환자에서의고강도항레트로바이러스요법 1. 2 (NRTI backbone) + 1, 3 (A-I). 2. NRTI backbone tenofovir/emtricitabine abacavir/lamivudine (A-I), NRTI backbone zidovudine/lamivudine (B-I). 3. ritonavir-boosted darunavir, ritonavir-boosted atazanavir, ritonavir-boosted lopinavir (A-I), unboosted atazanavir (B-I)., unboosted atazanavir tenofovir. 4. efavirenz, HIV RNA RNA < 100,000 copies/ml rilpivirine (A-I). 5. raltegravir cobicistat-boosted elvitegravir (A - I). Cobicistat-boosted elvitegravir tenofovir/emtricitabine/elvitegravir/cobicistat.

13 HIV 감염치료지침 대한에이즈학회 1) 서론 (1). (2) Pubmed( , / (International AIDS Society Conference, International AIDS Conference, Conference on Retroviruses and Opportunistic Infections, ID Week, Interscience Conference on Antimicrobial Agents and Chemotherapy, International Workshop on Antiviral Drug Resistance). Clinical Trial. FDA (prescribing information). (3) -? -?? - 3?? - 3?? - 3?? -? 2) 초치료환자에서고강도항레트로바이러스요법은어떤약제들로구성하는가? 1. 2 (NRTI backbone) + 1, 3 (A-I). (1) 2 1 3,,, (A-I B-I). Table 5, column A B. LPV/r preferred regimen. Department of Health and Human Service, International AIDS Society - USA panel, European AIDS Clinical Society. European AIDS Clinical Society LPV/r preferred regimen LPV/r alternative regimen. LPV/r 2. HIV 2 HIV LPV/r LPV/r preferred regimen [72]. ABC/3TC DRV/r RPV, RAL alternative regimen preferred regimen. 3) 어떤뉴클레오시드역전사효소억제제조합을우선적으로고려하는것이타당한가? 각뉴클레오시드역전사효소억제제조합의장단점및특징은? 2. NRTI backbone tenofovir/emtricitabine abacavir/lamivudine (A-I), NRTI backbone zidovudine/lamivudine (B-I). (1) (Table 5 column A) Tenofovir/emtricitabine (A-I) Tenofovir/emtricitabine 1, tenofovir/emtricitabine 1 1 NRTI backbone. tenofovir/emtricitabine/elvitegravir/cobicistat 1 1.,. Tenofovir/emtricitabine HBV HIV HBV.,, atazanavir unboosted atazanavir. Tenofovir/emtricitabine zidovudine/lamivudine ( efavirenz 3 )

14 대한에이즈학회 HIV 감염치료지침 Table 5. Initial combination regimen for antiretroviral-naïve patients Select 1 combination in column A and 1 drug in column B Preferred (A-I) TDF/FTC a, b, c PI/r h [73]. Tenofovir/entricitabine abacavir/lamivudine ACTG 5202, RNA 100, 000 copies/ml tenofovir/emtricitabine [74]. HEAT tenofovir/emtricitabine abacavir/lamivudine [75]. tenofovir/emtricitabine [76-87]. Tenofovir,,, (glycosuria) [88, 89]., HIV,,,, cobicistat [75, 88, 90-95]., A a, d, e, f, g ABC/3TC DRV/r Alternative (B-I) ZDV/3TC a, n PI B LPV/r i, j ATV/r NNRTI EFV k RPV l INSTI RAL EVG/COBI m ATV o a FTC could be substituted by 3TC or vice versa. b TDF should be prescribed with caution in patients with renal diseases and/or decreased bone mineral density. c TDF and FTC co-formulated drug is available. d Fatal hypersensitivity reaction could be happen by ABC, retrial is contraindicated when hypersensitivity reaction is suspicious. e Hypersensitivity to ABC is related to HLA-B*5701. f Special caution is required when ABC is used in patients with (a) cardiovascular risk factor(s). g ABC and 3TC co-formulated drug is available. h Ritonavir-boosted PI. i Either LPV/r 400 mg/100 mg bid or 800 mg/200 mg qd is acceptable. j The frequency of side effects is higher than other PIs. k Special attention is required, when administered during 1 st trimester and alternative regimen should be considered in sexually active women with no effective and consistent contraception. l Only if HIV RNA <100,000 copies/ml. m Available only as a single coformulated tablet as tenofovir/emtricitabine/ elvitegravir/cobicistat. n ZDV and 3TC co-formulated drug is available. o Unboosted ATV should not be used with TDF. [96, 97]. Tenofovir, tenofovir/emtricitabine abacavir/lamivudine [98, 99]., tenofovir [100]. Abacavir/lamivudine (A-I), abacavir/lamuvudine 1 1 NRTI backbone. abacavir, HIV RNA 100,000 copies/ml tenofovir/emtricitabine,., HLA-B*5701 abacavir, HLA-B*5701 [16, 19, 101], HLA-B*5701 [102]. HLA-B*5701 HLA-B*5701 [17, 103]. ACTG 5202 abacavir/lamivudine tenofovir/emtricitabine [104]., D:A:D, SMART abacavir [ ]. abacavir [108, 109]. abacavir.,. ACTG 5202, HIV RNA <100,000 copies/ ml abacavir/lamivudine tenofovir/emtricitabine, HIV RNA 100,000 copies/ml abacavir/lamivudine tenofovir/emtricitabine [74, 110]., HEAT abacavir/lamivudine tenofovir/emtricitabine [75]. Abacavir/lamivudine zidovudine/lamivudine ( efavirenz 3 ) CD4+ T abacavir/lamvudine [111]. Zidovudine/lamivudine (B-I) Zidovudine/lamivudine (1 2 ),

15 HIV 감염치료지침 대한에이즈학회. 2, zidovudine,,. Zidovudine/lamivudine tenofovir/emtricitabine ( efavirenz 3 ), zidovudine/lamivudine tenofovir/emtricitabine, [73]., zidovudine/lamivudine abacavir/lamivudine ( efavirenz 3 ),, 48 CD4+ T zidovudine/lamivudine 155 /mm 3, abacavir/lamivudine 209 /mm 3 abacavir/lamivudine [111]. zidovudine/lamivudine + efavirenz, tenofovir/emtricitabine + efavirenz, didanosine/emtricitabine + atazanavir zidovudine/lamivudine + efavirenz tenofovir/emtricitabine + efavirenz, didanosine/emtricitabine + atazanavir [112]. 4) 제 3의약물로단백분해효소억제제를사용해야하는경우어떤약제를선택해야하는가? 각단백분해효소억제제의장단점및특징은? 3. ritonavir-boosted darunavir, ritonavir-boosted atazanavir, ritonavir-boosted lopinavir (A-I), unboosted atazanavir (B-I)., unboosted atazanavir tenofovir. (1) 3 (Table 1 column B) (genetic barrier to resistance),., CYP3A4, CYP, (,, ),. atazanavir boosted atazanavir [113], boosted darunavir. Ritonavir-boosted darunavir (A-I) Ritonavir-boosted darunavir,. ARTEMIS ritonavir-boosted darunavir ritonavir-boosted lopinavir ( tenofovir/emtricitabine ) 48, 192 ritonavir-boosted darunavir., ritonavir-boosted darunavir [85, 114]., ritonavir-boosted darunavir ritonavir-boosted lopinavir [115]. Darunavir 300 mg 400 mg, darunavir darunavir 800 mg ritonavir 100 mg 1 1.., darunavir sulfonamide moiety sulfa allergy [116]. Ritonavir-boosted atazanavir (A-I) Ritonavir-boosted atazanavir,.,, (acidity),. [ ]. CASTLE ritonavir-boosted atazanavir ritonavir-boosted lopinavir ( tenofovir/emtricitabine ) 2, CD4+ T <50 /mm 3 HIV RNA 100,000 copies/ml ritonavir-boosted atazanavir [84, 94]. CASTLE, 48 ritonavir-boosted atazanavir (n=42) 83%, ritonavir-boosted lopinavir (n=41) 90% ( )[121]., ritonavir-boosted lopinavir, ritonavir-boosted atazanavir [84, 94]. Ritonavir-boosted atazanavir, ritonavir-boosted darunavir, raltegravir ACTG ( tenofovir/emtricitabine ), 3. bilirubin,

16 대한에이즈학회 HIV 감염치료지침 ritonavir-boosted atazanavir [122]. Atazanavir (gastric acidity),, tenofovir [123]. Ritonavir-boosted lopinavir (A-I) Ritonavir-boosted lopinavir., lopinavir ritonavir ritonavir.,,,. ACTG 5142 ritonavir-boosted lopinavir efavirenz ( 2 ), efavirenz, CD4+ T ritonavir-boosted lopinavir [124]., (lipoatrophy) efavirenz [125]. ritonavir-boosted atazanavir ritonavir-boosted darunavir ritonavir-boosted lopinavir, ritonavir-boosted lopinavir [84, 85, 94, 114]. ritonavir-boosted lopinavir 200 mg/50 mg 2 2, 4 1 [76, 126, 127]. 4 1 (B-II). ritonavir-boosted lopinavir 3 2 (C-III)., D:A:D ANRS ritonavir-boosted lopinavir [107, 109], D:A:D ritonavir-boosted lopinavir [128]. Unboosted atazanavir (B-I) Unboosted atazanavir.,, (gastric acidity),. Tenofovir, proton pump atazanavir unboosted atazanavir [123] unboosted atazanavir ritonavir-boosted atazanavir ( stavudine/ lamivudine ), [129]., 2 atazanavir ritonavir-boosted atazanavir [130, 131]. 5) 제 3의약물로비뉴클레오시드역전사효소를사용해야하는경우어떤약제를선택해야하는가? 각약제들의장단점및특징은? 4. efavirenz (A-I), efavirenz rilpivirine (B-I). (1) 3 (Table 1 column B),.., CYP3A4, (efavirenz). nevirapine [132] (A-I). Efavirenz (A-I) Efavirenz [78-81, 86, 124, ]. 1.,,., efavirenz [25, 139],., efavirenz efavirenz.,,, ( 5-6 ),, efavirenz,, meta-analysis efavirenz

17 HIV 감염치료지침 대한에이즈학회 [139, 140]., efavirenz [141]. ACTG 5142 efavirenz ritonavir-boosted lopinavir ( 2 ), CD4+ T ritonavir-boosted lopinavir [124]. Rilpivirine (A-I) Rilpivirine 1, 1, K103N [142]., 2015 tenofovir/emtricitabine/rilpivirine 1 1. HIV RNA,, rifabutin/rifampin/rifapentine proton pump inhibitors, HIV RNA >100,000 copies/ ml. Rilpivirine ECHO THRIVE. 2 tenofovir/emtricitabine NRTI backbone rilpivirine efavirenz. HIV RNA 100,000 copies/ml, HIV RNA >100,000 copies/ml, CD4+ T 200 /mm 3 rilpivirine efavirenz.,, rilpivirine [86, 87, 137, 138, ]. Rilpivirine efavirenz STaR (tenofovir/emtricitabine/rilpivirine tenofovir/emtricitabine/efavirenz ) rilpivirine efavirenz, HIV RNA 100,000 copies/ml rilpivirine, HIV RNA >500,000 copies/ml efavirenz [148]. 6) 제 3의약물로통합효소억제제를사용할경우어떤약제를선택해야하는가? 각약제들의장단점및특징은? 5. raltegravir cobicistat-boosted elvitegravir (A - I). Cobicistat-boosted elvitegravir tenofovir/emtricitabine/elvitegravir/cobicistat. (1) 3 (Table 1 column B), raltegravir elvitegravir(tenofovir/emtricitabine/elvitegravir/cobicistat ). Raltegravir (A-I) Raltegravir,., 2. 1 (efavirenz, nevirapine). STARTMRK 5 raltegravir efavirenz ( tenofovir/emtricitabine ), raltegravir efavirenz, [78-81, 149]. Raltegravir, ritonavir-boosted atazanavir, ritonavir-boosted darunavir ACTG ( tenofovir/emtricitabine ), 3., raltegravir ritonavir-boosted atazanavir ritonavir-boosted darunavir, ritonavir-boosted atazanavir [122]. Raltegravir (NRTI sparing regimen), PROGRESS. raltegravir + ritonavir-boosted lopinavir tenofovir/emtricitabine + ritonavir-boosted lopinavir. 96, 2 [150]. tenofovir/emtricitabine + ritonavir-boosted lopinavir., raltegravir + ritonavir-boosted darunavir tenofovir/emtricitabine + ritonavir boosted darunavir raltegravir + ritonavir-boosted darunavir [151]. Cobicistat-boosted elvitegravir (A-I) Cobicistat-boosted elvitegravir tenofovir/emtricitabine/elvitegravir/cobicistat. 1 1.,., elvitegravir raltegravir CYP3A,., rifabutin/rifampin/rifapentine. Tenofovir/emtricitabine/elvitegravir/cobicistat creatinine clearance <70 ml/

18 대한에이즈학회 HIV 감염치료지침 min, creatinine 0.4 mg/dl [152]. Tenofovir/emtricitabine/elvitegravir/cobicistat tenofovir/emtricitabine/efavirenz (102 ), tenofovir/emtricitabine/elvitegravir/cobicistat tenofovir/emtricitabine + ritonavir-boosted atazanavir (103 ) 144 tenofovir/emtricitabine/elvitegravir/cobicistat [153, 154]. Cobicistat CYP3A, elvitegravir elvitegravir. Cobicistat creatinine MATE1 transporter. cobicistat GFR creatinine clearance [152]. 7) 고강도항레트로바이러스요법에서피해야할약제조합은? (1) 1-4. (2) 2 Efavirenz nevirapine. Etravirine etravirine. 2. (3) efavirenz Efavirenz efavirenz, (1st trimester)., 5-6, efavirenz, efavirenz efavirenz. (4) didanosine + tenofovir,., didanosine. (5) Emtricitabine + lamivudine Emtricitabine lamivudine cytidine,. (6) Etravirine + unboosted protease inhibitor Etravirine unboosted PI. etravirine unboosted PI. (7) Etravirine + ritonavir-boosted atazanavir Etravirine ritonavir-boosted atazanavir. etravirine ritonavir-boosted atazanavir. (8) CD4+ T cell >250 cells/mm 3 CD4+ T cell >400 cells/ mm 3 nevirapine,. (9) Unboosted Darunavir Unboosted darunavir,. darunavir ritonavir. 4. 치료력이있는환자에서항레트로바이러스제투여 1.. (A-III) copies/ml, copies/ml. ( copies/ml) (A-III). 3. (A-I). (A-I) 4 (A-II). 4 (C-III). 4. ( < 50 copies/ml) (A-I). 5.

19 HIV 감염치료지침 대한에이즈학회 (A-II). 2, 3 (A-I). 6. CD4+ T,. 7. CD4+ T (A-I)... (coformulation) [155, 156]. :?? 1) 항레트로바이러스제치료실패. (50 copies/ml).,,., CD4+ T,, (, ),,,,.. CD4+ T,,,,,,., [155](A-III)..,,.,. ( ), ( zidovudine abacavir ),..,.. (A-I). (A-I) 4 (A-II). 4 (C-III). 2) 항레트로바이러스제치료실패에대한조치 (1) (50 copies/ml). 200 copies/ml copies/ml copies/ml [157], [158, 159]. 51-1,000 copies/ml [160]. (A-II). 2, 3 [ ](A-I).. etravirine, darunavir, raltegravir, elvitegravir, CCR5 maraviroc, enfuvirtide. 50-1,000 copies/ml :.

20 대한에이즈학회 HIV 감염치료지침 50 copies/ml copies/ml 3 (A-III) ,000 copies/ml, 500 copies/ml (B-III). 1,000 copies/ml : (genotypic resistance test) (C-III). : 50 copies/ml... efavirenz efavirenz efavirenz etravirine. raltegravir, elvitegravir, enfuvirtide. 2, 3 (A-II).. [166]. : 50 copies/ml log 10 copies/ml [167] ,000-20,000 copies/ml [168, 169]. (B-II). CD4+ T 100 /mm 3 (C-I).. (2) 4-7 CD4+ T /mm 3 [170]. CD4+ T. 6 CD4+ T 200 /mm 3 42% CD4+ T 500 /mm 3. CD4+ T /mm 3 66%, 350 /mm 3 85% CD4+ T 500 /mm 3 [171]. CD4+ T 4-6 [172, 173]. CD4+ T. [174].,, [175]. CD4+ T CD4+ T <200 /mm 3,, HIV-2, HTLV-1, HTLV-2, HCV, zidovudine tenofovir + didanosine,,.. interferon,,, zidovudine, tenofovir + didanosine.. HCV, HTLV-1, HTLV-2. CD4+ T 200 /mm 3. Interleukin-2 (A-I). (3) 3 (immune reconstitution syndrome).

21 HIV 감염치료지침 대한에이즈학회 2.5 7%, 20% [176]. 3. (B-III). 5. HIV/HBV 및 HIV/HCV 동시감염환자치료? - HIV/HBV? - HIV/HBV? - HIV/HBV? - HIV/HBV HBV (, lamivudine, entecavir)? - HIV/HBV HIV? 1) 서론 (1) B (hepatitis B virus; HBV) C (hepatitis C virus; HCV). HIV HBV/HCV (antiretroviral therapy; ART). HIV HBV/ HCV,,, (suboptimal response). HIV HCV - HIV HCV? - HIV/HCV? - HIV/HCV? - HIV/HCV? - HIV/HCV? (2) HIV HBV HIV HCV HBV HCV,., boseprevir telaprevir. (3) DHHS guideline (2014), European AIDS clinical society (EACS, 2014), 2011 B ( ), C (2013 ). PubMed ( KoreaMed ( org) ( HIV HIV Human immunodeficiency virus, HBV HBV hepatitis B virus, HCV HCV hepatitis C virus, therapy treatment management. (4) HIV HBV - HIV HBV 2) HIV 감염자에서 HBV 감염여부는어떻게선별검사해야하며바이러스간염에대한예방은어떻게해야하는가? 1. HIV HBV (A-III). 2. HIV A B, anti-hbsab B, anti-hav IgG A (A-III). 3. B 1 anti-hbs, (anti-hbs <10 IU/mL) (B-III). HBV (B-III). (1) HBV B,, [58]. B HIV CD4+ T [177, 178]. HIV/HBV HBV,,.

22 대한에이즈학회 HIV 감염치료지침 (2) HIV HBV? HBV, HBsAg, anti-hbc, anti-hbs. HBsAg 6 2 HBV, HBeAg, anti-hbe, HBV DNA HBV. A anti-hav. Anti-HBs B, anti-hav IgG A. B (anti-hbs <10 IU/mL). 1 anti-hbsab <0 IU/mL HBV. CD4 T HBV HBV CD4+ T 350 (A-II)., CD4+ T CD4 T+ 350 HBV (A-II). (3) HIV/HBV HIV/HBV, HBV. 3) HIV/HBV 동시감염자에서치료전평가는어떻게해야하는가? 4. HBsAg HBV DNA (A-III). HBsAg HIV HBV DNA (A-III). HIV/HBV HBV. HBV, CBC, ALT, AST, albumin, bilirubin, prothrombin time 6 (A-I). HBV HBeAg, anti-hbe, HBV DNA (A-I). B (Hepatocellular carcinoma; HCC),. (A-I). HBV DNA (>2,000 IU/mL) ALT B.. HBV B HBV DNA 6-12 HBV. 4) HIV/HBV 동시감염환자에서치료시작시점은? 5. CD4+ T HIV/HBV HIV HBV (A-II). CD4+ T HIV/HBV HIV HBV (A-II)., ART HBV pegylated interferon α 48 adefovir (C-III). HBV. (1) HBeAg ALT HBV (B-I). (2) HBeAg HBV DNA 20,000 IU/mL ALT 1-2 (B-II). (A-I). (3) HBeAg HBV DNA 2,000 IU/mL ALT 2 (A-I). ALT 2 (B-II). (A-I). (4) HBV DNA 2,000 IU/mL ALT (B-I). (5) HBV DNA ALT (B-I). 5) HIV/HBV 동시감염환자에서치료제의선택은어떻게해야하는가? 6. HIV/HBV : Emtricitabine (FTC), Lamivudine (3TC), Tenofovir (TDF) HIV HBV, HBV HIV TDF + FTC TDF+3TC (A-I). 7. HBV TDF, HBV entecavir (B- I). HBV peginterferon-α telbivudine, adefovir 3TC FTC (B-II).

23 HIV 감염치료지침 대한에이즈학회 8. Entecavir HIV M184V (mutation) entecavir (A-II). (1) Emtricitabine, lamivudine, tenofovir HIV HBV. HBV [179]. HIV/HBV HBV lamivudine Lamivudine HBV lamivudine 2 40%, 4 90%. lamivudine HBV (A-II) [180]. Entecavir -HIV HIV/HBV M184V lamivudine emtricitabine., HIV/HBV entecavir [181] (A-II). (2) HIV/HBV HBV, Emtricitabine (FTC), Lamivudine (3TC), Tenofovir (TDF) HIV HBV, HBV HIV TDF + FTC TDF + 3TC [63, 182, 183] (A-I)., HBV TDF, HBV entecavir (A- II). Entecavir HIV [184] (B-II). Entecavir lamivudine, entecavir lamivudine entecavir., lamivudine HBV, entecavir 0.5 mg/ 1 mg/. lamivudine HBV entecavir HBV DNA (, 3 ). HBV peginterferon-α telbivudine, adefovir 3TC FTC [63, 185, 186] (B-II)., peginterferon-α. (3) HBV (immune reconstitution). HBV [187]. (4). HIV/HBV [188, 189].. (alanine aminotransferase; ALT) HIV/HBV HBeAg (seroconversion),. HBeAg HBeAg anti-hbe, HBV DNA. (5) HIV/HBV HBV DNA 12. HBeAg HBeAg 6.. (primary non-response) 12 HBV DNA 1 log 10. (complete virological response) real time PCR HBV DNA. 24 HBV DNA. 24 HBV DNA 1 log 10 (partial virologic response). (sustained virologic response) 6. (primary non-response) (B-I). (partial virologic response) (B-I). (virologic breakthrough), (A-I). (A-I).

24 대한에이즈학회 HIV 감염치료지침 6) HIV/HBV 동시감염환자에서항 HBV 효과를갖는약제 ( 예. lamivudine, entecavir) 를중단해야할경우유의할점은? 9. HBV (, lamivudine, entecavir) : HBV HBV HBV (A-II). HBV,. HBV adefovir dipivoxil, entecavir, telbivudine [179]., HBV. 7) HIV/HBV 동시감염환자에서사람면역결핍바이러스치료실패로항레트로바이러스약제를교체해야할경우유의할점은? 10. HBV HBV (A-III)., HBV HBV (A-III). (1) HIV HCV HCV 33% 20 [190, 191].,,, [57, ]. HIV/HCV HCV 3 [194] CD4+ T. HIV/HCV HCV., HCV HIV. (2) HIV HCV HIV HCV. anti- HCV.., HCV (seroconversion) (window period),, anti-hcv (indeterminate) HCV RNA [195]. HIV (<1%). Anti-HCV HCV-RNA. HCV- RNA HCV HCV., HCV-RNA. 8) HIV감염자에서 HCV감염여부는어떻게선별검사해야하며바이러스간염에대한예방은어떻게해야하는가? 11. HIV C, (A-III). 12. anti-hcv, (A-II). 13. Anti-HCV HCV-RNA (A-III). 14. HCV,. (barrier precaution) HCV (B-III). 15. HIV/HCV, HCV, HAV HBV (A-III). (3) HCV, [ ]. (barrier precaution) HCV (STD) (B-III). HCV peginterferon ± ribavirin [199, 200]., HCV HIV HCV (A-II)., C/C IL28B 3-6 [201]. HCV PegIFN/ribavirin [199, 200, 202](A-II). HIV/HCV, HCV,

25 HIV 감염치료지침 대한에이즈학회 HAV HBV (A-III). 9) HIV/HCV 동시감염환자에서치료전평가는어떻게해야하는가? 16. HCV HCV, IL28B (A-II). HCV (sustained virological response; SVR), SVR HCV 6. SVR HIV HCV. SVR,,,. (1) HIV/HCV HIV/HCV HCV.. HCV HCV HCV ( 2 > 3 > 1 4) HCV. HCV 1 (A/B). IL28B (Interleukin lambda) 28B (IL-28B) (genetic polymorphism) HCV C IFN [203, 204]. 19q13 rs C/C C/T T/T. IL-28B HCV HIV [205]. IL-28B, IL-28B HCV. ALT AST. ALT AST, ALT [206].,,.,, (<0.5%), (0.09%), HCV. 10) 고강도항레트로바이러스요법치료경험이없는 HIV/HCV 동시감염환자에서언제항레트로바이러스치료를시작하는가? 17. HIV/HCV CD4+ T (B-II). HIV/HCV HIV HCV,. HIV/ HCV CD4+ T CD4+ T 500 /mm 3 HCV. 18. CD4+ T <200 /mm 3 CD4+ T HCV (C-III). ( ) HIV/HCV, CD4+ T ( 350 /mm 3 ). HCV [57, 207, 208]. [59-61]., HIV/HCV., HIV/HCV CD4 (B-II)., HIV HCV,, CD4+ T 500 /mm 3 HCV. 11) HIV/HCV 동시감염환자에서어떠한약제를사용해야하는가? 19. HIV/HCV (A-III)., HCV. 20. HCV Peginterferon alfa (PegIFN) ribavirin HIV/HCV (A-I). (1) HIV HCV HIV/HCV.. HCV,.

26 대한에이즈학회 HIV 감염치료지침 (liver decompensation) Child-Turcotte-Pugh Child- Pugh class B C. HIV/HCV HCV,.. Didanosine ribavirin didanosine ( /,, ) [209] (A-II). Zidovudine ribavirin, zidovudine ribavirin ribavirin [210] (A-II). Abacavir peginterferon ribavirin. [ ]., HCV abacavir (B-III). 1 3 AST/ ALT. HCV. ( 5 ) (, A B,, ). [195]. (2) HIV/HCV (drug induced liver injury, DILI) HIV HIV/HCV. HIV/HCV (,, ) [214]. HCV [215]., ( 5 ) stavudine, nevirapine, (full-dose) ritonavir (600 mg daily) [216]., stavudine, didanosine, ziduvudine [217], didanosine [218] RTV boosted tipranavir. 12) HIV/HCV 동시감염환자의치료는어떻게해야하는가? 21. HIV/HCV PegIFN/ribavirin 48 (A-I)., HCV genotype 2, 3 4, 24 (C-III). 22. Ribavirin PegIFN (B-II). SVR. 23. PegIFN/ribavirin (A-II) (aspartate aminotransferase, AST)/ (alanine aminotransferase, ALT). HCV. ( 5 ) (, A B,, ). (A-II). (1) HIV HCV HIV/HCV PegIFN/ribavirin 48 (A-I)., HCV 2, 3 4, 24 (C-III). Ribavirin PegIFN (B-II). SVR. PegIFN/ribavirin. IFN (antigrowth) (antiproliferative). ribavirin (teratogenicity) FDA X. ribavirin ribavirin 6 (A-III). (C-III). (2) HIV HCV : HCV RNA,,. 4 : 4 HCV RNA SVR. PegIFN/ribavrin 4 1 log 10 SVR 5%

27 HIV 감염치료지침 대한에이즈학회. (rapid virological response; 4 ) 80% SVR. 12 : PegIFN/ribavirin, 2 log 10 (null virologic response) PegIFN/ribavirin. 2 log 10 (partial early virologic response). (complete early virologic response). SVR 60-65%. 24 : 12 (partial early virologic response) 24. SVR 20%, (B-I). ( ): (viral breakthrough). :, 24 HCV RNA. SVR. 6. 임신부의항레트로바이러스치료 1. HIV HIV (A-I). 2. Nevirapine CD4 (>250 /mm 3 ) (A-I). 3. Efavirenz (teratogenic) (A-III), HIV efavirenz (B-III). 4. HIV, (A-I). 5. HIV,, (A-III). 6., (A-III). 7. HIV RNA 500-1,000 copies/ml (A-I). 8. HIV, 1 efavirenz (A-III). 9. efavirenz 1 HIV efavirenz (C-III). 10. HIV RNA 1,000 copies/ml zidovudine (A-I) ,000 copies/ml zidovudine., (B-II). 12. HIV RNA 1,000 copies/ml 38 (A-II). 13. HIV (A-II). 1) 임신전관리 HIV HIV (A-I).,,, cytochrome P (CYP) 450, [ ]., nevirapine CD4 (>250 /mm 3 ) [ ] (A-I)., (lactic acidosis) stavudine, didanosine, zidovudine NRTI [225].,, / [226, 227]., efavirenz (teratogenic)

28 대한에이즈학회 HIV 감염치료지침 (AIII), HIV efavirenz [228] (B-III)..,. Protease inhibitor (PI) Non-nucleoside reverse transcriptase inhibitor (NNRTI) ethinyl estradiol, norethindrone, norgestimate, ergesterone progestin [ ]. Efavirenz ethinyl estradiol norgestimate progestin, ritonavir-boosted PI estradiol.,. (intrauterine device, IUD) HIV [233, 234]. 2) 분만전임신기간중항레트로바이러스제치료 HIV HIV RNA. 5-6, 4-6 HIV, (A-I). 28 HIV RNA 50 copies/ml 20-30% % [235, 236]., HIV,, (A-III)., (A-II)., (A-III)., HIV RNA 500-1,000 copies/ ml (A-I). HIV, 1 efavirenz (A-III)., [237]., efavirenz 1 HIV efavirenz (C-III). 3) 분만중항레트로바이러스제치료 zidovudine HIV., zidovudine. HIV, 95% zidovudine zidovudine (0.9%, 95/10,239) (1.8%, 9/514) (P=0.06)[238]., HIV RNA 1,000 copies/ml zidovudine (0%, 0/369) (0.6%, 47/8,132) (P>0.20). (HIV RNA >1,000 copies/ml) zidovudine zidovudine (2.5% 10.2%, P<0.01), 2 (4.8% 4.1%, P =0.83)., HIV RNA 1,000 copies/ml zidovudine [228] (A-I). Zidovudine 3. 1 (2 mg/kg) 2 (1 mg/kg/hr). 1,000 copies/ml zidovudine., (B-II). HIV RNA 1,000 copies/ml 38 [239] (A-II). HIV RNA., HIV RNA HIV RNA DNA [240]. 4) 분만후처치 HIV, (CD4 ), (HIV RNA ) HIV

29 HIV 감염치료지침 대한에이즈학회. ( ) HIV,. HIV., HIV [241] (A-II)., HIV. 부록. 항레트로바이러스제내성 1. 개요.,,.,.,.,.,,., CCR5 1) X4 virus (overgrowth), 2) HIV gp120 (, V3 loop ) gp41 CCR5 CCR5. 1..,..,.,.,. 2. 내성검사해석의일반적원칙과임상적응용 1) 내성장벽 (resistance barrier) (resistance threshold)., 1.. 2) 내성검사의종류 (genotypic test) (phenotypic test).,.. standard cloning %. single genome sequencing, pyrosequencing, allelespecific PCR, parallel allele-specific PCR [ ].. 3) 내성검사의해석의일반적원칙.,, (minor resistant variant).,..

30 대한에이즈학회 HIV 감염치료지침. K70R, M184V, T215Y, Y181C [32, 246]. 4.,,,., (plasma). proviral DNA [247],. 4) 내성장벽, 약물반감기, 치료실패, 내성의발현 lamivudine (emtricitabine) < < lamivudine (emtricitabine) <. 1 (INSTI, integrase strand transfer inhibitor) IC 50., IC 50. Lamivudine lamivudine. abacavir/lamivudine + efavirenz. lamivudine < efavirenz < abacavir., abacavir < lamivudine << efavirenz., efavirenz. efavirenz lamivudine.,. 5) 내성검사결과에따른항레트로바이러스약제의선택 (fully active agents)..,. 2 etravirine 1 etravirine 1 [248] dolutegravir [ ]. 2 1.,.,.. M184V zidovudine, stavudine, tenofovir [254], K65R, L74V, Y181C zidovudine [ ]., (, TAM-1, M184V) [258]. boosted atazanavir I50L [259], N88S boosted fosamprenavir [260].,...,,. 3. 각약제에내한내성돌연변이 IAS-USA(International Antiviral Society USA) [261],. 1) 뉴클레오시드역전사효소억제제내성,. 2

31 HIV 감염치료지침 대한에이즈학회 [ ]., DNA primer unblocking, primer rescue, pyrophosphorolysis, nucleotide excision. Thymidine (thymidine analogue mutation, TAM) TAM 2., DNA NRTI discrimination. tenofovir, abacavir, lamivudine, emtricitabine, didanosine. K65R, L74V, M184V, Q151M.,. NRTI discrimination, M184V [ ]., primer unblocking NRTI discrimination [ ]. M184V. M184V lamivudine, emtricitabine zidovudine, stavudine, tenofovir [255, 273]. M184V lamivudine, emtricitabine. TAM thymidine zidovudine, stavudine. TAM type 1 type 2 M41L, L210W, T215Y type 1, D67N, K70R, L215F, K219Q/E type 2 [ ]. TAM-2 TAM-1. TAM-1 TAM-2., D67N TAM-1, zidovudine stavudine TAM-1 TAM-2. TAM zidovudine, stavudine, TAM 2-3 didanosine, abacavir, tenofovir [273].. T215Y Y T 2. T215Y T A/C/D/E/G/H/I/L/N/S/ V [ ]. T215A/C/D/ E/G/H/I/L/N/S/V revertant TAM-1. K65R abacavir, tenofovir abacavir, didanosine, tenofovir, lamivudine, emtricitabine. K65R zidovudine, zidovudine [255, 282]. K65R non-subtype B [283, 284]. L74V didanosine, abacavir, didanosine, abacavir [ ]. L74V zidovudine, tenofovir [256]. 2) 비뉴클레오시드역전사효소억제제내성,. 2. K103N/S, Y181C/I/V, V106A/M, G190A/S/E. efavirenz K103N [256, 288, 289]., 1. rilpivirine E138K [87, 290], 2 eravirine ripivirine 1 K103N [142, 256, 291]. K103N., V106A, Y188C, G190S [ ]. 1 nevirapine efavirenz IAS-USA 1. etravirine 1. Etravirine,. etravirine [291]. 3.0: Y181I/V 2.5: K101P, L100I, Y181C, M230L 1.5: E138A, V106I, G190S, V179F

32 대한에이즈학회 HIV 감염치료지침 1.0: V90I, V179D, K101E, K101H, A98G, V179T, G190A HIV RNA >5,000 copies/ml 1 (DUET study) 24, etravirine + boosted-darunavir + etravirine %, %, %. E138A etravirine [296]., etravirine K103N. K103N L100I, K101P [256]. HIV-2 [297]. 3) 단백분해효소억제제내성.,,., [ ]. (cleft). major mutation, minor mutation. Stanford HIV Drug Resistance Database ( D30N, G48V, I50V, V82A/T, M46I/L, I54V, I84V, N88D/ S, L90M [ ]. boosted atazanavir < boosted lopinavir < boosted darunavir. Boosted atazanavir major mutation, [248]. boosted atazanavir. 4) 통합효소억제제내성 (integrase). raltegravir Q148R/H/K, N155H, Y143C/H/R, E92Q. Q148R/ H/K, N155H,. raltegravir 1. Q148H/K/R L74M, E138A/K, G140S, N155H L74M, E92Q, T97A, Y143H, G163K/R, V151I, D232N [163, ]. 1 raltegravir elvitegravir. Y143R/H/C raltegravir elvitegravir [ ]., E92Q elvitegravir, raltegravir, S147G elvitegravir raltegravir [163, 315, ]. 2 dolutegravir 1, Q148R + G140S, Q148K + E138K, Q148R + G140A 2 [249, 254, 321, 322]. Dolutegravir R263K pathway R263K M50I, H51Y, E138K [ ]. Dolutegravir 1 [327]., R263K pathway mutation viral fitness [328, 329]., dolutegravir dolutegravir.

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