역전사효소 억제제

3. 종류

역전사 효소 억제제(RTIs)는 크게 네 가지 종류로 나뉜다.^[24]

• 뉴클레오사이드 유사 역전사 효소 억제제 (NARTIs 또는 NRTIs)
• 뉴클레오타이드 유사 역전사 효소 억제제 (NtARTIs 또는 NtRTIs)
• 비뉴클레오사이드 역전사 효소 억제제 (NNRTIs)
• 뉴클레오사이드 역전사 효소 전좌 억제제 (NRTTIs)

3. 1. 뉴클레오사이드 유사 역전사 효소 억제제 (NRTIs)

3. 2. 뉴클레오타이드 유사 역전사 효소 억제제 (NtRTIs)

3. 3. 비뉴클레오사이드 역전사 효소 억제제 (NNRTIs)

3. 4. 뉴클레오사이드 역전사 효소 전좌 억제제 (NRTTIs)

4. 내성 기전

역전사 효소 중합효소 도메인의 아스파르트산 잔기 110, 185 및 186은 뉴클레오티드의 결합 및 삽입에 중요하다. 잔기 K65, R72 및 Q151의 측쇄는 다음에 들어오는 뉴클레오티드와 상호 작용한다. L74는 템플릿 가닥과 상호 작용하여 뉴클레오티드와의 염기쌍 형성을 위해 위치시키는 데 중요하다. 이러한 주요 아미노산의 돌연변이는 핵산유사체(약물)의 유전체 통합을 감소시킨다.

NRTI와 NNRTI는 모두 DNA 합성과 HIV 복제를 억제하는 데 효과적이지만, HIV는 약물에 대한 바이러스 내성 기전을 획득한다. HIV-1 역전사 효소는 교정 능력이 없다. 이는 약물로부터의 선택적 압력과 결합하여 역전사 효소에 변이를 유발하고, 바이러스가 NRTI 및 NNRTI에 대한 감수성을 낮아지게 한다.

4. 1. NRTI/NtRTI 내성

4. 2. NNRTI 내성

5. 한국의 HIV/AIDS 현황 및 정책 (추가 제안)

(이전 출력이 없으므로 수정할 내용이 없습니다. 원본 소스와 함께 이전 출력을 제공해주시면 수정 작업을 진행하겠습니다.)

참조

_[1] 문서 Islatravir
_[2] 학술지 Bench-to-bedside review: Severe lactic acidosis in HIV patients treated with nucleoside analogue reverse transcriptase inhibitors 2003
_[3] 학술지 Elsulfavirine: First Global Approval https://link.springe[...] 2017-10
_[4] 웹사이트 Elpida Combi (tenofovir+elsulfavirine+emtricitabine) Film-Coated Tablets. Full Prescribing Information. https://grls.rosminz[...]
_[5] 학술지 Role of islatravir in HIV treatment and prevention: an update https://pubmed.ncbi.[...] 2022-07-01
_[6] 학술지 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism
_[7] 학술지 Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids
_[8] 학술지 Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of ''pol'' gene mutations
_[9] 학술지 Multidrug-resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy
_[10] 학술지 Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance
_[11] 학술지 Pathways for the emergence of multi-dideoxynucleoside-resistant HIV-1 variants
_[12] 학술지 The role of steric hindrance in 3TC resistance of human immunodeficiency virus type-1 reverse transcriptase https://zenodo.org/r[...]
_[13] 학술지 A mechanism of AZT resistance: an increase in nucleotide-dependent primer unblocking by mutant HIV-1 reverse transcriptase
_[14] 학술지 Selective excision of AZTMP by drug-resistant human immunodeficiency virus reverse transcriptase
_[15] 학술지 Phenotypic mechanism of HIV-1 resistance to 3'-azido-3'-deoxythymidine (AZT): increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase
_[16] 학술지 The role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the therapy of HIV-1 infection
_[17] 학술지 Update of the drug resistance mutations in HIV-1: December 2009
_[18] 학술지 Crystal structures of clinically relevant Lys103Asn/Tyr181Cys double mutant HIV-1 reverse transcriptase in complexes with ATP and non-nucleoside inhibitor HBY 097
_[19] 학술지 The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance
_[20] 학술지 Structural mechanisms of drug resistance for mutations at codons 181 and 188 in HIV-1 reverse transcriptase and the improved resilience of second generation non-nucleoside inhibitors
_[21] 학술지 Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant
_[22] 학술지 Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance
_[23] 학술지 High resolution structures of HIV-1 RT from four RT-inhibitor complexes
_[24] 문서 Islatravir
_[25] 학술지 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism null
_[26] 학술지 Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids
_[27] 학술지 Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations
_[28] 학술지 Multidrug-resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy
_[29] 학술지 Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance
_[30] 학술지 Pathways for the emergence of multi-dideoxynucleoside-resistant HIV-1 variants
_[31] 학술지 The role of steric hindrance in 3TC resistance of human immunodeficiency virus type-1 reverse transcriptase https://zenodo.org/r[...]
_[32] 학술지 A mechanism of AZT resistance: an increase in nucleotide-dependent primer unblocking by mutant HIV-1 reverse transcriptase
_[33] 학술지 Selective excision of AZTMP by drug-resistant human immunodeficiency virus reverse transcriptase
_[34] 학술지 Phenotypic mechanism of HIV-1 resistance to 3'-azido-3'-deoxythymidine (AZT): increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase
_[35] 학술지 Pathways for the emergence of multi-dideoxynucleoside-resistant HIV-1 variants
_[36] 논문 The role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the therapy of HIV-1 infection
_[37] 논문 Update of the drug resistance mutations in HIV-1: December 2009
_[38] 논문 Crystal structures of clinically relevant Lys103Asn/Tyr181Cys double mutant HIV-1 reverse transcriptase in complexes with ATP and non-nucleoside inhibitor HBY 097 null
_[39] 논문 The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance https://semanticscho[...]
_[40] 논문 Structural mechanisms of drug resistance for mutations at codons 181 and 188 in HIV-1 reverse transcriptase and the improved resilience of second generation non-nucleoside inhibitors
_[41] 논문 Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant
_[42] 논문 Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance
_[43] 논문 High resolution structures of HIV-1 RT from four RT-inhibitor complexes
_[44] 저널 Bench-to-bedside review: Severe lactic acidosis in HIV patients treated with nucleoside analogue reverse transcriptase inhibitors 2003
_[45] 저널 K70Q adds high-level tenofovir resistance to "Q151M complex" HIV reverse transcriptase through the enhanced discrimination mechanism
_[46] 저널 Lamivudine (3TC) resistance in HIV-1 reverse transcriptase involves steric hindrance with beta-branched amino acids
_[47] 저널 Combination therapy with zidovudine and didanosine selects for drug-resistant human immunodeficiency virus type 1 strains with unique patterns of pol gene mutations https://archive.org/[...]
_[48] 저널 Multidrug-resistant human immunodeficiency virus type 1 strains resulting from combination antiretroviral therapy
_[49] 저널 Altered drug sensitivity, fitness, and evolution of human immunodeficiency virus type 1 with pol gene mutations conferring multi-dideoxynucleoside resistance https://archive.org/[...]
_[50] 저널 Pathways for the emergence of multi-dideoxynucleoside-resistant HIV-1 variants
_[51] 저널 A mechanism of AZT resistance: an increase in nucleotide-dependent primer unblocking by mutant HIV-1 reverse transcriptase
_[52] 저널 Selective excision of AZTMP by drug-resistant human immunodeficiency virus reverse transcriptase
_[53] 저널 Phenotypic mechanism of HIV-1 resistance to 3'-azido-3'-deoxythymidine (AZT): increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase
_[54] 저널 The role of non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the therapy of HIV-1 infection
_[55] 저널 Crystal structures of clinically relevant Lys103Asn/Tyr181Cys double mutant HIV-1 reverse transcriptase in complexes with ATP and non-nucleoside inhibitor HBY 097
_[56] 저널 The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance https://semanticscho[...]
_[57] 저널 Structural mechanisms of drug resistance for mutations at codons 181 and 188 in HIV-1 reverse transcriptase and the improved resilience of second generation non-nucleoside inhibitors
_[58] 저널 Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant
_[59] 저널 Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance
_[60] 저널 High resolution structures of HIV-1 RT from four RT-inhibitor complexes