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| − | !style="width:24%"|1<br>& | + | !style="width:24%"|1<br>≈ CD4 500- |
| − | !style="width:24%"|2<br>& | + | !style="width:24%"|2<br>≈ CD4 350-500 |
| − | !style="width:24%"|3<br>& | + | !style="width:24%"|3<br>≈ CD4 200-350 |
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2022年12月8日 (木) 18:36時点における版
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目次
疫学
マクロな疫学
AIDS発症はHICではPcPが最頻，LMICでは結核が最頻
ミクロな疫学
ウイルス学
細胞感染
- CD4 receptorに接合attach
- CCR5/CXCR4に結合 ←chemokine receptor antagonist
- 細胞膜融合
- viral RNAの逆転写（細胞質） ←RTase inhibitor;NRTI, NNRTI
- proviral RNA integration（核内） ←integrase inhibitor
- ウイルスタンパクのポリペプチドへの分解と再構成（細胞質） ←protease inhibitor
HIV-1 typing
- Group M
- clade: A,B,C,...,K,CRFs
- CRF=circulating recombinant forms
- clade: A,B,C,...,K,CRFs
- Group N
- Group O
- Group P
検査
予防
- Frequent testing
- Treatment as prevention; U=U
- PrPE
- PEP within 72 hrs
- Condom
PrEP
- 1 pill "Truvada"
- Tenefovir + Emtricitabine
- inhibits reverse transcriptase
- 20 USD/month
- >86% reduction
- high concentration in genital issues
- Administration options
- daily - for anal and vaginal sex
- event-based - for anal sex
- ≧4 doses/week - anal sex
daily PrEP
- 1 tablet/day
- effective for anal sex 1 day after of commencement
- effective for vaginal sex 7 days after of commencement
event-based PrEP
- 2 tabltes at 2-24 hours before anal sex + 1 tablet 24-48 hours after the sex
- not effective against vaginal sex
4 doses/week
how to stop
- have to continue for a certain duration after the last sex
monitoring
- test renal function every 3 mo
- annually for eGFR>90 or <40y/o
- check bone history including FRAX score
- test HIV, hepB, Urea, Electrolytes
- U/A
- offer STIs screening
contraindication of PrEP
- Renal dysfunction; eGFR<60
- Osteoprorosis
- event-based dosing is option for contraindicated people
clincal trials of PrEP
- PROUD study
- 86% reduction of HIV
- IMPACT study
Prevention of Mother to Child transmission (PMTCT)
- Primary prevention in women of childbearing age
- Voluntary counseling and testing (VCT) provided in prenatal care
- ART for PMTCT
WHO Consolidated Guidelines in 2021
- Consolidated guidelines on HIV prevention, testing, treatment, service delivery and monitoring: recommendations for a public health approach. 16 July 2021
- refer to 'Chapter 3.4 Infant prophylaxis' on pp.91 (134th as PDF)
- Mother
- Urgently commence ART for all HIV-infected pregnant and post-partum women irrespective of time or viral load
- All Infants
- Daily AZT+NVP from 0d to 6w
- Breastfed infants of high risk
- Additional AZT+NVP or NVP alone from 6w to 12w
- Breastfed infants of mother under ART
- Additional daily NVP from 6w to 12w
- Replacement fed infants of mother under ART
- Additional daily NVP from 6w to 10-12w
WHO Clinical staging
| Stage | 1 ≈ CD4 500- |
2 ≈ CD4 350-500 |
3 ≈ CD4 200-350 |
4 ≈ CD4 -200 |
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| Skin |
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| Oral GI tract |
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| Respiratory |
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| Neurological |
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| Systemic |
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| Malignancy |
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Treatment
|
WHO｜Update of recommendations on first- and second-line antiretroviral regimens - Policy brief |
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The Lighthouse - A Centre for Comprehensive HIV/AIDS Treatment and Care in Malawi |
原則
- 異なる2クラスで異なる3剤によるcombination Txが必須
- 生涯治療
Combination
- NRTI - Nucleoside reverse transcriptase inhibitor
- NNRTI - Non-Nucleoside reverse transcriptase inhibitor
- PI - Protease inhibitor
- INI - Integrase inhibitor
NRTI + NRTI + {NNRTI or INI or PI}
scheme
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NRTI | |||
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Tenofovir |
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| Tenofovir alafenamide fumarate TAF |
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| Lamivudine 3TC |
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| Emtricitabine FTC | |||
| Zidovudine AZT |
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| Abacavir ABC |
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NNRTI | ||
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Efavirenz |
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| Nevirapine NVP |
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INI | ||
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Dolutegravir |
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| Raltegravir RAL |
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PI | ||
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Lopinavir-Ritonavir |
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| Atazanavir ATV-r |
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WHO Guideline 2019
Adults and adolescents
| NRTI | ||
|---|---|---|
| Tenofovir TDF | ||
| Tenofovir alafenamide fumarate TAF | ||
| Lamivudine 3TC | ||
| Zidovudine AZT | ||
| Abacavir ABC | ||
| NNRTI | INI | PI |
| Efavirenz EFV |
Dolutegravir DTG |
Lopinavir-Ritonavir LPV-r |
| Nevirapine NVP |
Raltegravir RAL |
Atazanavir ATV-r |
| NRTI | ||
|---|---|---|
| Tenofovir TDF | ||
| Tenofovir alafenamide fumarate TAF | ||
| Lamivudine 3TC | ||
| Zidovudine AZT | ||
| Abacavir ABC | ||
| NNRTI | INI | PI |
| Efavirenz EFV 400mg |
Dolutegravir DTG |
Lopinavir-Ritonavir LPV-r |
| Nevirapine NVP |
Raltegravir RAL |
Atazanavir ATV-r |
| NRTI | ||
|---|---|---|
| Tenofovir TDF | ||
| Tenofovir alafenamide fumarate TAF | ||
| Lamivudine 3TC | ||
| Zidovudine AZT | ||
| Abacavir ABC | ||
| NNRTI | INI | PI |
| Efavirenz EFV |
Dolutegravir DTG |
Lopinavir-Ritonavir LPV-r |
| Nevirapine NVP |
Raltegravir RAL |
Atazanavir ATV-r |
Children
| NRTI | ||
|---|---|---|
| Tenofovir TDF | ||
| Tenofovir alafenamide fumarate TAF | ||
| Lamivudine 3TC | ||
| Zidovudine AZT | ||
| Abacavir ABC | ||
| NNRTI | INI | PI |
| Efavirenz EFV |
Dolutegravir DTG |
Lopinavir-Ritonavir LPV-r |
| Nevirapine NVP |
Raltegravir RAL |
Atazanavir ATV-r |
| NRTI | ||
|---|---|---|
| Tenofovir TDF | ||
| Tenofovir alafenamide fumarate TAF | ||
| Lamivudine 3TC | ||
| Zidovudine AZT | ||
| Abacavir ABC | ||
| NNRTI | INI | PI |
| Efavirenz EFV |
Dolutegravir DTG |
Lopinavir-Ritonavir LPV-r |
| Nevirapine NVP |
Raltegravir RAL |
Atazanavir ATV-r |
| NRTI | ||
|---|---|---|
| Tenofovir TDF | ||
| Tenofovir alafenamide fumarate TAF | ||
| Lamivudine 3TC | ||
| Zidovudine AZT | ||
| Abacavir ABC | ||
| NNRTI | INI | PI |
| Efavirenz EFV |
Dolutegravir DTG |
Lopinavir-Ritonavir LPV-r |
| Nevirapine NVP |
Raltegravir RAL |
Atazanavir ATV-r |
Neonates
| NRTI | ||
|---|---|---|
| Tenofovir TDF | ||
| Tenofovir alafenamide fumarate TAF | ||
| Lamivudine 3TC | ||
| Zidovudine AZT | ||
| Abacavir ABC | ||
| NNRTI | INI | PI |
| Efavirenz EFV |
Dolutegravir DTG |
Lopinavir-Ritonavir LPV-r |
| Nevirapine NVP |
Raltegravir RAL |
Atazanavir ATV-r |
| NRTI | ||
|---|---|---|
| Tenofovir TDF | ||
| Tenofovir alafenamide fumarate TAF | ||
| Lamivudine 3TC | ||
| Zidovudine AZT | ||
| Abacavir ABC | ||
| NNRTI | INI | PI |
| Efavirenz EFV |
Dolutegravir DTG |
Lopinavir-Ritonavir LPV-r |
| Nevirapine NVP |
Raltegravir RAL |
Atazanavir ATV-r |
| NRTI | ||
|---|---|---|
| Tenofovir TDF | ||
| Tenofovir alafenamide fumarate TAF | ||
| Lamivudine 3TC | ||
| Zidovudine AZT | ||
| Abacavir ABC | ||
| NNRTI | INI | PI |
| Efavirenz EFV |
Dolutegravir DTG |
Lopinavir-Ritonavir LPV-r |
| Nevirapine NVP |
Raltegravir RAL |
Atazanavir ATV-r |
NRTIs
- Nucleoside analogue 競合的にNRTを阻害する
- Tenofovir TDF 最重要
- Once daily
- hep Bにも有効
- 腎毒性；尿細管障害
- 尿dip stickでモニター
- 骨塩減少
- 小児には使いにくい
- Tenofovir alafenamide fumarate TAF；新しいプロドラッグ
- Zidovudine AZT
- 最初のARV in 1987
- 骨髄抑制；大球性貧血
- Twice daily
- Lamivudine 3TC /Emtricitabine FTC
- Lamivudine 3TC
- すべてのレジメンでbackbone
- high tolerance
- hep Bにも有効
- 耐性閾値が低い
- Emtricitabnine FTC
- 3TCのlong-acting type
- Lamivudine 3TC
- Abacavir ABC
- 他薬intolerance時の代替
- 主として小児
- HLA-B5701陽性者でのfebrile hypersensitivity
- HLA-B5701陽性者はアフリカでは極めて稀
- 他薬intolerance時の代替
NNRTIs
- Efavirenz EFV
- Nevirapine NVP
- Efavirenz EFV
- NNRTIの1st choice
- little interaction with Tb drugs
- dizzyness, insomnia, nightmare, depression, psychoses
- rash
- gynecomastia; 6% in Africa
- Nevirapine NVP
- あまり使われなくなった
- Rash→Stevens-Johnson
- 肝毒性
- 女性に多い
- CD4>250でリスク12倍
- HIV-2に無効
- RifampicinがNVP濃度を下げる
INIs
- Dolutegravir DTG
- Raltegravir RAL
- very well tolerated
- rapid viral suppression
- lesser drug interaction
- high threshold resistance
- Doltegravir DTG
- 1st line としてEFVに取って代わった
- once daily
- no food interaction
- neural tube defectがわずかに増加する；妊娠可能女性では十分な説明と同意
PIs
- 2nd line
- 下痢
- dyslipidemia, 耐糖能異常
- lipodystrophy syndrome
- CYP3A4阻害
- boosting PIs；PIをごく少量の他のPI ritonavirと併用
- -rを付す
- Lopinavir-Ritonavir LPV-r
- Atazanavir ATV-r
- 高ビリルビン血症，黄疸
WHO 1st line
- TDF+3TC+DTG
- TDF+3TC+EFV
WHO 2nd line
- NRTI+NRTI+INI
- NRTI+NRTI+PI
CPT
Co-trimoxazole preventive therapy
- 480-960mg/日 ST合剤
Treatment of advanced HIV
Minimum package of diagnostics for advanced HIV
IRIS
Immune reconstitution inflammatory syndrome
- importance to monitor IRIS
- CD4 count が低い状態で日和見感染を開始するときはARTは最低限1ヶ月空けてから
- paradoxical IRIS
フォローアップ
- 治療効果判定にはviral load
- CD4 countは初診時には有用だがフォローアップには無用；viral loadが大事
