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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

ウイルス学

細胞感染

1. CD4 receptorに接合attach
2. CCR5/CXCR4に結合　←chemokine receptor antagonist
3. 細胞膜融合
4. viral RNAの逆転写（細胞質）　←RTase inhibitor;NRTI, NNRTI
5. proviral RNA integration（核内）　←integrase inhibitor
6. 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
• Group N
• Group O
• Group P

予防

1. Frequent testing
2. Treatment as prevention; U=U
3. PrPE
4. PEP within 72 hrs
5. Condom

PrEP

• 1 pill "Truvada"
  • Tenefovir + Emtricitabine
  • inhibits reverse transcriptase
• 20 USD/month
• >86% reduction
• high concentration in genital issues

• Administration options

1. daily - for anal and vaginal sex
2. event-based - for anal sex
3. ≧4 doses/week - anal sex

daily

• 1 tablet/day
• effective for anal sex 1 day after of commencement
• effective for vaginal sex 7 days after of commencement

event-based

• 2 tabltes at 2-24 hours before anal sex + 1 tablet 24-48 hours after the sex
• not effective against vaginal sex

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

• Renal dysfunction; eGFR<60
• Osteoprorosis
• event-based dosing is option for contraindicated people

clincal trial

• PROUD study
  • 86% reduction of HIV
• IMPACT study

Treatment

WHO｜Update of recommendations on first- and second-line antiretroviral regimens - Policy brief

The Lighthouse - A Centre for Comprehensive HIV/AIDS Treatment and Care in Malawi

HIV drug interaction checker

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

NRTI Nucleoside Reverse Transcriptase Inhibitor
Tenofovir TDF	Once daily well tolerated	effective for Hep B	Renal toxicity (tubular damage) Fanconi syndrome hypophosphataemia glucosuria proteinuria Osteoporosis
Tenofovir alafenamide fumarate TAF	prodrug of tenofovir less side effects than TAF
Lamivudine 3TC	backbone for all regimens well tolerated 3TC and FTC have almost the same molecular structures	effective for Hep B
Emtricitabine FTC
Zidovudine AZT	Twice daily well tolerated the world-first anti-HIV		macrocytic anemia lipodystrophy
Abacavir ABC	in case of failure/intolerance of other NRTIs		febrile hypersensitivity with HLA-B5701 Caucasians need HLA-testing before treament

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
• 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

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

1. TDF+3TC+DTG
2. TDF+3TC+EFV

WHO 2nd line

1. NRTI+NRTI+INI
2. 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