HIV

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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

ミクロな疫学

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

検査

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

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

  • 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}

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