HIV

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}

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

Control

• Targeting 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