HIV

Navigation Menu

General issues of Vaccine
Cold chain Correlates of Protection Vaccines for Asplenia Vaccines for Pregnant women Vaccines for Immunocompromised hosts Vaccine hesitancy Additional materials of vaccine

General issues of Tropical med.

Definition of Tropical Medicine Matrices of tropical infection General issues of Helminths Neglected Tropical Diseases Sexually-transmitted infections Non-Communicable Diseases Maternal health and contraception Child health Malnutrition and Micronutrient Eosinophilia Fever in the tropics Diarrhea in the tropics Anemia in the tropics Dermatology in the tropics Ophthalmology in the tropics Neurology in the tropics Mental health in the tropics Surgery in the tropics Humanitarian emergency Epidemiology in outbreak Antimicrobial resistance Pathology of infectious diseases

General issues of Travel med.
Epidemiology of Travel health Last minute traveler Time zone issue High altitude medicine Diving medicine Pregnancy and travel Children and travel Elderly and travel

Immunology
Principle of human immune system Innate immunity Cellular immunity Humoral immunity Neutralizing antibody and its assay Antigenic Cartography Additional materials of immunology

Epi & Stats
Basics & Definition Epidemiology Odds in statistics and Odds in a horse race Collider bias Data distribution Statistical test Regression model Multivariate analysis Marginal effects Prediction and decision Table-related commands in STATA Missing data and imputation

Virus
HIV HIV-TB co-infection HIV-STI interaction Viral Hemorrhagic Fever Ebola Crimean-Congo hemorrhagic fever SFTS Rabies Polio Dengue Yellow fever Chikungunya Zika Japanese encephalitis Tick-borne encephalitis Viral hepatitis Measles Smallpox and Monkeypox Respiratory Syncytial virus

COVID-19
Bivalent BA.1/BA.4-5 mRNA vaccines Monovalent XBB-1.5 mRNA vaccine Private archives of the initial phase of the pandemic Private archives of lecture materials of COVID vaccine as of March 2021 厚生労働省が発出する保健行政関連の文書の読み解き方

Bacteria
Bacteriological tests Tuberculosis Tuberculosis in Children HIV-TB co-infection Leprosy Dermatological mycobacterium infecions Syphilis and Yaws Plague Pneumococcus Meningococcus Typhoid Salmonellosis Melioidosis Leptospirosis Brucellosis Bartonellosis Lyme disease and Relapsing fever Tularaemia Tetanus Diphtheria Anthrax Coxiellosis

Rickettsia
Rickettsiosis Scrub typhus Spotted fevers Epidemic typhus Murine typhus

Protozoa
Overview of protozoa Overview of medicine for protozoa Malaria Chagas disease African trypanosomiasis Leishmaniasis Trichomoniasis Toxoplasmosis Amoebiasis Giardiasis Cryptosporidiosis Cyclosporiasis Isosporiasis Pentatrichomoniasis Microsporidiasis Babesiosis

Fungi
General issues of fungi Coccidioidomycosis Paracoccidioidomycosis Histoplasmosis Talaromycosis Blastomycosis Sporotrichosis

Nematode (roundworm)
Nematode principles Lympatic filariasis Onchocerciasis Loiasis Microscopic differentiation of microfilariae Strongyloidiasis Ascariasis Ancylostomiasis (hookworm) Trichuriasis (whipworm) Enterobiasis (pinworm) Angiostrongyliasis (rat lungworm) Dracunculiasis (Guinea worm) Anisakiasis Trichinellosis (Trichinosis) Gnathostomiasis Spirurinasis Soil-transmitted helminths

Trematode (fluke, distoma)
General issues of Helminths Trematode principles Schistosomiasis Clonorchiasis Fascioliasis Paragonimiasis Metagonimiasis

Cestode (tapeworm)
General issues of Helminths Cestode principles Diphyllobothriasis Sparganosis Taeniasis Echinococcosis

Medical Zoology
Zoonosis Insectology Mosquitology Acarology Batology Snake toxicology Scorpion and spider toxicology Marine toxicology

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

NNRTI Non-Nucleoside Reverse Transcriptase Inhibitor
Efavirenz EFV	1st choice in NNTRIs	neuropsychiatric side effects dizzyness, insomnia, nightmares, depression, psychoses rash gynecomastia 5-6% in Africa
Nevirapine NVP	not effective against HIV-2	rash to Stevens Johnson syndrome hepatic toxicity interact with rifampicin never use in HIV-TB

INI Integrase Inhibitor
Dolutegravir DTG	well tolerated	insomnia dizzyness paresthesia weight gain
Raltegravir RAL

PI Protease Inhibitor
Lopinavir-Ritonavir LPV-r	Twice daily	diarrhea metaboilc disturbance dyslipidemia impaired glucose tolerance lipodystrophy CYP3A4 interactions
Atazanavir ATV-r	Once daily	hyperbilirubinemia, jaundice interact with rifampicin

WHO Guideline 2019

• WHO reference page is here

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