「HIV」の版間の差分

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 +
 
==疫学==
 
==疫学==
 
===マクロな疫学===
 
===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===
 
===ミクロな疫学===
 
==ウイルス学==
 
==ウイルス学==
10行目: 14行目:
 
#proviral RNA integration（核内）　←integrase inhibitor
 
#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
 
#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==
 
==検査==
  
 
==予防==
 
==予防==
−
==治療==
+
#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====
 +
*[https://www.who.int/publications/i/item/9789240031593 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==
 +
{{quote|content=[https://apps.who.int/iris/handle/10665/43699 WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children (2007)]
 +
}}
 +
 
 +
{|class="wikitable"
 +
|-
 +
!style="width:4%"|Stage
 +
!style="width:24%"|1<br>&asymp; CD4 500-
 +
!style="width:24%"|2<br>&asymp; CD4 350-500
 +
!style="width:24%"|3<br>&asymp; CD4 200-350
 +
!style="width:24%"|4<br>&asymp; CD4 -200
 +
|- style="vertical-align:top"
 +
!Skin
 +
|
 +
|
 +
*Herpes zoster
 +
*Papular pruritic eruptions
 +
*Seborrheic dermatitis
 +
*Fungal nail infections
 +
|
 +
|
 +
*Herpes simplex infection (oral, genital) > 1 month
 +
*[[Talaromycosis|Talaromycosis]] (Asia only)
 +
|- style="vertical-align:top"
 +
!Oral<br>GI tract
 +
|
 +
|
 +
*Angular cheilitis
 +
*Oral ulcer, recurrent
 +
|
 +
*'''Oral''' candidiasis
 +
*Oral hairy leukoplakia (EBV-associated)
 +
*Acute necrotizing ulcerative stomatitis/gingivitis/periodontitis
 +
*Diarrhea > 1 month, unexplained
 +
|
 +
*'''Esophageal''' candidiasis
 +
*Cryptosporidiasis, chronic
 +
*Isosporiasis, chronic
 +
|- style="vertical-align:top"
 +
!Respiratory
 +
|
 +
|
 +
*URIs, recurrent
 +
|
 +
*Bacterial LRIs
 +
*Pulmonary TB, '''pluribacillary'''
 +
|
 +
*Severe bacterial LRIs, recurrent
 +
*Pulmonary TB, '''paucibacillary'''
 +
*Pneumocystis pneumonia (PcP)
 +
|- style="vertical-align:top"
 +
!Neurological
 +
|
 +
|
 +
|
 +
|
 +
*CNS toxoplamosis (Toxoplasmoma)
 +
*HIV encephalopathy
 +
*CNS cryptococcal infection (Cryptococcoma)
 +
*Progressive multifocal leukoencephalopathy
 +
|- style="vertical-align:top"
 +
!Systemic
 +
|
 +
*Asymptomatic
 +
*Acute HIV infection
 +
*Lymphadenopathy, persistent
 +
|
 +
*Weight loss '''<10%''', unexplained
 +
|
 +
*Weight loss '''>10%''', unexplained
 +
*Fever > 1 month, unexplained
 +
*Sever bacterial infections (LRI, bone/joint infections, meningitis)
 +
*Anemia < 8g/dL of Hb, unexplained
 +
*Thrombocytopenia < 50<math>\times</math>10<math>^9</math>/L, unexplained
 +
|
 +
*HIV wasting syndrome
 +
*Extrapulmonary TB
 +
*Cytomegalovirus infection
 +
*Non-typhoidal salmonellosis (NTS), recurrent
 +
*[[Coccidioidomycosis|Coccidioidomycosis]] (America only)
 +
*[[Histoplasmosis|Histoplasmosis]]
 +
*Atypical disseminated leishmaniasis
 +
*HIV-associated nephrophathy
 +
*HIV-associated cardiomyopathy
 +
|- style="vertical-align:top"
 +
!Malignancy
 +
|
 +
|
 +
|
 +
|
 +
*Kaposi's sarcoma
 +
*Lymphoma
 +
*Cervical carcinoma
 +
*HIV-associated solid tumors
 +
|}
 +
 
 +
==Treatment==
 
{{Quote|content=
 
{{Quote|content=
 
[https://www.who.int/hiv/pub/arv/arv-update-2019-policy/en/ WHO｜Update of recommendations on first- and second-line antiretroviral regimens - Policy brief]}}
 
[https://www.who.int/hiv/pub/arv/arv-update-2019-policy/en/ WHO｜Update of recommendations on first- and second-line antiretroviral regimens - Policy brief]}}
 
{{Quote|content=
 
{{Quote|content=
 
[https://www.who.int/hiv/pub/prev_care/malawi/en/ The Lighthouse - A Centre for Comprehensive HIV/AIDS Treatment and Care in Malawi]}}
 
[https://www.who.int/hiv/pub/prev_care/malawi/en/ The Lighthouse - A Centre for Comprehensive HIV/AIDS Treatment and Care in Malawi]}}
 +
{{Quote|content=
 +
[https://www.hiv-druginteractions.org/ HIV drug interaction checker]}}
  
 
原則
 
原則
31行目: 213行目:
  
 
NRTI + NRTI + {NNRTI or INI or PI}
 
NRTI + NRTI + {NNRTI or INI or PI}
 +
 +
===scheme===
 +
{|class="wikitable" style="width:1200px"
 +
|-
 +
!colspan="4"|
 +
NRTI<br>Nucleoside Reverse Transcriptase Inhibitor
 +
|-
 +
!style="width:25%"|
 +
Tenofovir<br>TDF
 +
|style="width:25%"|
 +
*Once daily
 +
*well tolerated
 +
|style="width:25%" rowspan="2"|
 +
*effective for Hep B
 +
|style="width:25%" rowspan="2"|
 +
*Renal toxicity (tubular damage)
 +
**Fanconi syndrome
 +
**hypophosphataemia
 +
**glucosuria
 +
**proteinuria
 +
*Osteoporosis
 +
|-
 +
!Tenofovir alafenamide fumarate<br>TAF
 +
|
 +
*prodrug of tenofovir
 +
*less side effects than TAF
 +
|-
 +
!Lamivudine<br>3TC
 +
|rowspan="2"|
 +
*backbone for all regimens
 +
*well tolerated
 +
*3TC and FTC have almost the same molecular structures
 +
|rowspan="2"|
 +
*effective for Hep B
 +
|rowspan="2"|
 +
|-
 +
!Emtricitabine<br>FTC
 +
|-
 +
!Zidovudine<br>AZT
 +
|
 +
*Twice daily
 +
*well tolerated
 +
*the world-first anti-HIV
 +
|
 +
|
 +
*macrocytic anemia
 +
*lipodystrophy
 +
|-
 +
!Abacavir<br>ABC
 +
|
 +
*in case of failure/intolerance of other NRTIs
 +
|
 +
|
 +
*febrile hypersensitivity with HLA-B5701
 +
**Caucasians need HLA-testing before treament
 +
|}
 +
 +
<div style="float:left; padding-right:1em;">
 +
{|class="wikitable" style="width:400px"
 +
|-
 +
!colspan="3"|
 +
NNRTI<br>Non-Nucleoside Reverse Transcriptase Inhibitor
 +
|-
 +
!style="width:33.3%"|
 +
Efavirenz<br>EFV
 +
|style="width:33.3%|
 +
*1st choice in NNTRIs
 +
|style="width:33.3%|
 +
*neuropsychiatric side effects
 +
**dizzyness, insomnia, nightmares, depression, psychoses
 +
*rash
 +
*gynecomastia 5-6% in Africa
 +
|-
 +
!Nevirapine<br>NVP
 +
|
 +
*not effective against HIV-2
 +
|
 +
*rash to Stevens Johnson syndrome
 +
*hepatic toxicity
 +
*interact with rifampicin
 +
**never use in HIV-TB
 +
|}
 +
</div>
 +
 +
<div style="float:left; padding-right:1em;">
 +
{|class="wikitable" style="width:400px"
 +
|-
 +
!colspan="3"|
 +
INI<br>Integrase Inhibitor
 +
|-
 +
!style="width:33.3%"|
 +
Dolutegravir<br>DTG
 +
|style="width:33.3%"|
 +
*well tolerated
 +
|style="width:33.3%"|
 +
*insomnia
 +
*dizzyness
 +
*paresthesia
 +
*weight gain
 +
|-
 +
!Raltegravir<br>RAL
 +
|
 +
|
 +
|}
 +
</div>
 +
 +
<div style="float:left; padding-right:1em;">
 +
{|class="wikitable" style="width:400px"
 +
|-
 +
!colspan="3"|
 +
PI<br>Protease Inhibitor
 +
|-
 +
!style="width:33.3%"|
 +
Lopinavir-Ritonavir<br>LPV-r
 +
|style="width:33.3%"|
 +
*Twice daily
 +
|style="width:33.3%"|
 +
*diarrhea
 +
*metaboilc disturbance
 +
**dyslipidemia
 +
**impaired glucose tolerance
 +
**lipodystrophy
 +
*CYP3A4 interactions
 +
|-
 +
!Atazanavir<br>ATV-r
 +
|
 +
*Once daily
 +
|
 +
*hyperbilirubinemia, jaundice
 +
*interact with rifampicin
 +
|}
 +
</div>
 +
 +
<div style="clear:both;"></div>
 +
 +
===WHO Guideline 2019===
 +
*[https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/hiv/treatment/monitoring-toxicity-of-antiretrovirals WHO reference page is here]
 +
 +
====Adults and adolescents====
 +
<div style="float:left; padding-right:1em;">
 +
{|class="wikitable" style="width:400px; text-align:center"
 +
|+1st line
 +
|-
 +
!colspan="3"|NRTI
 +
|-
 +
!colspan="3" style="background-color:gold"|Tenofovir<br>TDF
 +
|-
 +
|colspan="3"|Tenofovir alafenamide fumarate<br>TAF
 +
|-
 +
!colspan="3" style="background-color:gold"|Lamivudine<br>3TC
 +
|-
 +
|colspan="3"|Zidovudine<br>AZT
 +
|-
 +
|colspan="3"|Abacavir<br>ABC
 +
|-
 +
!style="width:33.3%"|NNRTI
 +
!style="width:33.3%"|INI
 +
!style="width:33.3%"|PI
 +
|-
 +
|Efavirenz<br>EFV
 +
!style="background-color:gold"|Dolutegravir<br>DTG
 +
|Lopinavir-Ritonavir<br>LPV-r
 +
|-
 +
|Nevirapine<br>NVP
 +
|Raltegravir<br>RAL
 +
|Atazanavir<br>ATV-r
 +
|}
 +
</div>
 +
 +
<div style="float:left; padding-right:1em;">
 +
{|class="wikitable" style="width:400px; text-align:center"
 +
|+Alternative 1st line
 +
|-
 +
!colspan="3"|NRTI
 +
|-
 +
!colspan="3" style="background-color:gold"|Tenofovir<br>TDF
 +
|-
 +
|colspan="3"|Tenofovir alafenamide fumarate<br>TAF
 +
|-
 +
!colspan="3" style="background-color:gold"|Lamivudine<br>3TC
 +
|-
 +
|colspan="3"|Zidovudine<br>AZT
 +
|-
 +
|colspan="3"|Abacavir<br>ABC
 +
|-
 +
!style="width:33.3%"|NNRTI
 +
!style="width:33.3%"|INI
 +
!style="width:33.3%"|PI
 +
|-
 +
!style="background-color:gold"|Efavirenz<br>EFV 400mg
 +
|Dolutegravir<br>DTG
 +
|Lopinavir-Ritonavir<br>LPV-r
 +
|-
 +
|Nevirapine<br>NVP
 +
|Raltegravir<br>RAL
 +
|Atazanavir<br>ATV-r
 +
|}
 +
</div>
 +
 +
<div style="float:left; padding-right:1em;">
 +
{|class="wikitable" style="width:400px; text-align:center"
 +
|+Special circumstances
 +
|-
 +
!colspan="3"|NRTI
 +
|-
 +
|colspan="3"|Tenofovir<br>TDF
 +
|-
 +
|colspan="3"|Tenofovir alafenamide fumarate<br>TAF
 +
|-
 +
|colspan="3"|Lamivudine<br>3TC
 +
|-
 +
|colspan="3"|Zidovudine<br>AZT
 +
|-
 +
|colspan="3"|Abacavir<br>ABC
 +
|-
 +
!style="width:33.3%"|NNRTI
 +
!style="width:33.3%"|INI
 +
!style="width:33.3%"|PI
 +
|-
 +
|Efavirenz<br>EFV
 +
|Dolutegravir<br>DTG
 +
|Lopinavir-Ritonavir<br>LPV-r
 +
|-
 +
|Nevirapine<br>NVP
 +
|Raltegravir<br>RAL
 +
|Atazanavir<br>ATV-r
 +
|}
 +
</div>
 +
 +
<div style="clear:both;"></div>
 +
 +
====Children====
 +
<div style="float:left; padding-right:1em;">
 +
{|class="wikitable" style="width:400px; text-align:center"
 +
|+1st line
 +
|-
 +
!colspan="3"|NRTI
 +
|-
 +
|colspan="3"|Tenofovir<br>TDF
 +
|-
 +
|colspan="3"|Tenofovir alafenamide fumarate<br>TAF
 +
|-
 +
!colspan="3" style="background-color:khaki"|Lamivudine<br>3TC
 +
|-
 +
|colspan="3"|Zidovudine<br>AZT
 +
|-
 +
!colspan="3" style="background-color:khaki"|Abacavir<br>ABC
 +
|-
 +
!style="width:33.3%"|NNRTI
 +
!style="width:33.3%"|INI
 +
!style="width:33.3%"|PI
 +
|-
 +
|Efavirenz<br>EFV
 +
!style="background-color:khaki"|Dolutegravir<br>DTG
 +
|Lopinavir-Ritonavir<br>LPV-r
 +
|-
 +
|Nevirapine<br>NVP
 +
|Raltegravir<br>RAL
 +
|Atazanavir<br>ATV-r
 +
|}
 +
</div>
 +
 +
<div style="float:left; padding-right:1em;">
 +
{|class="wikitable" style="width:400px; text-align:center"
 +
|+Alternative 1st line
 +
|-
 +
!colspan="3"|NRTI
 +
|-
 +
|colspan="3"|Tenofovir<br>TDF
 +
|-
 +
|colspan="3"|Tenofovir alafenamide fumarate<br>TAF
 +
|-
 +
!colspan="3" style="background-color:khaki"|Lamivudine<br>3TC
 +
|-
 +
|colspan="3"|Zidovudine<br>AZT
 +
|-
 +
!colspan="3" style="background-color:khaki"|Abacavir<br>ABC
 +
|-
 +
!style="width:33.3%"|NNRTI
 +
!style="width:33.3%"|INI
 +
!style="width:33.3%"|PI
 +
|-
 +
|Efavirenz<br>EFV
 +
|Dolutegravir<br>DTG
 +
!style="background-color:khaki"|Lopinavir-Ritonavir<br>LPV-r
 +
|-
 +
|Nevirapine<br>NVP
 +
|Raltegravir<br>RAL
 +
|Atazanavir<br>ATV-r
 +
|}
 +
</div>
 +
 +
<div style="float:left; padding-right:1em;">
 +
{|class="wikitable" style="width:400px; text-align:center"
 +
|+Special circumstances
 +
|-
 +
!colspan="3"|NRTI
 +
|-
 +
|colspan="3"|Tenofovir<br>TDF
 +
|-
 +
|colspan="3"|Tenofovir alafenamide fumarate<br>TAF
 +
|-
 +
|colspan="3"|Lamivudine<br>3TC
 +
|-
 +
|colspan="3"|Zidovudine<br>AZT
 +
|-
 +
|colspan="3"|Abacavir<br>ABC
 +
|-
 +
!style="width:33.3%"|NNRTI
 +
!style="width:33.3%"|INI
 +
!style="width:33.3%"|PI
 +
|-
 +
|Efavirenz<br>EFV
 +
|Dolutegravir<br>DTG
 +
|Lopinavir-Ritonavir<br>LPV-r
 +
|-
 +
|Nevirapine<br>NVP
 +
|Raltegravir<br>RAL
 +
|Atazanavir<br>ATV-r
 +
|}
 +
</div>
 +
 +
<div style="clear:both;"></div>
 +
 +
====Neonates====
 +
<div style="float:left; padding-right:1em;">
 +
{|class="wikitable" style="width:400px; text-align:center"
 +
|+1st line
 +
|-
 +
!colspan="3"|NRTI
 +
|-
 +
|colspan="3"|Tenofovir<br>TDF
 +
|-
 +
|colspan="3"|Tenofovir alafenamide fumarate<br>TAF
 +
|-
 +
!colspan="3" style="background-color:yellow"|Lamivudine<br>3TC
 +
|-
 +
!colspan="3" style="background-color:yellow"|Zidovudine<br>AZT
 +
|-
 +
|colspan="3"|Abacavir<br>ABC
 +
|-
 +
!style="width:33.3%"|NNRTI
 +
!style="width:33.3%"|INI
 +
!style="width:33.3%"|PI
 +
|-
 +
|Efavirenz<br>EFV
 +
|Dolutegravir<br>DTG
 +
|Lopinavir-Ritonavir<br>LPV-r
 +
|-
 +
|Nevirapine<br>NVP
 +
!style="background-color:yellow"|Raltegravir<br>RAL
 +
|Atazanavir<br>ATV-r
 +
|}
 +
</div>
 +
 +
<div style="float:left; padding-right:1em;">
 +
{|class="wikitable" style="width:400px; text-align:center"
 +
|+Alternative 1st line
 +
|-
 +
!colspan="3"|NRTI
 +
|-
 +
|colspan="3"|Tenofovir<br>TDF
 +
|-
 +
|colspan="3"|Tenofovir alafenamide fumarate<br>TAF
 +
|-
 +
!colspan="3" style="background-color:yellow"|Lamivudine<br>3TC
 +
|-
 +
!colspan="3" style="background-color:yellow"|Zidovudine<br>AZT
 +
|-
 +
|colspan="3"|Abacavir<br>ABC
 +
|-
 +
!style="width:33.3%"|NNRTI
 +
!style="width:33.3%"|INI
 +
!style="width:33.3%"|PI
 +
|-
 +
|Efavirenz<br>EFV
 +
|Dolutegravir<br>DTG
 +
|Lopinavir-Ritonavir<br>LPV-r
 +
|-
 +
!style="background-color:yellow"|Nevirapine<br>NVP
 +
|Raltegravir<br>RAL
 +
|Atazanavir<br>ATV-r
 +
|}
 +
</div>
 +
 +
<div style="float:left; padding-right:1em;">
 +
{|class="wikitable" style="width:400px; text-align:center"
 +
|+Special circumstances
 +
|-
 +
!colspan="3"|NRTI
 +
|-
 +
|colspan="3"|Tenofovir<br>TDF
 +
|-
 +
|colspan="3"|Tenofovir alafenamide fumarate<br>TAF
 +
|-
 +
!colspan="3" style="background-color:yellow"|Lamivudine<br>3TC
 +
|-
 +
!colspan="3" style="background-color:yellow"|Zidovudine<br>AZT
 +
|-
 +
|colspan="3"|Abacavir<br>ABC
 +
|-
 +
!style="width:33.3%"|NNRTI
 +
!style="width:33.3%"|INI
 +
!style="width:33.3%"|PI
 +
|-
 +
|Efavirenz<br>EFV
 +
|Dolutegravir<br>DTG
 +
!style="background-color:yellow"|Lopinavir-Ritonavir<br>LPV-r
 +
|-
 +
|Nevirapine<br>NVP
 +
|Raltegravir<br>RAL
 +
|Atazanavir<br>ATV-r
 +
|}
 +
</div>
 +
 +
<div style="clear:both;"></div>
  
 
===NRTIs===
 
===NRTIs===
115行目: 713行目:
 
#NRTI+NRTI+INI
 
#NRTI+NRTI+INI
 
#NRTI+NRTI+PI
 
#NRTI+NRTI+PI
 +
 +
===CPT===
 +
Co-trimoxazole preventive therapy
 +
*480-960mg/日 ST合剤
 +
 +
==Treatment of advanced HIV==
 +
 +
[https://www.youtube.com/watch?v=Tmbt1n5Fm_Q 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==
 
==フォローアップ==
 
*治療効果判定にはviral load
 
*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
 
*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
 +
 +
==Additional materials of HIV==
 +
{{quote
 +
|content=[https://www.nature.com/collections/mghkkdjlgx Nature Materials in HIV research]
 +
 +
https://www.nature.com/collections/mghkkdjlgx
 +
}}

2023年9月14日 (木) 15:04時点における最新版

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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 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

WHO Clinical staging

WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children (2007)

Stage 1
≈ CD4 500- 		2
≈ CD4 350-500 		3
≈ CD4 200-350 		4
≈ CD4 -200
Skin
  • Herpes zoster
  • Papular pruritic eruptions
  • Seborrheic dermatitis
  • Fungal nail infections
  • Herpes simplex infection (oral, genital) > 1 month
  • Talaromycosis (Asia only)
Oral
GI tract
  • Angular cheilitis
  • Oral ulcer, recurrent
  • Oral candidiasis
  • Oral hairy leukoplakia (EBV-associated)
  • Acute necrotizing ulcerative stomatitis/gingivitis/periodontitis
  • Diarrhea > 1 month, unexplained
  • Esophageal candidiasis
  • Cryptosporidiasis, chronic
  • Isosporiasis, chronic
Respiratory
  • URIs, recurrent
  • Bacterial LRIs
  • Pulmonary TB, pluribacillary
  • Severe bacterial LRIs, recurrent
  • Pulmonary TB, paucibacillary
  • Pneumocystis pneumonia (PcP)
Neurological
  • CNS toxoplamosis (Toxoplasmoma)
  • HIV encephalopathy
  • CNS cryptococcal infection (Cryptococcoma)
  • Progressive multifocal leukoencephalopathy
Systemic
  • Asymptomatic
  • Acute HIV infection
  • Lymphadenopathy, persistent
  • Weight loss <10%, unexplained
  • Weight loss >10%, unexplained
  • Fever > 1 month, unexplained
  • Sever bacterial infections (LRI, bone/joint infections, meningitis)
  • Anemia < 8g/dL of Hb, unexplained
  • Thrombocytopenia < 50[math]\displaystyle{ \times }[/math]10[math]\displaystyle{ ^9 }[/math]/L, unexplained
  • HIV wasting syndrome
  • Extrapulmonary TB
  • Cytomegalovirus infection
  • Non-typhoidal salmonellosis (NTS), recurrent
  • Coccidioidomycosis (America only)
  • Histoplasmosis
  • Atypical disseminated leishmaniasis
  • HIV-associated nephrophathy
  • HIV-associated cardiomyopathy
Malignancy
  • Kaposi's sarcoma
  • Lymphoma
  • Cervical carcinoma
  • HIV-associated solid tumors

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

Adults and adolescents

1st line
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
Alternative 1st line
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
Special circumstances
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

1st line
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
Alternative 1st line
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
Special circumstances
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

1st line
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
Alternative 1st line
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
Special circumstances
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
  • 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

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

Additional materials of HIV

「http://vaccipedia.jp/index.php?title=HIV&oldid=2937」から取得