HIV Flashcards
Who are considered high-risk for HIV infection?
1- Sharing needles
2- High-risk sexual behaviors (men who have sex with men, sex with multiple partners, etc.)
3- History of TB or Hepatitis infection
Signs of an Acute (early) Infection?
Non-specific flu-like symptoms
-Lasts few days to several weeks
-Patients become asymptomatic after this initial phase
When is the testing window for HIV detection?
4-12 weeks
Diagnostic Testing of HIV
Step 1: HIV antigen/antibody immunoassay
Step 2: If positive, a confirmatory test is needed to differentiate HIV-1 from HIV-2.
-HIV-1 is predominately in USA
Step 3: If confirmatory test is ‘Indeterminate’ or ‘Negative’, HIV Nucleic Acid Test is done to quantify the viral load.
Stage 1 & Stage 2 of HIV infection
Stage 1: Binding/Attachment
HIV attaches to a CD4 receptor and the CCR5 and/or CXCR4 co-receptors on the surface.
DRUGS:
-Maraviroc (CCR5 ONLY antagonist)
-Fostemsavir (Attachment inhibitor)
-Ibalizumab (Post-attachment inhibitor)
Stage 2: Fusion
The HIV viral envelope fuses with the CD4 cell membrane. HIV enters the host cell and releases HIV RNA, viral proteins and enzymes needed for replication.
DRUGS:
-Enfuvirtide (Fusion inhibitor)
Stage 3 & Stage 4 of HIV infection
Stage 3: Reverse Transcription
HIV RNA is converted to HIV DNA by reverse transcriptase. HIV DNA can then enter the CD4 cell nucleus.
DRUGS:
-NRTI: Emtricitabine, Tenofovir, Abacavir, Lamivudine, Zidovudine
-NNRTI: Efavirenz, Rilpivirine
Stage 4: Integration
Once inside of the CD4 nucleus, Integrase is released and used to insert HIV DNA into the host-cell DNA.
DRUGS:
INSTI: Bictegravir, Dolutegravir, Raltegravir, Elvitegravir
“-tegravir”
*NRTI: Nucleoside Reverse Transcriptase Inhibitor
NNRTI: Non-nucleoside reverse transcriptase inhibitor
INSTI: Integrase strand transfer inhibitors
Stage 5, Stage 6, Stage 7 of HIV Infection
Stage 5: Replication
Host cell is used to transcribe and translate HIV DNA into HIV RNA and proteins
DRUGS: None
Stage 6: Assembly
New HIV RNA, proteins and enzymes move to the cell surface and assemble into immature HIV.
DRUGS: None
Stage 7: Budding and Maturation
Immature HIV pushes out of the CD4 cell and protease creates mature HIV that can infect other cells.
DRUGS:
-PI: Atazanavir, Darunavir, etc
ending with ‘navir’
*PI: Protease Inhibitors
What important test should be done BEFORE starting Abacavir?
HLA-B*5701 allele
What important test should be done BEFORE starting Maraviroc?
Tropism Assay
Goals of ART
1- Achieve and Maintain suppression through undetectable viral load.
-Consider non-adherence or resistance if this is not achieved.
2- Restore and Preserve Immune Function through increased CD4 count
HIV ART Regimen
Backbone: 1 base + 2 NRTI
Base - Boosted PI, NNRTI or INSTI
NRTI backbone:
-TDF or TAF or Abacavir PLUS
-Emtricitabine or Lamivudine
*PI can be boosted with Ritonavir or Cobicistat
Preferred Initial ART Regimens for treatment-naive adults
One tablet daily:
1- Biktarvy (Bictegravir/Emtricitabine/TAF)
2- Triumeq (Dolutegravir/Abacavir/Lamivudine)
3- Dovato (Dolutegravir/Lamivudine)
Two tablets daily
1- Trivicay + Truvada (Dolutegravir + Emtricitabine/TDF)
2- Trivicay + Descovy (Dolutegravir + Emtricitabine/TAF)
*lamivudine and emtricitabine are interchangeable but should not be used together.
*All the above contains an integrase inhibitor with a high barrier to resistance (Bictegravir and Dolutegravir)
When should we avoid Dovato?
-HIV RNA > 500,000 copies/mL
-Known/Unknown Hepatitis B coinfection
-HIV genotyping testing is not yet available
What are the NRTIs?
- Abacavir (Ziagen)
- Emtricitabine (Emtriva)
- Lamivudine (Epivir)
- Tenofovir DF (Viread) <– greater systemic exposure compared to TAF
- Tenofovir AF
- Zidovudine (Retrovir)
MOA: Competitively inhibit the reverse transcriptase enzyme.
-Resistance develops easily in this class, that is why we need 2 in our regimen
-Zidovudine is administered IV during labor and delivery in patients with an unknown HIV RNA level or RNA > 1000 copies/mL
NRTI Issues and Features
- All NRTI: warning for lactic acidosis and hepatomegaly
-Common side effects: nausea, diarrhea
-Abacavir: test for HLA-B*5701 - contraindicated if positive
-Tenofovir (TDF>TAF): renal impairment and decreased bone mineral density
Boxed Warnings for ART drugs
1) Emtricitabine, Tenofovir, Lamivudine: Severe acute HBV liver damage if abrupt discontinuation with HBV co-infection
2) Maraviroc: Hepatotoxicity
What are the INSTIs?
1- Bictegravir (In Biktarvy)
2- Dolutegravir (Trivicay)
3- Elvitegravir (In Genvoya and Stribild)
4- Raltegravir (Isentress)
5- Cabotegravir
‘-tegravir’
MOA: Block the integrase enzyme, preventing HIV DNA from inserting into the host cell DNA.
Side Effects: Weight gain and nervous/psychiatric effects
*Elvitegravir is co-formulated with cobicistat, a strong CYP3A4 inhibitor
*All INSTIs interact with cations. Take INSTI 2 hours before or 6 hours after
What are the NNRTIs?
1- Efavirenz
2- Rilpivirine
3- others (Doravirine, Etravirine, Nevirapine)
MOA: non-competitively inhibit the reverse transcriptase enzyme.
Side Effects: Hepatotoxicity, Rash (SJS/TEN)
*Rilpivirine requires an acidic environment for absorption. It has a drug interaction with acid suppressants.
*Efavirenz should be taken on an empty stomach, preferrable at bedtime. Associated with psychiatric symptoms
What are the most common PI?
1- Atazanavir (Reyataz) - take with food, needs acidic environment
2- Darunavir (Prezista) - take with food
Less common PI include:
-Fosamprenavir
-Lopinavir/Ritonavir
-Tipranavir
*All PIs are recommended to be administered with a PK booster (Ritonavir or Cobicistat).
*No renal adjustments needed
Key Features with Protease Inhibitors
Atazanavir:
- Hyperbilirubinemia (reversible)
- Unboosted: avoid PPIs
- Boosted: take 12 hours after PPI
Darunavir:
- Sulfa allergy
HIV PK Boosters
1- Cobicistat (150 once daily)
2- Ritonavir (100-200 once/twice daily)
-Take with food
Drugs which are contraindicated or should generally be avoided with PI & PK boosted drugs?
1) Alpha-1: Alfuzosin, Silodosin, Tamsulosin
2) Amiodarone, Dronedarone
3) Apixaban, Rivaroxaban, Ticagrelor
4) Azole Antifungals
5) Lovastatin, Simvastatin
6) Sildenafil, Tadalafil
7) Strong CYP3A4 inducers (St. johns Wort, Rifampin, Carbamazepine)
Entry, Attachment and Capsid Inhibitors
-Less commonly used
-Usually reserved for treatment-experienced patients who has developed resistance
-Both are substrates for CYP3A4
1) Maraviroc (CCR5 Antagonist)
2) Fostemsavir (Attachment Inhibitor)
3) Ibalizumab (Post-Attachment Inhibitor) (Trogarzo) - IV
4) Enfuvirtide (Fusion Inhibitor) -subQ injection
5) Lenacapavir (Capsid Inhibitor)
*Lenacapavir has a PO loading dose then subQ injection every 6 months
What are the 3-component INSTI Combination Products?
1) Biktarvy (Bictegravir/Emtri/TAF) - 1st line
2) Triumeq (Dolutegravir/Abacavir/Lamivudine) -1st line
3) Stribild (Elvitegravir/Cobi/Emtri/TDF)
4) Genvoya (Elvitegravir/Cobi/Emtri/TAF)
Triumeq requires HLA-B5701 testing
*Stribild and Genvoya needs to be taken with food because of Cobicistat.
