HIV Flashcards
What type of virus is HIV? What cells does it infect? How is it spread?
- HIV is a single-stranded RNA retrovirus
- Infects and replicated in CD4 T-helper cells, which destroys CD4 cells in the process
- Spread through blood, breast milk, and seminal, vaginal, and rectal fluid
Who should get screened for HIV?
- All patients between 13 and 64 should be tested once
- Annual testing should be done in high risk population
Symptoms of acute infection of HIV? Signs of progression to AIDS?
Acute infection - symptoms last a few days to weeks
- non-specific flu-like symptoms (fever, myalgia, swollen lymph nodes, rash)
Progression to AIDS
- CD4 count < 200
- AIDS-defining condition: opportunistic infections, malignancy (Kaposi’s sarcoma), HIV wasting syndrome (treatment - dronabinol, megestrol)
What are the 4 things we can test to try to detect HIV?
- HIV RNA: increases immediately
- p24 antigen (most abundant HIV protein)
- Anti-HIV antibody (developed by the body): takes about 3 months to fully develop
- CD4
What is the HIV diagnostic testing algorithm?
Initial screening: HIV antigen/antibody immunoassay (p24 antigen and/or HIV antibodies)
- negative
- positive (reactive): move onto confirmatory testing
Confirmatory testing: differentiates HIV-1 from HIV-2
- Indeterminate or negative: do HIV nucleic acid test - if viral load undetectable, likely no HIV, but if detectable, that confirms HIV diagnosis
- Positive: HIV diagnosis & subtype confirmed
What is available OTC for HIV diagnosis?
OraQuick In-Home HIV Test - detects HIV antibodies from oral swab.
- if positive (2 lines), must follow up with blood draw
- false-negative may occur if <3 months post-exposure
What is the HIV life cycle?
- binding and attachment - HIV virus approaches CD4 cell. interaction between co-receptors CCR5 and/or CXCR4 on surface of CD4 cell.
- fusion - outer viral envelop fuses with cell membrane. HIV enters the cell and releases its inner capsid, containing HIV RNA and viral enzymes.
- reverse transcription - HIV RNA converted to HIV DNA by reverse transcriptase.
- nuclear import - HIV capsid is transported into the cell nucleus through a nuclear pore.
- integration - integrase (an HIV enzyme) inserts HIV DNA into the host cell DNA.
- transcription and translation - host cell machinery is used to transcribe and translate HIV DNA into HIV RNA and proteins.
- assembly - new HIV RNA, proteins, and enzymes assemble at cell surface.
- budding and maturation - immature virus pinches off cell. Protease breaks up the long viral protein chains, forming the viral capsid and a mature virus that can infect other cells.
What do we monitor for HIV therapy?
Initial Monitoring:
- CD4 count: major indicator of immune function and need for OI ppx
- Viral load: indicator of response to ART (goal - undetectable)
- Resistance testing: detects mutations that confer resistance to ART
- CMP, CBC, lipids, UA: monitoring SCr, LFTs, lipids, infection
- Hep B and C, STIs: coinfection possible (also ARVs treat HBV or have interactions with HCV)
- Pregnancy test: aids in selecting appropriate ART
- Therapy specific tests: HLA-B*5701 (abacavir), tropism assay (miraviroc)
What are goals of HIV therapy?
Monitoring parameters
- viral load
- CD4 count
Viral load: goal is to achieve and maintain suppression (want undetectable viral load)
- achieving undetectable viral helps to prevent transmission. When HIV RNA is undetectable, the disease cannot be transmitted
CD4 count: goal is to keep CD4 above 200, so we can restore and preserve immune function
- this directly relates to reducing morbidity and mortality
What are the preferred initial ART regimens in most treatment-naive adults? (4)
bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy) - 1 pill
dolutegravir/lamivudine (Dovato) - 1 pill
- only if pre-treatment viral load is < 500,000 copies/mL, no HBV, and no resistance shown
dolutegravir + emtricitabine/tenofovir DF (Tivicay + Truvada) - 2 pills
dolutegravir + emtricitabine/TAF (Tivicay + Descovy) - 2 pills
- These all contain an integrase inhibitor with a high barrier to resistance
- Also most often have two NRTIs as the backbone
- all once daily
- these are fixed doses. Should not be used if CrCl <30 mL/min
What makes up a “complete” HIV antiretroviral regimen?
Base (choose 1):
- INSTI (ex. raltegravir)
- Boosted PI (ex. darunavir/ritonavir)
- NNRTI (ex. doravirine)
PLUS
NRTI backbone (choose 2):
- abacavir or tenofovir
PLUS
- emtricitabine or lamivudine
How do we alter/choose ART in pregnancy? What do we use for perinatal transmission ART?
In most cases, patient can continue pre-pregnancy ART
New-starts: 3 components recommended
- dolutegravir OR boosted darunavir
PLUS
- dual NRTI backbone
Perinatal transmission ppx:
- maternal administration of IV zidovudine prior to delivery
- neonatal administration of ART
What is Immune Reconstitution Inflammatory Syndrome (IRIS)?
IRIS - the worsening of an underlying condition after ART initiation and as the CD4 count begins to recover
- more likely when CD4 count is low when ART is initiated (ex. less than 50)
Key points:
- continue ART
- treat underlying condition
- provide supportive care
nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) - what are the drugs in this class (Z LATTE)and what are some notes (2)?
Z LATTE
- zidovudine: administered IV during labor
- lamivudine: doses for HBV are lower and should not be used for HIV
- abacavir
- tenofovir alafenamide (TAF)
- tenofovir disoproxil fumarate (TDF) (Viread): oral powder should be mixed with yogurt or applesauce to avoid bitter taste
- emtricitabline
- all require renal dose adjustment (except abacavir)
- most are QD
nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) - key features and safety issues?
- all NRTIs (2)
- emtricitabine, lamivudine, and tenofovir (1)
- abacavir (1)
- emtricitabine (1)
- tenofovir (2)
- zidovudine (1)
All NRTIs:
- warning for lactic acidosis and hepatomegaly with steatosis
- common side effects: nausea, diarrhea
Emtricitabine, lamivudine, & tenofovir:
- HBV coinfection boxed warning: severe acute HBV exacerbation can occur if abrupt discontinuation
Abacavir:
- boxed warning for hypersensitivity reaction. Screen for HLA-B*5701. If positive, increased risk for the hypersensitivity reaction. NEVER rechallenge
Emtricitabine:
- hyperpigmentation of palms of hands and feet. purely cosmetic, not harmful
Tenofovir:
- TDF has more renal impairment and causes decreased bone mineral density
- TAF can cause lipid abnormalities
Zidovudine:
- hematologic toxicities (neutropenia and anemia)
Integrase Strand Transfer Inhibitors (INSTIs) - what are the drugs in this class and some notes and creatinine clearance cutoffs?
B CRED
- bictegravir: only in Biktarvy
- cabotegravir (Apretude): component of Cabenuva
- raltegravir (Isentress, Isentress HD)
- elvitegravir: only in Genvoya and Stribild
- dolutegravir (Tivicay): also in Triumeq and Dovato
- most are QD, except Isentress is BID
Creatinine clearance cutoffs:
- < 70mL/min: do not start Stribild
- < 50 mL/min: d/c Stribild
- < 30 mL/min: do not start Biktarvy or Genvoya
Vocabria: PO cabotegravir for optional lead-in/bridge for IM cabotegravir
Apretude: ER IM cabotegravir for PrEP
INSTIs - key features and safety issues
- All INSTIs (2)
- bictegravir and dolutegravir (1)
- dolutegravir and raltegravir (2)
- cabotegravir (1)
- dolutegravir (1)
- elvitegravir (1)
All INSTIs:
- weight gain
- nervous system/psychiatric effects (Ex. insomnia, depression)
Bictegravir and dolutegravir:
- increased SCr, no effect on GFR
Dolutegravir and raltegravir:
- muscle toxicity
- hypersensitivity reactions
Cabotegravir:
- injection site reaction
Dolutegravir:
- hepatotoxicity (particularly in coinfection with hep B or C)
Elvitegravir:
- coformulated with cobicistat, a strong CYP3A4 inhibitor
What is an important counseling point for INSTIs?
all INSTIs interact with polyvalent cations
take INSTI 2 hours before or 6 hours after cations
EXCEPT: dolutegravir and bictegravir can be taken with calcium or iron-containing supplements if also taken with food
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) - drugs in this class? How to take (counseling)?
REDEN
- rilpivirine: PO (take with meal and water, requires acidic environment) and IM
- efavirenz: take on empty stomach due at night to risk of CNS side effects
- doravirine
- etravirine
- nevirapine
NNRTIs - key features and safety issues
- All NNRTIs (2)
- efavirenz (2)
- rilpivirine (4)
All NNRTIs
- hepatotoxicity
- severe rash, including SJS/TEN
Efavirenz
- psychiatric symptoms (depression, suicidal thoughts)
- CNS effects (impaired concentration, abnormal/vivid dreams), should resolve after 2-4 weeks
Rilpivirine
- depression
- artificial increase in SCr, no effect on GFR
- not recommended if pretreatment VL > 100,000 or CD4 < 200
- Cabenuva IM: injection site reactions
NNRTIs - drug interactions?
All NNRTIs are CYP3A4 substrates
- do not use rilpivirine or doravirine with strong 3A4 inducers
- efavirenz and etravirine are moderate CYP3A4 inducers
Rilpivirine needs acidic environment for absorption, so do not use with PPIs, and separate from H2RAs and antacids
- take H2RA 12 hours before or 4 hours after
- take antacid 2 hours before or 4 hours after
protease inhibitors (PIs) - drugs in this class? notes?
(-navir)
Atazanavir
Darunavir
- All PIs are recommended to be administered with a PK booster (ritonavir or cobicistat)
- darunavir and atazanavir are to be taken with food to decrease GI upset
- atazanavir needs an acidic gut for absorption
- ritonavir is only used at low doses for PK boosting, not for antiviral activity
PIs - key safety features?
- All PIs (5)
- atazanavir (2)
- darunavir (1)
- lopinavir/ritonavir (1)
All PIs
- diarrhea, nausea
- hyperglycemia/insulin resistance, dyslipidemia, lipodystrophy
- hepatotoxicity
- hypersensitivity reactions
- drug interactions (CYP3A4 substrate and inhibitor)
Atazanavir
- hyperbilirubinemia (reversible, not harmful)
- requires acidic gut for absorption, avoid PPI with unboosted atazanavir, separate boosted atazanavir by 12 hours & do not exceed 20mg omeprazole
Darunavir
- caution with sulfa allergy
Lopinavir/ritonavir
- PO solution has 42% alcohol, which could cause disulfiram reaction with metronidazole
PI PK boosters - names (2)? MOA? dosing? notes?
MOA - inhibit CYP3A4, so it inhibits metabolism of the PI to enhance levels/effect
Cobicistat: 150mg PO QD with food
- can artificially elevate SCr, no effect on GFR
Ritonavir: 100-200mg PO QD-BID with food
- administer at the same time as the drug that requires boosting
- not interchangeable
