HIV Flashcards
How is HIV transmitted?
- direct contact between infected body fluid (blood, semen, vaginal/rectal secretions, and breast milk)
- direct contact with mucous membranes or open wounds (IV drug use)
- mother-to-child/ vertical transmission through pregnancy, childbirth, or breastfeeding
How often is HIV testing recommended for all patients 13-64 y/o?
once unless other RF
What patients should have HIV screening annually?
- history of other STIs, hepatitis, or TB
- those engaging in high-risk activities (sex with multiple partners/unknown sexual history, MSM, anal/vaginal sex with someone who has HIV, sharing needles/syringes for IV drugs)
What are the symptoms of acute HIV infection?
- non-specific flu-like symptoms few days to several weeks (fever, myalgia, headache, lymphadenopathy, pharyngitis, rash)
- asymptomatic
- no antibody response for weeks -months
When is AIDs diagnosed?
CD4 count <200 cells/mm3
OR
Aids defining condition:
1. opportunistic infection
2. cancers (Kaposi’s sarcoma)
3. HIV wasting syndrome
What medications can be utilized to treat HIV wasting syndrome?
- dronabinol (Marinol, Syndros)
- megestrol (a progestin)
How is HIV diagnosed?
- initial screening for antibodies or antigens
- confirmatory test
- nucleic acid test detecting HIV RNA viral load (if confirmatory test is negative/ indeterminant)
How long does it take for HIV antibodies to be detected?
4-12 weeks after infection; up to 6 months
What OTC HIV test detects the presence of antibodies and provides immediate results?
OraQuick In-Home HIV Test
What are counseling points for OraQuick In-Home HIV Test?
- swab upper and lower gums with the test stick then insert into a test tube containing liquid
- result can be read in 20 minutes
- 1 line (control) is a negative result; 2 lines is a positive result
- testing <3 months after exposure can lead to false negative due to a lag in antibody production
- positive result must follow up for a confirmatory test
What type to virus is HIV?
RNA retrovirus that uses host cell processes to replicate
What are the 8 stages of HIV replication?
- blinding and attachment
- fusion
- reverse transcriptase
- nuclear import
- integration
- transcription/translation
- assembly
- budding and maturation
Why is it important that patients with HIV are adherent to ART (antiretroviral therapy)?
prevent resistance and prolong life
What is tested as an indicator of immune function and will determine the need to prevent OIs?
CD4 count
What is tested as an indicator of ART response?
HIV viral load
What should happen to CD4 count and HIV viral load as a result of starting ART?
- increased CD4
- decreased HIV viral load
What should be monitored for the efficacy of ART?
- CD4 count
- HIV viral load
What are warnings with NRTIs?
- lactic acidosis
- hepatomegaly with steatosis (fatty liver)
What are SEs with NRTIs?
- nausea
- diarrhea
What are the treatment goals of ART?
- achieve and maintain an undetectable viral load
- restore and maintain immune function
- reduce HIV-related morbidity (OIs)
- reduce mortality
- prevent transmission
What are the preferred once-daily, single-tablet regimens for initial ART?
- Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide)
- Triumeq (dolutegravir/abacavir/lamivudine)
- Dovato (dolutegravir/ lamivudine)
What are the preferred once-daily, two-tablet regimens for initial ART?
- Tivicay + Truvada (dolutegravir + emtricitabine/tenofovir disoproxil fumarate)
- Tivicay + Descovy (dolutegravir + emtricitabine/ tenofovir alafenamide)
What drug classes are preferred to include in ART?
2 NRTIs + 1 INSTI
What are the 2 most common NRTI regimens?
- emtricitabine/ tenofovir alafenamide (Descovy)
- emtricitabine/tenofovir disoproxil fumarate (Truvada)
Which 2 NRTIs are both cytosine analogs that would result in antagonism of each other and should not be used together?
lamivudine and emtricitabine
Which medication should not be used for initial treatment if HIV viral load >500,000 or Hep C co-infection (or unknown status)?
Dovato (dolutegravir/lamivudine)
What medication requires HLA-B* 5701 allele testing and what does it mean?
- Triumeq (dolutegravir/abacavir/lamivudine)
- A positive result indicates a higher risk of for severe hypersensitivity reaction in any abacavir-containing product and is CI
What HIV medication has more flexible dosing for CrCl<30?
Biktarvy; the individual components (bictegravir/emtricitabine/tenofovir alafenamide) can be given separately to allow for renal dosage adjustment
How should most HIV medications be dispensed?
dispensed in the manufacturer’s bottle; most medications will come in a 1 month’s supply in the original container
Why are alternative ART regimens using single products/combination products less ideal?
- increased resistance (except PIs)
- decreased patient tolerability
- higher potential for drug interactions
What drugs make up an alternative ART regimen?
1 base (PI (boosted) / NNRTI/INSTI) + 2 NRTIs
How should pregnant patients be treated for HIV?
- continue if already taking ART
- most HIV meds are considered safe in pregnancy
What are preferred regimens in ART-naive pregnant patients?
INSTI (dolutegravir preferred) OR boosted PI (darunavir preferred)
PLUS 2 NRTIs
What medication can be given around the time of delivery to prevent verticle transmission of HIV?
IV zidovudine to mother and newborn
What is immune reconstitution inflammatory syndrome (IRIS)?
unexpected (paradoxical) worsening of a known or unidentified underlying condition after ART is started or starting a more effective ART; the immune system is now capable of mounting an immune response
What conditions may typically worsen due to IRIS?
- OIs
- Hep B and C
- HSV/VZV (shingles)
- autoimmune conditions
- some cancers
When does IRIS typically occur?
when a low CD4 count begins to recover
How is IRIS managed?
continue ART as symptoms are usually self-limiting; treat the unmasked condition
How can the NRTIs be remembered?
Z LATTE
What drugs are in the NRTI class?
Zidovudine
Lamivudine
Abacavir
Tenofovir disoproxil fumarate
Tenofovir alafenamide
Emtricitabine
What is the MOA of NRTIs?
competitively inhibit the reverse transcriptase enzyme, preventing the conversion of HIV RNA to HIV DNA
What NRTI does NOT need renal dosage adjustment?
Abacavir
Why are 2 NRTIs included in a typical ART regimen?
low barrier to resistance (high rates of resistance)
What NRTIs are available as once-daily regimens?
- both forms of Tenofovir
- abacavir
- lamivudine
What NRTIs are available as twice-daily regimens?
- Zidovudine
- abacavir
- lamivudine
What are warnings with all NRTIs
- lactic acidosis
- hepatomegaly with steatosis (fatty liver)
What are BOXED warnings with Zidovudine?
- lactic acidosis
- hepatomegaly with steatosis (fatty liver)
What are the boxed warnings for HBV and HIV co-infections?
- severe acute HBV exacerbation can occur if NRTI is D/C
- Do NOT use Epivir-HBV for the treatment of HIV (contains lower dose of lamivudine than what is needed to treat HIV)
What is a boxed warning for abacavir
risk for hypersensitivity reaction
What type of screening should be done before starting abacavir?
HLA-B*5701 allele; CI if positive
What are warnings with tenofovir TDF>TAF?
- renal impairment including acute renal failure and Fanconi syndrome (renal tubular injury and electrolyte abnormalities)
- decreased bone mineral density; consider calcium/ vitamin D and DEXA scan if at risk
What should be done if a patient on abacavir experiences HSR?
- D/C and never rechallenge
- must carry a medication card indicating the HSR (N/V/D, fatigue, fever, rash, dyspepsia, cough) is an emergency
Abacavir
Ziagen
What is a unique SE with emtricitabine?
hyperpigmentation of the palms of hands or soles of feet
What SE is exclusive to zidovudine and requires monitoring?
- hematologic toxicity
- neutropenia and anemia
- macrocytosis (high MCV) is a sign of adherence
What SE is exclusive to TAF and requires monitoring?
lipid abnormalities; monitor lipids if switching from TDF to TAF
Emtricitabine
Emtriva
Lamivudine
Epivir
tenofovir disoproxil fumarate TDF
Viread
tenofovir alafenamide TAF
Vemlidy (SINGLE ENTITY ONLY USED FOR HBV; combination only for HIV)
Zidovudine
Retrovir
How can integrase strand transfer inhibitors (INSTIs) be remembered?
B CRED; ends in -gravir
What is the MOA of INSTIs?
inhibit the integrase enzyme; prevents HIV DNA from inserting into the host cell DNA
What are SEs with all INSTIs (-tegravir)?
- weight gain
- insomnia
- risk of depression and suicidal ideation in those with pre-existing psychiatric conditions (rare)
Which INSTIs have a higher barrier to resistance?
bictegravir
dolutegravir
What are unique SEs with doultegravir?
- increase SCr (by inhibiting tubular secretion) no change in eGFR
- increase CPK, myopathy, and rhabdomyolysis
- HSR syndrome (rash, fever, symptoms of allergic reaction)
- hepatotoxicity especially if co-infection with hep B or hep C
What are unique SEs with bictegravir?
increase SCr (by inhibiting tubular secretion) no change in eGFR
What are unique SEs with raltegravir?
- increase CPK, myopathy, and rhabdomyolysis
- HSR syndrome (rash, fever, symptoms of allergic reaction)
What are CIs to starting/ continuing Stribild?
CrCl<70: do not start
CrCl<50: discontinue
What is a CI to starting Biktarvy or Genvoya?
CrCl<30
What are unique SEs with IM cabotegravir?
injection site reactions
What are DIs with INSTIs?
polyvalent cations can chelate and decrease absorption; take INSTIs 2 hours before or 6 hours after products containing Al, Ca, Mg, Fe (dolutrgravir and bictegravir can be taken with Ca and Fe if also taken with food)
What are indications for PO cabotegravir?
- optional lead in treatment to assess tolerability prior to cabotegravir/rilpivrine injection
- bridge therapy in patients that will miss a scheduled cabotegravir/rilpivrine injection for >7 days
What are the indications for cabotegravir extended-release injection?
pre-exposure prophylaxis
cabotegravir PO
Vocabria
cabotegravir extended-release injection
Apretude
dolutegravir
Tivicay
Raltegravir
Isentress
Isentress HD
What is the MOA of non-nucleoside reverse transcriptase inhibitors (NNRTIs)?
non-competitively inhibits the reverse transcriptase enzyme, preventing conversion of HIV RNA to HIV DNA
How can NNRTIs be remebered?
REDEN; -vir-
What are extremely important counseling points for rilpivirine effectiveness?
- take with a meal and water (do not substitute with a protein drink)
- requires an acidic environment for absorption; avoid PPIs and separate administration of antacids and H2RAs
What is an extremely important counseling point for efavirenz?
take on an empty stomach at night to decrease and sleep through CNS SEs; food increases the bioavailability and risk of CNS effects
What are SEs with all NNRTIs?
- hepatotoxicity
- severe rash, including SJS/TENS
What are unique SEs with efavirenz?
- psychiatric symptoms (depression, suicidal thoughts)
- CNS effects (impaired concentration, abnormal dreams, confusion); generally resolves in 2-4 weeks in most patients
- increased total cholesterol and TGs
What are unique SEs with rilpivirine?
- depression
- increased SCr with no effect on GFR
- do not use if initial viral load >100,000 copies/mL and/or CD4 count <200 cells/mm3 (high failure rate)
- injection site reactions (IM Cabenuva)
What should be noted about nevirapine SEs?
highest risk of hepatotoxicity and severe rash (SJS/TENS) out of all NNRTIs
What are drug interactions with NNRTIs?
all NNRTIs are major CYP3A4 substrates
Which NNRTIs should not be used with strong CYP3A4 inducers (phenytoin, rifampin, rifapentine, carbamazepine, oxcarbazepine, phenobarbital, St.Johns Wart)?
- rilpivirine
- doravirine
Which NNRTIs are moderate CYP3A4 inducers and have many interactions?
- efavirenz
- etravirine
Rilpivirine
Edurant
Doravirine
Pifeltro
Etravirine
Intelence
How should rilpivirine be taken with H2RAs?
take H2RAs 12 hours before or 4 hours after rilpivirine
How should rilpivirine be taken with antacids?
take antacids 2 hours before or 4 hours after rilpivirine
How can protease inhibitors be remembered?
“-navir”
What is the MOA of protease inhibitors?
inhibit the HIV protease long viral protein chains from being broken down into the smaller chains needed to produce mature (infectious) virus during the budding and maturation stage
What medications must be used with a PI to act as a “booster”?
- ritonavir
- cobicistat
Which PI is only used at low doses for pharmacokinetic boosting?
Ritonavir
What are the warnings with all PIs?
- metabolic abnormalities: HLD/insulin resistance, dyslipidemia, increased body fat and lipodystrophy
- increase CVD risk
- hepatic dysfunction: increased LFTs, hepatitis, and/or exacerbation of pre-existing hepatic disease
- HSR: rash including SJS/TEN, angioedema, bronchospasm, anaphylaxis
What are common SEs with PIs?
- diarrhea
- nausea
Which PI product contains 42% alcohol in its oral formulation and can cause a disulfiram reactions with metranidazole?
Lopinavir/Ritonavir (Kaletra)
What PIs should be used with caution in those with a sulfa allergy?
- darunavir
- fosamprenavir
- tipranavir
What are unique SEs with atazanavir?
- hyperbilirubinemia (jaundice or scleral icterus, remember with “bananavir”)
- requires acidic gut for absorption
What PIs should be taken with food to decrease GI upset?
- darunavir
- atazanavir
What medications should be separated from atazanavir since it requires an acidic gut for absorption?
- antacids
- H2RAs
- avoid PPIs (unboosted atazanavir)
When can PPIs be used with boosted atazanavir?
take boosted atazanavir 12 hours after the PPI (dose should not exceed omeprazole 20mg or equivalent)
What CYP inducers will decrease concentrations of all PIs?
strong CYP3A4 inducers
What does not need to be considered when dosing PIs?
renal function
Atazanavir
Reyataz
Darunavir
Prezista
Tipranavir
Aptivus
Ritonavir
Norvir
Cobicistat
Tybost
Maraviroc
Selzentry
Fostemsavir
Rukobia
Ibalizumab-uiyk
Trogarzo
Enfuvirtide
Fuzeon
Lencapavir
Sunlenca
Bictegravir/emtricitabine/ tenofovir alafenamide
Biktarvy
Cabotegravir/rilpivirine
Cabenuva
Dolutegravir/abacavir/lamivudine
Triumeq
Dolutegravir/lamivudine
Dovato
Dolutegravir/rilpivirine
Juluca
Elvitegravir/cobicistat/emtricitabine/
tenofovir disoproxil fumarate
Stribild
Elvitegravir/cobicistat/emtricitabine/
tenofovir alafenamide
Genvoya
Doravirine/lamivudine/tenofovir disoproxil fumarate
Delstrigio
Efavirenz/lamivudine/tenofovir disoproxil fumarate
Symfi
Rilpivirine/emtricitabine/tenofovir disoproxil fumarate
Complera
Rilpivirine/emtricitabine/tenofovir alafenamide
Odefsey
Darunavir/cobicistat/emtricitabine/ tenofovir alafenamide
Symtuza
Abacavir/lamivudine
Epzicom
Emtricitabine/tenofovir alafenamide
Descovy
Emtricitabine/tenofovir disoproxil fumarate
Truvada
Lamivudine/zidovudine
Combivir
lamivudine/tenofovir disoproxil fumarate
Cimduo
Atazanavir/cobicistat
Evotaz
Darunavir/cabicistat
Prezcobix
What is dosing for ritonavir?
100-200mg PO (oral powder or tablet) QD/BID with food + boosted drug
What is dosing for cobicistat?
150mg PO QD with food + boosted drug
How does ritonavir and cobicistat boost PIs?
inhibitors of CYP3A4, inhibit ART metabolism which increases ART/therapeutic level
Why is ritonavir not utilized as a PI?
not well tolerated at higher doses; booster doses are lower with reduced metabolic side effects
Can cobicistat and ritonavir be interchanged?
NO
What drugs are contraindicated/ avoided with boosted PIs?
- alpha-1blockers (tamsulosin, silodosin, alfuzosin)
- amiodarone, dronedarone
- anticoagulants/antiplatelets (apixaban, rivaroxaban, ticagrelor)
- azole antifungals
- hepatitis C protease inhibitors (grazoprevir, galeprevir)
- Lovastatin/simvastatin
- PDE-5 inhibitors used for pulmonary hypertension (sildenafil, tadalafil)
- Strong CYP3A4 inducers (carbamazepine, phenytoin, rifampin, st.john’s wort
- inhaled, systemic, and intranasal steroids (except beclomethasone)
What is the MOA of maraviroc?
a CCR5 antagonist; blocks HIV from binding (and subsequently entering the CD4 cell in virus strains that use the CCR5 coreceptor
What baseline testing is required for maraviroc use?
must have tropism assay results before starting (determines if HIV strain infecting the patient can only bind to the CCR5 co-receptor
Why is testing required before using maraviroc for HIV treatment?
if the HIV strain can bind to CXCR 4 or mixed co-receptors maraviroc will not work HIV can still get into the cell
What are warnings/ SEs with maraviroc?
- hepatotoxicity (boxed warning)
- HSR including SJS/TENS
- orthostatic hypotension on those with renal impairment
What patients should maraviroc not be used in?
- severe renal impairment (CrCl<30_
- potent CYP3A4 inducers/inhibitors
What is the MOA of fostemavir?
converted to temsavir which binds to the gp120 subunit of HIV envelope proteins, inhibiting the interaction between the virus and the CD4 host cell; attachment inhibitor
What are warnings and SEs with fostemavir?
- do not use with strong CYP3A4 inducers
- must maintain effective HBV treatment in patients coinfected with HBV
- can increase SCr (higher risk for underlying renal disease)
- indicated in combination with other ARTs in heavily treatment-experienced patients who are failing current therapy
What is the MOA of Ibalizumab-uiyk?
monoclonal antibody that binds to a select domain of CD4 cell receptors, blocking the entry of the virus into the cell; fusion inhibitor
What are warnings/SEs for ibalizumab-uiyk?
- infusion-related reactions (observe for 1 hour after the first infusion)
- diarrhea
- dizziness
- nausea
- rash
- indicated in combination with other ARTs in heavily treatment-experienced patients who are failing current therapy
How is ibalizumab-uiyk administered?
IV injection administered by a health care professional
What is the MOA of Lencapavir?
inhibits multiple stages of the HIV cycle including capsid transport into the nucleus, virus assembly and capsid formation, resulting in a malformed capsid; capsid inhibitor
What are warnings/SEs wit lencapavir?
- CI with strong CYP3A4 inducers
- local injection site reactions: erythema, induration, nodule, pain swelling
- indicated in combination with other ARTs in heavily treatment-experienced patients who are failing current therapy
How is lencapavir administered?
oral loading dose followed by SQ injection into the abdomen every 6 months
What is the MOA of Enfuvirtide?
prevents HIV from fusing to the CD4 cell membrane, preventing virus entry into the cells; fusion inhibitor
What are warnings/SEs with enfuvirtide?
- risk of bacterial pneumonia, hypersensitivity reactions
- local injection site reactions (occur in nearly all patients): erythema, nodule, pain, swelling, cysts,
- ecchymosis (bleeding under the skin)
- nausea
- diarrhea
- fatigue
- reserved for use as salvage therapy in patients with extensive HIV resistance
How is enfuvirtide administered?
powder for injection (self-administered SQ into the abdomen, front of the thigh, or back of the arm
What medications are first line for HIV treatment?
- Biktarvy
- Triumeq
- Dovato
What is the indication for Cabenuva and Juluca?
only indicated to replace a stable ART regimen in patients with virologic suppression and no history of treatment failure or known resistance
How is Cabenuva administered?
IM once monthly by a healthcare professional (may be preceded by lead-in treatment with oral cabotegravir to assess tolerability
When should tenofovir disoproxil fumarate products not be started in patients with impaired renal function?
CrCl <50 (CrCl <70 for Stribild)
When should tenofovir alafenamide products not be started in patients with impaired renal function?
CrCl <30
Which ART medications must be taken with food?
Stribild & Genvoya (taken with food due to cobicistat component)
What is pre-exposure prophylaxis (PrEP)?
prescribing ART to prevent HIV infection in patients who engage in high risk activities
What oral regimens are used for PrEP?
Truvada and Descovy taken daily with no more than a 90 day supply dispensed at a time
What injectable regimen can be used for PrEP?
Apretude; long-acting cabotegravir administered by a healthcare provider monthly for 2 doses, then once every 2 months
What tests must be done before starting PrEP?
- confirm pt is HIV negative
- ask about recent symptoms
- confirm CrCl≥60 (if using Truvada; cut off higher for PrEP) and CrCl≥30 (if using Descovy)
- Screen for Hep B and STIs
What tests must be done while PrEP is continued/follow-up testing?
- test for HIV at each visit and confirm negative test before refilling PrEP treatment
- follow-up every 3 months for oral treatments; follow up 1 month after the first injection then every 2 months (Apretude)
- STI screening, renal function, and adverse drug reactions are recommended to be monitored at every follow-up visit
When is post-exposure prophylaxis (PEP) used/recommended?
for emergency situations when a non-infected person is exposed to body fluids that are known to be or could be infected with HIV
What are the types of PEP?
- nonoccupational (nPEP); after sex without a condom, injection drug use, or other type of occupational exposure
- occupational (oPEP); typically used for healthcare personnel who are exposed to body fluids that could be infectious (needle stick injury)
When should PEP treatment be started and how long is treatment?
ASAP within 72 hours of the exposure and is continued for 28 days
For those taking PEP how often should they be tested for HIV after the exposure?
4-6 weeks, 3 months, and 6 months after the exposure
Which INSTI-containing regimens are once-daily?
- Biktarvy
- Stribild
- Genvoya
- Isentress HD
- Tivicay
- Triumeq
- Dovato
Which INSTI-containing regimens are twice-daily?
- Insentress
- Tivicay (twice daily only for treatment-experienced patients, those with INSTI resistance, or taking UGT1A1/CYP3A4 inducers)