HIV Dr. Cluck EXAM 4 Flashcards
When is a patient considered virally suppressed?
< 200 copies/mL
What is the main Mechanism of Transmission of HIV?
Sexual contact (>80%)
-MSM accounts for nearly 70%
others:
-Injection Drug Use
-Transfusion of contaminated blood or blood products
-Perinatal transmission (also known as vertical transmission or MTCT)
What is the Rule of 3 regarding the risk of needle stick exposure to viruses?
HBV: 30%
HCV: 3%
HIV: 0.3%
When is the latest a patient should receive prophylaxis after occupational exposure to a virus?
72 hours after exposure
occupational (needle stick for example)
non-occupational (sexual contact)
Which antiviral drug regimen is recommended for post-exposure prophylaxis PEP?
TDF/FTC + Raltegravir (or DTG) for 4 weeks (within 72 hours)
TDF/FTC= Truvada
Tenofovir Disoproxil Fumarate/Emtricitabine
for Occupational and Non-occupational exposure
Newest data suggests which antiviral drug regimen for post-exposure prophylaxis?
TAF/FTC/BIC (Biktarvy) !!
-small tablet (better adherence)
-once daily
for Occupational and Non-occupational exposure
When should antiviral therapy be started after exposure to a virus?
immediately as long the patient is willing to start
“Rapid Start”
How likely is HIV transmitted from a person who has an undetectable viral load?
very unlikely
-U=U (undetectable = untransmittable)
What should be done before starting antiretroviral therapy to improve adherence?
!!!
-Reassure about normal life expectancy, tolerable therapy
-discuss interest in starting immediate ART
-perform a physical exam
-counsel on medication adherence !!!
-support and empower through positive messaging including U=U
How does a patient with acute HIV infection present?
Acute Retroviral Syndrome
-fever (80-90%)
-rash
-fatigue
-pharyngitis
-generalized lymphadenopathy (swollen lymph nodes)
-myalgia/arthralgia
-mucocutaneous ulceration (canker sores)
What lab test should be done for patients starting therapy?
-HIV antibody testing (to know the HIV stage)
-CD4 T-cell count (or CD4 %, to check immune function)
-Plasma HIV RNA (viral load, to see the baseline viral load))
-CBC, chemistry profile, transaminase levels,
BUN and creatinine, urinalysis, and serologies for
hepatitis A, B, and C viruses
-Fasting blood glucose and serum lipids
-genotypic resistance testing regardless of treatment plan (needs detectable viral load for the test)
-screen for other STIs
If a patient fails ART, within what time frame of discontinoung the agent should they get a resistance test to isolate the virus strain?
What might happen beyond that time frame?
within 4 weeks of stopping the drug
-Archived Phenomen”:
it becomes harder to detect the resistant strain, bc after stopping the drug the non-resistant strain will outgrow the resistant strain
What needs to be done before starting therapy with Abacavir?
HLA-B*5701 test, if positive they are at risk for hypersensitive reaction (nonspecific: GI, rash, respiratory)
-Abacavir is not used often anymore, 2nd line
The Trofile assay must be done before starting which drug?
Maraviroc (HIV entry inhibitor)
the drug only works if the patient predominantly has R5 receptors
(expensive assay)
Which test is used to monitor the response to therapy and determine the risk for opportunistic infections?
CD4 count (does not tell when to start therapy, (should start therapy ASAP if the patient is ready)
CD4 count < 200: risk for PJP
What other lab test is used to check for response to therapy?
viral load
-Integrase inhibitors are effective in reducing viral load
-the goal is to reduce viral load to undetectable
How long after starting therapy do we expect suppression of the virus?
12-24 weeks
-if the viral load is still high, check the patient’s adherence
How frequently should an HIV patient’s viral load be monitored?
every 3-4 months
every 6 months in stable patients
When to use PrEP vs PEP
What is the pharmacological difference between TAF and TDF?
TDF is predominantly converted into the active form TFV (tenofovir) in the plasma, rather than at the target site (PBMC)
-higher plasma concentration means more side effects, also higher dose needed
TAF conversion to TFV is mainly on the target site (PBMC), 90% less in the plasma
What are the limitations of FTC/TAF (Descovy) antiviral therapy for PrEP?
-not approved for cis-gender women (yet) !!! for PrEP (HIV treatment is fine?)
-not approved for on-demand dosing (taken when planning to have sexual contact)
Which antiviral drug used for PrEP can be used for all genders?
FTC/TDF (Truvada)
-may be used with on-demand dosing (taken when having sex Vs daily) only in MSM with infrequent sex
Which drugs are used for PrEP (Pre-Exposure Prophylaxis)?
FTC/TAF (Descovy)
FTC/TDF (Truvada)
Cabotegravir (IM every 2 months)
Lenacapavir (SC every 6 months after oral loading)
HIV treatment commonly consists of which two drug classes?
Integrase inhibitor (ex: raltegravir)
Nucleoside reverse transcriptase inhibitors (NRTIs)
regimen that includes Bictegravir (BIC) is often the right answer on the exam !!
Early HIV treatment
-recommended regardless of CD4 count
-recommended for pregnant women with early HIV infection
-can start ART before drug resistance test results are back -> DTG or protease inhibitor + 2 NRTIs to prevent resistance in this setting
What should be considered when creating a regimen for HIV patients with chronic Hep B?
-use a regimen with tenofovir (it covers Hep B) for chronic Hep B patients
Antiretroviral Drug classes
-Nucleoside/tide reverse transcriptase inhibitors (NRTIs)
-Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
-Protease Inhibitors (PIs)
-Integrase Inhibitors (INSTIs)
-Fusion Inhibitors
-Chemokine receptor antagonists (CCR5)
-Capsid inhibitor (Lenacapavir)
Name the Nucleoside reverse transcriptase inhibitors (NRTIs).
-Retrovir (zidovudine/AZT)
-Ziagen (abacavir/ABC)
-Epivir (lamivudine/3TC)
-Emtriva (emtricitabine/FTC)
-Videx EC (didanosine/ddI) - not often used, toxic
-Viread (tenofovir disoproxil fumarate or TDF)
-tenofovir alafenamide (TAF)
Which two NRTIs should not be given together?
Epivir (lamivudine/3TC) and Emtriva (emtricitabine/FTC)
-because they are both cytidine analogs -> duplication
What are the class toxicities of NRTIs?
-lactic acidosis (from mitochondrial toxicity)
high lactate, low pH or bicarbonate, N/V, SOB
-Hepatomegaly with steatosis (fat build-up)
What are the toxicities specific to Retrovir (zidovudine/AZT)?
Anemia
neutropenia
headache
malaise
What are the toxicities specific to Didanosine (Videx)?
-Non-cirrhotic portal hypertension
-pancreatitis
-CD4 toxicity with tenofovir disoproxil fumarate
What are the toxicities specific to Abacavir?
Hypersensitivity
increased risk for MI?
benefit:
no renal dose adjustment
What are the toxicities specific to Tenofovir?
especially with Tenofovir Disoproxil Fumarate bc higher concentrations in the plasma
-Renal dysfunction (Fanconi’s syndrome)
-Decreased bone mineral density
less with Tenofovir alafenamide, but more weight gain
Non-NRTIs
-Sustiva (efavirenz/EFV)
-Viramune (nevirapine/NVP)
-Intelence (etravirine/ETR)
-Edurant (rilpivirine/RPV)
-Pifeltro (doravirine/DOR
What are the class toxicities of Non-NRTIs?
-Hepatoxicity
-Rash
-CNS effects specifically with Efavirenz (Sustiva)
caution in patients with psychiatric diseases, increased suicidality, vivid dreams
Oral Rilpivirine (Edurant) cannot be used with which drugs?
PPIs
long-acting formulations of Rilpivirine are fine
oral rilpivirine has to be taken with food
Protease Inhibitors
-avir
-Reyataz (atazanavir/ATV) - commonly used, but can cause jaundice, icterus
-Prezista (darunavir/DRV) - most often used, mutation-resistant
-Viracept (nelfinavir/NFV)
-Invirase (saquinavir/SQV)
-Norvir (ritonavir/RTV)
-Crixivan (indinavir/IDV) - not on the market
-Kaletra (lopinavir/LPV PLUS ritonavir)
-Lexiva (fosamprenavir/FPV)
What should be considered when using Protease inhibitors?
should be combined with pharmacokinetic enhancers (CYP inhibition) ritonavir or cobicistat
-watch for DDI
What are the class side effects of Protease Inhibitors?
-Lipodystrophy (long-term) - mostly with ritonavir
-metabolic abnormalities (hyperglycemia and hyperlipidemia)
-morphologic abnormalities (fat atrophy and fat deposition)
Integrase inhibitors
-tegravir
-Isentress/Isentress-HD (raltegravir/RAL)
-Genvoya/Stribild (elvitegravir/EVG)* - need pharmacokinetic enhancer
-Tivicay (dolutegravir/DTG)
-Biktarvy (bictegravir/BIC)* - most often used
-Cabenuva/Apretude (cabotegravir)
Which drugs are in Genvoya/Stribild?
Elvitegravir/Cobicistat/Emtricitabin/Tenofovir
Which drugs are in Biktarvy?
BIC, emtricitabine & tenofovir alafenamide
What is the difference between Cabenuva and Apretude?
Integrase inhibitors?
Apretude = Cabotegravir (IM)
approved for PrEP
Cabenuva = Cabotegravir + rilpivirine (IM)
for HIV treatment (used to switch therapy, not for patient naive)
-> low viral load (<50) is required before switching to Cabenuva (need strong viral suppression to avoid mutation and resistance)
Entry inhibitor
Selzentry (maraviroc)
Fusion inhibitor
Fuzeon (enfuvirtide/T-20)
-SC
-no DDIs, but has many other issues
Which drugs are reserved for heavily treatment-experienced patients (drug resistance, tried other agents and failed)?
What is the MOA of these drugs?
Attachment inhibitor
-Trogarzo (ibalizumab)
-Rukobia (fostemsavir)
Capsid inhibitor
-Sunleca (lenacapavir)
Advantage/Disadvantage of Bictegravir
Advantage:
-STR once daily as Biktarvy (TAF/FTC/BIC)
-few drug and food interactions
-high barrier to resistance
Disadvantage:
-least amount of data
-only available as STR
-no safety data in pregnancy
Advantage/Disadvantage of Dolutegravir (Trivicay)
Advantages
-STR once daily as Triumeq (dolutegravir/ABC/3TC)
-high barrier to resistance
-few interactions
-preferred in pregnancy (2nd, 3rd trimester)
Disadvantages:
-the STR has ABC (MI risk, hypersensitivity)
-increases metformin levels
-concerns with conception, early pregnancy
Advantage/Disadvantage of Elvitegravir
Advantages
-STR with TAF/FTC/Cobicistat
Disadvantage
-many DDIs due to Cobicistat
-not recommended in pregnancy
Advantage/Disadvantage of Raltegravir
Advantages
-longest experience (oldest)
-few interactions
-option for pregnant patients
Disadvantage
-multiple pills, no STR
-limited data at conception
TAF/FTC and TDF/FTC are often used as backbone drugs for HIV treatment, what are the brand names?
TAF/FTC = Descovy
TDC/FTC = Truvada
Which drug regimen should be used carefully due to DDIs?
Genvovy/Stribild
contains Elvitegravir -> which needs an enhancer (Cobicistat), Cobicistat has multiple DDIs
When can a patient use Cabenuva for HIV treatment?
-it is used for patients who are on HIV treatment and want to switch to a simpler regimen
-need a low viral load <50 copies/ml (strong viral suppression, to avoid mutations and resistance)
Which of the following are full regimen options for a patient who was newly diagnosed with HIV?
A. Biktarvy
B. Cabenuva
C. Descovy
D. Truvada
Biktarvy (right answer)
Cabenuva is not for naive patients and needs a low viral load
Descovy and Truvada by themselves are not full regimens, they only contain NRTIs -> need to add an Integrase inhibitor (dolutegravir, raltegravir)
What are things to be cautious about in patients who receive boosted Protease inhibitor therapy?
Protease inhibitors (-avir)
-they need pharmacokinetic enhancers (ritonavir or cobicistat)
-DDI due to pharmacokinetic enhancers (CYP) !!!
-renal dysfunction if ritonavir or atazanavir is used with TDF
-lipid effects (hyperlipidemia, Lipodystrophy, fat atrophy), also hyperglycemia
-hyperbilirubinemia
Which drug has a DDI with PPIs and must be given with food?
Oral rilpivirine (RPV)
-less effective with high viral load
-high risk for resistance
How do Ritonavir and Cobicistat affect CYP activity?
Ritonavir
inhibitor of CYP3A4, 2D6 and P-glycoprotein
Cobicistat
inhibitor of CYP3A4 (may inhibit 2D6)
-avoid with corticosteroids (also nasal corticosteroids - cushioning effect (increases lvl of corticosteroid)
Which antiretroviral agents are less preferred in renal dysfunction?
TDF
ATV/RTV (protease inhibitors)
What are the most lipid neutral antiretroviral agents?
Raltegravir (RAL)
Dolutegravir (DTG)
Rilpivirine (RPV)
Which antiretroviral drugs are associated with increased CV risk?
Abacavir (ABC) !!!
Didanosine (ddi)
Lopinavir (LVP)
Ritonavir (RTV)
Which drug is preferred if a patient presents with HIV and Hep B?
Tenofovir DF (TDF) + 3TC or FTC
What antiretrovirals are without any known drug interactions?
-ibalizumab
-enfuvirtide (fusion inhibitor)
