RxPrep/UWorld - Human Immunodeficiency Virus

Define HIV

HIV is a single stranded RNA retrovirus that uses the machinery in host CD4 T-helper cells (T cells) to replicate

How is AIDS diagnosed?

AIDS is diagnosed when the CD4 count falls below 200 cells/mm or the patient develops an AIDS defining condition

body can no longer ward off opportunistic infections and aids-specific malignancies

How can HIV be transmitted?

body fluids ( blood, semen, vaginal secretion, rectal secretion and breast milk)

mucus membranes

open wounds

sharing drug needles

unprotected sex

vertical transmission (mom to baby via preg, childbirth, or breastfeeding)

True or False: Most infections are caused by unprotected vaginal and rectal sex and sharing injection drug equipment, including needles

True

How do vertical transmission occur?

Vertical transmission (from mother to child) may occur, either during pregnancy, at birth or through breastfeeding

HIV screening recommedations:

everyone

high-risk (+ what are high risk)

Once for all patients

Annual testing:

hx of stis

hx of hepatitis

hx of TB

multiple sexual partners

sharing drug needles

What symptoms will a person with acute HIV infection experience?

how long do sx last?

non specific flu like symptoms, such as fever, fatigue/malaise, myalgia/arthralgias, lymphadenopathy and rash

few days to weeks

Criteria for AIDS diagnosis

HIV wasting syndrome treatment

stimulate appetite w/

dronabinol (cannabis-related drug)

megestrol (progestin)

When can HIV antibodies be detected?

4-12 weeks post-infection

initial HIV screening includes testing for what?

p24 antigens

and/or hiv1/hiv2 antibodies

after a positive initial screening for hiv antibodies, what must be done next?

confirmatory testing to differentiate b/t hiv 1 and hiv 2

if hiv confirmatory test to distinguish between hiv 1 and hiv 2 is...what comes next?

intermediate

negative (non reactive)

positive (reactive)

intermediate, negative: hiv 1 nucleic acid test to quantify viral load. if viral load undetectable, prob no hiv. if viral load +, then hiv

positive: HIV dx and subtype confirmed

What over the counter HIV test detects the presence of HIV antibodies and provides immediate results?

The OraQuick In Home HIV Test

When should the otc hiv test oraquick be done?

>3 months

if earlier may have false neg d/t lag in antibody production

HIV lifecycle

binding&attachment

, fusion,

reverse transcription, integration,

replication,

assembly,

budding

Define Stage 1: Binding/Attachment

HIV attaches to a CD4 receptor and the co-receptors (CCR5 and/or CXCR4) on the surface of the CD4+ host cell. The virus must bind/ attach to both a CD4 receptor and a co-receptor for the next step of viral replication to occur.

Define 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.

Define Stage 3: Reverse Transcription

HIV RNA is converted to HIV DNA by reverse transcriptase. HIV DNA can then enter the CD4 cell nucleus

Define Stage 4: Integration

Once inside the CD4 cell nucleus, integrase is released and used to insert HIV DNA into the host cell DNA

Define Stage 5: Replication

Host cell machinery is used to transcribe and translate HIV DNA into HIV RNA and long chain proteins

Define Stage 6: Assembly

New HIV RNA, proteins and enzymes moves to the cell surface and assemble into immature HIV

Define Stage 7: Budding and Maturation

Immature HIV pushes out of the CD4 cell and protease breaks up the long viral protein chain, creating mature virus that can infect other cells

What drug class target Stage 1: Binding/Attachment?

step: Hiv attaches to CD4 receptor and Coreceptor CCR5 and or CXCR4

CCR5 Antagonist: Maraviroc (Selzentry) - tropism test prior to use

Post Attachment Inhibitors: Ibalizumab-uiyk (Trogarzo) - cd4 diected

Attachment Inhibitor: Fostemsavir (Rukobia) - blocks gp120

What drug class target Stage 2: Fusion?

step: HIV viral envelope fuses with cell membrane

Fusion Inhibitors: Enfuvirtide (Fuzeon)

What drug class target Stage 3: Reverse Transcription?

step: Hiv rna converted to hiv dna via reverse transcriptase (hiv enzyme)

Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs) (eg. emcitritabine) - compete w nucleosides for active site on RT causing chain termination and stop hiv replicaiton

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs) (eg. riplivirine)

- bind allosteric site to conformational change that prevents conversion hiv rna to hiv dna

What drug class target Stage 5: Integration?

step: Integrase (hiv enzyme) inserts hiv dna into host cell dna

Integrase Strand Transfer Inhibitors (INSTIs): Bictegravir (Biktarvy), Dolutegravir (Tivicay) , Raltegravir (Isentress)

block action of integrase so hiv dna cant enter host cell dna

What drug class target Stage 8: Budding and Maturation?

step 8: Immature virus pinches off the cell protease (hiv enzyme) breaks up viral protein chains to form mature virus that can infect other cells

Protease Inhibitors (PIs): Atazanavir (Reyataz), Darunavir (Prezista)

block maturation of HIV by inh protease

Capsid inhibitors

disrupt hiv capsid

work on

nuclear import (step 4) budding/maturation (step 8), and assembly (step 7)

lenacapavir

in which step in the hiv lifecyle do no drugs work?

step 6: Transcription and translation

host cell machinery is used to transcribe and translate HIV DNA into HIV RNA and long chain proteins

What are the routine lab tests for initial evaluation in monitoring of HIV?

CD4 count

Hiv viral load

Hiv genotypic testing

CMP

Hepatitis B and C screening pregnancy test

HLAB*5701 allele (abacavir)

ccr5 tropism test (maraviroc)

HIV evaluation and monitoring:

what does a cd4 count indicate?

indicates the need for?

does it increase or decrease with treatment?

Indicator of immune function

Determines the need for OI prophylaxis

CD4 count increases with ART

HIV evaluation and monitoring:

hiv viral load indicates what?

If a patient is being treated, what does a high viral load indicate?

Antiretroviral therapy response

If still high after starting treatment, may be d/t Medication non adherence or drug resistance

Guidelines recommend initial treatment with what class of HIV medications for most patients with newly diagnosed HIV?

INSTI based regimens for most pts

Most preferred HIV regimens for treatment naive patients contain what?

2 NRTIs + 1 INSTI

What two drugs in their components make up the NRTI backbone in most HIV regimens?

emtricitabine/tenofovir disoproxil fumarate (truvada)

emtricitabine/tenofovir alfenamide (descovy)

which two drugs in NRTI are interchangeable? can they be used together, why or why not?

emcitritabine and lamuvidine

no, Both are cytosine analogs and would be antagonistic if taken together

Preferred initial art regimen in most treatment naive adults - hiv:

generic, brand, pill burden

+ what class do they contain

all contain an integrase inhitor With a high barrier to resistance (bictegravir or dolutegravir)

plus 2 nrtis (emcitritabine + taf or tdf

Preferred initial art regimen in most treatment naive adults - hiv:

how are they all dosed?

renal impairment?

all qd

biktarvy, triumeq, dovato, tivicay, descovy: CI if crcl <30

all except biktarvy can be given components separately to allow for renal adjustment (so larger pill burden)

Which of the following is consider first line treatment regimen for a patient with newly diagnosed HIV (one pill)?

Biktarvy (Bictegravir/ Emtricitabine/ Tenofovir Alafenamide)

Triumeq (Dolutegravir/ Abacavir/ Lamivudine)

Dovato (Dolutegravir/ Lamivudine)

when can dolutegravir/lamivudine (dovato) be used 1st line for Treatment naive patients?

do not use if

viral load >500,000

hep b coinfection or unknown

hiv genotype not done OR resistance to either drug

Which of the following antiretroviral therapy should not be started in patients if HIV RNA >500,000 copies/mL or if a hepatitis B confection is present or HIV genotypic testing not yet available?

Dovato (Dolutegravir/ Lamivudine)

Which of the following antiretroviral therapy requires testing for the HLA-B*5701 allele before using?

Triumeq (Dolutegravir/ Abavacir/ Lamivudine)

Epzicom (Abavacir/ Lamivudine)

Trizivir (Abavacir/ Lamivudine /Zidovudine)

Which of the following antiretroviral therapy should not be used if CrCl <30 mL/min?

Biktarvy (Bictegravir/ Emtricitabine/ Tenofovir Alafenamide)

Triumeq (Dolutegravir/ Abacavir/ Lamivudine)

Dovato (Dolutegravir/Lamivudine)

Truvada (Emtricitabine/ Tenofovir Disoproxil Fumarate)

Descovy (Emtricitabine/ Tenofovir Alafenamide)

Biktarvy

Bictegravir/ Emtricitabine/ Tenofovir Alafenamide

Triumeq

Dolutegravir/ Abacavir/ Lamivudine

Dovato

Dolutegravir/ Lamivudine

Tivicay + Truvada

Dolutegravir + Emtricitabine/ Tenofovir Disoproxil Fumarate

Tivicay + Descovy

Dolutegravir + Emtricitabine/ Tenofovir Alafenamide

Isentress + Truvada

Raltegravir + Emtricitabine/ Tenofovir Disoproxil Fumarate

Isentress + Descovy

Raltegravir + Emtricitabine/ Tenofovir Alafenamide

Alternative Complete hiv antiretroviral regimens contain

(aka 2nd line treatments for treatment naive pts)

ART in pregnancy:

if pt already on art

newly diagnosed while pregnant

continue art regimen

new: 3 components rec'd

dolutegravir (insti) or boosted darunavir (PI) PLUS

dual nrti backbone (eg. emcit/tenofovir)

ART in pregnancy:

perinatal transmission prophylaxis

IV zidovudine near time of delivery to mother and newborn

What is the mechanism of action for NRTIs?

Competitively inhibit the reverse transcriptase enzyme, preventing the conversion of HIV RNA to HIV DNA in stage 3 of the HIV life cycle

Match the generic name with the correct brand name NRTIs (hint: Z Loves LATTE

Zidovudine (Retrovir)

Lamivudine

(Epivir)

Abacavir (Ziagen)

Tenofovir disoproxil

fumarate (Viread)

Tenofovir alafenamide (Vemlidy brand is for hep b only)

Emtricitabine (Emtriva)

Which NRTIs are dosed once daily?

Tenofovir (both formulations)

Abacavir (Ziagen)

Lamivudine (Epivir)

Which NRTIs are dosed twice daily?

Zidovudine (Retrovir)

Which NRTIs requires renal dose adjustment?

All NRTIs except Abacavir requires DECREASE dose with renal impairment

Which NRTI is administered IV during labor and delivery in women with HIV RNA >1,000 copies/mL?

Zidovudine (Retrovir)

ALL NRTIs have a warning for what?

all: lactic acidosis, hepatomegaly with steatosis (fatty liver)

Which nrtis have BBW for reactivation of HBV if dc'd?

emcitritabine

lamivudine

tenofovir products

what is the BBW for abacavir?

risk for hypersensitivity reaction (HSR)

must test prior for

hlab5701

pts must carry card indicating HSR (fever, rash, nvd, dyspnea, cough) are emergency

never rechallenge pts with hsr symptoms

what is the BBW for zidovudine?

lactic acidosis and hepatomegaly with steatosis

What are the common side effects of NRTIs?

Nausea

Diarrhea

Headache

Increase LFTs

Which NRTI can cause hyperpigmentation of the palms of the hands or soles of the feet?

Emtricibine (Emtriva)

Which NRTI decrease bone mineral density?

Tenofovir Formulations - consider calcium/vitamin D supplementation and DEXA scan if at risk

higher risk with tdf v taf

NRTIs:

what are specific side effects/warning for tenofovir products?

which is higher risk?

tdf higher risk v taf

renal impairment (aki, fanconi syndrome)

decreased bone mineral density

NRTIs:

what monitoring must be done if switching from tdf to taf?

monitor lipids

taf is associated with lipid abnormalities

Which NRTI can cause hematologic toxicity (neutropenia and anemia)?

Zidovudine (Retrovir), prolonged use has been associated with symptomatic myopathy

Which NRTIs can cause pancreatitis and peripheral neuropathy?

Didanosine (Videx, Videx EC)

Stavudine (Zerit)

Testing for the HLA-B 5701 allele is required before prescribing which medication?

Abacavir (Ziagen)

Which NRTI has a boxed warning for the risk of serious hypersensitivity reaction?

Abacavir (Ziagen)

Which of the following NRTIs should patients with CVD avoid due to a potential increase risk for MI?

Abacavir (Ziagen)

What is the mechanism of action for INSTIs?

Block the integrase enzyme preventing HIV DNA from inserting into the host cell DNA in stage 4 of the HIV life cycle

Match the generic name with the correct brand name INSTIs (hint: BCRED)

Bictegravir only in combination drug (Bikatarvy)

cabotegravir (apretude, cabenuva -combo)

Raltegravir (Isentress, Isentress HD)

Elvitegravir only in combination drugs (Genvoya and Stribild)

Dolutegravir (Tivicay, triumeq & dovato-combos)

names end in -tegravir

Which INSTIs are dose once daily?

Biktarvy

Raltegravir (Insentress HD onlyw)

Elvitegravir (Stribild)

Elvitegravir (Genvoya)

Dolutegravir (Tivicay, triumeq, dovato)

which INSTI is twice daily?

Raltegravir (Insentress)

isentress hd (high dose) is ONCE daily

Do not start Stribild in which of the following conditions?

CrCl of <70 mL/min

Discontinue Stribild in which of the following conditions?

CrCl of <50 mL/min

Do not start Bictegravir (Bikatarvy) and Elvitegravir (Genvoya) in which of the following conditions?

CrCl of <30 mL/min

Which INSTIs increase Scr?

Bictegravir (Biktarvy)

Dolutegravir (Tivicay)

what is cabotegravir (apretude) used for?

er IM injection used for post exposure prophylaxis ONLY

What are the most common side effects associated with Raltegravir (Isentress, Isentress HD)?

Increase CPK

Myopathy

Rhabdomyolysis

What is the most common side effect associated with Elvitegravir (Genvoya and Stribild) ?

Proteiniuria

Which of the following statements are true concerning Dolutegravir (Tivicay)?

Hypersensitivity reaction with severe rash and organ dysfunction including hepatotoxicity

Small risk of neural tube defects in women (though still a preferred drug for treatment of HIV during pregnancy)

INCREASE CPK

Myalgia

All INSTIs can cause

Insomnia,

depression &suicidal ideations in patients with pre existing psychiatric condition

weight gain

diarrhea

INSTI drug interactions + counseling

polycalent cations decrease insti absorption ->

separate INSTIs from polyvalent cations (eg. antacids, supplements (ca, iron))

take INSTI 2 hours before or 6 hours after products containing Al, Ca, Mg, Fe

Which antiretroviral class should be administered separately from antacids?

Integrase Strand Transfer Inhibitors

eltegravir drug interactions

coformulated with cobicistat

strong cyp 3a4 inh

which INSTIs may be taken with oral calcium or iron if also taken with food

Dolutegravir (Tivicay) and Bictegravir

What is the mechanism of action for NNRTIs?

Non competitively inhibit the reverse transcriptase enzyme, preventing the conversion of HIV RNA to HIV DNA in stage 3 of the HIV life cycle

Match the generic name with the correct brand name NNRTIs (hint: REDEN)

Rilpivirine (combo: complera, odefsey, cabenuva)

Efavirenz

Doravirine

Etravirine

Nevirapine

why are NNRTIs not first line?

have lower barrier to resitance (easier to gain resistance) than instis or PIs

How must ripivirine (complera, odefsey, cabenuva (im)) PO be administered?

Take with a meal and water do not substitute with a protein drink

Which NNRTIs needs an acidic gut for absorption? why is this important? (think drug interactions)

rilpivirine (complera, odefsey, cabenuva (im))

requires acidic environment for absorption; can not be used with PPIs

what is the IM version of rilpiverine?

cabenuva - cabotegravir/rilpivirine

a pt with heartburn that is taking rilpivirine (complera, odefsey, cabenuva (im)) should to not take which medication class?

CI with PPis

How should a pt on H2RAs be counseled to take rilpivirine (complera, odefsey, cabenuva (im)?

should be taken at least 12 hours before or 4 hours after Rilpivirine (Edurant)

how should a pt on rilpivirine (complera, odefsey, cabenuva (im) be counseled on how to take Antacids?

should be taken at least 2 hours before or 4 hours after rilpivirine (complera, odefsey, cabenuva (im))