Target Cell - ___ binds to CD4 receptors on T cells, macrophages, and dendritic cells - The primary target cell of HIV is the ___ (cell-mediated immunity, protect against viruses, ___ bacteria, and certain cancers)

- Glycoprotein 120 (gp120) - CD4 T helper/inducer lymphocyte - intracellular

Routes of Transmission 1. Exposure of ___ or damaged tissue to infected body fluids 2. ___ exposure to infected body fluids 3. Mother-to-child infected body fluids include - Blood, ___ , pre-seminal fluid, rectal fluid, ___ secretions, ___ - HIV not found in urine, feces, sweat, or tears

- mucous membrane - Blood stream - semen, vaginal, breast milk

HIV/AIDS Flashcards by Reagan Smith

Target Cell

___ binds to CD4 receptors on T cells, macrophages, and dendritic cells
The primary target cell of HIV is the ___ (cell-mediated immunity, protect against viruses, ___ bacteria, and certain cancers)

Glycoprotein 120 (gp120)
CD4 T helper/inducer lymphocyte
intracellular

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Routes of Transmission

Exposure of ___ or damaged tissue to infected body fluids
___ exposure to infected body fluids
Mother-to-child

infected body fluids include
- Blood, ___ , pre-seminal fluid, rectal fluid, ___ secretions, ___
- HIV not found in urine, feces, sweat, or tears

mucous membrane
Blood stream
semen, vaginal, breast milk

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Mucous Membrane Transmission

___ transmission is most common method
- Certain sexual exposures carry more risk than
others
- 94% of HIV cases in 2018

Factors that increase risk of transmission
- high ___ ___of the infected partner
- presence of an ___
- tearing/abrasions
- menstruation

sexual
viral load
STI

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Stages of HIV Infection

1) acute ___ syndrome
2) ___ HIV infection (asymptomatic)
3) ___ (symptomatic)

1) retroviral
2) chronic
3) AIDS

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Screening Recommendations

Patients aged __ - __ in any health-care setting
- Should be repeated annually in high-risk groups

All pregnant women as early as possible during
each pregnancy
- Consider repeat test in ___ trimester

All patients initiating treatment for ___

All patients attending ___ clinics during each visit
for a new complaint

13-64
3rd
TB
STD

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Diagnosis

Positive results from a multitest algorithm
- Initial and supplemental tests must be ___

Positive virologic test
- viral ___
- qualitative HIV ___

different
load
NAT

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Rapid Testing

Multiple tests available on the market
- Results available in 1-30 minutes
- ___ In-Home test using oral fluid is available
OTC

OTC Rapid Test Counseling
- if positive, go to Dr for confirmatory testing
- if negative, counsel on the seroconversion window ( __ months for the OraQuick), ___ test if risk event occurred within the window period, methods of risk reduction and prevention

OraQuick
3, repeat

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HIV Surrogate Markers

CD4 T lymphocyte cell count
- ___ marker of immunocompetence
- Most useful ___ initiation of therapy
- Lower levels are indicative of a more compromised immune system

HIV RNA PCR (viral load)
- Used to assess the ___ of therapy
- Most useful ___ initiation of therapy
- Higher baseline levels are predictive of ___ disease progression

primary
before
effectiveness
after
faster

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Disease Staging - CD4 count (cells/mm3)

stage 1: ≥ ___
stage 2: ___ - __
stage 3: ≤ ___ or ___ diagnosis

1) 500
2) 200-499
3) 200, OI

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Non-Nucleos(t)ide Reverse Transcriptase Inhibitors

MOA: Bind to an ___ site of the reverse transcriptase enzyme reducing functionality

Class adverse effects: ___

Precautions and interactions
- Use with caution in patients with ___ impairment
- Many significant DIs exist
- High-level ___ develops easily and quickly to agents (particularly ___ and ___ )

allosteric
rash
hepatic
resistance, nevirapine, efavirenz

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Nucleos(t)ide Reverse Transcriptase Inhibitors

MOA: Synthetic ___ and ___ analogues which result in elongation ___ of growing proviral DNA chain

Class AE: ___ toxicity and ___ acidosis with or without hepatomegaly and hepatic steatosis
- Seen much less frequently with ___ , ___ , ___ , ___

Precautions and interactions
- Require dosage adjustment in ___ insufficiency (except ___ )

purine, pyrimidine, termination
Mitochondrial, lactic
tenofovir, emtricitabine, abacavir, lamivudine
renal, abacavir

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Protease Inhibitors (PIs)

MOA: Inhibit the action of the viral protease preventing the ___ , maturation, and release of new ___

Class adverse effects
- ___ intolerance (N/V/D) , ___ resistance, and ___

Precautions and interactions
- Many are not recommended in severe ___
impairment
- Many, many significant drug interactions exist
- Highly favorable ___ profile, but greater ___ burden

assembly, virions
GI, insulin, lipodystrophy
hepatic
resistance, pill

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“Boosting”

Ritonavir and cobicistat are incredibly potent inhibitors of ___
- ___ anti-HIV activity seen at doses of 600mg BID
- ___ has no anti-HIV activity

Used at low doses as a pharmacokinetic enhancer to “boost” the concentrations of other ARTs
- Ritonavir 100-200mg 1-2 times daily
- Cobicistat 150mg daily

Benefits of Coadministration
- Increased ___ , lengthened elimination half-life, reduction in drug dose and ___ , and increase in systemic concentrations

Ritonavir
Cobicistat
absorption, frequency

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Integrase Strand Transfer Inhibitors (INSTIs)

MOA: Inhibits HIV integrase, preventing the proviral DNA ___ into the host cell genome

Class AE: weight ___

Precautions and interactions
- Fewer drug interactions than NNRTIs and PIs (except for ___ which must be boosted)
- Resistance can develop easily to first-generation INSTIs ( ___ and ___ ), but second-generation INSTIs ( ___ and ___ ) have a resistance profile on par with boosted-PIs

integration
gain
elvitegravir
raltegravir, elvitegravir
dolutegravir, bictegravir

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Attachment Inhibitor

MOA:
- ___ is a prodrug of temsavir
- Temsavir binds to ___ on the surface of ___ , blocking attachment to the CD4 T-cell co-receptor

Precautions and interactions
- Contraindicated with strong CYP3A4 ___ as coadministration results in significant ___ in temsavir concentrations

Fostemsavir
gp120, HIV
inducers, decreases

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Post-Attachment Inhibitor

MOA: Binds to domain __ of the ___ co-receptor and interrupts the post-attachment steps required for ___ of HIV into the host cell

Precautions and interactions
- In-clinic IV administration after ___ in 250mL of NS
- No drug interactions expected
- Rarely used clinically: reserved for deep salvage ( ___ ) regimens

D2, CD4 T-cell, entry
dilution
last-line

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Chemokine Coreceptor 5 (CCR5) Antagonist

MOA: Binds to ___ on the CD4 cell surface, blocks the binding of ___ , and prevents ___ of HIV into the host cell

Precautions and interactions
- Before treatment can be considered, a tropism assay must be performed: Only active against ___ -tropic strains of HIV
- ___ of CYP3A4, so watch dosing!

CCR5, gp120, entry
CCR5
Substrate

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Capsid Inhibitor

MOA: Binds to the interface between capsid protein ( ___ ) subunits. Interferes with multiple steps of the viral lifecycle:
- uptake of proviral ___
- virus ___ and ___
- ___ core formation

Precautions and interactions
- Half-life of 8-12 weeks
- residual concentrations may remain for ___ months or longer
- ___ of CYP3A4
- Currently only approved in patients with multidrug resistant infection who are ___ their antiretroviral regimen - may begin to be used more commonly in the future when other long- acting agents are available

p24
DNA
assembly, release
capsid
12
substrate
failing

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Benefits of Therapy

Reduces HIV-related morbidity and mortality for all stages
- reduces immune activation and ___ (limits CV, thromboembolic events, cancer, neurocognitive dysfunction, and frailty)

Reduces ___ of HIV

Suppresses viremia
- Prevents selection of drug ___ associated mutations
- preserves and improves ___ count

inflammation
transmission
resistance
CD4

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Limitations of Therapy

Not curative

Interruptions in therapy have serious consequences
- rebound ___
- risk of ___
- worseningn of immune function
- increased morbidity and mortality

must be continued ___

viremia
resistance
indefinitley

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When to Start

ART is recommended for all HIV-infected persons, ___ of CD4 count
- ART should be initiated ___ after diagnosis

Early initiation is particularly important for
- AIDS-defining conditions (except ___ from ___ or ___ )
- Acute or recent HIV infection
- Pregnancy

regardless
ASAP
meningitis, TB, cryptococcus

What to Start

T or F: Monotherapy and most dual-ART drug combos are recommended for intital therapy

FALSE
- Incomplete and transient viral suppression
- Development of ART resistance

What to Start

Two ___ in combination with a third active ART from one of three drug classes
1. ___ : Recommended for most patients
2. ___ , or
3. ___ boosted with a pharmacokinetic enhancer ( ___ or ___ )

Data also support the two-drug regimen, ___ plus ___ , for initial treatment
- Not all two-drug regimens are as equally efficacious

NRTIs
1) INSTI
2) NNRTI
3) PI, ritonavir, cobicistat
dolutegravir, lamivudine

Recommended Initial Regimens for Most People with HIV

(no history of long-acting cabotegravir use for HIV prevention)

INSTI plus 2 NRTIs
- Biktarvy: ___ , ___ , and ___
- ___ + tenofovir alafenamide (or tenofovir disoproxil fumarate) + ____ (or ___ )

INSTI plus 1 NRTI
- ___ / ___ (coformulated as Dovato), except for individuals with HIV RNA > ___ copies/mL, ___ co-infection, or in whom ART is to be started before the results of HIV genotypic resistance testing or HBV testing are available

Bictegravir, tenofovir alafenamide, emtricitabine
Dolutegravir, emtricitabine, (lamivudine)
Dolutegravir/lamivudine, 500,000, HBV

Truvada, Cimduo, and Temixys

tenofovir disoproxil fumarate/emtricitabine

Descovy

tenofovir alafenamide/emtricitabine

# Recommended Initial Regimens in Certain Clinical Situations INSTI-Based Regimen - ___ / ___ /lamivudine (coformulated as Triumeq) if ___ negative and without chronic ___ co-infection PI-Based Regimen - ( ___ /cobicistat or ritonavir) + (tenofovir alafenamide or tenofovir disoproxil fumarate) + (emtricitabine or lamivudine) - (Darunavir/cobicistat or ritonavir) + ___ /lamivudine if ___ negative NNRTI-Based Regimen - ___ /tenofovir disopril fumarate/lamivudine (coformulated as Delstrigo) - Doravirine + tenofovir alafenamide/emtricitabine - ___ /tenofovir alafenamide/emtricitabine (coformulated as Odefsey) if HIV RNA < ___ copies/mL and CD4 > ___ cells/mm3

- Dolutegravir, abacavir, HLA-B*5701, HBV - Darunavir - abacavir, HLA-B*5701 - Doravirine - Rilpivirine, 100,000, 200

# Drug Interactions Always run a drug interaction screen! * Extensive drug interaction tables in the guidelines * website: ___ * Search “HIV iChart” on your phone’s app store

- www.hiv-druginteractions.org

# ART Drug Interaction Principles Boosted-PIs are strong CYP3A4 ___ - Ritonavir has a complex inhibition/induction profile - ___ is not an inhibitor of CYP3A4 NNRTIs are CYP3A4 ___ - ___ and ___ are not a CYP3A4 inducers – only substrates INSTIs are ___ substrates, and have fewer clinically significant drug interactions Maraviroc, fostemsavir, and lenacapavir are ___ of 3A4 The NRTIs, ibalizumab, and enfuvirtide have few clinically significant drug interactions

- inhibitors, Tipranavir - inducers, Rilpivirine, doravirine - UGT1A1 - substrates

# Summary of Drug Interactions Acid Reducers: Separate antacids from PO ___ by __ hours, but never give ___ with Al or Mg. - Atazanavir and PO rilpivirine are reduced by acid reducers; rilpivirine is CI with ___ Benzodiazepines: With ___ and ___ , preferred benzodiazepines are ___ , ___ , and ___ (LOT) Corticosteroids: With PI and cobicistat, ___ is preferred.

- INSTIs, 6, rilpivirine - PPIs - PI, cobicistat, lorazepam, oxazepam, and temazepam - beclomethasone

# Summary of Drug Interactions Statins: With protease inhibitors and cobicistat, ___ doses of atorvastatin, rosuvastatin, pitavastatin, or pravastatin are preferred. With NNRTIs, dose may need ___ Biguanide: ___ increases metformin, so a dose decrease of metformin may be necessary. PDE5 Inhibitors: With PI and cobicistat, use very ___ doses q48-72 hours. Polyvalent Cation Supplements: With integrase inhibitors, space apart by __ hours. Coadministration of Ca/Fe with ___ or ___ OK if also taken with food.

- low, increased - Dolutegravir - 6, Dolutegravir, bictegravir

# Resistance – Types of Mutations ___ – naturally occurring variants in the absence of therapy - not associated with decreased susceptibility to antiretrovirals ___ – amino acid substitutions (point mutations) which confer reduced susceptibility to one or more antiretrovirals posing a survival advantage ___ – accessory mutations which have little to no effect on drug susceptibility, but may increase the replication fitness of a virus with a major mutation

- Polymorphic - Major - Minor

# Resistance-Associated Mutations Transmitted - Obtained with initial HIV infection or superinfection - Rate is location-dependent Acquired - Inadequate ___ (most common cause) - Inadequate dosing (prescriber error) - Inadequate drug concentration (drug interaction or malabsorption

- adherence

# Resistance Testing At entry to care - Regardless of whether ART is initiated immediately or deferred Virologic failure or suboptimal viral response - Genotype is recommended when ___ 1st or 2nd regimen - Sequence integrase if failing INSTI-based regimen - Specimen should contain > ___ copies/mL for best likelihood of yielding a successful standard resistance test results, but should still be considered if >200 copies/mL - Phenotype should be considered in patients with extensive treatment history

- failing - 500

# Virologic Failure - Inability to achieve or maintain suppression of viral replication to a viral load of < ___ copies/mL Management - Assess adherence and drug-drug/drug-food interactions - if failure persists, perform resistance testing - Never add a single drug to a failing regimen New Regimens: - two fully active drugs if at least one with a high resistance barrier is included (e.g. ___ or boosted- ___ ); or - three fully active drugs Monitor closely for the next 4-8 weeks to assess for tolerability and viral rebound

- 200 - dolutegravir, darunavir

# Prevention UNEXPOSED - condoms - STD treatment - circumcision PRE-EXPOSURE - PrEP POST-EXPOSURE - tablets for ___ days INFECTED - U = U

- 28 days

# Undetectable Equals Untransmittable - Maintaining a plasma HIV RNA < ___ copies/mL with ART prevents sexual transmission of HIV to sexual partners - Another form of prevention should be used for at least the first __ months and until HIV RNA < 200 copies/mL has been documented (condoms, pre-exposure prophylaxis (PrEP), abstinence)

- 200 - 6

# Nonpharmacologic Prevention ___ and polyurethane male and female condoms - estimated 80% reduction in transmission risk with real-world use Seropositioning: sexual positioning that lowers the uninfected partner’s risk of acquisition ___ -based lubricants and spermicides that do not contain ___ * Circumcision * Syringe exchange programs * Frequent testing

- latex - water, nonoxynol-9

# Pre-Exposure Prophylaxis (PrEP) Use of antiretroviral agents in HIV-negative persons at high risk for HIV acquisition for the purpose of HIV prevention - Not ___ - Reassess risk regularly

not lifelong

# Contraindications for PrEP HIV infection Weight < ___ lbs Estimated creatinine clearance (eCrCl) * < __ mL/min for TDF/FTC * < __ mL/min for TAF/FTC Possible HIV exposure within the past __ hours * Instead offer ___ (to be discussed later), then consider PrEP

- 77 lbs - 60 mL/min - 30 mL/min - 72 hrs - PEP

# PrEP Regimens: Oral Daily - ___ / ___ 200/300mg PO daily for all risk groups - ___ / ___ 200/25mg PO daily for men and transgender women who have sex with men; Persons with risk of acquiring HIV through receptive vaginal sex were excluded from DISCOVER trial

- Emtricitabine/tenofovir disoproxil fumarate - Emtricitabine/tenofovir alafenamide

# PrEP Regimens: Oral On-Demand Emtricitabine/tenofovir disoproxil fumarate 200/300mg PO for men who have sex with men - 2 tabs PO taken 2-24 hours prior to having sex, then - 1 tab PO 24 hours after first 2 tabs taken, then - 1 tab PO 48 hours after first 2 tabs taken - Continue 1 tab PO daily until 48 hours after last sexual encounter

Not FDA approved

# PrEP Regimens: Injection ___ 600 mg IM (gluteal muscle) - (Optional: CAB 30 mg PO daily x 30 days as oral lead-in before 1st injection) Initial dose - 2nd dose 1 month after 1st dose, then - Every 2 months thereafter Residual concentrations of cabotegravir may remain in the systemic circulation of individuals for prolonged periods (up to ___ months or longer) - There is a risk of CAB ___ if infected with HIV during this time

Cabotegravir 12 resistance

# Lab screening prior to PrEP initiation All - HIV test within __ week before starting PrEP (ideally HIV Ag/Ab) - HIV RNA (if possibly infected within the past 2-4 weeks) - STI testing: gonorrhea/chlamydia (throat, rectum, and genital/urine screening according to sites of exposure), syphilis, hepatitis C (HCV) Ab, consider hepatitis A IgG If considering oral PrEP, also obtain: - ___ - ___ sAb/cAb/Ag - For TAF/FTC: ___ and ___

- 1 week - CrCl - HBV - cholesterol, TG

# Follow up monitoring Oral PrEP - ___ month (appropriate in some cases to ensure patient is still HIV uninfected), then at least every __ months: HIV Ag/Ab, HIV RNA, screen for STIs, pregnancy test - Every __ months: CrCl for persons age ≥ ___ or eCrCl < 90 - Every ___ months: cholesterol and triglyceride levels. HCV Ab for MSM, transgender women, people who inject drugs Injection PrEP - __ month: HIV RNA - Every __ months: HIV Ag/Ab and HIV RNA. Pregnancy test as appropriate. - Every __ months: HIV RNA, STI testing

- 1 month, 3 months - 6 months, 50 - 12 month - 1 month - 2 months - 4 months

# PrEP Key Messages - 90% effective when used correctly - TDF/FTC, maximum blood and rectal tissue drug levels are reached after __ days and in vaginal tissue after __ days (For TAF/FTC and CAB, no data on time to protective drug levels are available) - If planning to stop daily oral PrEP, continue for ___ days after last potential HIV exposure - If a potential high-risk HIV exposure occurs while NOT on PrEP, start ___ (within ___ hours) for ___ days, then restart PrEP if still HIV Ag/Ab negative - PrEP Medical Assistance Program (PrEP MAP) is a statewide assistance program for uninsured and underinsured individuals to access PrEP

- 7, 20 - 28 - PEP, 72, 28

# Pre- vs Post-Exposure Prophylaxis PrEP - ___ + (Tenofovir AF OR Tenofovir DF) daily OR Injectable ___ PEP - ___ / ___ DF daily for 28 days + ( ___ twice a day for 28 days OR ___ daily for 28 days)

- Emtricitabine, cabotegravir - Emtricitabine/Tenofovir DF, Raltegravir, Dolutegravir

# PEP Considerations Absolute risk per exposure to - Needlestick contaminated with HIV-infected blood: 0.3% - Mucous membrane exposure to HIV-infected blood: 0.09% - Non-intact skin exposure to HIV-infected blood: < 0.09% - Exposures to other fluids/tissues ___ blood

# PEP Regimen ___ / ___ 200/300mg PO daily for 28 days + ( ___ 400mg po BID for 28 days OR ___ 50mg po daily for 28 days) - Should be initiated as soon as possible - Must be initiated within ___ hours or little benefit will be obtained - Approximately 81% reduction in risk of transmission

- Emtricitabine/tenofovir disoproxil fumarate - Raltegravir, Dolutegravir - 72

# PEP Monitoring & Counseling Rapid testing at baseline - If ___ , do not initiate PEP Repeat testing at __ - __ weeks and at ___ months Counseling - Use precautions (e.g. barrier contraception, avoidance of blood/tissue donation, pregnancy, and breastfeeding) to prevent secondary transmission, esp. during first 6-12 wks - Possible drug toxicities - Importance of adherence - If at ongoing risk, undergo evaluation for PrEP

- positive - 4-6, 3