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178 Cards in this Set

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What is the MOA of amphotericin B?
Binds to ergosterol component of fungal cell membrane and alters permeability to allow leakage of ions and other intracellular components
What is the basis for selective toxicity of amphotericin B?

What can cause cytotoxicity?
Greater selectivity for fungal membranes because they contain ergosterol instead of cholesterol;

binding of cholesterol component in mammalian cells
What is the MOA of Flucytosine (5FC)?
5FC is transported into fungal cells by a perm ease and is then converted to fluorouracil. The metabolite 5-FdUMP is formed and inhibits thymidylate synthetase stopping DNA synthesis
What is the basis of selective toxicity of Flucytosine?
perm ease affected by this drug is not found in mammalian cells
What is the MOA for Azole antifungals (ketoconazole)?
Inhibits P450 isoenzyme that converts lanosterol to ergosterol. Inhibition of ergosterol production results in deficient fungal membranes with increased permeability and leakage of cellular components/inhibition of fungal growth
What is the MOA for Capsofungin?
inhibits synthesis of an essential cell wall component (beta-1,3-D-glucan) in aspergillus species resulting in osmotic fragility and fungal death
What is the basis of selective toxicity for Capsofungin?
It targets the cell wall, which humans don't have
What is the MOA of griseofulvin?
Interacts with the fungal cell wall microtubules to disrupt the mitotic spindle and inhibit mitosis.
Where does griseofulvin accumulate?
in infected keratin-containing tissues creating unfavorable growth conditions
What is the basis of selective toxicity for griseofulvin?
Targets cell walls, which are not present in humans
What is the MOA of Terbinafine?
Inhibits squalene epoxidase which is an essential enzyme in fungal sterol synthesis. Produces a deficiency of ergosterol and an accumulation of squalene inside the fungal cell resulting in death.
What is the MOA of Nystatin?
are polyene abx similar in structure and MOA to amphotericin B (alters cell membrane permeability)
What is the basis of selectivity for nystatin?
similar to amphotericin B
Amphotericin B can be either fungicidal or fungostatic depending on.....
tissue concentration achieved and organisms susceptability
What is the broadest spectrum anti fungal?
amphotericin B
What is the DOC (anti fungal) for immunocompromised patients?
amphotericin B
Is amphotericin B effective against meningitis? What routes of administration are there?
achieves nontherapeurtc elves in CSF with/without inflammation however in some cases, IV administration may produce therapeutic levels for cryptococal meningitis
What are the indications for the use of the liposomal formulations of Amphotericin B?
Patients who cannot tolerate or fail the conventional IV formulation or for renal impairment where unacceptable toxicity occurs.

Includes: invasive aspergillosis, neutropenic pts with fungal infection, candidiasis, etc.
What are some advantages to using the liposomal formulation of Amphotericin B?
Increased circulation time and reaches higher concentrations in vascularized areas (inflammation, infection, tumors) while being essentially impermeable to normal tissues;

Localizes the drug at disease sites and allows drug levels to be increased several times higher than amounts achieved with free drug from conventional products;

intended to reduce serious renal toxicity by decreasing binding of drug in renal tissues
When you are going to use the amphotericin B, what pretreatments would you want to use?
NSAIDs, antihistamines, and steroids
What is the major toxicity associated with amphotericin B?
nephrotoxicity (decreased GFR And creatinine clearance, K+ loss)
What is the mechanism of synergism between flucytosine and amphotericin B?

Is this combination efficacious for meningitis?
Amphotericin B alters the membrane permeability to flucytosine.

yes- effective against cryptococcus neorformans and candidia
Are systemic azole antifungals fungicidal or fungistatic?

Are they broad or narrow spectrum?
both depending on dose;

Broad spectrum treatment for systemic mycoses
Which azole anti fungal is effective against meningitis? What is the route?
fluconazole (excellent penetration info CSF)

oral tablets, suspensions or IV injections
Why is concurrent use of amphotericin B with azole antifungals contraindicated?
azoles contraindicate the actions of amphotericin B
What are the indications for which fluconazole is the DOC?
cryptococcal meningitis, serious systemic candidiasis (URI, peritonitis, pneumonia), and coccidiodomycosis
What are the two serious ADRs associated with itraconazole?
Risk of CHF in pts with existing heart disease; hepatic dysfunction
Describe the method of pulse dosing of itraconazole for onychomycosis.
each pulse is 200mg BID for one week per month;

need 2 for fingernails, 3-4 for toenails (grow slower)
Symptoms of endocrine disorders associated with the use of ketoconazole include:

What is the mechanism that causes these symptoms?
gynecomastia, impotence, loss of libido, menstrual irregularities;

inhibits gonadal steroid synthesis in humans
You don't want to take ketoconazole with things that ____ gastric acidity or with ______ since it is required for dissolution and absorption.
decrease, food
Ketoconazole can ______ the P450 system and cause....
inhibit; toxicity of other drugs
Which other azole anti fungal possibly has hepatic effects and needs to be monitored?
Which other azole anti fungal causes hepatic dysfunction and has strong warnings against liver failure?
Voriconazole is the first line agent for the treatment of what three conditions?
acute invasive aspergillosis * (in pts over 12)

esophageal candidiasis

nonneutropenic pts with candidemia or deep tissue candida infection
What are the two indications for Posoconazole?
prophylaxis of invasive aspergillosis and candidiasis who are severely immunocompromized;

oropharyngeal candidiasis
Echinocandins have potent activity against ____ and ___ except for which 3 species?
aspergillosis; candidiasis

candida neoformans, zygomycetes, fusarium
Capsofungin is used to treat what 4 conditions?
Aspergillosis, esophageal candidiasis, disseminated candida infections, empirical tx of presumed fungal infections in febrile neutropenic patients
What is the DOC for secondary prophylaxis of PCP?
Is primary prophylaxis (in HIV+ pts) recommended/done for candidiasis, cryptococcosis, and aspergillosis infections?
What is the strongest recommendation of ART in a TB patient?
Pts with CD4 cell counts less than 50 cells/mm and it should be initiated within 2 weeks of starting TB treatment.
What are the major toxicities associated with indinavir and what precautions must be taken?
acute nephrolitiasis;

ensure adequate hydration, drinking about 1.5L of liquids per 24 hours
What is the advantage of using the combination product Combivir compared to dosing with the two individual components? (antiretroviral drug)
has synergistic antiretroviral activity and is taken without regard to meals.
What is the parameter used to decide whether ART regimens should be modified?
regular monitoring of the viral load, CD4+ T cell count and pts clinical condition
What are the 6 classic ADRs associated with Antiretroviral agents?
lactic acidosis, hepatomegaly with steatosis, hyperglycemia, rash, hyperlipidemia, GI intolerance
What are the three major characteristics of all preferred ART Regimens?
use at least 3 drugs; use a combination of drugs with different MOAs, and are class sparing
What is the spectrum of activity of Griseofulvin?
What are the indications for Griseofulvin?
only active aginst dermatophytes (trichophytan, microsporum and epidermophyton) and in the treatment of severe tinea infections that dont respond to other antifungals
What are some ADRs with Griseofulvin
GI distress, photosensitivity, possible antabuse reaction with alcohol
What are some symptoms of an Antabse reactioin?
tachycardia and flushing
How may the oral absorption of Grisofulvin be enhanced?
Using ultra-fine crystalline preps and eating with high fat meals
Where does Griseofulvin distribute to?
keratinized tissues (skin, hair, nails)
How long must therapy with griseofulvin be continued for?
until normal tissue replaces infected tissue (weeks to months)
What is the current clinical use of amantadine and rimantadine?
against influenza A virus
What is the oral availability for ACY (acyclovir) and DHPG (gangciclovir)?
Describe how Acyclovir is given via IV to avoid nephrotoxicity.
Given by a slow infusion over at least 1 hour with adequate hydration. Make sure to establish sufficient urine flow over the 1st 2 hours post-infusion
How does the spectrum of activity for gangciclovir differ from acyclovir?
the same but also effective against CMV
What is the boxed warning for gangciclovir and what are the resulting hematological effects?
myelosuppression. Monitor for neutropenia, anemia and thrombocytopenia
What is the action and indication for penciclovir dermatological cream?
Antiviral activity against HSV-1 and HSV-2; indicated for treatment of recurrent herpes labialis in adults (cold sores)
What is the DOC for tx of PCP pneumonia?

Alternate agent (mod-severe)?
Alternate agent (mild-mod)?
TMP-SMX, IV pentamidine, atovaquone
What is the DOC for post-exposure primary prophylaxis?
varicella-zoster immune globulin ASAP for at least 3 weeks
What is the DOC for varicella infection?
What is the spectrum of activity for Terbinafine?
What are the indications for Terbinafine?
tx of onychomycosis of the toenail or fingernail due to dermatophytes (superior to griseofulvin)
What are the ADR of Terbinafine?
GI distress, ageusia, asx elevation of liver enzymes, less commonly neutropenia, derm eruptions and ophthalmic complaints
How may oral absorption of terbinafine be enhanced?
take with food to increase bioavailability
How do the distribution properties of terbinafine relate to the clinical uses?
highly lipophilic with slow elimination from skin and adipose tissue
How long must therapy of terbinafine be continued?
treatment can last weeks to months
What are the three preparations of ciclopirox and what are their indications?
Cream/lotion= tinea infections;

shampoo=seborrheic dermatitis

nail lacquer= nail infections
What are the preparations of nystatin and what are they used for?
Topical (cream, ointment, powder)= superficial cutaneous candida;

Oral (swish and swallow)= oral/mucous membrane candidiasis

Oral tablet= intestinal candida

Vaginal tablet= vulvovaginal candidiasis
What are the preparations and clinical uses of Clotrimazole?
OTC cream or solution= tinea infections

OTC intravaginal cream= VVC

Rx buccal tablet= tx and prophylaxis of oropharyngeal candidiasis
What are the preparations and clinical uses of Miconazole?
Intravaginal cream and suppository= VVC

topical cream= cutaneous candidiasis
What is the clinical use of Butoconazole?
What is the DOC for trichomoniasis? What infections can Trich cause?

vaginitis, NG urethritis, prostatitis
What is the preferred regimen of Metronidazole for use against trichomonas?

What is the alternative regimen
2g PO single dose;

500mg BID x 7 days
If treatment failure occurs with metrondiazole, what do you want to do?

what do you want to take metronidazole with and what do you want to avoid?

If you are allergic to metronidazole, what do you want to do?
tx with a single 2 g dose once daily x 5 days;

food; alcohol;

desensitize the pt
What is the proposed MOA of mebendazole?
selectively and irreversibly inhibits glc uptake in susceptible adult intestinal-dwelling helminthes; also a spindle poison that induces chromosome nondisjunction
What is mebendazole indicated for?
pinworms (worms in general)
When treating a pt with pinworms with mebendazole, what other things must be taken into consideration?
repeat dosing may be needed adn may need to treat family members in close contact. Also hygiene precautions need to be taken to prevent reinfection
What organisms are susceptible to acyclovir?
HSV-1/2, varicella and ebstein barr
Why is CMV resitant to acyclovir?
it lacks a specific viral thymidine kinase
What are the 4 groups of patients for whome ART is recommended regardless of CD4 cell count?
pregnancy, Hx of an AIDS-defining illness, HIV-associated nephropathy, HIV/hepatitis B coinfection
What is the CD4+ t cell count associated with the strongest ART recomendation?
<350 cells/mm3
What are the specific toxicities associated with Zidovudine?
myelosuppression, neutropenia, severe anemia
What is the resulting drug interaction of Zidovudine with ganciclovir?
additive hematology toxicity
What is the major boxed warning for nevirapine?
severe, life-threatening skin reactions (steven-johnson syndrome, Toxic epidermal necrolysis) and potentially fatal hepatotoxicity
State what effect the following drugs have on the P450 system:



strong inhibitor
Which ART drug inhibits the P450 system but is also a substrate for the enzyme (3A4) so induces of 2A4 may decrease the concentration of this drug?
When using Zidovudine during pregnancy, what is the route of administration and when is it given?
IV; at onset of labor until delivery
When using Zidovudine in the infant, what is the route of administration and what are the treatment recommendations?
Oral; 2x daily as soon after birth as possible (within 6-12 hours) and continues for up to 6 weeks
For the post-exposure prophylaxis of HIV, what is the duration of all regiments used?

What is the basic regimen?

What is a reason for using the expanded regimen?

What is the preferred expanded regimen?
4 weeks;

ZDV + lamivudine;

for exposures posing an increased risk of transmission or where resistance to one or more of the agents is known or suspected;

basic regimen plus lopinavir/ritonavir
What is the DOC for primary prophylaxis of Pneumocystic jirovecci pneumonia?

What are the alternative regimens?

dapsone, dapsone plus pyrimethamine (plus leucovorin), Aerosolized pentamidine or atovaquone
What other parasitic infection is covered by the DOC for the treatment of PCP pneumonia? (TMP-SMZ)
What is the regimen used for prophylaxis of PCP and toxoplasmosis when tolerance to TMP-SMZ occurs?
dapsone + pyrimethamine + leucovorin
What is the DOC for the tx of toxoplasmosis?
pyrimethamine plus sulfadiazine plus leucovorin
Why is leucovorin included in the treatment for toxoplasmosis?
to prevent megaloblastic anemia effects that can occur from the pyrimethamine
What is the major toxicity of sulfadiazine and what precaution must be taken?
neutropenia, interstitial nephritis, crystalluria and nephrolitiasis.

drink 2-3L of fluid/day to decrease risk of crystalluria
What is the alternative regimen for toxoplasmosis (for those allergic to sulfas)
pyrimethamine plus leucovorin plus clindamycin
What is the MOA for pyrimethamine?
inhibits dihydrofolate reductase preventing the conversion of dihydrofolate to the active form tetrahydrofolate. Activity is highly selective for DHFR from plasmodium or toxoplasma parasites
What is the clinical uses for pyrimethamine?
chemoprophylaxis of malaria; and as part of the treatment for toxoplasmosis
What are some precautions that need to be taken when using pyrimethamine?
may cause folate deficiency (give leucovorin), may also precipitate hemolytic anemia in G6PD deficient patients
What is the DOC for esophageal candidiasis?
What is the DOC for oropharyngeal candidiasis?
What is the DOC for cryptococcal meningitis?
amphotericin B plus flucytosine
What is the DOC for aspergillosis?
For the treatment of TB in HIV patients, what are the induction phase drugs and how long are they used?

How about the continuation phase?
8 weeks; INH, RIF (or RBN), PZA and EMB;

18 weeks; either INH and RIF (or RBN) every day (((OR))) INH and RIF 3x weekly
Is the use of DOT strongly recommended for HIV pts undergoing tx for TB?
What is the preferred rifamycin drug used when a protease inhibitor-based ART regimen is to be used? Why?
Rifabutin; less potent 3A4 inducer
What is the preferred agent for the primary prophylaxis of mycobacterium avium complex in adults with HIV?
clarithromycin (or azithro)
What is the the preferred agent for the treatment of an active MAC infection?
clarithromycin with ethambutol. Addition of rifabutin may be considered (but need to think about DIs)
What is the recommendations for the primary prophylaxis of CMV?
not generally recommended
What is the treatment of CMV retinitis?
ganciclovir intraocular impant and valganciclovir PO
What are the disadvantages of the ganciclovir ocular implant?
cannot prevent CMV infection in the contralateral eye or systemic infection which is why concurrent PO treatment is needed
What are some alternative therapies for treatment of cytomegalovirus?
IV ganciclovir, foscarnet, or cidofovir
What are the dosing recommendations for cidofovir and why?
once weekly;has a very long intracellular half-life
What major ADR is associated with cidofovir? What precautions are needed to be taken?
nephrotoxicity (dose-limited);

adequate hydration with NS and concurrent probenecid (along with avoiding other nephrotoxic drugs)
What is the DOC for secondary prophylaxis of CMV?
What is the MOA for Zanamavir?
selective inhibition of influenza virus neuraminidase.
What is the function of viral neuraminidase?
allows viral release from infected cells, prevents virus aggregation and decreases viral inactivation by mucus
What are the indications for zanamavir?
uncomplicated acute illness due to influenza A or B in pts >7 years old who have had sx less than 2 days
Which antiviral is also used for prevention of influenza illness in pts over 5 years old?
What is the route of administration of zanamavir?

What is the dose and course of treatment?
oral inhalation using a diskhaler devise

2 inhalations BID x 5 days
When is Zanamavir treatment not recommended?
in pts with underlying airway disease due to risk of severe bronchospasm
What is the MOA of Oseltamavir?
Oral prodrug which is converted by hepatic esterases to the active agent in vivo (oseltamivir carboxylate) which then inhibits viral neuraminidase altering virus partical release and aggregation
What are the indications for Oseltamavir?
Type A and B influenza infections in pts over 1 year of age who have had sx for less than 2 days
What is the route of administration for Oseltamavir?
oral suspension
What are the major toxicities/ADRs with Oseltamavir?
What are the 4 major goals of ART therapy
reduction of HIV-related morbidity/mortality and to increase duration/QOL;

Restoration and preservation of immunologic fxn;

Maximal and durable suppression of viral load (goal=to suppress to undetectabe levels after 3-6 mo of tx);

Prevent HIV transmission
What is the spectrum of antiviral activity for Ribavirin?
active vs RSV and some activity vs Influenza A and B (low efficacy when given PO)
What are the indications of Ribavirin?
Tx of severe lower respiratory tract infections due to RSV in hospitalized infants and young children (not adults!)
What is the method of administration of Ribavirin?
Aerosol given via a generator, mechanically-ventilated through ET tube, via oxygen hood/tent/face mask
What are some serious problems that result from the mode of administration of Ribavirin?
Drug precipitation in ET tube and ventilators has caused inadequate ventilation and gas exchange with sudden deterioration of respiratory function;

is also absorbed systemically and accumulates in RBCs decreasing their half-life to 40 ays
Ribavirin is contraindicated in which patients?

What are precautions that need to be taken?
Pregnant women and male partners of pregnant women.

Child-bearing aged women must use effective contraception during therapy and for 6 mo post-tx
What toxicity can Ribavirin cause in caregivers with reactive airway diseases?
bronchospasm and chestpain
What is the MOA for palivizumab?
monoclonal Ab that neutralizes and has fusion-inhibitor activity against RSV and inhibits RSV replication
What are the indications for Palivizumab?
prevention of serious lower resp tract disease caused by RSV in high risk ped patients (premies, bronchopulm dysplasia pts, hemodynamically significant congestive heart disease pts)
What is the dosing of Palivizumab?
15 mg/kg once a month during RSV season IM in anterolateral thigh
What are the toxcities associated with Efavirenz (given once daily)?
Rash, CNS/Psych symptoms, Teratogenicity in pregnancy, other symptoms (diarrhea, fever, and cough in ped pts)
What are some symptoms of acute primary HIV infections?
fever, lymphadenopathy, pharyngitis, rash, myagia/arthralgia, diarrhea (similar to flu, mono, etc and even asx)
What is the first step in the MOA of Acyclovir?

What are the subequent steps that form the ACY-triphosphates?
acyclovir is a synthetic acyclic guanosine analog that is posphorylated in the viral-infected cell by the viral enzyme thymidine kinase;

monophosphate form is converted by host cell to the diphosphate and triphosphate forms. ACYTP competes with the endogenous substrate deoxyguanosine triphosphate as the substrate for viral DNA polymerase
What is the basis for selective toxicity of acyclovir?
reaction occurs 100x more rapidly inside the virus-infected cell that non-infected host cells
What are the effects of Acyclovir on viral DNA polymerase?
ACYTP is incorporated into the viral DNA causing premature chain termination; ACYTP inactivates viral DNA polymerase but is less reactive towards the host DNA polymerase
What is the first step of the MOA of ganciclovir?

What occurs in CMV-infected cells?

What are the subsequent steps that form the final product?
Prodrug which is converted intracellularly to an active triphosphate form.

A viral protein kinase is responsible for the initial phosphorylation of ganciclovir and the subsequent phosphorylation steps to the active form.

same as acyclovir (?-look up)
What are the effects of ganciclovir on DNA polymerase?
competitive inhibition of viral DNA polymerase and direct incorporation into viral DNA which terminates DNA elongation
What is the active drug produced from famciclovir?
What are the indications (4) for acyclovir?
Initial and recurrent mucosal and cutaneous HSV1/2 and VAV infections in immunocompromised pts;

severe initial genital herpes in immunocompetent pts;

initial and recurrent genital herpes in adults (PO);

Acute tx of herpes zoster in immunocompetent adults (PO)
How is the oral availability of Famciclovir different from the active drug penciclovir?

Where does the conversion of the prodrug form occur?
is well absorbed;

liver and gut wall
Famciclovir (and active drug) are indicated for...
acute treatment of herpes zoster, genital herpes in immunocompetent pts, and recurrent mucocutaneous HSV infections in HIV-infected pts
What is the active drug produced from Valacyclovir?
How is the oral availability different in valacyclovir compared to acyclovir?
PO availability increases 3-5x resulting in increased acyclovir concentrations
What are the indications for valacyclovir (and active drug form)?
acute tx of herpes zoster, genital herpes in immunocompetent pts, recurrent mucocutaneous HSV infections in HIV-infected pts
What is the major clinical uses of Foscarnet sodium?
CMV retinitis in AIDS pts, tx of acyclovir-resistant or ganciclovir-resistant mucocutaneous herpes virus infections in immunocompromised pts
What is the 3rd line tx for CMV retinitis in AIDS pts?
What are the two boxed warnings for Foscarnet?
renal dysfunction and seizures
What are the two boxed warnings for Cidofovir?
nephrotoxicity and neutropenia
What is the major risk factor for developing seizures when using foscarnet?
low serum calcium
Why does hypocalcemia occur when using foscarnet?

What are some symptoms?
chelation of divalent cations may cause the hypocalcemia;

perioral tingling, numbness/paresthesias in lower extremities and seizures
What precautions must be taken when giving Cidofovir to prevent nephrotoxicity?
give via a slow IV infusion with probenecid and IV saline prehydration
What are the major clinical uses of ophthalmic antiherpetic agents (Trifluridine)
Primary keratoconjunctviitis and recurrent epithelial keratitis due to HSV1/2, epithelial keratitis that has not repsonded to topical idoxuridine or when ocular toxicity or hypersensitivity to this drug occurs, and in kids over 6 for tx of corneal inflammation due to HSV
What are the major boxed warnings associated with abacavir?

Why is rechallenge contraindicated?
hypersensitivity reactions (fever, skin, rash, NVD, etc), lactic acidosis, severe hepatomegaly with steatosis;

severe outcomes (hypotension, hepatic failure and renal failure), anaphylaxis or death can occur
What are class sparing regimens/what is the idea behind it?
Idea is that if you use only 2 of the 3 classes of hte preferred regimen, you have 'spared' one class in this category and you can use the spared one in the next regimen because resistance wont have been developed
What are preferred regimens (definition)?
treatments that have been shown to have optimal and durable virologic efficacy, have favorable tolerability and toxicity profiels are easy to use
Why can viral load serve as a marker for improved clinical outcome due to ART?
trials have shown a significant association between a decrease in plasma viremia and improved clinical outcome
Viral load reduction to below limits of assay detection in an ART-naive pt usually occurs within the first _____ weeks of therapy.
What levels are generally very high in acute HIV infections?
You can dx an HIV infection even though there are no Abs formed against the virus in early infections by testing for...
What are the two major toxicities associated with didanosine?
pancreatitis and fatal lactic acidosis
Which drugs have significant DIs with didanosine and what occurs?

Ribavirin (increases intracellular levels of active metabolite of didanosine)

Tenofovir (increases didanosine levels)
Didanosine is formulated as a ________ bead that degrades in acid and needs to be taken on a......
delayed-release capsule/enteric coated;

Intrapartum IV zidovudine is recommended for all HIV-infected pregnant women regardless of.....
their antepartum regimen to reduce perinatal transmission of HIV
For women who are receiving a stavudine-containing antepartum regimen, this drug should be ______ during labor while IV zidovudine is being administered.
For women who have received antepartum ARV drugs but have suboptimal viral suppression near delivery, what is recommended?
If the confirmatory HIV test is positive in a women who had an unknown status at presentation of labor, what do you want to do?
give infant ARV drugs for 6 weeks
ART Regimen #1 contains what 2 classes of drugs?

What drugs were specified in the notes?

What class does this spare?
one NNRTI and two NRTI's;

efavirenz plus tenofovir/emtricitabine;

Tenofovir is a...... (ART drug class)......
nucleotide RTI
Emtricitabine is a ......(ART drug class).........
nucleoside RTI
ART regimen #4 contains which drug classes?

What drugs were specified in the notes?

What classes does this spare?
INSTI plus 2 NRTIs;

Raltegravir plus tenofovir/emtricitabine;

In boosted regimens, Ritonavir is used at a lower dose that is not antiretroviral but is at a level that does what? This is so that.....
inhibits the P450 system; it blocks the metabolism of another PI drug so the combined use results in a 20x increase in plasma levels
ART Regimens #2 and #3 contain which drug classes?

Which 2 regimens were listed in the notes?

What classes were spared?
Ritonavir boosted PI plus NRTIs;

Ritonavir-boosted atazanavir plus tenofovir/emtricitabine;
Ritonavir-boosted darunavir plus tenofovir/emtricitabine;