Term
|
Definition
| <200 cells/mm3 (Normal range is 1,000–1,600 cells/mm3), T-helper cells |
|
|
Term
|
Definition
• Bacterial infections, multiple or recurrent
• Candidiasis of bronchi, trachea, or lungs
• Candidiasis of esophagus
• Cervical cancer, invasive
• Coccidioidomycosis, disseminated or extrapulmonary
• Cryptococcosis, extrapulmonary
• Cryptosporidiosis, chronic intestinal (>1 month’s duration)
• Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age >1 month
• Cytomegalovirus retinitis (with loss of vision)
• Encephalopathy, HIV related
• Herpes simplex: chronic ulcers (>1 month’s duration) or bronchitis, pneumonitis, or esophagitis (onset at age >1 month)
• Histoplasmosis, disseminated or extrapulmonary
• Isosporiasis, chronic intestinal (>1 month’s duration)
• Kaposi sarcoma
• Lymphoid interstitial pneumonia or pulmonary lymphoid hyperplasia complex
• Lymphoma, Burkitt (or equivalent term)
• Lymphoma, immunoblastic (or equivalent term)
• Lymphoma, primary, of brain
• Mycobacterium avium complex or Mycobacterium kansasii, disseminated or extrapulmonary
• Mycobacterium tuberculosis of any site, pulmonary,†§ disseminated,† or extrapulmonary
• Mycobacterium, other species or unidentified species, disseminated† or extrapulmonary
• Pneumocystis jirovecii pneumonia
• Pneumonia, recurrent
• Progressive multifocal leukoencephalopathy
• Salmonella septicemia, recurrent
(if you have HIV and one of these it's aids) |
|
|
Term
|
Definition
| viral load (prognostic indicator), CD4 count (measure of immune system) |
|
|
Term
|
Definition
| primary infection, acute HIV syndrome, clinical latency/viral set point, consititutional symptoms, opportunistic disease |
|
|
Term
|
Definition
| fuse to host cell, HIB RNA reverse transcriptase integrase viral proteins enter cell, viral DNA formed, viral DNA integrated into host dna, new viral RNA used to make viral proteins, new viral RNA and proteins and a new HIV virus forms and is released |
|
|
Term
| Antiretroviral Therapeutic Classes |
|
Definition
• Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
• Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
• Protease inhibitors (PIs)
• Integrase inhibitors (INSTIs)
• Entry inhibitors |
|
|
Term
| NRTIs that resemble pyrimidines? |
|
Definition
| Pyrimidines Cytosine and Thymidine (Lamivudine, Zidovudine, Emticitabine, Stavudine) (letmeviewdine, zillowviewdine, emtciteanddine, starvendine) |
|
|
Term
| NRTIs that resemble purines? |
|
Definition
| purines- adenosine and guanosine (Didanosine, Abacavir, Tenofovir disoproxil) (did a nosy, abracadabra, tendtofavor, dishproxy) |
|
|
Term
MOA incorporated into the viral RNA, which causes nonsense mutations
• They block the RNA-dependent DNA polymerase-reverse transcriptase from synthesizing viral complementary DNA (cDNA) from HIV RNA
• Backbone of ART
• All drugs in this class are analogues of native nucleotides |
|
Definition
Nucleos(t)ide reverse transcriptase inhibitors (NRTIs) (Lamivudine (Epivir®, 3TC)/Emtricitabine (Emtriva®, FTC), Abacavir (Ziagen®, ABC), Tenofovir disoproxil fumarate (Viread®, TDF) and Tenofovir alafenamide (Vemlidy®, TAF), Zidovudine (Retrovir®, AZT), Stavudine and Didanosine)
(Lamivudine, Zidovudine, Emticitabine, Stavudine) (letmeviewdine, zillowviewdine, emtciteanddine, starvendine)
(Didanosine, Abacavir, Tenofovir disoproxil) (did a nosy, abracadabra, tendtofavor, dishproxy) |
|
|
Term
has ADE:
inhibition of mitochondrial DNA function and replication
• Class-wide warnings:
• Lactic acidosis (rare)
• Hepatic steatosis (rare)
• Peripheral neuropathy (didanosine)
• Lipodystrophy (stavudine) |
|
Definition
NRTIs (Lamivudine (Epivir®, 3TC)/Emtricitabine (Emtriva®, FTC), Abacavir (Ziagen®, ABC), Tenofovir disoproxil fumarate (Viread®, TDF) and Tenofovir alafenamide (Vemlidy®, TAF), Zidovudine (Retrovir®, AZT), Stavudine and Didanosine)
(Lamivudine, Zidovudine, Emticitabine, Stavudine) (letmeviewdine, zillowviewdine, emtciteanddine, starvendine)
(Didanosine, Abacavir, Tenofovir disoproxil) (did a nosy, abracadabra, tendtofavor, dishproxy) |
|
|
Term
| NRTIs associated with mitochondrial dysfunction |
|
Definition
• Didanosine (ddI) > stavudine (d4T) > zidovudine (ZDV) >> lamivudine/emtricitabine (3TC/FTC) = abacavir (ABC) = tenofovir
• LeastassociatedwithADEsresultingfrommitochondrial dysfunction:
• Lamivudine
• Emtricitabine
• Abacavir
• Tenofovir
• The risk with NRTIs used today is very minimal as didanosine and stavudine are no longer used in the U.S. |
|
|
Term
Current use: nearly the backbone of all currently recommended antiretroviral regimens
active against Hepatitis B, although they are not used routinely due to resistance developing
on therapy
• Caution: when discontinuing |
|
Definition
Lamivudine (Epivir®, 3TC) and Emtricitabine (Emtriva®, FTC)
• Emtricitabine is chemically related to lamivudine
• Never used together
• Caution: when discontinuing lamivudine or emtricitabine in patients co-infected with HBV because HBV rebound and worsening hepatitis can occur |
|
|
Term
has ADE:
• Very well tolerated
• Rare
• Headache • Nausea
• Fatigue |
|
Definition
|
|
Term
• Synthetic guanosine analogue
• Food: with or without food |
|
Definition
|
|
Term
has ADE:
• Most significant acute adverse effect is
hypersensitivity syndrome
• Manifestation:
• Fever, abdominal pain, and rash
• Starts within two weeks of starting
• Fatal when re-challenged
• Associated with the HLA-B*5701 allele (found via blood testing)
• 5–8% of white HIV-infected populations
• HLA-B*5701 testing required before starting |
|
Definition
|
|
Term
• Nucleotide adenosine 5’-monophosphate derivative
• Note: can be used for Hepatitis B
• Caution when discontinuing in patients co-infected with HBV because HBV rebound and worsening hepatitis can occur |
|
Definition
| Tenofovir disoproxil fumarate (Viread®, TDF) and Tenofovir alafenamide (Vemlidy®, TAF) |
|
|
Term
| Tenofovir disoproxil fumarate (Viread®, TDF) versus Tenofovir alafenamide (Vemlidy®, TAF) |
|
Definition
| TAF has not been shown to cause renal toxicities or decreased bone mineral density (and has greater antiviral activity) |
|
|
Term
• Thymidine analogue
• Current use: prevent maternal to child transmission (IV formulation)
• Food: can be given with or without |
|
Definition
| Zidovudine (Retrovir®, AZT) |
|
|
Term
|
Definition
• Notes: tenofovir-containing regimens have largely replaced zidovudine-containing regimens as the preferred first-line regimens
• Superior virologic outcomes
• Reduced drug resistance
• Less frequent dosing |
|
|
Term
has ADE:
peripheral neuropathy, lipodystrophy, pancreatitis, lactic acidosis, and hepatic steatosis |
|
Definition
|
|
Term
has ADE:
mitochondrial associated toxicities, pancreatitis, and peripheral neuropathy |
|
Definition
|
|
Term
| no longer used in US for ART |
|
Definition
|
|
Term
| Combinations of NRTI Drugs |
|
Definition
Combivir®
Zidovudine 300 mg + Lamivudine 150 mg
1 tablet PO Q 12h
Epzicom®
Abacavir 600 mg + Lamivudine 300 mg
1 tablet PO daily
Truvada®
Tenofovir disoproxil 300 mg + Emtricitabine 200 mg
1 tablet PO daily
Descovy®
Tenofivir alafenamide 25 mg + Emtricitabine 200 mg
1 tablet PO daily |
|
|
Term
| What is the advantage of tenofovir alafenamide over the older formulation tenofovir disoproxil fumarate? |
|
Definition
|
|
Term
• Mechanism of action:
• Non-competitive inhibitors of reverse transcriptase • Non-allosteric |
|
Definition
NNRTIs (Efavirenz (Sustiva®, EFV), Etravirine (Intelence®, ETV), Rilpivirine (Edurant®), Atripla, Complera®, Odefsey®, Juluca®, Nevirapine (Viramune®, NVP))
Effavirus, et'savirus, rilepriviknee, atriple, complement, odesey, juleyuca, neverpine |
|
|
Term
• Long half-lives
• Low levels of drug: double-edged sword
• Low barrier of resistance
• Single point mutations in RT can inactivate all members of this class (K103N)
• Except etravirine
• Hepatically metabolized
• Drug interactions!
• All are CYP450 substrates
• Some are also inhibitors/inducers |
|
Definition
NNRTIs (Efavirenz (Sustiva®, EFV), Etravirine (Intelence®, ETV), Rilpivirine (Edurant®), Atripla, Complera®, Odefsey®, Juluca®, Nevirapine (Viramune®, NVP))
Effavirus, et'savirus, rilepriviknee, atriple, complement, odesey, juleyuca, neverpine |
|
|
Term
• Current use: previous preferred agent for initial antiretroviral regimens now not as commonly used in the U.S.
• Food: taken on an empty stomach
• High fat meal increases bioavailability and toxicity
• Contraindicated: CYP3A4 substrates (i.e. carbamazepine,
posaconazole)
• Adverse effect: CNS adverse effects (vivid dreams, insomnia, dizziness, and difficult concentration) and teratogenicity
(neural tube defects)
• Teratogenicity: debatable |
|
Definition
| Efavirenz (Sustiva®, EFV) |
|
|
Term
• Current place in therapy: overcomes K103N mutation and therefore used for salvage therapy
• Drug-drug interaction: substrate and inducer of CYP3A4
• Ingestion without food decreases etravirine |
|
Definition
| Etravirine (Intelence®, ETV) |
|
|
Term
• Caution in hepatic dysfunction
• Note: not as potent as efavirenz, better adverse effect profile
• More failures when VL >100,000 (avoid) |
|
Definition
|
|
Term
• Drug-drug interactions:
• Metabolized by CYP3A4, 2C19, 1A2; moderate inducer of 2C19,
1A2, and 3A4
• Protease inhibitors and azole antifungals increase plasma levels
• Contraindicated with strong CYP3A4 inducers (carbamazepine, oxcarbazepine, phenytoin, phenobarbital, rifampin/rifapentine)
-needs acidic environment for absorption
• PPIs are contraindicated (avoid!)
• H2 receptor antagonists at least 12 hours before or 4 hours after
• Antacids at least 2 hours before or 4 hours after |
|
Definition
|
|
Term
|
Definition
Atripla®
Tenofovir 300 mg + Emtricitabine 200 mg + Efavirenz 600 mg
1 tablet PO daily on empty stomach
Complera®
Tenofovir 300 mg + Emtricitabine 200 mg + Rilpivirine 25 mg
1 tablet PO daily with a meal
Odefsey®
Tenofovir AF 25 mg + Emtricitabine 200 mg + Rilpivirine 25 mg
1 tablet PO daily with a meal
Juluca®
Rilpivirine 25 mg + Dolutegravir 50 mg
1 tablet PO daily with a meal |
|
|
Term
induces its own metabolism via CYP3A4
• Current place in therapy: has lost favor particularly to efavirenz largely because of inferior clinical effectiveness and problematic toxicities that include rash, Stevens-Johnson syndrome, and hepatic necrosis
• Adjustment: hepatic
• DDIs: avoid with strong CYP3A4 inhibitors
• Contraindications: elevated risk of liver damage
• Avoid in women with CD4 >250 cells/mm3 and men >400 cells/mm3 |
|
Definition
| Nevirapine (Viramune®, NVP)- NNRTI No Longer Used in the U.S. for ART |
|
|
Term
• Inhibitprotease,theenzymenecessaryfor cleavage of viral polyprotein precursors into individual functional proteins needed to make infectious HIV
• Inhibiting protease results in immature noninfectious particles
-shooting blanks |
|
Definition
Protease Inhibitors
1st class:
• Ritonavir (Norvir®, RTV)
• Indinavir (Crixivan®, IDV)
• Saquinavir (Invirase®, SQV) • Nelfinavir (Viracept®, NFV)
2nd class:
• Lopinavir/ritonavir (Kaletra®, LPV/r)
• Fosamprenavir (Lexiva®, f-APV)
• Tipranavir (Aptivus®, TPV)
3rd class:
• Atazanavir (Reyataz®, ATV)
• Darunavir (Prezista®, DRV) |
|
|
Term
has ADE:
- GI intolerance
• Nausea/vomiting/diarrhea
-Lipodystrophy
• Long-term complication that results from metabolic and morphologic abnormalities
• Morphologic include fat atrophy and fat deposition
-Lipid abnormalities (hypertriglyceridemia/cholesterolemia)
-Insulin resistance (hyperglycemia and type 2 diabetes)
• Mainly with first generation PIs
-Major drug interactions!
• All protease inhibitors inhibit/are substrates of CYP3A4
• Ritonavir is the most potent 3A4 inhibitor
• Avoid drugs that are major substrates of CYP3A4, due to extreme increases in drug levels with PIs (i.e., simvastatin, voriconazole, etc.)
• Lopinavir/ritonavir, ritonavir, and tipranavir also inhibit CYP 2D6
-Food affects bioavailability of most PIs |
|
Definition
| Protease Inhibitors (More Common With First Generation) |
|
|
Term
| highest risk for lipid abnormalities |
|
Definition
| • Lopinavir/ritonavir is the highest risk |
|
|
Term
| has lowest risk of lipid abnormalities |
|
Definition
| atazenavir unboosted (w/o ritonavir) |
|
|
Term
| First gen protease inhibitors |
|
Definition
• Ritonavir (Norvir®, RTV)- wroteonair
• Indinavir (Crixivan®, IDV)- indyonair
• Saquinavir (Invirase®, SQV)- sackhimonair
• Nelfinavir (Viracept®, NFV)- kneelfinonair |
|
|
Term
| second gen protease inhibitors |
|
Definition
• Lopinavir/ritonavir (Kaletra®, LPV/r)- looponair/wroteonair
• Fosamprenavir (Lexiva®, f-APV)- forsampleonair
• Tipranavir (Aptivus®, TPV)- tiprightonair |
|
|
Term
| third gen protease inhibitors |
|
Definition
• Atazanavir (Reyataz®, ATV)- atazonair
• Darunavir (Prezista®, DRV)- dareemonair |
|
|
Term
• Originally marketed as a stand-alone protease inhibitor
• Use in therapy: pharmacologic boosting agent to increase Cmax and AUC by inhibiting CYP metabolism of other PIs
• Increases bioavailability and increases the half-life
• Improves PI efficacy and decreases the occurrence of protease inhibitor resistance after virologic failure
• Leads to significant drug-drug interactions |
|
Definition
|
|
Term
Has ADE:
GI side effects, particularly diarrhea and nausea
• Typically at HIV dosing, not booster dosing |
|
Definition
|
|
Term
• Food: taken with food
• Adjustment: hepatic—use not recommended in mild-
severe impairment
• Drug interactions: substrate and inhibitor of CYP3A4
• Contraindicated with substrates of CYP3A4 (midazolam)
• Needs acidic environment for absorption
• Antacids 2 hours after or 1 hour before
• PPIs: omeprazole 20 mg daily max dose; must space out by 12 hours
• H2 antagonists must be spaced (at the same time or 10 hours after) |
|
Definition
| Atazanavir (Reyataz®, ATV) |
|
|
Term
has ADE:
nausea, indirect bilirubin elevations
(Gilbert Syndrome)
• Less effect on serum cholesterol and triglycerides than other PIs
• Note: usually active against HIV in patients who have failed other PIs (unique resistance mutation-I50L) |
|
Definition
| Atazanavir (Reyataz®, ATV) |
|
|
Term
• Activity against some PI-resistant viruses
• Drug interactions: substrate and inhibitor of CYP3A4
• Contraindicated with substrates of CYP3A4 (midazolam) |
|
Definition
| Darunavir (Prezista®, DRV) |
|
|
Term
Has ADE:
favorable lipid profile compared to other PIs |
|
Definition
| Darunavir (Prezista®, DRV) |
|
|
Term
• Only available as a co-formulation with ritonavir (same drug-drug interactions)
• First well tolerated boosted drug
• Food: with or without regard to food, solution should be taken with meals |
|
Definition
| Lopinavir/Ritonavir (Kaletra®, LPV/R) |
|
|
Term
has ADE:
gastrointestinal (diarrhea or loose stools, nausea, and, less commonly, vomiting); hypercholesterolemia; hypertriglyceridemia |
|
Definition
| Lopinavir/Ritonavir (Kaletra®, LPV/R) |
|
|
Term
• Non-peptidic protease inhibitor approved for use in treatment-experienced patients with resistance to multiple other PIs
• Used for salvage therapy
• Food: with high-fat meal
• Adjustment: hepatic |
|
Definition
| Tipranavir (Aptivus®, TPV) |
|
|
Term
has ADE:
severe hepatotoxicity and intracranial hemorrhage |
|
Definition
| Tipranavir (Aptivus®, TPV) |
|
|
Term
|
Definition
Boosting Agents:
• Both equally potent inhibitors of CYP3A4
• Cobicistat is more selective, specifically for CYP3A4
• No HIV activity
• Has no inducing properties
• Ritonavir affects additional CYP enzymes
• CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19
• These differences should be taken into consideration when altering a medication regimen |
|
|
Term
• Boosted atazanavir formulation in one pill
• Food: take with meals
• Note: must monitor CYP3A4 drug interactions
due to cobicistat + atazanavir
• Contraindicated: carbamazepine, phenytoin, phenobarbital, midazolam, rifampin, fluticasone, simvastatin, voriconazole |
|
Definition
| Atazanavir/Cobicistat (Evotaz®) |
|
|
Term
• Boosted darunavir formulation in one pill
• Food: take with meals
• Note: must monitor CYP3A4 drug interactions due to cobicistat + darunavir
• Contraindicated: carbamazepine, phenytoin, phenobarbital, midazolam, rifampin, fluticasone, simvastatin, voriconazole |
|
Definition
| Darunavir/Cobicistat (Prezcobix®) |
|
|
Term
|
Definition
| block the strand transfer of HIV cDNA to cellular DNA |
|
|
Term
| Integrase Inhibitors (INSTI) agents |
|
Definition
Raltegravir (Isentress®, RAL)- raltethegravy
Elvitegravir- elitegravy
Stribild®- scribbled
Genvoya®- geneva
Dolutegravir (Tivicay®, DTG)- dilutegravy
Bictegravir (Biktarvy®)- biteofgravy
Triumeq®- tryme
Juluca®- juleslucky |
|
|
Term
• First approved INSTI inhibitor
• Current place in therapy: use is declining due to...
• BID dosing
• Found to be inferior to dolutegravir at week 48 of therapy [SAILING Study]
• Food: can be given with or without
• Drug interactions: increase the dose (800 mg twice
daily) when concomitant with rifampin |
|
Definition
| Raltegravir (Isentress®, RAL) |
|
|
Term
|
Definition
| Raltegravir (Isentress®, RAL) |
|
|
Term
• Only comes in combination pills
Stribild® and Genvoya® |
|
Definition
|
|
Term
Has ADE:
well tolerated nausea and diarrhea |
|
Definition
|
|
Term
• Food: take with food
• Adjustment: renally adjusted
• Avoid initiating in patients with CrCl <70 mL/min
• Discontinue in patients with CrCl <50 mL/min
• Adjustment: CYP3A4 and CYP2D6 inhibitor
• Contains cobicistat: major 3A4 inhibitor |
|
Definition
| Stribild® (tenofovir DF/ emtricitabine/cobicistat/elvitegr avir) |
|
|
Term
“The new and improved Stribild®...”
• Food: take with food
• Adjustment: renal—avoid initiating with CrCl <30 mL/min
• Adjustment: CYP3A4 and CYP2D6 inhibitor
• Contains cobicistat: major 3A4 inhibitor |
|
Definition
| Genvoya® (tenofovir AF/ emtricitabine/cobicistat/ elvitegravir) |
|
|
Term
• Food: can be given with or without
• Current place in therapy: more potent than raltegravir and less
frequent dosing
• Adjustment: avoid in severe hepatic insufficiency
• Drug-drug interactions: CYP3A4, P-glycoprotein/ABCB1, UGT1A1, UGT1A3, UGT1A9, and inhibits OCT2
• Increase dose with CYP3A4 inducers carbamazepine, phenytoin, phenobarbital
• Maximum daily dose of metformin with dolutegravir is 1,000 mg given inhibition of OCT2 |
|
Definition
| Dolutegravir (Tivicay®, DTG) |
|
|
Term
• Adjustment: avoid in severe hepatic insufficiency and CrCl <30 mL/min
• Drug-drug interactions: substrate of CYP3A4, P-glycoprotein, and inhibits OCT2 and MATE1
• Strong inducers and inhibitors of CYP3A4 can affect bictegravir levels
• Contraindicated with dofetilide, rifampin, rifabutin, rifapentine
• Maximum daily dose of metformin with bictegravir is 1,000 mg given inhibition of OCT2
• Should be taken 2 hours before antacids containing aluminum and calcium and alongwith or 2 hours after aluminum and calcium containing supplements |
|
Definition
|
|
Term
| Combination With INSTI Inhibitors |
|
Definition
Stribild®
Tenofovir 300 mg + Emtricitabine 200 mg + Elvitegravir 150 mg + Cobicistat 150 mg
1 tablet PO daily with a meal
Genvoya®
Tenofovir AF 25 mg + Emtricitabine 200 mg + Elvitegravir 150 mg + Cobicistat 150 mg
1 tablet PO daily with a meal
Triumeq®
Abacavir 600 mg + Lamivudine 300 mg + Dolutegravir 50 mg
1 tablet PO daily
Juluca®
Rilpivirine 25 mg + Dolutegravir 50 mg
1 tablet PO daily with a meal
Biktarvy®
Bictegravir 50 mg + Emtricitabine 200 mg + Tenofovir AF 25 mg
1 tablet PO daily |
|
|
Term
• Not used commonly (reserved for resistant virus)
• HIV-1 surface glycoproteins gp120 and gp41 mediate viral binding to and membrane fusion with host target cells
• Binding gp120 to its primary receptor on the cell surface, CD4, is the first step leading to membrane fusion
• Causesaconstitutionalchange
• The gp41 forms a metastable conformation, which allows the N-terminus to penetrate the cell membrane |
|
Definition
|
|
Term
|
Definition
Enfuvirtide (Fuzeon®)- envyfortide
Maraviroc (Selzentry®)- marsonarock |
|
|
Term
• Current role in therapy: utilized only for salvage therapy in patients with resistant virus
• Adjustment: none
• Drug interactions: none
• Adverse effects: injection site reactions (>90%), nausea, diarrhea, fatigue, and insomnia |
|
Definition
|
|
Term
• First and only approved CCR5 antagonist
• MOA: allosteric inhibitor of the gp120-CCR5 interaction
• Blocks HIV attachment to target cells and thereby reduces viral replication
- Dose adjustment:
• Severe renal impairment
• Concomitant use of CYP3A4
• inhibitor/inducer with CrCl <30
- Major drug interactions:
• CYP 3A4 inhibitors: reduce dose
to 150 mg
• CYP 3A4 inducers: increase dose to 600 mg
• Note: all patients should be screened with the tropism test before starting
• Should not be used in patients with evidence of circulating CXCR4-using virus |
|
Definition
|
|
Term
| Recommended initiation of ART therapy |
|
Definition
| • All HIV-infected patients, regardless of CD4 count |
|
|
Term
|
Definition
• Prior to the start of ART therapy
• Prevents the risk of abacavir hypersensitivity reaction
• If the test is positive, should not receive abacavir |
|
|
Term
| Plasma Viral Load Monitoring |
|
Definition
• Viralloadmonitorisnecessarytoassessthe response to ART and durability of virologic suppression
• Goal:
• Ultimate at 16–24 weeks: <50 copies/mL • 4 weeks: one log reduction in viral load
• Viral loads should be measured
• Before the start of therapy
• 4–6 weeks later
• 4–8 week intervals until HIV RNA is no longer detectable |
|
|
Term
|
Definition
• Should be monitored every 3–6 months
• Patients with plasma virus loads less than 200 copies/mL and CD4 counts greater than 300 cells/mm3
• >97%chanceofmaintainingdurableCD4countsgreaterthan 200 cells/mm3 for 4 years
• Once ART is started
• Increase between 50 to 150 cells/mm3 in the first year
• Increase more to 50 to 100 cells/mm3 in the second year
• Starting when CD4 count is fall below 200 cells/mm3
• Few people actually have a CD4 count greater than 500 cells/mm3 after 4 years |
|
|
Term
| Recommended ART regimen in treatment naïve patients: |
|
Definition
• Two NRTIs + integrase inhibitor (INSTI-based regimen) • Recommendedasinitialtherapyinmostpatients
• Alternative (no longer first line)
• TwoNRTIs+boostedPI(PI-basedregimen)
• TwoNRTIs+oneNNRTI(NNRTI-basedregimen) |
|
|
Term
| deciding on a INSTI-based regimen in treatment naive pts |
|
Definition
• Dolutegravir/abacavir/lamivudine(Triumeq®:1tabletoncedaily)
• Elvitegravir/cobicistat/tenofovirAF/emtricitabine (Genvoya®: 1 tablet once daily)
• Raltegravir+tenofovir/emtricitabine(Truvada®) |
|
|
Term
| INSTI advantages vs disadvantages |
|
Definition
advantages:
• Virologic response noninferior to EFV
• Fewer drug-related adverse events
• Fewer drug-drug interactions than PI and NNRTI regimens (excluding Cobicistat containing products)
disadvantages:
• Lower genetic barrier to resistance than boosted PI regimens
• Increase in CK, myopathy, and rhabdomyolysis
• Cobicistat in Stribild/Genvoya interacts with CYP3A4 inducers, inhibitors and substrates |
|
|
Term
| PI advantages vs disadvantages |
|
Definition
advantages:
• Higher genetic barrier to resistance than NNRTIs and RAL
• PI resistance uncommon with failure while on first PI regimen
disadvantages:
and RAL
• PI resistance uncommon with failure while on first PI regimen
PI class
• Metabolic complications
• GI adverse effects
• CYP3A4 inhibitors and substrates, therefore potential for drug interactions |
|
|
Term
| NNRTI advantages vs disadvantages: |
|
Definition
advantages:
• Long half-lives (+/-)
disadvantages:
• Greater risk of resistance at the time of treatment failure with NNRTIs than PIs
• Potential for cross resistance
• Skin rash
• Potential for CYP450 drug interactions
• Transmitted resistance more common with NNRTIs than PIs |
|
|
Term
| Picking a combination of NRTIs to serve as backbone |
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Definition
- Preferred combinations:
• Emtricitabine and tenofovir AF (Descovy®)
-Alternative combinations:
• Emtricitabine and tenofovir disoproxil fumarate (Truvada®) • Abacavir and lamivudine (Epzicom®)
• Zidovudine and lamivudine (Combivir®) • Can be used if patient is pregnant |
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Term
| NRTI combo that Can be used if patient is pregnant |
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Definition
| Zidovudine and lamivudine (Combivir®) |
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Term
| Regimen for Virologically Suppressed Patients |
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Definition
• Juluca® (rilpivirine 25 mg + dolutegravir 50 mg)—“non- nuke” one pill once a day
• Only for patients who are virologically suppressed ≥6 months with no history of treatment failure or resistance to either rilpivirine or dolutegravir |
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Term
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Definition
• Metabolized by CYP3A4, 2C19, 1A2; moderate inducer of 2C19, 1A2, and 3A4
• Protease inhibitors and azole antifungals increase plasma rilpivirine levels
• Contraindicated with strong CYP3A4 inducers (carbamazepine, oxcarbazepine, phenytoin, phenobarbital, rifampin/rifapentine)
• Rilpivirine needs acidic environment for absorption
• PPIs are contraindicated(avoid!)
• H2 receptor antagonists at least 12 hours before or 4 hour safter rilpivirine
• Antacids at least 2 hours before or 4 hours after rilpivirine
• Maximum daily dose of metformin with dolutegravir is 1,000 mg, given inhibition of OCT2 |
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Term
| Plasma Viral Load Monitoring: Failure |
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Definition
• Marker usually greater than 1,000 HIV viral copies shows failure
• Inabilitytoachieveaundetectableviralload after 24 weeks of therapy
• If viral load is detectable there is a strong possibility of resistance
• HIVdrugresistancetesting
• Determining HIV co-receptor usage (tropism test for maraviroc)
• Viral loads are needed greater than 1,000 copies/mL to accurately perform co-receptor usage testing |
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