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PHARM MIDTERM2 > ANTIRETROVIRAL DRUGS > Flashcards

ANTIRETROVIRAL DRUGS Flashcards

1
Q

HIV TRANSMISSION

DIAGNOSIS

A
  • Contact with body fluids (blood, semen, vaginal secretions, breast milk etc)
  • From mother to child transplacentally or perinatally in 30-50% cases
  • Transmission by saliva or droplets produced by coughing or sneezing is extremely unlikely

HIV DIAGNOSIS:

  • *• Antibody or antigen testing** (usually within few weeks of infections)
  • *• ELISA / Western Blot**

• New rapid tests (< 30 min) on blood & saliva available (usually confirmed by standard blood tests)

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2
Q

HIV TREATMENT

WHEN TO START?

WHAT CONDITIONS STRONGLY RECOMMEND STARTING?

A

Therapy is usually initiated when CD4+ cells ≤500 cellsmm3

Regardless of CD4 count, initiation of therapy is strongly recommended for individuals with the following conditions:

• 1) Pregnancy

  • 2) History of an AIDS-defining illness
  • 3) HIV-associated nephropathy (HIVAN)
  • 4) HIV/hepatitis B virus (HBV) co-infection
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3
Q

HIV PRIMARY TREATMENT GOALS:

A

Primary treatment goals:

• reduce HIV-related morbidity and prolong survival,

  • improve quality of life,
  • restore and preserve immunologic function,
  • maximally and durably suppress viral load, and

• prevent vertical HIV transmission

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4
Q

CURRENT HIV TREATMENTS

(DRUG CLASSES and examples)

A

1) Nucleoside/-tide Reverse Transcriptase Inhibitors (NRTIs)

  • Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine,Tenofovir, Zidovudine

2) Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)

  • Delavirdine, Efavirenz, Etravirine, Nevirapine

3) Protease Inhibitors

  • Atazanavir, Darunavir, Indinavir, Lopinavir, Nelfinavir, Ritonavir, Tipranavir

4) Entry Inhibitors

  • Enfuvirtide, Maraviroc

5) Integrase Inhibitor

Raltegravir

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5
Q

COMBINATOIN THERAPY/HAART

A

Current studies suggest a prevalence of HIV drug resistance of 6%–16% in antiretroviral treatment-naïve patients.

HAART (Highly Active Antiretroviral Therapy) / combination therapy was initiated in 1996

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6
Q

NUCLEOSIDE/TIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTI’S)

MOA

A

MOA

  • Analogs of native ribosides (lack 3’OH)
  • Phosphorylated by cellular enzymes and incorporated into viral DNA by reverse transcriptase

• Lack of 3’OH terminates DNA elongation
–> ie. they are competitive inhibitors of reverse

_transcriptase***_
• Most have activity against BOTH HIV-2 as well as HIV-1

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7
Q

NUCLEOSIDE/TIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTI’S)

RESISTANCE

PK

AE

A

RESISTANCE:

  • Emerges rapidly if used alone
  • Most common mutation at viral codon 184: lamivudine

(restores sensitivity to zidovudine & tenofovir)
• Cross-resistance between agents of same analog class

can occur

PK: dosage adjustements required with RENAL INSUFFICIENCY

AE:

  • If more than one NRTI given toxicities may overlap
  • AE mainly due to inhibition of ****_mitochondrial DNA polymerase_: _peripheral neuropathy, myopathy, lipoatrophy (localized loss of fat tissue) & lactic acidosis******_
  • Pancreatitis, myelosuppression & cardiomyopathy can also occur
  • Liver toxicity is rare but fatal (lactic acidosis, hepatomegaly with steatosis).
  • Zidovudine & stavudine may be particularly associated with dyslipidemia & insulin resistance
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8
Q

NRTI’S

DRUG INTERACTIONS

A

T, increases D (Titties increase Dick), when coadministered

—> therefore must decrease D dose (don’t let as many dicks in the bar)

• Didanosine & tenofovir

  • Tenofovir increases plasma didanosine levels ~60%.
  • Doses of didanosine have to be reduced.

• NRTIs are not generally metabolized by cytochrome enzymes

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9
Q

ZIDOVUDINE

A

NRTI

ZIDOVUDINE –> causes BONE MARROW SUPPRESSION –> causes bone marrow to “ZZZZZZZ”

-is a nucleoSIDE analog

PK: oral, penetrates the BBB well

–> dosage adjustement required in patients with CIRRHOSIS

AE:

  • ***BONE MARROW SUPPRESSION*** (neutropenia, anemia)
  • GI INTOLERANCE, headaches, insomnia

CONTRAINDICATIONS:

  • Toxicity potentiated by coadmin. of probenecid, acetaminophen, lorazepam, indomethacin & cimetidine.
  • Stavudine & ribavirin activated by same pathways (might reduce active levels of zidovudine)
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10
Q

STAVUDINE

A

NRTI

STAVUDINE –> STAB U DINING –> stabs both the Boy (beta) and Girl (gamma) DNA (dinner) polymerases

Strong inhibitor of beta and gamma DNA polymerases (high affinity for mitochondrial DNA polymerase, which can lead to toxicity) –> can cause PERIPHERAL NEUROPATHY (b/c just got stabbed, as well as MUSCLE BREAKDOWN –> therefore LACTIC ACIDOSIS

Nucleoside Analog = Thymidine

Pharmacokinetics

  • Oral
  • Dosage adjustment required in renal insufficiency

AE: PERIPHERAL NEUROAPTHY, LACTIC ACIDOSIS

–> HYPERLIPIDEMIA, NEUROMUSCULAR WEAKNESS

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11
Q

DIDANOSINE

A

NRTI

DIDANOSINE = DI DAN SIGN –> smart drug because take in FASTING state (acid labile) and combined with an ANTACID –> but DAN PAN DAN –> look out for PANCREATITIS –> don’t give it to somebody who already has pancreas problems!!!!!!

NucleoSIDE Analog –> Adenosine

Pharmacokinetics

• Absorption best if taken in fasting state (ACID LABILE) or

combined with antacid

  • Penetrates into CSF
  • Dosage adjustment required in renal insufficiency

Adverse Effects

High affinity for mitochondrial DNA polymerase

  • _Pancreatitis***_ (esp. alcoholics and patients with hypertriglyceridemia)
  • Peripheral neuropathy, diarrhea, hepatic dysfunction
  • CNS effects

NOTE IF PATIENT ALREADY HAS PANCREAS PROBLEMS, THIS DRUG IS CONTRAINDICATED!!!

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12
Q

TENOFOVIR

A

NRTI

TENOFOVIR –> is 10/10 –> IS THE PREFERRED NRTI IN CURRENT REGIMENS!!

–> Remember TEN TITTIES –> raises DICKS (didanosine)

_**One of preferred NRTIs in currently recommended_ _regimens**_

Nucleotide Analog –> Adenosine

Fixed-Dose Combinations Available

  • *• Tenofovir + emtricitabine**
  • *• Tenofovir + emtricitabine + efavirenz**

Pharmacokinetics

  • Should be _taken with food to increase bioavailability***_
  • Long t1/2 (can dose once daily)

Adverse Effects

• GI (nausea, diarrhea, vomiting, flatulence)

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13
Q

TENOFOVIR

CONTRAINDICATIONS

A

NRTI

REMEMBER: TENOFOVIR (Ten TITTIES) raises DICKS, but it DECREASES AT AZZZZ

  • Serum creatinine monitored with renal insufficiency
  • Only NRTI with sig. drug interactions
  • 1) increases DIDANOSINE concentrations and dosage reductions are usually required****
  • 2) Decreases concentrations of atazanavir.
    • Atazanavir can be ‘boosted’ with ritonavir
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14
Q

LAMIVUDINE

A

LAMIVUDINE –> LAME DINING –> does NOT have many AE, does not affect mitochondrial DNA synthesis, or bone marrow precursor cells

_****DOES NOT affect mitochondrial DNA synthesis or bone marrow precursor cells****_

Nucleoside Analog –> Cytosine

Resistance

• High level resistance occurs with single amino acid substitutions

Pharmacokinetics

• Dosage adjustment required with renal insufficiency

Adverse effects (very few!!!)

• Few significant (headache, dry mouth)

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15
Q

EMTRICITABINE

A

NRTI

EMTRICITABINE –> Where’s Seattle from? “Emmm.. Tricity? obivously.. EM-TRICITY –> SEATTLE –> HYPERPIGMENTATION of PALMS + SOLES b/c WALKING (soles) to their local starbucks and holding onto the coffee (palms) –> is one of the preferred NRTIs in currently recommended regimens

Structural relative of lamivudine

One of preferred NRTIs in currently recommended regimens

Nucleoside Analog –> Cytosine

Pharmacokinetics

Once-a-day administration

AE: ***_HYPERPIGMENTATION OF PALMS + SOLES***_ (occurs most frequently in dark-skinned people)

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16
Q

ABACAVIR

A

NRTI

ABACAVIR –> think of ABACADABRA!!! –> POOF all of a sudden get a quick hypersensitivity reaciton –> sensitized inidivuals should never be rechallenged

–> is a GUANISINE ANOLOG (guanisine for GENIE)

Nucleotide Analog –> Guanosine

Resistance

• HIV resistance requires several mutations and tends to develop slowly.

Adverse Effects

  • GI, headache, dizziness
  • 5% - ***_‘hypersensitivity’ reaction****_ (one or more of rash, GI, malaise, respiratory distress).
  • Sensitized individuals should NEVER be rechallenged (can be genetically screened)
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17
Q

NNRTIs

MOA

A

NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS

MOA (only works on HIV-1, NOT on HIV-2)

  • Highly selective, noncompetitive inhibitors of HIV-1 RT
  • Bind at a distinct site away from active site (NNRTI pocket)
  • All NNRTI’s bind within the same pocket
  • All result in inhibition of RNA- and DNA-dependent DNA polymerase
  • DO NOT REQUIRE PHOSPHORYLATION BY CELLULAR ENZYMES
  • Lack in vitro activity against HIV-2
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18
Q

NNRTIs

Advantages + Disadvantages

AEs

A

Advantages

  • Lack of effect on host blood-forming elements
  • Lack of cross resistance with NRTIs (binding sites are distinct)

Disadvantages

  • Cross-resistance with NNRTIs (ie with itself)
  • Drug interactions
  • High incidence of hypersensitivity reactions (eg, rash)

AE:

  • 1) *****_Skin rash (including Stevens-Johnson syndrome)*****_
  • GI intolerance
  • All are CYP3A4 substrates and can act as inducers, inhibitors or both of CYPs
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19
Q

NEVIRAPINE

PK + AE

A

NEVER A PINE –> is an NNRTI –> can never cut down a pine right away –> need 14 day titration period to get sapp out, at half dose? –> if not syrup can be sour and can cuase potential severe HEPATOTOXICITY + RASH (from pine needles)

Pharmacokinetics

• Excreted mainly in urine as metabolites (CYP 3A4 & CYP 2B6)

Adverse Effects

  • Potential severe hepatotoxicity (don’t use in women with CD4+ counts >250 cells/mm3 & men >400 cells/mm3)
  • Rash (16%), dermatologic effects (Stevens-Johnson syndrome & toxic epidermal necrolysis)
  • 14 day titration period at 1⁄2 dose is mandatory to reduce risk of serious epidermal reactions
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20
Q

NEVIRAPINE

CONTRAINDICATIONS

RESISTANCE

A

NEVER-A-PINE –> contraindicated in most popular places = CYP3A4 –> it INDUCES A RIOT b/c people want those trees to still stand –> INDUCES THE METABOLISM OF PROTEASE INHIBS

Contraindications

  • Inducer of CYP 3A4
  • Increases metabolism of PI’s (no dosage adjustment necessary), oral contraceptives, ketoconazole, methadone, metronidazole, quinidine, theophylline & warfarin

Resistance

• Target site of nevirapine is HIV-1 specific & not essential to enzyme (reverse transcriptase), thus mutations and resistance can develop rapidly

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21
Q

DELAVIRDINE

CLINICAL APPLICATIONS

PHARMACOKINETICS

AEs

A

DEL-A-VIRDINE –> DELL –> think of DELL COMPUTERS –> not used as much anymore because they have short half lives –> RASH = #1 ADVERSE EFFECT, IF ASK RASH IT WILL BE ABOUT DELL COMPUTERS –> because people putting them togetehr exposed to so many chemicals –> is also TERATOGENIC (contraindicated in pregnancy)

Clinical Applications

• Not as widely used as other NNRTIs due to short t1/2

Pharmacokinetics

• Well absorbed orally (especially at pH <2; antacids, H2

blockers etc may decrease absorption)

  • Excreted mainly in urine as metabolites (CYP 3A4 & 2D6)
  • Non-linear PK (t1/2 increases with increasing doses)

Adverse Effects

  • Rash (18-36%), ****Stevens-Johnson syndrome & toxic epidermal necrolysis
  • Fever, headache & depression also common
  • Teratogenic
22
Q

DELAVIRDINE

A

DELL COMPUTERS –> won’t let you do ANYTHING –> is an INHIBITOR

Contraindications

  • Inhibitor of and substrate of CYP3A4
  • CYP 3A4 inducers (eg, rifampin, phenytoin) may decrease

delavirdine concentrations

• Pregnancy (Cat C)

Resistance

• Target site of delavirdine is HIV-1 specific & not essential to enzyme (reverse transcriptase) therefore resistance develops rapidly

23
Q

ETRAVIRINE

clinical applications

PK

A

ETRAVIRINE –> see the E think EXPERIENCED PATIENTS

Clinical Applications

  • Approved for use in treatment-experienced patients
  • May be effective against HIV strains resistant to first-generation NNRTIs

Pharmacokinetics

  • Metabolized by CYP 3A4, 2C9 and 2C19
  • Metabolites have ~10% HIV activity of parent compound
24
Q

ETRAVIRINE

ADVERSE EFFECTS

CONTRAINDICATIONS

A

ETRAVIRINE –> think EXPERIENCED PATIENTS and also think ENZYME ELEVATION –> TRANSAMINASE ELEVATIONS!!!

Adverse Effects

  • Rash (normally resolves within 1-2 weeks), nausea, diarrhea
  • Transaminase elevations (esp. in patients co-infected with hepatitis)

Contraindications

  • CYP 3A4 inducer
  • CYP 2C9 and 2C19 inhibitor
  • Some interactions are difficult to predict
25
Q

EFAVIRENZ (not ETRAVINE)

CLINICAL APPLICATIONS

PHARMACOKINETICS

A
  • ********_Preferred NNRTI on DHHS guidelines*********** EFAVIRENZ DOES ERRRYTHINGGGGG B/C DRUG GOES ALL THE WAY TO THE END OF THE ALPHABET (Z)_
  • Results in increased CD4+ counts & decreased viral load

Pharmacokinetics

  • Oral
  • t1/2 >40h _(once-a-day dosing)*****_
  • Extensively metabolized to inactive products
26
Q

ETRAVIRENZ

AE

Contraindications

A

EFAVIRENZ –> it ZZZZZZZ’S –> dizziness, vivid DREAMZZZZZZ

DON’T GIVE TO PZYCHHOOOOOSSSS

Adverse Effects

  • 1) Mostly CNS (50%) (dizziness, headache, vivid dreams, loss of concentration) – resolve after few weeks.
  • 2) Rash (25%)
  • 3) Increased triglycerides, HDL and total cholesterol (lipid levels must be monitored at beginning of and during therapy)

Contraindications

  • Potent inducer of CYP P450 enzymes.
  • Pregnancy (D) (can be used after 1st trimester if considered best choice)
27
Q

PROTEASE INHIBITORS

A

MOA:

  • Reversible inhibitors of HIV aspartyl protease (enzyme responsible for cleavage of viral polyprotein into RT, protease & integrase)
  • Protease inhibition prevents virus maturation & results in production of non-infectious virions
  • DO NOT REQUIRE INTRACELLULAR ACTIVATION
  • Active against both HIV-1 and HIV-2
28
Q

PROTEASE INHIBITORS

PK

A

Pharmacokinetics

  • Poor oral bioavailability
  • High-fat meals can increase (nelfinavir) or decrease (indinavir) bioavailability
  • Substrates for CYP 3A4
  • Substrates for P-glycoprotein pump
  • Bound to plasma proteins (a1-acid glycoprotein which can increase in response to trauma & surgery)
29
Q

PROTEASE INHIBITORS

AE

A

PROTEASE INHIBS —> MAKE YOU A PORKER!!!! —> FUCKS WITH LIPID METABOLISM –> FAT REDISTRIBUTION + ACCUMULATION

Adverse Effects

  • Parathesias, nausea, vomiting, diarrhea
  • Disturbances in lipid metabolism (diabetes, hypertriglyceridemia, hypercholesterolemia)
  • Chronic admin –> _*****fat redistribution & accumulation*****_ resulting in central obesity, dorsocervical fat enlargement, peripheral & facial wasting, breast enlargement and a cushingoid appearance
  • Atazanavir has less side effects than other PI’s
30
Q

PROTEASE INHIBITORS

DRUG INTERACTIONS

A

• Potent inhibitors and substrates of CYP isoforms

eg, rhabdomyolysis (simvastatin or lovastatin),

excessive sedation (midazolam or triazolam),

respiratory depression (fentanyl)

  • Warfarin, sildenafil & phenytoin require dosage adjustments
  • Rifampin & St.Johns Wort are contraindicated

RESISTANCE

• Accumulation of stepwise mutations of protease gene. Can lead to high levels of resistance.

31
Q

RITONAVIR

A

PROTEASE INHIBITOR

RITONAVIR –> RIT –> RAMPS UP IE ENHANCER/BOOSTER OF OTHER PI’S d/t INHIBITION OF CYP3A4

CLINICAL APPLICATION:

– enhancer/booster of other PIs

-potent INHIBITOR of CYP3A4

CONTRINDICATIONS:

-numerous d/t inhibition of CYP

32
Q

ATAZANAVIR

A

ATAZANAVIR –> ATAZMANIAN DEVIL –> can’t give with PPI’s b/c it inhibits them (give 12 hours apart from PPIs) –> thrives in the acidic environment (that tazmanian devil) –> go home and watch 1 CARTOON A DAY –> IS THE PREFERRED CARTOON TO WATCH, is the ONCE-DAILY PREFERED PI

–> is structurally unrealted to the others because is just a cartoon (not a human)

Clinical Application:

  • is a once-daily preferred PIs (as is Ritonavir)

PK:

-structurally UNRELATED to other PIs

–> is well absorbed with food, highly protein bound

CONTRAINDICATIONS:

  • metabolized by and inhibits CYP3A4
  • contraindicated with a proton pump inhibitor
  • administration must be >12 HOURS APART FROM H2 BLOCKERS + ANTACIDS

-less incidence of side-effects than other PIs

33
Q

DARUNAVIR

A

PROTEASE INHIBITOR

DA-RUN-AVIR –> think about running, in order to run well, need to absorb what you’re taking quickly, so is BEST ABSORBED WITH FOOD

  • inhibits HIV protease resistant to other PIs
  • well absorbed with FOOD
  • is metabolized by CYP3A4, but also INHIBITS it as well
34
Q

INDINAVIR

A

PROTEASE INHIBITOR

INDIAN-AVIR –> must be given with RITONAVIR b/c INDIANS AREN’T THAT STRONG

–> eat way too much INDIAN FOOD –> GET RENAL STONES!!!

  • is given with RITONAVIR
  • least protein bound (60%)

–> absorption DECREASED when taken with meals

-dosage should be REDUCED with hepatic insufficiency

AEs:

  • is well tolerated but can also get
  • NEPHROLITHIASIS + HYPERBILIRUBINEMIA (adequate hydration important)
35
Q

LOPINAVIR

A

PROTEASE INHIBITOR

LOPINAVIR –> LOW-PIN-AVIR –> can cause INSULIN RESISTANCE

–> is an INducer –> contains alcohol which makes you do things, therefore don’t give with disulfiram or metro)

–> warts are the size of PINS –> CYP INDUCER FOR ST. JOHNS WARTS

  • one of the PREFERRED Protease Inhibitors
  • is given with RITONAVIR
  • has poor intrinsic stability

CONTRAINDICATIONS:

–> is an ENZYME INDUCER, therefore St. Johns Wort should be avoided

-oral solution contains EtOH (avoid disulfiram or metronidazole)

36
Q

NELFINAVIR

A

PROTEASE INHIBITOR

NELFINAVIR –> NEW ELF –> is the best elf that santa has –> it is already working at maximum efficiency so cannot be boostd by RTV

  • CANNOT be boosted by Ritonavir
  • metabolized by SEVERAL CYPs

–> major metabolite (CYP2C19) has antiviral actiivity equal to parent compound

CONTRAINDICATIONS: NUMEROUS (d/t inhibition of CYP)

AE:

-diarrhea (controlled by loperamide), nausea, flatulence

37
Q

TIPRANAVIR

A

PROTEASE INHIBITOR (don’t confuse with DARUNAVIR which is well-absorbed w food)

TIPRANOVIR –> if run on TIPTOES –> will make your head go crazy –> INTRACRANIAL HEMORRHAGE –> can also cause FATAL HEPATITIS –> can feel the TIP of your liver while you’re RUNNING (can feel the stich with your right hand)

  • inhibits HIV protease resistant to other PIs
  • twice-daily should be given with RITONAVIR
  • is well absorbed with food
  • is an INDUCER of CYP P450

AES:

1) SEVERE + FATAL HEPATITIS
2) FATAL + NONFATAL INTRACRANIAL HEMORRHAGES

38
Q

ENTRY/FUSION INHIBITORS

A

FUSION INHIBITOR

1) ENFUVIRTIDE

ENTRY INHIBITOR

1) MARAVIROC

39
Q

ENFUVIRTIDE

A

FUSION INHIBITOR

ENFUVIRTIDE –> like the thing tries to enter but it hits the cell and hits the tide and bounces back, ie it is a FUSION INHIBITOR –> is structurally –> when do u see the tide? when you’re 41 years old, able to afford a YACHT —> acts like a gp41

  • First approved drug that inhibits viral fusion
  • Approved for use in treatment-experienced adults with evidence of HIV replication

• No activity against HIV-2

-most common adverse effect = _PAIN AT INJECTION SITE!!! –> ENFU as in EFF YOU!!!!_

MOA

  • Structurally similar to gp41 (HIV protein mediates membrane fusion)
  • Binds to gp41 subunit of the viral envelope glycoprotein, preventing ability of virion to fuse cell membrane

PK: parenteral administration only

AE:

  • Injection-related (3% discontinue)
  • Hypersensitivity reactions & eosinophilia rarely
  • No drug interactions with other antiretrovirals have been noted
40
Q

MARAVIROC

A

ENTRY INHIBITOR

MARAVIROC —> think MARRY –> ENTRY INTO MAIRRAGE/NEW PART IN YOUR LIFE –> CCR5 is the song that you play at your mairrage –> binds on surface of T cells/monocytes, inhibiting interaction with gp120.

MOA

  • Binds specifically and selectively to CCR5 (one of two coreceptors necessary for entrance of HIV into CD4+ cells)
  • Result in blocking HIV entry (only CCR5-tropic virus can be treated with maraviroc)

Pharmacokinetics

• Metabolized by CYP 3A4 (reduce dose when given with PIs)

AE’s:

–> well tolerated, risk of hepatotoxicity

41
Q

RALTEGRAVIR

A

INTEGRASE STRAND TRANSFER INHIBITOR (INSTI)

RALTEGRAVIR —> R GRAVE –> when you’re dying you start decomposing, start INTEGRATING into the soil –> this INHIBITS the INTEGRASE enzyme –> Leads to specific inhibition of the final step in integration of viral DNA into host cell DNA –> ie you’re put in grave and eveyrthign is allowed to occur but the final step of decomposition is inhibited

–> metabolized by UGT1A1-mediated glucuronidation ie think GUT (ugt mixed around)

–> note also that PPI’s INCREASE the concentration for when you’re decomposing

Clinical Applications

• In combination with other antiretrovirals, raltegravir is approved for treatment-experienced and treatment- naive patients with evidence of viral replication

MOA

  • Binds integrase (enzyme essential to the replication of both HIV-1 and HIV-2)
  • Leads to specific inhibition of the final step in integration of viral DNA into host cell DNA

Pharmacokinetics

• Metabolism via UGT1A1-mediated glucuronidation

AE:

  • Well tolerated (nausea, headache, diarrhea)
  • Can cause increases in creatine phosphokinase

Drug Interactions

  • Rifampin, tipranavir & efavirenz may decrease [raltegravir]
  • PPI’s may increase [raltegraivr]
42
Q

TREATMENT FOR NAIVE PATIENTS

A

Goals:

• Maximally & durably suppress viral load replication

• Restore & preserve immunologic function
• Reduce HIV-related morbidity & mortality
• INCREASE QUALITY OF LIFE

43
Q

WHICH REGIMINS TO START FOR NAIVE PATIENT?

A

Start with one of the following regimens:
(1) NNRTI & 2 x NRTI

(2) PI (preferably boosted with ritonavir) & 2 x NRTI
(3) INSTI & 2 x NRTI

44
Q

FACTORS TO CONSIDER WHEN SELECTING AN INTIAL REGIMEN IN A NAIVE PATIENT

A

Factors to consider when selecting an initial regimen:

  • Comorbid conditions
  • Potential adverse drug effects
  • Potential drug interactions
  • Pregnancy or pregnancy potential
  • Results of genotypic drug resistance testing
  • Patient adherence potential
  • Convenience
45
Q

SELECTION IS BASED ON:

A

Selection is based on:

  • Avoiding the use of 2 agents of the same nucleotide analog
  • Avoiding overlapping toxicities and genotypic and phenotypic characteristics of the virus
  • Patient factors such as disease symptoms and concurrent illnesses
  • Impact of drug interactions; and
  • Ease of adherence to a frequently complex administration regimen
46
Q

CURRENT RECOMMENDATIONS FOR TREATMENT OF NAIVE PATIENTS:

A
47
Q

CURRENT REGIMEN FOR PREGNANT PATIENTS:

A

1) RITONAVIR-BOOSTED LOPINAVIR (twice daily)

AND

2) ZIDOVUDINE/LAMIVUDINE

48
Q

CURRENT RECOMMENDATIONS FOR INFANT BORN TO HIV INFECTED MOTHER

A

1) ZIDOVUDINE (start immediately after birth and administer for 6 weeks)

49
Q

HIV PROPHYLAXIS following a NEEDLE STICK

A

Upon exposure to HIV, healthcare personnel should immediately receive a postexposure prophylaxis regimen containing at least 3 antiretroviral drugs

Preferred regimen:

1) Raltegravir + (Integrase inhibitor)

2) tenofovir + (NRTI)

3) emtricitabine (NRTI)

Regimen is given for 28 days and can be stopped if source is shown to be HIV-negative.

50
Q

HIV PROPHYLACTIC VACCINES

recommended?

contraindicated?

A

• 1) Streptococcus pneumoniae

  • 2) Hepatitis A
  • 3) Hepatitis B and
  • 4) Influenza

are generally recommended for all HIV-infected patients

CONTRAINDICATED:

Live vaccines eg,

_• MMR
• Varicella and_

• Zoster

Other vaccines may be administered without regard to the patient’s CD4+

PHARM MIDTERM2 (18 decks)

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