Pogue: Treatment of HIV and Opportunistic Infections Flashcards
HIV eradication:
When are CD4 cells infected?
How long does it persist?
Complete eradication of HIV is currently not possible:
Pool of infected CD4 cells established during early stages of infection
Persists with a long half-life even with prolonged suppression of plasma viremia
JJ is a 62 y/o male with a nursing home associated UTI. What organism would NOT need empiric coverage? – A) Pseudomonas – B) E.coli – C) Enterobacter spp. – D) Clostridial spp.
D) Clostridial spp.
PO is a 31 y/o male with recent HAP who
received 14 days vanco/cefepime. He is now
presenting with diarrhea (1.5 L/day), abdominal
pain, leukocytosis (WBC 43K), and fever. He is
diagnosed with severe c.diff. The treatment of
choice is
– A) IV vancomycin
– B) IV metronidazole
– C) PO vancomycin
– D) PO metronidazole
C) PO vancomycin
Which of the following conditions would we not treat asymptomatic bacteriuria? – A) pregnancy – B) renal transplant – C) high urine leukocyte esterase – D) neonates
high urine leukocyte esterase
Which of the following is false regarding
treatment of gonorrhea
– A) disseminated infection needs to be ruled out
– B) treat chlamydia regardless of whether detected
– C) sexual partners should be treated
– D) the drug of choice is a fluoroquinolone
D) the drug of choice is a fluoroquinolone
Optimal treatment is:
Optimal treatment is dynamic: routinely check to see preferred regimen (always changing)
Treatment Goals:
Reduce HIV-related morbidity and prolong survival
Improve quality of life
Restore and preserve immunologic function
Suppress viral load
May be difficult to achieve maximal suppression in some cases due to pre-existing resistance mutations
Prevent HIV transmission
Current Therapy should contain how many drugs?
Should contain at least 2 (preferably 3) active drugs from multiple drug classes (avoid resistance)
Recommendations for When to Treat
Pt has: CD4 <: First time recommended in: Pregnant women: Nephropathy: Co-infected with:
- Patient has an AIDS defining illness
- Patient has CD4 500
o Note: this may change soon to treat everyone early (evidence shows it lowers transmission rates)
- Pregnant women (regardless of CD4)
- Patient has HIV-associated nephropathy (regardless of CD4)
- Patient is co-infected with HBV and undergoing treatment (regardless of CD4)
Importance of Educating Patient:
COMPLIANCE: need to be highly compliant in order to ensure effectiveness (otherwise, resistance can develop quickly); if it is unclear if a patient will be compliant, need to delay treatment
6 Classes of HIV Drugs:
- Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)
- Nonnucleoside RT inhibitors (NNRTIs)
- Protease Inhibitors (PIs)
- Fusion Inhibitors (FIs)
- CCR5 Antagonists
- Integrase Inhibitors
What do HIV treatment regimens consist of?
Generally 2 NRTI backbone, PLUS one or more of the following:
One NNRTI
One boosted PI
Raltegravir (integrase inhibitor)
Considerations in Decision:
o Co-morbidities o Adverse drug reactions o Potential DDIs o Pregnancy/pregnancy potential o Some drug-specific concerns o Adherence issues
NNRTI Based Regimens
What does the therapy consist of?
One NNRTI + dual NRTI therapy
NNRTI Based Regimens
One NNRTI + dual NRTI therapy
Alternative NNRTI During Pregnancy:
Others:
Alternative During Pregnancy: Nevirapine
Others:
Delavirdine
Ertavirine
NNRTI Based Regimens
One NNRTI + dual NRTI therapy
What is the preferred NNRTI?
Except:
Efavirenz (preferred NNRTI): except during pregnancy or in patients with high pregnancy potential
NNRTI Class Characteristics
MOA:
Resistance:
MOA: non-competitive inhibitors of reverse transcriptase
Resistance: if it develops, is conferred to the entire class (can even occur in treatment naïve patients)
NNRTI Class Characteristics
Half-life:
Effect on dosing:
Long-Half Life: can be good (less frequent dosing) or bad (if you forget a dose, low levels remain in system for longer periods of time, increasing risk for resistance development)
Efavirenz
Adverse Effects: (3)
Does it affect adherence?
CNS or psychiatric symptoms: up to half of patients; usually doesn’t affect adherence
Teratogenic: neural tube defects (avoid in early pregnancy)
Rash or SJS
Atripla consists of: (3)
Atripla: entire regimen in one pill taken once daily
Efavirenz + tenofovir + emtricitabine
Nevirapine
Adverse Effects: (2)
Recommendation:
Hepatotoxicity: usually occurring early in treatment and seen with HIGHER CD4 counts
- Recommendation: do not initiate in women with CD4 >250; men >400
Skin Rash: in roughly half of patients; may present as SJS or with flu-like symptoms
NNRTI Based Regimens
General Advantages and Disadvantages:
Advantages:
o Save PI for future use
o Long-half lives
Disadvantages:
o Low genetic barrier to resistance (making compliance extremely important)
PI Based Regimens consist of:
One PI (boosted or unboosted) with dual NRTI therapy
Preferred PIs: (4)
Atazanavir + ritonavir
Darunavir + ritonavir
Fosamprenavir + ritonavir
Lopinavir + ritonavir (co-formulation)
Alternative PIs: (3)
Atazanavir (unboosted)
Fosamprenavir (unboosted)
Saquinavir
PI Class Characteristics
MOA:
Binds to and inhibits HIV protease, which normally activates HIV polyproteins
PI Class Characteristics
Adverse Events: (5)
o *Dyslipidemia: except atazanavir (unless boosted)* o Fat maldistribution o Insulin resistance o GI effects o Skin rash
PI Class Characteristics
DDIs:
Inhibitors AND substrates of CYP 3A4: all to differing degrees.
Ritonavir
What is it itself?
Why is it added?
What is this effect known as?
A protease inhibitor itself
Added because it is a POTENT INHIBITOR of CYP3A4, allowing for decrease in dosing frequency and pill burden due to higher concentrations achieved
This is known as BOOSTING
PI Based Regimens
General Advantages
High genetic barrier to resistance
PI Based Regimens
General Disadvantages: (3)
Metabolic complications
GI side effects
CYP 3A4 issues
Backbone of all initial HAART regimens:
NRTIs
NRTIs
Preferred Regimen:
Tenofovir/emtricitabine (co-formulation)
