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)
