HIV Drugs Flashcards
Principles of Antiretroviral Therapy (ART)
Does not eradicated/cure HIV, just limits damage
- decreases viral load over time
- restore and preserve immunological function
- reduces risk of transmission
Patient adherence is essential to effectiveness of treatment
Monotherapy is never recommended since it can increase chances of resistance
- usually consists of 2 NRTIs and one of the other classes (and possibly a CYP450 inhibitor)
How long does it usually take to achieve an undetectable viral load and to maintain it
6 months as long as treatment is taken every day
1-6 months = depress viral load to undetectable levels
6 months and on = maintain the undetectable viral load
What are the 5 classes of ART
NRTIs (nucleoside/tide reverse transcriptase inhibitors)
NNRTIs (nonnucleoside/tide reverse transcriptase inhibitors)
Pls (protease inhibitor)
Fls (fusion/entry inhibitors)
INSTIs (integrase inhibitors)
What two pharmacokinetic boosters are used to increase protease inhibitor levels?
Ritonavir
Cobicistat
Both inhibit CYP450 which increases apparent dose
What 3 ART treatments are recommended only for patients with HLA-B 5701 negative
Dolutegravir/abacavir/ lamivudine
Produces hyper sensitive in patients who are positive with this allele so cant give it to them
Specific clinical citations that eliminate certain ART therapies
Low CD4 count (<200 cells/mm3)
High HIV RNA load
Positive for 5701 allele
Co-infections
Pregnant populations
Options used to fix resistance or treatment failure
Boosted protease inhibitor
Add/change integrase inhibitors or NRTIs with longer half lives
NEVER give NNRTIs to failing treatments
Common clinical features of ART
Oral formation that has long enough half-life to permit daily dosing one time
Interact with CYP enzymes
Common ADRs
- headaches
- nausea
- vomiting
- diarrhea
- hepatotoxicty
- myelosuppression
NRTIs MOA
Analogs of nucleotides that prevent elongation of transcribe
DNA and competitively inhibit RT
Are used against HIV-1 and 2
3 steps
1) patient takes nucleotide/side analogs
2) analog is phosphorylated by cellular machinery into Triphosphate form
3) competitively inhibit RT and lead to premature chain termination
Are eliminated via renal system and have low plasma protein binding
Are NOT metabolized via CYP
- are cytotoxic if cant be eliminated or too strong of a dose*
What two NRTIs does lipoatrophy and insulin resistance occur most frequently
Stavudine and zidovudine
dont use with diabetes patients
NNRTIs MOA
Inhibit reverse transcriptase via binding to active site on RT and denaturing it. (negative allosteric modulation)
No chemical modification/activation
ONLY works on HIV-1 and high chance of resistance developing
- NEVER use as monotherapy and NEVER add to a failing therapy
- NEVER use a NNRTI if a previous NNRTI is resistant
Common ADRs with NNRTIs
Hyper sensitivity
Dizziness
Neuropsychiatric effects (efavirenz)
- Rilpivirine is recommenced for pregnant women*
Maraviroc MOA
Fusion inhibitor that functions by deleting the CCR5 gene in host cells preventing HIV attachment
- some strains use CXCR4 instead of CCR5 which then makes it immune to these drugs
Can cause severe heaptotoxicity and upper respiratory infections
Enfuvirtide MOA
Fusion inhibitor that inhibts gp41 protein binding.
- MUST be administered IM
Protease inhibitors
Are reversible inhibitors or HIV aspartyl protease
- prevents cleaving of HIV proteins
Recommended as first line with initial regiments in patients with uncertain HIV strain and/or have issues adhering to regiments
Two.most commonly used are
- atazanavir
- darunavir
What drugs cannot be used with Protease inhibitors
Statins = rhabdomyolysis
Midazolam and triazolam = sedation
Fentanyl = respiratory depression
Rifampin and St. John’s wort = treatment failure
Ritonavir and cobicistat
Ritonavir = elevates levels of second Protease inhibitor
Cobicistat = increases bioavailability of both atazanavir and darunavir
- increases serum creatinine levels via blocking kidney tubules
Integrase inhibitors (INSTIs)
raltegravir
Bictegravir
Elvitegravir
Dolutegravir
Prevent incorporation of HIV DNA into host genome and are often first line agents for newly diagnosed HIV patients
small chance at preventing infection all together if given very soon to first exposure
Requires cheating cations to prevent integrase activity, so DONT take with dairy and antacids
Integrase inhibitor ADRs and contraindications
Raltegravir = severe rhabdomyolysis (stop treating if occurs)
All others except raltegravir (teratogenic no pregnancy)
- raltegravir can only be used after 1st trimester though
Examples of OIs in HIV infections
Varicella zoster
Oral candidiasis
P. Jirovecii infections
Non-Hodgkin lymphoma
Cryptococcal Meningitis
Cytomegalovirus and mycobacteria infections
Immune reconstitution inflammatory syndrome
Patients experience inflammatory reactions that are associated with immune reconstitution
- often associated with rapid increases in CD4 counts
Treated with corticosteroids only in severe reactions
Continue ART unless in life-threatening reactions occur
Reconstitution syndrome
Seen in patients taking way too much ART or little control over the ART therapy
- it works really well in bring CD4 T-cell levels back to normal, but too well and too quick and induces an autoimmune reaction to the new CD4 T cells
