HIV Therapy Flashcards
1
Q
when is highly active antiretroviral therapy (HAART) initiated?
A
- AIDS-defining illness
- low CD4 cell counts (<500 cells/mm3)
- high viral load
2
Q
HAART regimen
A
3 drugs to prevent resistance
- 2 NRTIs plus…
- 1 NNRTI or 1 protease inhibitor or 1 integrase inhibitor
3
Q
protease inhibitors
A
“-navir”
- Atazanavir
- Darunavir
- Fosamprenavir
- Indinavir
- Lopinavir
- Ritonavir
- Saquinavir
4
Q
protease inhibitors
mechanism
A
- assembly of virions depends on HIV-1 protease (pol gene)
- cleaves polypeptide products of HIV mRNA
- **prevents maturation of new viruses **
- Ritonavir “boosts” other drug conc (inhibits CYP450)
5
Q
protease inhibitors
toxicity
A
- hyperglycemia
- GI intolerance (nausea, diarrhea)
- lipodystrophy
- indinavir
- nephropathy
- hematuria
6
Q
NRTIs
A
- Abacavir (ABC)
- Didanosine (ddl)
- Emtricitabine (FTC)
- Lamivudine (3TC)
- Stavudine (d4T)
- Tenofovir (TDF)
- Zidovudine (ZDV, formerly AZT)
7
Q
NRTIs
mechanism
A
- competitively inhibit nucleotide binding to reverse transcriptase & terminate DNA chain (lack a 3’ OH group)
- Tenofovir is a nucleoTide (rest are nucleosides)
- ZDV
- general prophylaxis
- pregnancy (decrease fetal transmission)
8
Q
NRTIs
toxicity
A
- bone marrow suppression
- reversed w/ G-CSF & erythropoietin
- peripheral neuropathy
- lactic acidosis (nucleosides)
- rash (non-nucleosides)
- anemia (ZDV)
- pancreatitis (didanosine)
9
Q
NNRTIs
A
- Efavirenz
- Nevirapine
- Delavirdine
10
Q
NNRTIs
mechanism
A
- bind to reverse transcriptase at site different from NRTIs
- do not require phosphorylation to be active or compete w/ nucleotides
11
Q
NNRTIs
toxicity
A
- rash & hepatotoxicity
- efavirenz - vivid dreams & CNS symptoms
- contraindicated in pregnancy: delavirdine & efavirenz
12
Q
Integrase inhibitors
A
Raltegravir
13
Q
Integrase inhibitors
mechanism
A
- inhibits HIV genome integration into host cell chromosome
- reversibly inhibits HIV integrase
14
Q
intregrase inhibitors
toxicity
A
hypercholesterolemia
15
Q
Fusion inhibitors
A
- Enfuvirtide
- Marviroc