HIV Therapy Flashcards
when is highly active antiretroviral therapy (HAART) initiated?
- AIDS-defining illness
- low CD4 cell counts (<500 cells/mm3)
- high viral load
HAART regimen
3 drugs to prevent resistance
- 2 NRTIs plus…
- 1 NNRTI or 1 protease inhibitor or 1 integrase inhibitor
protease inhibitors
“-navir”
- Atazanavir
- Darunavir
- Fosamprenavir
- Indinavir
- Lopinavir
- Ritonavir
- Saquinavir
protease inhibitors
mechanism
- 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)
protease inhibitors
toxicity
- hyperglycemia
- GI intolerance (nausea, diarrhea)
- lipodystrophy
- indinavir
- nephropathy
- hematuria
NRTIs
- Abacavir (ABC)
- Didanosine (ddl)
- Emtricitabine (FTC)
- Lamivudine (3TC)
- Stavudine (d4T)
- Tenofovir (TDF)
- Zidovudine (ZDV, formerly AZT)
NRTIs
mechanism
- 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)
NRTIs
toxicity
- bone marrow suppression
- reversed w/ G-CSF & erythropoietin
- peripheral neuropathy
- lactic acidosis (nucleosides)
- rash (non-nucleosides)
- anemia (ZDV)
- pancreatitis (didanosine)
NNRTIs
- Efavirenz
- Nevirapine
- Delavirdine
NNRTIs
mechanism
- bind to reverse transcriptase at site different from NRTIs
- do not require phosphorylation to be active or compete w/ nucleotides
NNRTIs
toxicity
- rash & hepatotoxicity
- efavirenz - vivid dreams & CNS symptoms
- contraindicated in pregnancy: delavirdine & efavirenz
Integrase inhibitors
Raltegravir
Integrase inhibitors
mechanism
- inhibits HIV genome integration into host cell chromosome
- reversibly inhibits HIV integrase
intregrase inhibitors
toxicity
hypercholesterolemia
Fusion inhibitors
- Enfuvirtide
- Marviroc
Fusion inhibitors
mechanism
-
Enfuvirtide
- binds gp41
- inhibits viral entry
-
Maraviroc
- binds CCR5 on surface of Tcells/monocytes
- inhibits interaction w/ gp120
Fusion inhibitors
toxicity
skin rxn at injection sites
interferons
mechanism
- glycoproteins normally synthesized by virus-infected cells
- wide range of antiviral & antitumoral properties
interferons: clinical use
- IFN-α
- IFN-ß
- IFN-γ
-
IFN-α
- chronic HepB & C
- Kaposi sarcoma
- hairy cell leukemia
- condyloma acuminatum
- renal cell carcinoma
- malignant melanoma
-
IFN-ß
- multiple sclerosis
-
IFN-γ
- chronic granulomatous disease
interferons
toxicity
- neutropenia
- myopathy
antibiotics to avoid in pregnancy
SAFe Children Take Really Good Care
- Sulfonamides
- Aminoglycosides
- Fluoroquinolones
- Clarithromycin
- Tetracyclines
- Ribavirin (antiviral)
- Griseofulvin (antifungal)
- Chloramphenicol
antibiotics to avoid in pregnancy
sulfonamides
kernicterus
antibiotics to avoid in pregnancy
aminoglycosides
ototoxicity
antibiotics to avoid in pregnancy
fluoroquinolones
cartilage damage
