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
antibiotics to avoid in pregnancy
clarithromycin
embryotoxic
antibiotics to avoid in pregnancy
tetracyclines
- discolored teeth
- inhibition bone growth
antibiotics to avoid in pregnancy
ribavirin (antiviral)
teratogenic
antibiotics to avoid in pregnancy
griseofulvin (antifungal)
teratogenic
antibiotics to avoid in pregnancy
chloramphenicol
“gray baby” syndrome
