retroviral agents

• NNRTIs


  • bind directly to HIV-1 reverse transcriptase → resulting in allosteric inhibition of RNA & DNA-dependent polymerase
• 1st Generation NNRTIs



  • Delavirdine
  • Efavirenz
• 2nd Generation NNRTIs


  • Etravirine
  • Nevirapine
  • Rilpivirine
• Delavirdine


  Known teratogen; skin rashes occur during 1-3 weeks of therapy
• Efavirenz


  Long t 1⁄2 (40-55 hours); toxicity occurs when taken w/ high fat meal (taken NPO); principal toxicity involves the CNS; recommended for use in pregnancy (initiated after 8 weeks AOG)
• Etravirine


  Designed to be effective against strains of HIV that had developed resistance to 1st gen NNRTIs
• Nevirapine


  Excellent oral BA (>90%); single dose of nevirapine (200 mg) can prevent transmission from mother to newborn when administered at the onset of labor, then 2-mg/kg dose to the neonate within 3 days of delivery
• Rilpivirine


  Must be administered w/ a meal (preferably high fat or >400 kcal); dependent on gastric acid environment for absorption; recommended for use in pregnancy
• PROTEASE INHIBITORS (PI)


  preventing post-translational cleavage of the Gag-Pol polyprotein →prevent the processing of viral proteins into functional conformations →production of immature, noninfectious viral particles
• All of the PIs are extensively metabolized by CYP3A4
• Atazanavir


  Recommended for use in pregnancy; requires acidic medium for absorption and exhibits pH- dependent aqueous solubility
• Darunavir


  Recommended for use in pregnancy; co- administered with ritonavir or cobicistat; contains sulfa moiety
• Fosamprenavir


  Prodrug of amprenavir; contains sulfa moiety
• Indinavir


  Requires acidic medium for absorption; most common AE unconjugated hyperbilirubinemia and nephrolithiasis; insulin resistance is noted
• Lopinavir


  Available only in combi with low-dose ritonavir as a pharmacologic “booster”; recommended for use in pregnancy
• Nelfinavir


  Most common AEs associated are diarrhea and flatulence
• Ritonavir


  Pharmacologic “booster”; Di w/ saquinavir → QT prolongation, PR interval prolongation
• Saquinavir


  Should be taken within 2 hours after a fatty meal for enhanced absorption
• Tipranavir


  Use for treatment-experienced patients who harbor strains resistant to other PI agents; DI with ritonavir →IC hemorrhage
• Enfuvirtide


  binds to the gp41 subunit of the viral envelope glycoprotein →preventing fusion of the viral and cell membrane
• Maraviroc


  approved for use in combination w/ other ARV in adult px infected only with CCR5-tropic HIV-1
• INTEGREASE INHIBITORS


  integrase, a viral enzyme essential to the replication of both HIV-1 and HIV-2
• Dolutegavir


  increase serum concentration of dofetilide & metformin
• Elvitegravir


  Requires boosting with an additional drug, as well as certain intestinal transport proteins or ritonavir
• Raltegravir


  Recommended for use in pregnancy; does not interact w/ CYP450 system; metabolized by glucuronidation the CYP450 system but is metabolized by glucuronidation, particularly UGT1A1
• Palivizumab


  Prevention of RSV infection in high-risk infants and children
• Imiquimod


  Topical treatment of external genital and perianal; effective for molluscum contagiosum