HIV Flashcards
HIV therapy initiated when patients present with AIDS-defining illness, CD4<500, or high viral load.
HAART - Highly active antiretroviral therapy
3 Drugs making up the HAART regimen to prevent resistance
2 nucleoside reverse transcriptase inhibitors (NRTIs) + 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) OR 1 protease inhibitor OR 1 integrase inhibitor
What are the main protease inhibitors
NAVIR (never) TEASE a PROTEASE - Atazanavir, Darunavir, Fosamprenavir, Indinavir, Lopinavir, Ritonavir, Saquinavir
Mechanism of Protease inhibitors (-Navirs)
Assembly of virions depends on HIV-1 protease (pol gene), which cleaves the polypeptide products of HIV mRNA into their functional parts. Thus, protease inhibitors prevent maturation of new viruses.
Toxicity of Protease inhibitors
Ritonavir can “boost” other drug concentrations by inhibiting cytP450. Also, hyperglycemia, GI intolerance (nausea, diarrhea), lipodystrophy. Nephropathy
What toxicity is specific to indinavir
Hematuria
What are the main NRTIs?
Abacavir (ABC), Didanosine (ddl), Emtricitabine (FTC), Tenofovir (TDF),
Zidovudine (ZDV, formerly AZT), Lamivudine (3TC), Stavudine (d4T),
Mechanism of the NRTIs
Competitively inhibit nucleotide binding to reverse transcriptase and terminate the DNA chain (lack a 3’ OH group). Tenofovir is a nucleoTide; the others are nucleosides and need to be phosphorylated to be active.
What is ZDV used for?
General prophylaxis and during pregnancy to decrease risk of fetal transmission
What are toxicities of NRTIs - Vudines?
Bone marrow suppression (can be reversed with granulocyte colony-stimulating factor (G-CSF) and erythropoietin, peripheral neuropathy, lactic acidosis (nucleosides), rash (non-nucleosides), anemia (ZDV), pancreatitis (didanosine)
What are the main NNRTIs?
Delavirdine, Efavirenz, Nevirapine (DEN)
What is the mechanism of NNRTIs?
Bind to reverse transcriptase at site different from NRTIs. Do not require phosphorylation to be active or compete with nucleotides
Toxicity of NNRTIs
Rash and hepatotoxicity are common to all NNRTIs. Vivid dreams and CNS symptoms are common with efavirenz. Delvirdine and efavirenz are contraindicated in pregnancy
What are the main Integrase inhibitors
Raltegravir
What is the mechanism of integrase inhibitors
Inhibits HIV genome integration into host cell chromosome by reversibly inhibiting HIV integrase
What is the main toxicity of Raltegravir
Hypercholesterolemia
What are the main Fusion inhibitors?
Enfuvirtide and Maraviroc
What is the mechanism of Enfuvirtide?
Binds gp41, inhibiting viral entry
What is the main toxicity of enfuvirtide?
Skin reaction at injection sites
What is the mechanism of Maraviroc?
Binds CCR5 on surface of T cells/monocytes, inhibiting interaction with gp120
