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| Pregunta | Respuesta |
| HIV Life Cycle | 1) Attachment of virus at the CD4 receptor 2) Viral fusion and uncoating 3) Reserve transcriptase makes a single DNA copy of the viral RNA and then makes another to form a double stranded viral DNA and migrates to nucleus 4) Transcription and RNA processing 5) Protease enzyme cleaves polypeptides into functional HIV proteins 6) Virion budding and maturation |
| Classes of Drugs in Clinical Use | 1) Nucleoside and nucleotide Reverse Transcriptase (NRTIs) Inhibitors 2) Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) 3)Protease Inhibitors 4) Entry Inhibitors 5) Integrase Inhibitors 6) Investigational Agents |
| 2 Drug Regimen Post Exposure Prophylaxis (PEP) | Retrovir (zidovudine) + Epivir (lamivudine) twice daily This combination preparation is recommended in pregnancy |
| 3 Drug Regimens Post Exposure Prophylaxis (PEP) | Retrovir (Zidovudine) + Epivir (Lamivudine) twice daily + Kaletra (Lopinavir + Ritonavir) twice daily. |
| Nucleoside and nucleotide reverse transcriptase (NRTIs) inhibitors Drug Examples | Zidovudine Lamivudine |
| Nucleoside and nucleotide reverse transcriptase (NRTIs) inhibitors Zidovudine, Lamivudine Information | Acts as chain terminators or inhibitors at the substrate binding site of Reverse Transcriptase Imitate Adenosine, Guanine, Thymidine, Cytosine Incorporate into the growing DNA and inhibit chain formation All NRTIs have mitochondrial toxicity Epivir (Lamivudine), Abacavir, Didanosine |
| Nucleoside and nucleotide reverse transcriptase (NRTIs) inhibitors Adverse Drug Reactions | Lactic acidosis, Dyslipidemia, and Insulin Resistance may occur. |
| First anti-HIV drug approved | NRTI known as ASZT or Zidovudine (1987) |
| Non-nucleoside reverse transcriptase Inhibitors (NNTRIs) Examples | Nevirapine Efavirenz |
| Non-nucleoside reverse transcriptase Inhibitors (NNTRIs) MOA | Reverse Transcriptase inhibitors (NNRTIs) inhibit viral DNA replication by binding to reverse transcriptase, and inhibit DNA polymerase |
| Non-nucleoside reverse transcriptase Inhibitors (NNTRIs) Adverse Reactions | GI disturbances, skin rashes, SJS |
| Non-nucleoside reverse transcriptase Inhibitors (NNTRIs) Metabolism | Metabolized by CYP450 enzyme system and may be inducers or inhibitors, thus the drug interactions |
| Protease Inhibitors (PIs) Examples | Ritonavir Indinavir |
| Protease Inhibitors (PIs) MOA | During the reproduction cycle of HIV a specific protease is needed to form mature HIV components If protease is missing, noninfectious HIV bud are produced HIV protease inhibitors are specific to HIV protease because it differs significantly from human protease |
| Protease Inhibitors (PIs) Adverse Effects | "Cushing" like Syndrome |
| Entry Inhibitors Example | Enfuvirtide |
| Entry Inhibitors MOA | Enfuvirtide is a synthetic peptide which block entry of the virus into cell, by preventing conformational change Binding of the HIV virus to the CD4 lymphocyte receptor is the first step to viral replication This binding causes a conformational change to the site and allows the viral envelope to fuse w/ cell membrane |
| Entry Inhibitor Delivery | Must be given by subcutaneous injection and is not subject to hepatic enzyme degradation |
| Entry Inhibitors Adverse Effects | Local injection site reaction may occur Eosinophilia and hypersensitivity reaction may occur |
| Integrase Inhibitors Example | Raltegravir |
| Integrase Inhibitors MOA | Integrase is a viral enzyme essential for HIV replication Promotes the integration of viral DNA strands into the host DNA Raltegravir is a pyrimidine analog that binds integrase and prevents the action Used in adults patients resistant to other agents |
| Investigational Agents Bevirimat, TNX-355 | New agents claim better activity, lesser side effects and convenient dosing. Virus maturation inhibitors [Bevirimat], CD4 Receptor Inhibitor (TNX-355) |
| Antiretroviral Therapy Guidelines | Should be initiated in all patients with a hx of an AIDS-defining illness or with CD4 count <200 cells/mm3 |
| Conditions during which Antiretroviral Therapy should always be initiated regardless of CD4 count | Pregnancy, HIV-associated nephropathy, HBV co-infection |
| Highly Active Anti-Retroviral Therapy (HAART) Initial Regimine | 2 NRTIs w/ an NNTI or a Ritronavir-boosted PI or an Integrase inhibitor |
| Highly Active Anti-Retroviral Therapy (HAART) Treatment Goals | In antiretroviral therapy failure, the goal of subsequent tx is suppression of HIV-1 RNA to below detection levels |
| Highly Active Anti-Retroviral Therapy (HAART) Suggested Combos and Restrictions | Tenofovir/Emtricitrabine (a combination of two NRTIs) and Efavirenz (NNRTI) Efavirenz should not be given to a pregnant women Tenofovir/emtricitabine and Raltegavir (an Integrase inhibitor) Tenovir/emtricitabine, Ritonavir and Darunavir (Protease inhibitors) |
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