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  1. HIV
    Human Immunodeficiency Virus
    • A retrovirus: Lacks ability to self-replicate~ Obligate intracellular parasite
    • RNA is genetic material rather than DNA
    • Reverse transcriptase is enzyme needed to transcribe RNA to DNA
    • Two types ( First described in 1981 )
    • HIV-1 Found world-wide
    • HIV-2 Found mainly in west Africa (increased population mobility will cause HIV-2 to travel globally too.)
    • Be aware that there are different genotypes/phenotypes. Will become important to identify which group the individual belongs to.)
  2. What are CRFs?
    Circulating Recombinate Forms: Different genotypes/phenotypes may combine (ie A and C) to form a new form that is both A and C.
  3. HIV
    • Target CD4 T Helper Cells (Helper T lymphocytes)
    • Immune system undergoes progressive decline
    • Person becomes more susceptible to opportunistic infections
  4. HIV Clinical Course
    Triphasic (three phases of treatment)

    • Initial Phase ~ Massive replication of virus
    • Experience flu-like acute retroviral syndrome
    • Middle Phase ~ Prolonged clinical latency
    • Late Phase ~ CD4 T cells drops below critical level (<350mm/cm3) At this point you should be treating to increase CD4 T cell count. Will help to prevent HIV from becoming AIDS.
    • HIV damages many cell types including
    • Immune
    • Nervous system, ie peripheral neuropathies like numbness, tingling, feeling like walking on cotton balls, "sleeping" limbs.
  5. Tests for HIV
    • Viral Load (Plasma HIV-RNA): Antibody tests like...
    • Enzyme Immunoassy (EIA)- 2 weeks for results
    • Rapid HIV antibody test- 10 to 20 minutes
    • Western Blot Test- confirms Rapid HIV in 2 weeks.

    • CD4 T Cell Count
    • HIV Drug Resistance
    • Two types of Assays available
    • Genotypic and Phenotypic
  6. HIV Drugs
    general info
    • 31 drugs on the market for HIV
    • Only 6 have been approved since 2004
    • 3 years ago---7 drugs in stage 3
    • none have made it to market
    • Only 2 remain in the final stage
  7. What are the 4 Major Classes of HIV Drugs?
    • HIV Fusion Inhibitors (Entry Inhibitors): Prevent HIV from entering cells
    • Reverse Transcriptase Inhibitors
    • Nucleoside Reverse Transcriptase Inhibitors (NRTI”S)
    • Nonnucleoside Reverse Transcriptase Inhibitors (NNRTI’S)
    • Nucleotide reverse transcriptase inhibitors
    • (NtRTI’S)
    • Protease Inhibitors: Most effective drug available. Its the first one used.
    • Integrase Inhibitors
    • Usually multi-drug therapy to prevent virus from becoming immune to the one drug your taking.
  8. Who is at highest risk for contracting HIV in US
    Homosexual black males.
  9. Fusion Inhibitors
    Enfuvirtide (T-20 )
    • Blocks entry of HIV into CD4 T cells
    • Requires 2 x day Sub –q injections
    • Cost $20,000 a year
    • Must be taken with other drugs
    • Will develop resistance if taken alone
    • Drug company is recommending both phenotype and genotype resistance testing
  10. Adverse reactions to Enfuvirtide (T-20)
    • Skin reactions at injection sites
    • Redness
    • Itching, redaness, swelling, hardened skin, lumps
    • Peripheral neuropathy
    • HA
    • Pain and numbness in legs and feet
    • Dizziness
    • Loss of sleep
    • Eosinophilia: Eleveted eosinophils (T-cells which respond to foreign proteins) counts. Becomes harder to diagnose cause of histamine responses. Allergies will become worse.
  11. NRTI's
    Zidovudine (AZT)
    • Reduces viral load
    • Increases CD4 T Cell counts
    • Delays onset of disease symptoms
    • Reduces symptom severity
    • 1st drug administered in new HIV pts.
  12. NRTI's
    Zidovudine (AZT)
    • Action: Inhibits HIV replication; Blocks viral DNA synthesis by inhibiting reverse transcriptase--becomes incorporated into growing viral DNA strand
    • Penetrates CNS well--assists in relieving cognitive symptoms and periferal neuropathies.
    • Should be combined with at least one other agent
  13. Adverse Effects of NRTI's
    Zidovudine (AZT)
    • *** Anemia and Neutropenia ***
    • Especially seen with multiple drug therapy and advanced disease
    • May require repeated blood transfusions
    • Epoetin--Stimulates increased production of RBCs
    • Sargramostim--Stimulated increased production of WBCs
    • Determine hematologic status before treatment then q (every) 2 wks for first 8 wks ….then q 4 wks
    • Lactic Acidosis (pts with HepB and HepC)
    • With severe hepatomegaly and hepatic stenosis. Dosing then becomes an issue.
    • Will tire more easily and rapid respirations
    • Neutrophils: 1st line of defense against foreign agents.
  14. Patient Education with NRTIs
    Zidovudine (AZT)
    • Take exactly as ordered -- around the clock
    • Does not cure disease and does not reduce the risk of transmission. Will only decrease amount of virus and increase CD4 T cells.
    • Notify Health Care Provider of S&S (signs and symptoms) because will become open to all of the fungal infxns of infection
    • Avoid OTC medications because this Rx will interact with just about everything, especially St. Johns Wart as well as other herbs. Will increase risk and severity of SEs.
    • Importance of regular follow-up exams and blood counts
  15. Nonnucleotide Reverse Transcriptase Inhibitors (NNRTIs)
    Nevirapine (Viramune)
    • Binds directly to HIV reverse transcriptase and disrupts active center of enzyme
    • Only for HIV- 1
    • Resistance develops rapidly if drug is used alone
  16. Nonnucleotide Reverse Transcriptase Inhibitors (NNRTIs)Nevirapine (Viramune)
    Adverse Effects
    • Rash ~ All over body, may advance to Epidermal Necrolysis (aka Stephen Johnson's syndrome)
    • Especially during the 1st month of therapy
    • D/C med (is now contraindicated)
    • Hepatoxicity
    • Monitor liver enzyme levels ~ AST and ALT
    • Especially during 1st 6 months of therapy
    • Those with Hepatitis B or C
  17. Nonnucleotide Reverse Transcriptase Inhibitors (NNRTIs)Nevirapine (Viramune)
    • Same as AZT
    • Plus
    • Women of childbearing age should use an additional , nonhormonal BC Measure other than BC Pills like condomns.
    • Does not protect you from multiple strains of HIV.
  18. Nucleotide Reverse Transcriptase Inhibitors (NtRTIs)
    Tenofovir (Viread)
    • Works exactly the same as NNRTI
    • Only one on market, Tenofovir (Viread)
  19. Protease Inhibitors
    • Most effective antiretroviral drugs available
    • When used with other drugs … Viral levels are reduced to levels not detected by current assays
    • All inhibit Cytochrome P450…dosing is a challenge
    • Never use alone
  20. Protease Inhibitors
    • Binds to the active site of HIV protease preventing the enzyme from cleaving HIV polyprotein. Therefore,
    • the structural proteins and enzymes of HIV are unable to function and the virus remains immature and noninfectious.
  21. Protease Inhibitors
    Adverse Effects
    • Hyperglycemia. Essentially puts pt into a diabetic state.
    • Monitor blood glucose levels prior to and during therapy
    • Assess for signs of Hyperglycemia like:
    • Polydipsia ~ Increased thirst. Body's effort to dilute excess sugar in the body.
    • Polyphagia ~ hunger
    • Unexplained weight loss
    • Polyuria ~ Increased urination
    • Fatigue due to lack of glucose.
    • Dry, itchy skin
    • Managed with Insulin and oral hypoglycemics

    • Fat Redistribution to:
    • Abdomen
    • Breasts
    • Between the shoulder blades
    • Fat is lost from the arms, legs, face and buttocks
    • Skinny arms/legs, "buffalo" hump.
    • (Muscle mass and strength is not affected.)

    • Hyperlipidemia
    • Elevated levels of cholesterol and triglycerides. Related to fat redistribution. Can lead to cardiovascular disease.
    • Can occur regardless of fat redistribution
    • May lead to CV disease, pancreatitis
    • Monitor lipid levels prior to and during treatment
    • Avoid treatment with lovastatin andsimvastatin
    • Inhibition of P450--Toxic levels

    • Increased bleeding in Hemophiliacs
    • Usually seen in 1st month of treatment, usually in joints and soft tissue
    • May need to increase coagulation factors

    • Reduced Bone Mineral Density
    • Studies found 10-21 % taking Protease Inhibitors developed osteoporesis
    • Elevation of Serum Transaminase
    • Indicates Liver Injury
    • Monitor Liver enzymes prior to and during treatment
    • Especially in those with Hepatitis and cirrhosis
  22. Protease Inhibitors
    Drug Interactions
    • Too many to identify.
    • Related to P450 effects
    • May cause severe adverse rxn
    • NO OTC meds should be taken
  23. What is the Protease Inhibitor synergistic Rx
    • Ritonavir (Norvir)
    • Is not used for its antiviral proberties
    • Used to “Boost” other HIV meds
  24. Integrase Inhibitors
    Insentress (Raltegravir)
    • Action
    • Inhibits the catalytic activity of HIV-1 which is required for viral replication

    • Side Effects
    • Diarrhea, Nausea
    • Nephrotoxicity. Increased levels of creatine kinase. Be sure to check creatinine clearance.
  25. Combination Rx
    • Atripla (multi – class)
    • Efavirenz ( NNRTI )
    • Emtricitabine ( NRTI )
    • Tenofovir disoproxil fumarate ( NRTI )

    • Truvada
    • Emtricitabine (NRTI)
    • Tenofovir (PI)

    Side effects of multidrugs are multiplied x4!
  26. General Drug Interactions of all HIV/AIDS drugs
    St John’s Wort -- Reduce levels of NNRTI’s and PI’s related to accelerated induction of P450

    Garlic supplements can decrease levels of PI’s…. Up to 50%, so Dietary garlic should be kept to minimum
Card Set:
2012-06-04 21:27:42
HIV drugs

Chapter on HIV drugs
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