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Antiretroviral Drugs

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    • 1. Antiretroviral Drugs
    • 2. HIV/AIDS
      • Basics
      • HIV is a retrovirus
      • -Cell has RNA (instead of usual DNA)
      • When in host cell, the RNA, via the enzyme reverse tran- scriptase, makes DNA that gets into host DNA and replicates
    • 3. Body Fluids: Transmissible
      • Blood
      • Semen
      • Vaginal secretions
      • Breast milk
      • Cerebral spinal fluid
      • Synovial fluid
      • Pleural & amniotic fluid
    • 4. Transmission Activities
      • Unprotected sex-oral, anal, vaginal
      • Blood to blood-sharing needles, occupational exposure, fighting, tattooing, body piercing, transfusions
      • Mother to newborn-in utero, childbirth, breast feeding
    • 5. Body Fluids: Non-transmissible Important to know how you DON”T get HIV!
      • Urine
      • Sweat
      • Saliva
      • Tears
      • Vomit
      • Mucous
      • Feces
    • 6. AIDS
      • AIDS: Acquired Immunodeficiency Syndrome
        • CD4<200
      • Opportunistic infections:
        • PCP – pnuemocystis carinii
        • MAC – mycobacterium aviary complex
        • CMV – cytomegalovirus
      • Other opportunists:
        • HSV – herpes simplex virus
        • C. albicans – thrush
        • Toxoplasma gondii – exposure to cats
        • Cryptosporidium – causes diarrhea a/o obstructive jaundice
    • 7. Disease Spectrum
      • 1-3 MONTHS:
      • HIV infection
      • flu like symptoms
      • 1-10+ YEARS:
      • Asymptomatic
        • No symptoms
      • Symptomatic
        • Fatigue
        • Diarrhea
        • Fever
        • Thrush
        • Skin rash
        • Weight loss
        • Swollen glands
    • 8. The Immune System & HIV
      • Function = prevent/fight disease:
        • Control or eliminate viruses and other microbes that threaten the body with infection and disease.
        • Eliminate damaged cells that are or may be cancerous.
      • The immune system is divided into two branches according to their response to disease:
        • Antibody-mediated immune response  copes with disease causing microbes in the blood
        • Cell-mediated immune response  copes with microbes located within cells
    • 9. Helper T Cells - CD4 Cells
      • Helper cells because they coordinate & activate both B lymphocytes [antibody mediated] & cell-killing cytotoxic (CD8) lymphocytes [cell mediated]
      • Cell-mediated immune response  copes with microbes located within cells.
      • HIV infects & destroys CD4 cells
      • Loss of cells  immune system collapse & HIV disease.
      • Decline in CD4 cells is used as a marker of the progression of HIV.
    • 10. Cytotoxic T-Cells: CD8 Cells
      • Important in initial immune response to HIV & at latent stage
      • Kills infected cells that are producing virus
      • Secrete soluble factors that suppress HIV replication-these factors block by occupying receptors necessary for the entry of certain strains of HIV into the target cell
      • New information shows two new strains of the HIV virus that target CD8 cells
    • 11. When to Treat Indicators
      • CD4 TESTING RESULTS:
      • Vital to the immune process
      • Count=number of cells/mm3
      • Measurement of immune function
      • Measure every 3-6 months
      • VIRAL LOAD TESTING:
      • Measures plasma HIV levels
      • Indicator of disease progression
      • Measure every 3 months
    • 12. AIDS
      • SYMPTOMATIC:
      • any CD4/viral load value
      • treat
      • ASYMPTOMATIC:
      • CD4<500, Viral load >10,000 women, 20,000 men
      • treatment should be offered
      • CD4>500, Viral load<10,000 women, 20,000 men
      • delay treatment and monitor
    • 13. New Guidelines-Recommendations Defer; some treat if viral load is >55,000 / mL >350 Asymptomatic Treat; some defer especially if viral loads < 20,000 / mL 200-349 Asymptomatic Treat < 200 Asymptomatic Treat Any Symptomatic Recommendations CD4 / mcL Category
    • 14. HAART: Highly Active Antiretroviral Treatment
      • Combination of multiple antiretrovirals to achieve maximum effect in viral load suppression to a goal of undetectable viral load levels
      • Base changes in Tx on:
        • CD4 decline measured on 2 occasions
        • Virologic failure (increased HIV viral load)
        • Toxicity
        • Patient tolerance
        • Inability to comply with regimen
    • 15. HAART: Highly Active Antiretroviral Treatment
      • Obtain genotypic or phenotypic resistance testing while on old regimen and use information to guide selection of new regimen
      • Always change at least two of the retrovirals in the regimen
      • Avoid choosing agents with overlapping resistance patterns with those that have failed
      • Avoid agents with similar side effects as those to which a patient is intolerant
      • Simplify next regimen if possible
    • 16. Antiretrovirals Non-nucleoside Analogs Nucleoside Analogs SUBCLASS Delavirdine mesylate (DLV) Nevirapine (NVP) Efavirenz (EFV) Didanosine (ddI) Lamivudine (3TC) Stavudine (d4T) Zalcitabine (ddC) Zidovudine (ZDV, AZT) Abacavir (ABC) Tenofivir Disoproxil Fumarate (TDF) AZT / 3TC AZT / 3TC / ABC GENERIC Rescriptor Viramune Sustiva Videx Epivir Zerit Hivid Retrovir Ziagen Viread Combivir Trizivir Reverse Transcriptase Inhibitors TRADE CLASS
    • 17. Antiretrovirals Crixivan Viracept Norvir Invirase Agenerase Reyatz Lexiva Kaletra Indinavir sulfate (IDV) Nelfinavir mesylate (NFV) Ritonavir (RTV) Saquinavir mesylate (SQV) Amprenavir (APV) Atazanavir Fosamprenavir (f-APV) LPV / RTV Protease Inhibitors Enfuvirtide GENERIC Fuzeon, T-20 Fusion Inhibitor TRADE CLASS
    • 18. Antiretrovirals: Major Categories
      • Reverse Transcriptase Inhibitors
        • Act early in the life cycle of the HIV
        • Prevent the HIV enzyme from creating HIV proviral DNA from viral RNA  prevents new viruses from being produced
          • Nucleoside: work by chain termination & competitive inhibition of nucleoside triphosphates
          • Non-nucleoside: Do NOT require intracellular phosphorylation for activation; directly bind to & disrupt catalytic site of reverse transcriptase  chain termination
    • 19. Antiretrovirals: Major Categories
      • Protease Inhibitors
        • Act late in the life cycle of the HIV
        • Block HIV enzyme protease  prevent creation or cleavage of HIV polyproteins necessary for production of new virions
      • Fusion Inhibitor
        • Attach to proteins on surface of T-cells or HIV
        • Prevent binding of proteins on HIV’s outer coat (GP 120, GP41) with surface receptors on T-cells (CCR5, CXCR4)
        • At present Enfurvirtide binds to GP 41
    • 20. Baseline Data Prior to Tx
      • T4 (CD4) count (immune status) & plasma HIV RNA measurement (viral load – severity of infection)
        • ALSO used to gauge efficacy of Tx
      • CBC with diff, folate, B12, ferritin, iron, percent iron saturation
      • Hx hepatitis or hepatomegaly & alcohol use/abuse – obtain LFTs & Hep A,B,C
      • Hx pancreatitis – obtain amylase (isoamylase fractionates: salivary vs. pancreatic)
      • Triglycerides & lipase levels
      • Peripheral neuropathies – timed vibratory sensation
    • 21. For IDV, monitor for nephrolithisis, UA for crystalluria, increased urine pH Urinalysis If Sx of lactic acidosis associated with NNRTIs Serum Lactate Q3-4 mo, monitor for NNRTIs If elevated at baseline, monitor within 1-2 mo Lipid Profile Q 3-6 mo, more closely for pancreatitis Amylase / Lipase Frequency / Indication Lab Test Q 3-6 mo, more freq for abnl values & elevated LFTs LFTs Q 3-6 mo, Glucose monitoring Q 3-4 mo Serum Chemistries B12 deficiency m neuropathy vs. HAART Tx induced neuropathy Vitamin B12 Q 3-6 mo, more freq with low values or bone marrow toxicities CBC with DIFF Dx, before Tx, 2-8 wks after start of Tx HIV Viral Load Dx, 3-6 mo, response to Tx CD4
    • 22. Tx During Pregnancy
      • Antiretroviral Pregnancy Registry (800-258-4263)  to monitor maternal-fetal outcomes of pregnant women who receive antiretrovirals
      • High risk of HIV transmission with breastfeeding – CDC advises against
    • 23. FDA Pregnancy Category Rating
      • Animal studies  fetal risk + no controlled studies in women OR
      • No available studies in women or animals
      C
      • Positive evidence of fetal risk but there may be certain situations where the benefit might outweigh the risk  life-threatening or serious diseases where other drugs are ineffective or carry a greater risk
      D
      • Animal studies  no risk to fetus + no controlled studies in pregnant women OR
      • Animal studies  fetal risk , but controlled studies in pregnant women  no risk
      B DESCRIPTION CATEGORY
    • 24. Patient Education
      • Compliance is essential
        • Non-compliance  development of resistance
      • Tx does NOT cure HIV infection
        • Tx does NOT prevent transmission  MUST follow safe sex practices
      • HIV(+) women: high risk of HIV transmission in breast milk
        • CDC recommends HIV(+) women  NO breastfeeding
      • Report:
        • ALL medication usage: OTC, herbal, etc.  MANY drug interactions!!!
        • S/Sx’s of pancreatitis  D/C if present
        • S/Sx’s of peripheral neuropathy  if medication D/C’d promptly, neuropathy may be reversible  if no improvement may be r/t B12 deficiency
    • 25. Didanosine (ddI, Videx)
      • Mechanism of action
        • Chain termination
        • Rapidly degraded in acidic pH  gastric secretions may inactivate drug  buffering agent provides proper pH for absorption
        • Antacids & H2 blockers increase absoprtion  may lead to toxic levels of drug
      • Contraindications
        • Hypersensitivity
        • S/Sx’s pancreatitis or serum amylase 1.5-2 x ULN
        • Excessive alcohol intake
        • Peripheral neuropathy
        • Pregnancy Category B
    • 26. Didanosine (ddI, Videx)
      • Warnings
        • IV pentamidine & sulfonamides  pancreatitis Restart ddI in 1-2 wks d/t long ½-life of petamidine
        • Use with caution in pancreatitis or prior Hx of alcohol abuse
        • Monitor LFT closely
        • High magnesium levels in patients with renal impairment
        • PKU pts: chewable form contains NutraSweet
      • Precautions
        • Coadministration with food reduces absorption
        • May restart at a lower dose when/if peripheral neuropathy resolves
        • Antacids & H2 blockers may increase bioavailability
        • Avoid concomitant administration of zalcitabine & stavudine d/t similar toxicity profiles
    • 27. Didanosine (ddI, Videx)
      • Adverse Effects
        • Pancreatitis
        • Peripheral neuropathy
        • Diarrhea
        • Hyperuricemia
        • Possible hepatic dysfunction
      • Overdose
        • Limited information on acute toxicity
        • Hemodialysis / peritoneal dialysis unknown
    • 28. Lamivudine (3TC, Epivir)
      • Mechanism of action
        • Competitive inhibition
        • Chain termination
        • If used alone  resistant mutation & loss of antiretroviral effect in 8-12 wks  NOT used alone!
        • If used in combination with AZT (combivir)  delays emergence of mutations susceptible to either drug
      • Contraindication
        • Hypersensitivity
        • Pregnancy category C
    • 29. Lamivudine (3TC, Epivir)
      • Warnings
        • Pancreatitis (rare)
      • Precaution
        • Reduction in dose in renal impairment
        • Bactrim increases blood concentration & decreases clearance of drug
    • 30. Lamivudine (3TC, Epivir)
      • Adverse effects
        • COMMON: headache, nausea, malaise, fatigue, peripheral neuropathy, insomnia, nasal s/Sx’s
        • May cause pancreatitis in children
      • Overdosage
        • No known antidote
        • Hemodialysis / peritoneal dialysis unknown
    • 31. Stavudine (D4T, Zerit)
      • Mechanism of action
        • Competitive inhibition of thymidine triphosphate
        • Premature chain termination
      • Contraindications
        • Hypersensitivity
        • S/Sx’s pancreatitis or serum amylase 1.5-2 x ULN
        • Excessive alcohol intake
        • Peripheral neuropathy
        • IN VITRO antagonistic antiviral effect with AZT  AVOID concomitant administration with AZT
        • Pregnancy Category C
    • 32. Stavudine (D4T, Zerit)
      • Warnings
        • MAJOR TOXICITY: peripheral neuropathy
        • Less frequent (1%) BUT fatal pancreatitis
        • IV pentamidine & sulfonamides  pancreatitis Restart D4T in 1-2 wks d/t long ½-life of petamidine
        • Carefully monitor if Hx of alcohol abuse
      • Precautions
        • Monitor for peripheral neuropathy & elevated liver transaminases  if toxicity  HOLD dose
        • If peripheral neuropathy & hepatic dysfunction resolve may restart D4T at lowered dose
        • Use with caution in combination with other reverse transcriptase inhibitors with similar toxicity profiles
        • Reduced dosage or contraindicated in renal impairment
    • 33. Stavudine (D4T, Zerit)
      • Adverse effects
        • MOST COMMON: peripheral neuropathy & asymptomatic elevation of hepatic transaminases
      • Overdosage
        • No acute toxicity noted
        • Complications of chronic overdosage: hepatic toxicity & peripheral neuropathy
        • Hemodialysis / peritoneal dialysis unknown
    • 34. Zalcitabine (ddC, Hivid)
      • Mechanism of action
        • Competitive inhibition of natural substrate in formation of reverse transcriptase  premature termination of growing DNA chain
      • Contraindications
        • Hypersensitivity
        • S/Sx’s pancreatitis or serum amylase 1.5-2 x ULN
        • Excessive alcohol intake
        • Peripheral neuropathy
        • Pregnancy category C
    • 35. Zalcitabine (ddC, Hivid)
      • Warnings
        • IV pentamidine & sulfonamides  pancreatitis Restart D4T in 1-2 wks d/t long ½-life of petamidine
        • Can cause severe peripheral neuropathy  best to avoid combinations with other antiretrovirals with similar toxicity profiles (e.g., ddI)
        • RARE BUT FATAL: lactic acidosis w/o hypoxemia & severe hepatomegaly w/steatosis; hepatic filaure & death in pts w/underlying hepatitis B
    • 36. Zalcitabine (ddC, Hivid)
      • Precautions
        • Hx pancreatitis & peripheral neuropathy
        • Obese women with known risk factors for liver disease
        • May cause myelosuppression
        • Concomitant use with cimetidine increases serum concentration  increased toxicity
        • Mg & Al antacids decreases absorption
        • Metoclopramide reduces bioavailability
        • Probenecid decreases elimination & may lead to toxic effects
        • Nephrotoxic drug (e.g., ampho B) may decrease renal clearance
        • Renal impairment  greater risk for toxicity d/t decreased clearance
        • Food decreases rate & extent of oral absorption
    • 37. Zalcitabine (ddC, Hivid)
      • Adverse effects
        • MOST COMMON: peripheral neuropathy, oral ulcers, aphthous stomatitis, esophageal ulceration, abnormal hepatic function, neutropenia, anemia, thrombocytopenia, fever, pruritic maculopapular rash
        • RARE BUT HIGH MORBIDITY/MORTALITY: pancreatitis also cardiomyopathy
      • Overdosage
        • No known antidote – Tx w/gastric lavage
        • Hemodialysis / peritoneal dialysis unknown
    • 38. Zidovudine (ZDV, AZT, Retrovir)
      • Mechanism of action
        • Competitive inhibition of thymidine triphosphate & prevents cross linkages
        • Premature chain termination
        • Penetrates CSF  effective in reducing AIDS dementia complex in adults & children
      • Contraindications
        • Life-threatening allergic reactions
        • Ribavirin antagonizes antiviral activity  do NOT give concomitantly
        • Pregnancy category C
    • 39. Zidovudine (ZDV, AZT, Retrovir)
      • Warnings
        • Hypersensitivity: rash & anaphylaxis
        • Metabolized by liver excreted in kidney  dosage reduction in renal impairment
        • Impaired liver function  increased toxicity risk
        • RARE BUT FATAL: lactic acidosis w/o hypoxemia & severe hepatomegaly w/steatosis (esp. in obese women)
    • 40. Zidovudine (ZDV, AZT, Retrovir)
      • Precautions
        • Bone marrow suppression (combined effect w/ganciclovir & interferon alpha or B12 & other deficiencies)
        • Elevated MCV (megaloblastic change MUST r/o B12 or folate deficiency)
        • Probenecid increases drug levels  flulike Sx’s
        • Trimethoprim increases serum levels
        • Alters dilantin levels
        • In combo with acyclovir  drowsiness & lethargy
        • Methodone increases serum concentration & toxicity risk
    • 41. Zidovudine (ZDV, AZT, Retrovir)
      • Adverse effects
        • MOST COMMON: myelosuppression (macrocytic anemia or granulocytopenia), myalgias, malaise, nausea & headaches (diminish over time), excessive eyelash growth, hyperpigmentation of nails (bluish)
        • LONG-TERM: myalgias & myositis (d/t mitochondrial toxicity)  D/C or dose reduction If inflammatory, myalgias may not improve on D/C
      • Overdosage
        • No fatal overdoses; one report of grand mal seizure
        • Hemodialysis & peritoneal dialysis  negligible effect on removal BUT elimination of primary metabolite enhanced
    • 42. Delavirdine Mesylate (DLV, Rescriptor)
      • Mechanism of action
        • Directly binds to reverse transcriptase & blocks process of viral RNA transcription into proviral DNA
      • Contraindications
        • Hypersensitivity
        • Pregnancy category C
    • 43. Delavirdine Mesylate (DLV, Rescriptor)
      • Warnings
        • Resistant virus emerges if given as monotherapy  always given in combination w/other retroviral
        • Inhibits P450 & can result in serious life threatening events
      • Precautions
        • Increases levels of certain drugs  watch for drug interactions (including coumadin & anticonvulsants)
        • Antacids decrease absorption; H2 blockers may do same
    • 44. Delavirdine Mesylate (DLV, Rescriptor)
      • Adverse effects
        • MOST COMMON: skin rash w/pruritis, headache, nausea, diarrhea, fatigue
        • Reversible elevations in liver enzymes & bilirubin
        • RARE: neutropenia & anemia
      • Overdosage
        • No specific antidote  gastric lavage or emesis
    • 45. Nevirapine (NVP, Viramune)
      • Mechanism of action
        • Directly binds to reverse transcriptase & blocks process of viral RNA transcription into proviral DNA
        • Autoinduction: induces own metabolism (clearance increases two-fold in first wks of use  requires increased dose at end of wk 2)
      • Contraindications
        • Hypersensitivity
        • Pregnancy category C
    • 46. Nevirapine (NVP, Viramune)
      • Warnings
        • Resistant virus emerges if given as monotherapy  always given in combination w/other retroviral
      • Precautions
        • No dosage increases if rash in first 14 days until rash resolves
        • Caution in renal or hepatic dysfunction
        • Hepatitis has been reported
        • Metabolized by P450 CYP3A  interactions with drugs that share same enzyme system
    • 47. Nevirapine (NVP, Viramune)
      • Adverse effects
        • MOST SIGNIFICANT (also common): Severe rash including SJS  can be life threatening
        • If severe rash or rash in combination w/ fever, blistering, oral lesion, conjunctivitis, swelling, myalgias or arthralgias  D/C immediately (usu. occurs in first 4 wks but may be as late as 8 wks)
        • MOST COMMON: fever, nausea, headache, abnormal LFTs
      • Overdosage
        • No known antidote
    • 48. Indinavir Sulfate (Crixivan)
      • Mechanism of action
        • Binds to active site on protease enzyme  inhibits activity of enzyme  blocks cleavage/division of viral proteins needed to make infectious HIV virions
      • Contraindications
        • Hypersensitivity
        • Metabolized through P450 CYP3A4 competes with & inhibits drugs which share same enzyme system  may lead to toxic levels of other drugs
        • Rifampin is a potent inducer of CYP3A4  decreases serum concentration of idinavir
        • Pregnancy category C
    • 49. Indinavir Sulfate (Crixivan)
      • Warnings
        • May cause nephrolithiasis d/t crystallization of drug  adequate hydration required
        • May require holding dose during acute episode
      • Precautions
        • Sensitive to moisture  keep in original bottle w/desiccant
        • Separate didanosine & indinavir by 2 hrs Normal gastric pH needed for absorption of indinavir BUT didanosine is degraded by acid & requires buffer
    • 50. Indinavir Sulfate (Crixivan)
      • Adverse effects
        • MOST SIGNIFICANT: nephrolithiasis
        • COMMON: abdominal pain, nausea, vomiting, diarrhea, back pain, headahce, insomnia, altered taste
        • Also: hyperbilirubinemia & increases in serum transaminases
        • Lactose intolerant may have greater difficulty w/diarrhea as primary inactive ingredient = lactose
      • Overdosage
        • No data available on overdosage
        • Hemodialysis / peritoneal dialysis unknown
    • 51. Nelfinavir Mesylate (Viracept)
      • Mechanism of action
        • Binds to active site on protease enzyme  inhibits activity of enzyme  blocks cleavage/division of viral proteins needed to make infectious HIV virions
        • Plasma concentrations 2-3x higher with food
      • Contraindications
        • Hypersensitivity
        • Metabolized through P450 CYP3A4 competes with & inhibits drugs which share same enzyme system  may lead to toxic levels of other drugs
        • Rifampin is a potent inducer of CYP3A4  decreases serum concentration of nelfinavir
        • Pregnancy category B
    • 52. Nelfinavir Mesylate (Viracept)
      • Precautions
        • Metabolized through P450 CYP3A4 competes with & inhibits drugs which share same enzyme system  may lead to toxic levels of other drugs
        • Give with caution in hepatic impairment
        • Plasma concentrations of OCPs may be decreased
        • Reduce rifabutin dose in half if given concomitantly (decreases plasma concentration of nelfinavir by 37-207%)
    • 53. Nelfinavir Mesylate (Viracept)
      • Adverse effects
        • MOST COMMON: diarrhea nausea & vomiting when given with AZT
      • Overdosage
        • No specific antidote
        • Emesis or gastric lavage
        • Also: activated charcoal
    • 54. Ritonavir (Norvir)
      • Mechanism of action
        • Binds to active site on protease enzyme  inhibits activity of enzyme  blocks cleavage/division of viral proteins needed to make infectious HIV virions
        • Absorption improved by 15% when taken with food
      • Contraindications
        • Hypersensitivity
        • Large increases in plasma concentrations of oxidatively metabolized drugs (esp. hypnotic & sedative drugs  dangerous toxicities including arrhthmias & respiratory depression  contraindicated w/ritonavir)
        • Pregnancy category B
    • 55. Ritonavir (Norvir)
      • Warnings
        • Large number of potential drug interactions
        • Caution in impaired liver function
        • Contains alcohol in formulation  coadministration of disulfuram or metronidazole  antabuse-type reaction
      • Precautions
        • Tobacco decreases plasma concentration
        • Many drug interactions including OCPs
    • 56. Ritonavir (Norvir)
      • Adverse effects
        • MOST COMMON: generalized weakness, nausea, vomiting, diarrhea, anorexia, abdominal pain, change in taste, numbness & tingling around mouth, paresthesias
        • Fewer GI side effects if taken w/high fat meal
        • GI effects sibside over time (4-5 wks)
        • LABS: elevations in hepatic transaminases, bilirubin, triglycerides, creatinine phosphokinase, & uric acid
      • Overdosage
        • Limited information & no specific antidote
        • Emesis or gastric lavage
        • Dialysis NOT helpful as drug is highly protein-bound& extensively metabolized by liver
    • 57. Saquinavir Mesylate (Invirase)
      • Mechanism of action
        • Binds to active site on protease enzyme  inhibits activity of enzyme  blocks cleavage/division of viral proteins needed to make infectious HIV virions
      • Contraindications
        • Hypersensitivity
        • Rifampin decreases serum concentration 80%
        • Metabolized through P450 CYP3A4 competes with & inhibits drugs which share same enzyme system  may lead to toxic levels of other drugs
        • Pregnancy category B
    • 58. Saquinavir Mesylate (Invirase)
      • Warnings
        • Metabolized through P450 CYP3A4 competes with & inhibits drugs which share same enzyme system  may lead to toxic levels of other drugs
        • Many drug interactions
      • Precautions
        • Caution in hepatic insufficiency
    • 59. Saquinavir Mesylate (Invirase)
      • Adverse effects
        • MOST COMMON: diarrhea, abdominal discomfort, nausea
        • Lactose intolerant may have greater difficulty w/diarrhea as primary inactive ingredient = lactose
      • Overdosage
        • Information limited
        • Emesis
    • 60. Enfuvirtide (Fuzeon, T-20)
      • Contraindications
        • Hypersensitivity
      • Warnings
        • Local injection site reaction: pain, induration, erythema, nodules, cysts, pruritis, ecchymosis
        • Increased rate of bacterial pneumonia – monitor for s/s of pneumonia
        • Hypersensitivity reaction may occur on rechallenge – D/C drug on development of Sx’s suggestive of systemic hypersensitivity
    • 61. Retrovirus: DNA Transcription
    • 62. Retrovirus: Viral RNA Transcription
    • 63. Retrovirus Production
    • 64. Viral Replication
    • 65. Steps of Viral Replication
      • HIV binds to CD4 cell.RNA, proteins & enzymes released.
      • HIV reverse transcriptase converts viral RNA into DNA.
      • HIV DNA moves to nucleus & spliced into host’s DNA.
      • HIV RNA moves out of the nucleus into cytoplasm & makes long chains of viral proteins & enzymes.
      • Immature viral particle forms containing cellular & HIV proteins. Chains cut into smaller pieces by protease.
      • Infectious viral particle ready to be released containing HIV RNA, viral proteins & enzymes.
    • 66. HIV Testing
      • p24 Antigen
        • Used to detect HIV antigen in children younger than 18 months
        • Test can be useful at any age
        • Only a positive result is significant
        • Two or more positive results are diagnostic for HIV infection
      • CD4+
        • Used to assess immune status, risk for disease progression, and need for PCP prophylaxis