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Antiretroviral Drugs

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Antiretroviral Drugs Antiretroviral Drugs Presentation Transcript

  • Antiretroviral Drugs
  • 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
  • Body Fluids: Transmissible
    • Blood
    • Semen
    • Vaginal secretions
    • Breast milk
    • Cerebral spinal fluid
    • Synovial fluid
    • Pleural & amniotic fluid
  • 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
  • Body Fluids: Non-transmissible Important to know how you DON”T get HIV!
    • Urine
    • Sweat
    • Saliva
    • Tears
    • Vomit
    • Mucous
    • Feces
  • 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
  • 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
  • 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
  • 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.
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Didanosine (ddI, Videx)
    • Adverse Effects
      • Pancreatitis
      • Peripheral neuropathy
      • Diarrhea
      • Hyperuricemia
      • Possible hepatic dysfunction
    • Overdose
      • Limited information on acute toxicity
      • Hemodialysis / peritoneal dialysis unknown
  • 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
  • Lamivudine (3TC, Epivir)
    • Warnings
      • Pancreatitis (rare)
    • Precaution
      • Reduction in dose in renal impairment
      • Bactrim increases blood concentration & decreases clearance of drug
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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%)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Retrovirus: DNA Transcription
  • Retrovirus: Viral RNA Transcription
  • Retrovirus Production
  • Viral Replication
  • 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.
  • 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