FUN2: 10:00-11:00Scribe: Ryan O’Neill

Friday, December 5, 2008Proof: Caitlin Cox

Dr. KingANTIVIRAL ANANTIRETROVIRAL PHARMACOLOGYPage1 of 15

HPV – Human Papillomavirus, CMV – Cytomegalovirus, HSV – Herpes Simplex Virus, VZV - Varicella Zoster VirusIFN – interferon, ASE – Adverse Side Effects, IV – intravenously, TK – thymidine kinase,

CYP450 – Cytochrome P450, PI - protease inhibitor, CDV – cidofovir, TP – triphosphate, HBV – Hepatitis B Virus, HCC – hepatocellular carcinoma

NOTE: The 95-slide lecture was combined into one transcript for convenience purposes, even though a break was taken between slides 65 and 66.

  1. Introduction [S1]:
  2. Objectives [S2]
  3. Virus Life Cycle
  4. Target steps for drug therapy
  5. Disease Management that are affected by the following viruses.
  6. Herpes Simplex Virus (HSV)/ Varicella Zoster Virus (VZV)
  7. Cytomegalovirus (CMV)
  8. Influenza Virus
  9. Hepatitis B and C
  10. HIV & Immunopharmacological agents
  11. Viral Replication [S3]
  12. Virus life cycle on right hand side of slide.
  13. There are various classes of drugs that work at 5 of the steps of the life cycle. Once a virus binds, fuses, and penetrates a host cell, the nucleic acids become available through uncoating. Once they are available, then transcription, translation and genomic replication can occur. Then the virus assembles and buds off as you will notice at the bottom of the diagram.
  14. Classes of drugs that work at various life cycle stages:
  15. Inhibitors of uncoating
  16. Inhibitors of transcription
  17. Inhibitors of translation
  18. Inhibitors of RNA or DNA genomic replication
  19. Inhibitors of virus release
  20. Note: the specific drugs weren’t mentioned here, but are mentioned later in the lecture.
  21. INHIBITORS OF UNCOATING [S4]
  22. Amantadine (Symmetrel) [S5]
  23. Note the picture of the influenza virus with the M2 protein and hemagglutinin highlighted.
  24. Mechanism of Action
  25. Inhibits uncoating of the virus (thus replication) by interfering with the influenza A virus M2 protein, which serves as an ion channel
  26. Amantadine only works on influenza A and not influenza B.
  27. Pharmacology
  28. Available orally
  29. Renal excretion (have to decrease the dose in renal dysfunction patients)
  30. Therapeutic Uses
  31. Influenza A virus prophylaxis and treatment
  32. Dose: preferred dose is twice a day compared to once a day; don’t need to know the dosing, just know that it comes with the side effects of side effects dizziness and insomnia. Twice a day will decrease the side effects.
  33. Resistance Issues
  34. 100% cross-resistant to rimantadine (next agent)
  35. Rimantadine (Flumadine) [S6]
  36. Mechanism of Action
  37. Same as amantadine (works on influenza A and M2 protein)
  38. Pharmacology
  39. Hepatic metabolism:  dose in hepatic disease
  40. Renal excretion :  dose in renal disease
  41. Therapeutic Uses
  42. Influenza A virus prophylaxis and treatment (just like Amantadine)
  43. Equally as effective as amantadine; less side effects
  44. Therefore, rimantadine is preferred over amantadine.
  1. Resistance Issues
  2. 100% cross-resistant to amantadine
  3. If a patient comes in with the flu and there is resistance to amantadine, then rimantadine is not going to work.
  4. These two drugs are rarely used.
  5. We will see later on in the lecture that Tamiflu is mostly used to treat influenza (slide 36).
  1. [SQ]: Are you saying that cross-resistance is when a drug is ineffective and a similar mechanism drug is also ineffective because of the similarity?
  2. [A]: Yes.It is due to the similar mechanisms of action.
  1. INHIBITORS OF TRANSCRIPTION [S7]
  2. Interferon (IFN) [S8]
  3. Family of cytokines that evoke complex intracellular effects:
  4. Antiviral, Antiproliferative, Immunomodulating
  5. 3 major classes of IFNs (alpha, beta and gamma) prepared by recombinant technology
  6. alpha and beta produce the antiviral effects (e.g. hepatitis B & C, HPV)
  7. gamma has immunomodulatory effects
  8. Interferon- 2b (Intron A) [S9]
  9. Mechanism of Action
  10. Precise mechanism unknown
  11. Stimulate cytokines and proteins causing a state of resistance to virus infection in uninfected cells.
  12. Pharmacology
  13. Administration-typically (subcutaneously) 3 x/week
  14. Therapeutic Uses
  15. Treatment of chronic hepatitis B & hepatitis C infection (in combination with ribavirin for hepatitis C)
  16. Interferon Side Effects [S10]
  17. INF has many side effects as listed on the slide. More prominent side effects are highlighted.
  18. Flu-like symptoms
  19. Depression
  20. Increase susceptibility to bacterial infections
  21. These are the three most common side effects.
  22. Pegylated Interferon [S11]
  23. A type of INF that has the attachment of polyethylene glycol [PEG] that results in:
  24. enhanced plasma half-life; increases time in the body.
  25. half life – time for plasma concentration to fall by 50%; it takes 4 to 5 half-lives for a drug to be cleared by the body; pegylation increases the amount of time the drug is in the body.
  26. lower toxicity
  27. increased drug stability and solubility
  28. Pegylation of a protein may increase the protein’s therapeutic efficacy by reducing the ability of the immune system to attack the compound.
  29. Pegylation increases the molecular weight which reduces excretion rates.
  30. PEG-Interferon- vs. Interferon- [S12]
  31. Half-life illustrated for the pegylated product: 40 hours vs. 4 hours.
  32. Cmax is the maximum concentration in the plasma after a drug is given.
  33. Cmax is much higher for the pegylated product (48-72 hours vs. 8-12 hours).
  34. Regular product is cleared must faster from the body compared to the pegylated.
  35. Concentration vs. time chart. Notice that with the INF (given subcutaneously 3x a week) you have intervals and with the pegylated product you have a steady concentration.
  36. It’s more convenient to give a subcutaneous drug once a week vs. 3 x a week.
  37. This is an advantage of pegylation. Look for the concept of pegylation on the test.
  38. INHIBITORS OF TRANSLATION [S13]
  39. Fomivirsen (Vitravene) [S14]
  40. Mechanism of Action
  41. Nucleotide sequence similar to a sequence in mRNA that encodes proteins needed for production of infectious CMV.
  42. Inhibits CMV replication by blocking translation through an antisense mechanism.
  1. Pharmacology
  2. Administered by intravitreal injection.
  3. Concentrations higher in the retina and iris.
  4. Half-life (t1/2) from the vitreous humor (where the drug is prominently working, especially those with CMV retinitis) is very high (62 hours).
  5. Therapeutic Uses
  6. CMV retinitis in patients with AIDS resistant to other agents that we will talk about.
  7. Adverse events: mostly ocular; blurred vision, inflammation, photophobia.
  8. THIS IS THE ONLY DRUG IN THIS CLASS.
  1. INHIBITORS OF RNA OR DNA GENOMIC REPLICATION [S15]
  2. Acyclovir [S16]
  3. Mechanism of Action
  4. Nucleoside analog of guanosine that is phosphorylated intracellularly to the ACTIVE triphosphate form (important concept for this drug and others within this class).
  5. It is acyclovir-triphosphate that actually has the pharmacological effect.
  6. Inhibits DNA polymerase kinase and terminates elongation of the DNA strand when incorporated as guanosine analog substitute; it mimics the guanosine analog and pretends to be something it is not.
  7. High degree of specificity for viral thymidine kinase, but a poor substrate for host cell-specified thymidine kinase.
  8. Inhibits replication of HSV and VZV in infected cells.
  9. Nucleoside Analog Mechanism of Action [S17]
  10. Acyclovir is phosphorylated by the Herpes thymidine kinase to the monophosphate, diphosphate and triphosphate forms. It is Acyclovir triphosphate that is actually incorporated and acts on the Herpes DNA polymerase.
  11. Acyclovir (Zovirax) [S18]
  12. Pharmacology
  13. Poorly absorbed after an oral dose; has to be given 5x a day, but there is a generic available so it is pretty inexpensive.
  14. Therapeutic Uses – very wide range
  15. Herpes genitalis
  16. Herpes zoster (shingles) and varicella (chickenpox)
  17. Variety of uses in immunocompromised patients, it just depends on the situation.
  18. Valacyclovir (Valtrex) [S19]
  19. The more important of these two drugs. It is actually a prodrug of acyclovir.
  20. Mechanism of Action
  21. L-valine ester of acyclovir (prodrug of acyclovir).
  22. Not active, it must be hydrolyzed in the intestine and/or liver to acyclovir and ultimately intracellular acyclovir triphosphate.
  23. Pharmacology
  24. Significantly enhanced absorption compared to acyclovir.
  25. Advantage of a prodrug – significant absorption compared to acyclovir.
  26. Therapeutic Uses
  27. Same as acyclovir but given QD (once per day) or BID (twice per day) compared to 5 times daily with acyclovir.
  28. Vidarabine (Ara-A) [S20]
  29. Mechanism of Action
  30. Nucleoside analog of adenosine activated by cellular enzymes (kinases) to the triphosphate form as opposed to being activated by the viral enzymes.
  31. Inhibition of cellular- and virus-specific DNA polymerases and ribonucleotides.
  32. Direct incorporation into cellular and viral DNA.
  33. Pharmacology
  34. Topical or intravenous administration only.
  35. Therapeutic Uses
  36. Topically for HSV keratitis and keratoconjunctivitis.
  37. Intravenously for HSV encephalitis, much less effective than acyclovir.
  38. Penciclovir (Denavir) [S21]
  39. Mechanism of Action
  40. Nucleoside analog of guanine that competes with endogenous dGTP for viral DNA polymerase, subsequently preventing viral DNA chain elongation.
  41. High affinity for virus specific thymidine kinase (selective).
  42. Pharmacology
  43. Topical administration that is a cream.
  44. Therapeutic Uses
  45. Predominantly used for cold sores.
  46. Famciclovir (Famvir) [S22]
  47. Mechanism of Action
  48. Prodrug of penciclovir.
  49. Guanine analog (like penciclovir) activated by viral thymidine kinase to penciclovir-TP, which inhibits virus-induced DNA polymerase.
  50. Pharmacology
  51. Oral administration (77% bioavailability – if you take a tablet, only 77% of that tablet actually gets into the systemic circulation).
  52. Therapeutic Uses
  53. Administered bid (twice daily) or tid (three times daily) compared with acyclovir 5 x daily.
  54. Drug of choice in this group tends to be valacyclovir because it is administered once or twice daily.
  55. Trifluridine (Viroptic) & Idoxuridine (Herplex) [S23]
  56. Both are thymidine analogs phosphorylated by cellular thymidine kinase.
  57. Trifluridine
  58. Mechanism of Action
  59. Thymidine analog phosphorylated by cellular TK.
  60. Trifluridine-TP competitively inhibits the natural nucleotide, thymidine triphosphate.
  61. Pharmacology
  62. 1% ophthalmic solution
  63. Therapeutic Uses
  64. Topical treatment of HSV keratitis
  65. Idoxuridine
  66. Mechanism of Action
  67. Thymidine analog phosphorylated by cellular TK.
  68. Produces faulty DNA which can not infect or destroy tissue.
  69. Pharmacology
  70. 0.1% ophthalmic solution
  71. Therapeutic Uses
  72. Topical treatment of HSV keratitis
  73. Ganciclovir (Cytovene) [S24]
  74. Mechanism of Action
  75. Analog of guanosine activated by cellular and viral enzymes to its triphosphate derivative. The viral enzyme is a specific enzyme,UL-97 phosphotransferase, which catalyzes the initial phosphorylation.
  76. Inhibition of CMV DNA polymerase and subsequent incorporation into viral DNA.
  77. (no chain termination)
  78. Pharmacology
  79. Poor oral absorption; Usually administered intravenously.
  80. Therapeutic Uses
  81. Prophylaxis of CMV disease.
  82. Toxicity: bone marrow suppression; also shown to be teratogenic.
  83. Ganciclovir/Valganciclovir Pharmacokinetics [S25]
  84. ASE: dose-related → myelosuppression and renal impairment.
  85. Drug Interactions
  86. Additive toxicity with other cytotoxic drugs.
  87. Nephrotoxic effect that increases SCr (serum creatinine) and patients also receive an amphotericin B or cyclosporine.
  88. Generalized seizures with imipenem.
  89. Valganciclovir
  90. Oral prodrug of ganciclovir.
  91. Note graph on chart with concentration on the y-axis, time on the x-axis.
  92. The line with the highest peak is the IV ganciclovir. If you were to take that same drug and give it orally, that line is indicated towards the bottom.
  93. If you were to shade in the area under the graph that would represent how much drug is in the body referred to as the “AUC” (area under curve).
  94. The middle line is for valganciclovir and its total systemic exposure.
  95. This is a picture representing how the prodrug gets a lot more drug into the body compared to the ganciclovir given orally.
  96. “Val” preceding the drug likely indicates that it is a prodrug (cf. with valacyclovir).
  97. Foscarnet (Foscavir) [S26]
  98. Mechanism of Action
  99. Pyrophosphate analog
  100. No phosphorylation is needed (does not have to be triphosphate to be active).
  101. Directly inhibits HSV DNA polymerase by preventing cleavage of the pyrophosphate from nucleoside triphosphates and thus blocking viral DNA synthesis.
  102. Pharmacology
  103. Poor oral absorption, so it is administered intravenously.
  104. Therapeutic Uses
  105. CMV retinitis
  106. Herpes zoster
  107. Toxicity: nephrotoxic, electrolyte imbalances (hypocalcemia), seizures.
  108. Cidofovir (Vistide) [S27]
  109. Mechanism of Action
  110. Nucelotide analog of cytidine; converted via cellular enzymes to the active diphosphate anabolite.
  111. Where other agents like acyclovir are phosphorylated to the triphosphate form, cidofovir diphosphate is the active component.
  112. Competitively inhibits viral DNA polymerase causing chain termination.
  113. Pharmacology
  114. IV administration only
  115. Therapeutic Uses
  116. Unique property of the drug – if you coadminister it with probenecid, plasma levels will increase
  117. Probenecid - uricosuric agent used for hyperuricemia (gout).
  118. Blocks active tubular re-absorption of uric acid at the proximal renal tubules thereby promoting urinary excretion.
  119. By blocking active tubular secretion and reabsorption, it increases cidofovir (CDV) plasma concentrations & decreases renal clearance (CL).
  120. Dose-dependent nephrotoxicity (59% incidence).
  121. IMPORTANT FACT ABOUT CIDOFOVIR: it is administered with probenecid to increase plasma cidofovir concentrations and decrease renal clearance.
  122. Ribavirin (Virazole) [S28]
  123. Mechanism of Action
  124. Guanosine analog, phosphorylated by cellular kinases to triphosphate active nucleotide with inhibitory activity against RNA and DNA viruses.
  125. Inhibitor of inosine monophosphate dehydrogenase, thus blocking synthesis of dGTP and therefore nucleic acid synthesis.
  126. Inhibits RNA polymerase of influenza viruses and dGTP-dependent 5'-capping of mRNA.
  127. Pharmacology
  128. Orally; good systemic bioavailability following inhalation.
  129. Therapeutic Uses
  130. Orally administered for the Influenza virus; Respiratory syncytial virus (RSV) in children
  131. Most often: chronic hepatitis C infection (with interferon -2b).
  132. Lamivudine (Epivir) [S29]
  133. The next two drugs will be covered briefly because they are discussed in the HIV portion of this lecture.
  134. Both were approved for HIV, but a lot have shown ASE.
  135. Mechanism of Action
  136. Used for hepatitis (and HIV)
  137. Phosphorylated intracellularly to lamivudine-TP form causing DNA chain termination.
  138. Pharmacology
  139. Has low cytotoxicity (not a lot of ASE, as well as with emtricitabine).
  140. Therapeutic Uses
  141. Hepatitis B (& HIV)
  142. Low cytotoxicity
  1. Emtricitabine (Emtriva) [S30]
  2. Mechanism of Action
  3. Similar to lamivudine
  4. Therapeutic Uses
  5. Approved for treatment of HIV, but active against HBV.
  6. One downside: potential cross-resistance with lamivudine if patient has become resistant.
  7. Adefovir dipivoxil (Hepsera) [S31]
  8. Other agent used for hepatitis.
  9. Mechanism of Action
  10. Phosphorylated intracellularly to adefovir diphosphate by cellular kinases.
  11. Inhibits HBV DNA polymerase causing chain termination.
  12. Therapeutic Uses
  13. Used for chronic hepatitis B virus infection.
  14. Originally developed for treatment of HIV, but at efficacious dose was too toxic and caused severe nephrotoxicity. But found out that lower doses could be used without nephrotoxic effects against hepatitis B; can avert toxicity.
  15. Advantage: Effective against 3TC (lamivudine) resistant strains.
  16. Nephrotoxicity can still occur, although it is lower; increased serum creatinine, decreased phosphorus are the main side effects.
  17. Entecavir (Baraclude) [S32]
  18. Mechanism of Action
  19. Nucleoside analog phosphorylated intracellularly to active triphosphate form.
  20. Inhibits HBV DNA polymerase.
  21. Therapeutic Uses
  22. Chronic hepatitis B virus infection.
  23. Less effective against lamivudine resistant HBV compared with wild type HBV.
  24. Wild type virus – someone who has never been exposed to that drug before.
  1. INHIBITORS OF VIRUS RELEASE [S33]
  2. Last group. 2 agents that work for influenza virus.
  3. Influenza viral replication [S34]
  4. Left hand side picture – describes the life cycle of influenza.
  5. Hemagglutnin is an important component of influenza that binds to cell-surface receptors to enter host cells, once inside the cell the viral genome replicates itself and viral proteins and the virions assemble at cell surface, and bud via neuraminidase-mediated cleavage. This enzyme is essential to free the virus from the host cell.
  6. Zanamavir (Relenza) [S35]
  7. Mechanism of Action
  8. Selective inhibitor of influenza A and B (compare with amantadine and ramantadine that only work for influenza A) virus neuraminidases.
  9. Prevents infection by stopping the release of newly formed virions from the surface of infected cells.
  10. Pharmacology
  11. Disadvantage: not orally bioavailable, only inhalation.
  12. [SQ]: On the top of the slides, which name do we need to be familiar with for testing?
  13. [A]: The first one, the generic name. The brand is included just for familiarity purposes.
  14. Oseltamivir (Tamiflu) [S36]
  15. Most used drug in this class.
  16. Mechanism of Action
  17. Ethyl ester prodrug requiring ester hydrolysis to the active form, oseltamivir carboxylate.
  18. Active against influenza type A and B and is a neuraminidase inhibitor.
  19. HERPES SIMPLEX VIRUS (HSV) AND VARICELLA ZOSTER VIRUS (VZV) [S37]
  20. Herpes Simplex Virus [S38]
  21. Viral infection of the skin and/or mucous membranes; often presents as bumps that burst.
  22. After initial infection, the virus can reside in nerve tissue.
  23. In some people, the virus remains dormant. Recurrent infection 4-5 times/year; infection reoccurs to decreased resistance to the disease (e.g. sun exposure, cold, stress).
  24. 2 subtypes of HSV: HSV-1 and HSV-2.
  25. Appearance of vesicles or skin lesions occurs 2-20 days post exposure.
  26. Infection occurs approximately 2 weeks.
  1. Oral Facial Herpes [S39]
  2. Cold sores are the most common and are represented by HSV-1 subtype.
  3. Pain, erythema or papular lesions followed by swelling.
  4. Drug of choice: penciclovir, but clinically more prescriptions are written for valacyclovir.
  5. Herpes Simplex Virus- Oral Manifestations [S40]
  6. Patients with recurrent intraoral herpes.
  7. Genital Herpes [S41]
  8. 45 million Americans have genital HSV infection (1 in 5 Americans).
  9. Early symptoms of a genital herpes outbreak include:
  10. Itching or burning feeling in the genital or anal area
  11. Discharge of fluid from the vagina
  12. Feeling of pressure in the abdomen
  13. Sores appear where virus entered body (2-20 days after exposure).
  14. Treatment options:
  15. Acyclovir – more affordable for those who don’t have insurance
  16. Valacyclovir – predominantly seen because it’s once or twice daily and acyclovir is generic
  17. Famciclovir
  18. Herpes Keratitis and Blepharitis [S42]
  19. Herpes Keratitis
  20. HSV-1 common pathogen
  21. Topical antivirals: trifluridine, idoxuridine, vidarabine
  22. Herpes Blepharitis (bottom picture)
  23. Primarily in children
  24. Pain, tenderness, increased lacrimation
  25. Treatment: warm saline with a topical drying agent.
  26. Trifluridine in cases with corneal involvement.
  27. Neonatal HSV and HSV encephalitis [S43]
  28. Complications of HSV include:
  29. Neonatal Herpes
  30. Acquired from infected genital secretions of mother at time of delivery.
  31. Presents in 1 of 3 forms:
  32. Localized to skin, eye and mouth
  33. Encephalitis
  34. Disseminated disease
  35. Treatment options:
  36. Vidarabine or acyclovir
  37. Acyclovir is shown to be more effective
  38. Herpes simplex virus encephalitis
  39. Acute onset of fever, headache, decreased consciousness and seizures
  40. As a result of HSV-1 and HSV-2.
  41. Drugs are the same: acyclovir vs. vidarabine.
  42. Administered intravenously - that’s why you wouldn’t use valacyclovir.
  43. Varicella Zoster Virus (Chickenpox) [S44]
  44. Vaccine became available in 1995.
  45. Complications include bacterial infection of skin and in some cases pneumonia.
  46. Acyclovir therapy
  47. Not recommended for healthy children.
  48. Only with patients with progress varicella, immunocompromised hosts.
  49. Supportive treatment - calamine lotion and/or diphenhydramine.
  50. Herpes Zoster (Shingles) [S45]
  51. Reactivation of dormant VZV in sensory neurons is known as Shingles.
  52. Typically seen in older patients - incidence increases with ↑ age or ↓ immune system.
  53. Aching, burning, sensitivity to touch
  54. Rash turns into vesicles that crust or burst in 7-10 days.
  55. Treatment:
  56. Acyclovir
  57. Valacyclovir
  58. Famciclovir
  59. Postherpetic neuralgia can be seen in patients with Shingles, there are burning sensations in fingers and toes with no treatment.
  1. CYTOMEGALOVIRUS (CMV) [S46]
  2. CMV [S47]
  3. Most people in a big city have been exposed to CMV.
  4. Remains dormant in body; only becomes a problem in patients who have a deficiency in cytotoxic T cells.
  5. Most significant syndromes occur among immunocompromised patients; seen in a lot of HIV patients.
  6. Causes:
  7. Retinitis (most common), colitis, encephalitis
  8. Prophylaxis: Ganciclovir
  9. Treatment:
  10. Ganciclovir / Valganciclovir
  11. Foscarnet
  12. Cidofovir
  13. Fomivirsen
  14. CMV Retinitis [S48]
  15. Left picture – appears to be a normal retina.
  16. Right picture – CMV retinitis that results in increased risk of retinal detachment, hemorrhages and inflammation of the retina.
  17. INFLUENZA [S49]
  18. Influenza [S50]
  19. Known as the flu.
  20. 30-55 million are infected during November-March.
  21. Yearly immunization is the primary strategy for preventing influenza.
  22. Vaccine alone does not protect against all strains of influenza.
  23. Treatment options:
  24. Amantadine
  25. Ramantadine
  26. Only type A because of M2 protein.
  27. Zanamivir
  28. Oseltamivir
  29. Work against type A and B.
  30. HEPATITIS B AND HEPATITIS C [S51]
  31. Extremely complicated diseases.
  32. Chronic Hepatitis B : Goals of Therapy [S52]
  33. Suppression of viral replication
  34. When we treat patients with hepatitis B, our goal is to decrease the amount of hepatitis B DNA in the system; elimination of circulating HBV DNA.
  35. Often affects the liver and liver enzymes become elevated.
  36. Treat the elevated liver enzymes by normalization of serum aminotransferase activity
  37. Normal ALT = decrease to 5 to 40 U/L
  38. Normal AST = decrease to 5 to 40 U/L
  39. Liver often increases in size so we want to decrease the inflammation on liver biopsy.
  40. Reduction in long-term sequelae of HBV-associated liver disease.
  41. There is also a hepatitis B vaccine now.
  42. Hepatitis C: Goals of Therapy [S53]
  43. Still a huge problem.
  44. Primary objective = sustained viral response
  45. No virus in the body
  46. Arrest progression of cancer, especially in the liver
  47. No symptoms
  48. Secondary objective
  49. Reduce progression of fibrosis
  50. Reduce progression to cirrhosis
  51. Prevent decompensation
  52. Prevent HCC
  53. Treatment
  54. Pegylated Interferon + Ribavirin
  1. Case #1 [S54]: MK, a 23 year old male, developed pain and erythematous skin lesions on his face and around his mouth over a 2-day period after a night of dancing at Bell Bottoms and kissing a girl with active lesions.