191: Antiviral Drugs

Question 1

What is the mechanism of action of Acyclovir in treating HSV and VZV infections?

Answer 1

Acyclovir is a triphosphate form that has a potent inhibitory effect on herpesvirus-induced DNA polymerases, causing premature termination of nascent viral DNA chains while having relatively little effect on host cell DNA polymerase.

Question 2

What are the primary indications for Acyclovir use?

Answer 2

Acyclovir is indicated for symptomatic primary or recurrent HSV1/2 infections, chronic suppression of HSV1/2 infections, HSV encephalitis, primary VZV infection, herpes zoster, prevention and treatment of neonatal HSV infection, HSV gingivostomatitis and orolabial cold sores (off-label), prevention of HSV, CMV, or VZV reactivation in hematopoietic stem cell transplant and HIV patients (off-label), and new onset Bell palsy (off-label).

Question 3

What are the common side effects and precautions associated with Acyclovir?

Answer 3

Common side effects and precautions include renal impairment, renal tubular crystallization with rapid IV administration, CNS toxicity, thrombo-phlebitis, and pregnancy category B.

Question 4

What is the bioavailability of Acyclovir when administered orally, and how does it distribute in the body?

Answer 4

Acyclovir has an oral bioavailability of 15-30% and is water soluble, allowing it to distribute widely throughout the body, including into the contents of vesicles, cerebrospinal fluid (CSF), and vaginal secretions.

Question 5

What is the half-life of Acyclovir in different patient populations?

Answer 5

The half-life of Acyclovir varies by patient population: Neonates: 4 hours, Children: 2-3 hours, Adults: 2-3.5 hours, Hemodialysis patients: 5 hours.

Question 6

What is the active form of Acyclovir, and how does it work?

Answer 6

The active form is acyclovir triphosphate, which inhibits herpesvirus-induced DNA polymerases and causes premature termination of viral DNA.

Question 7

What is the mechanism of action and pharmacokinetics of Valacyclovir?

Answer 7

Valacyclovir is readily absorbed from the GI tract and almost entirely converted to acyclovir by intestinal and hepatic esterases. Its spectrum of activity is identical to acyclovir but improved. Oral bioavailability is 55%. Half-life: Children: 1.3 - 2.5 hours, Adults: 30 minutes. Excretion is primarily renal.

Question 8

What are the indications for Valacyclovir?

Answer 8

Indications include initial and recurrent HSV genital infections, suppression and reduction of transmission of genital HSV infections, herpes zoster, herpes labialis, and varicella (chickenpox).

Question 9

What are the common side effects and precautions associated with Valacyclovir?

Answer 9

Common side effects include acute renal failure, CNS effects (e.g., agitation, hallucinations, seizures, encephalopathy), immediate hypersensitivity, and severe effects of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) among AIDS and transplant patients.

Question 10

What is the advantage of Valacyclovir over Acyclovir?

Answer 10

Valacyclovir has improved oral bioavailability (55%) compared to acyclovir (15-30%), making it more effective for oral administration.

Question 11

What is the mechanism of action of Famciclovir and Penciclovir?

Answer 11

Famciclovir is biotransformed to Penciclovir, which is phosphorylated to penciclovir triphosphate. This compound inhibits HSV-2 polymerase and viral DNA polymerases, similar to acyclovir, but allows for more DNA chain extension.

Question 12

What are the indications for using Famciclovir and Penciclovir?

Answer 12

Indications include initial and recurrent HSV genital infections, suppression of frequently recurring genital HSV infections, initial and recurrent HSV labialis infections, herpes zoster, and varicella infection in HIV patients (off-label).

Question 13

What are the dosing regimens for Famciclovir in treating primary HSV infection in an immunocompetent host?

Answer 13

Dosage: 250 mg 3x/d, Route: Oral, Duration: 7-10 days.

Question 14

What are the common side effects and precautions associated with Famciclovir and Penciclovir?

Answer 14

Common side effects include headache, nausea, diarrhea, and dizziness. Pregnancy category: B.

Question 15

What is the recommended time frame for initiating treatment with Famciclovir and Penciclovir after rash onset?

Answer 15

Treatment should be initiated within 72 hours of rash onset.

Question 16

What is the mechanism of action of Trifluridine?

Answer 16

Trifluridine is a pyrimidine nucleoside analog that acts as an irreversible competitive inhibitor of thymidylate synthetase and inhibits HSV DNA polymerase through its triphosphate form.

Question 17

What are the primary indications for Trifluridine?

Answer 17

Trifluridine is indicated for primary and recurrent HSV keratoconjunctivitis, keratitis, and acyclovir-resistant mucocutaneous HSV infections in patients with AIDS (off-label).

Question 18

What are the dosing regimens for Trifluridine?

Answer 18

For HSV keratoconjunctivitis, induction: 1 drop every 2 h (maximum, 9 drops/24 h), maintenance: 1 drop every 4 h (maximum, 6 drops/24 h). For acyclovir-resistant HSV infection in AIDS: 1 drop every 8 h.

Question 19

What are the common side effects and precautions associated with Trifluridine?

Answer 19

Common side effects include transient local burning or stinging, palpebral edema, epithelial and punctate keratopathy, and stromal edema. Pregnancy category: C.

Question 20

What is the mechanism of action of Ganciclovir in treating cytomegalovirus infections?

Answer 20

Ganciclovir is phosphorylated by viral kinases to a substrate that competitively inhibits the binding of deoxyguanosine triphosphate to DNA polymerase, thus inhibiting viral DNA synthesis.

Question 21

What are the primary indications for Ganciclovir and Valganciclovir?

Answer 21

Indications include CMV retinitis in immunocompromised patients, suppression and prevention of CMV disease in transplant recipients, and CMV esophagitis, colitis, or neurologic disease in HIV patients (off-label).

Question 22

What are the common side effects associated with Ganciclovir and Valganciclovir?

Answer 22

Common side effects include gastrointestinal issues (diarrhea, nausea, loss of appetite), hematologic issues (anemia, thrombocytopenia, bone marrow aplasia, aplastic anemia), acute renal failure, and neurological symptoms.

Question 23

What is the elimination half-life of Ganciclovir?

Answer 23

The elimination half-life of Ganciclovir is 4 hours.

Question 24

What are the dosing regimens for Ganciclovir in treating CMV retinitis?

Answer 24

Induction: 900 mg 2 times a day (oral) or 5 mg/kg every 12 hours (IV). Maintenance: 900 mg every day (oral) or 5 mg/kg every day (IV) until CD4 count >100 after 6 months of HAART.

Question 25

What is the mechanism of action of Foscarnet?

Answer 25

Foscarnet noncompetitively inhibits viral DNA polymerases at the pyrophosphate binding site.

Question 26

What are the primary indications for Foscarnet?

Answer 26

Foscarnet is indicated for CMV retinitis, acyclovir-resistant HSV infections, CMV esophagitis or colitis (off-label), and ganciclovir-resistant CMV infections (off-label).

Question 27

What are the dosing regimens for Foscarnet in treating CMV retinitis?

Answer 27

Induction: 90 mg/kg IV every 12 hours for 14-21 days. Maintenance: 90 mg/kg IV every 24 hours until CD4 count >100 on 6 months of HAART.

Question 28

What are the major side effects and precautions associated with Foscarnet?

Answer 28

Major side effects include renal toxicity, electrolyte imbalances, nausea/vomiting with diarrhea, anemia, granulocytopenia, fever, headache, and pregnancy category C risk.

Question 29

What drugs can potentiate the effects of Foscarnet?

Answer 29

Drugs that can potentiate the effects of Foscarnet include Acyclovir/Valacyclovir, aminoglycosides, amphotericin B, cyclosporine, QTc-prolonging agents, methotrexate, and tacrolimus.

Question 30

What are the indications for the use of Cidofovir?

Answer 30

Indications include CMV retinitis and acyclovir-resistant HSV infections (off-label).

Question 31

What are the contraindications for Cidofovir?

Answer 31

Contraindications include those with preexisting renal impairment (serum creatinine >1.5 or >2+ proteinuria).

Question 32

What is the dosing regimen for Cidofovir in treating CMV retinitis?

Answer 32

Induction: 5 mg/kg IV every week for 2 weeks. Maintenance: 5 mg/kg IV every 2 weeks until CD4 count > 100 after 6 months on HAART.

Question 33

What are the common side effects associated with Cidofovir?

Answer 33

Common side effects include nausea, alopecia, rash, fever, myalgias, asthenia, headache, abdominal pain, diarrhea, dyspepsia, flatulence, increased creatinine, pancreatitis, and hypophosphatemia.

Question 34

What serious renal side effects are associated with Cidofovir?

Answer 34

Serious renal side effects include renal tubular damage, dose-dependent proximal tubular injury (Fanconi-like), proteinuria, and elevated serum creatinine levels.

Question 35

What should Cidofovir not be used with?

Answer 35

Cidofovir must NOT be used with tenofovir disoproxil fumarate (TDF).

Question 36

What is the pregnancy category of Cidofovir?

Answer 36

Pregnancy category C.

Question 37

What are the mechanisms of action and pharmacokinetics of interferons?

Answer 37

Interferons have broad antiviral and immunomodulating effects and are commonly given subcutaneously.

Question 38

What are the contraindications for cidofovir?

Answer 38

Contraindications include preexisting renal impairment (serum creatinine >1.5 or >2+ proteinuria).

Question 39

What are the mechanisms of action and pharmacokinetics of interferons?

Answer 39

- Interferons have broad **antiviral** and **immunomodulating** effects. - Commonly given **subcutaneously**. - Plasma half-life: - > 2 to 3 hours after **IV administration**. - > 4 to 6 hours after **SC/IM administration**. - **Pegylated interferon** has a prolonged half-life.

Question 40

What are the indications for the use of interferons?

Answer 40

- **IFN-alpha**: viral infections, neoplastic diseases including melanoma. - **IFN-beta**: multiple sclerosis. - **IFN-gamma**: chronic granulomatous disease. - Off-label uses include: - Chronic myelogenous leukemia - Cutaneous T-cell lymphoma - Behçet disease - Desmoid tumor - Multiple myeloma - Neuroendocrine tumors - Renal cell carcinoma - West Nile virus

Question 41

What are the common side effects and precautions associated with interferons?

Answer 41

- Common side effects include: - **Flulike symptoms**: fever, chills, tachycardia, malaise, myalgia, headache (within 1 to 2 hours). - Injection site reactions, alopecia, psoriasis, fixed drug eruptions, eczematous drug reactions, sarcoidosis, lupus, pigmentary changes, and lichenoid eruptions. - Bone marrow suppression, GI- and hepatotoxicity. - Aggravate neuropsychiatric events. - Precautions: - Should NOT be used to treat hepatitis B-related cirrhosis or decompensated liver disease due to risk of further decompensation. - Pregnancy risk factor C. - Interferon + ribavirin is category X.

Question 42

What viral diseases are treated with interferon?

Answer 42

- **Condylomata acuminata** (intralesional). - **Chronic hepatitis C infection** (with or without ribavirin, IM, SC). - **Chronic hepatitis B infection** (IM, SC). - **AIDS-related Kaposi sarcoma** (IM, SC).

Question 43

What are the dosing regimens for interferons?

Answer 43

| Condition | Dosage | Route | Duration | |-----------|--------|-------|----------| | Kaposi sarcoma | IFN-α2b 30 million units 3x/week | IM, Subcutaneous | Dependent on response | | Condyloma acuminata | IFN-α2b 1 million units 3x/week | Intralesional | 3 weeks | | Chronic hepatitis C (with ribavirin) | PEG-IFN-α2a 180 µg once a week or PEG-IFN-α2b 1.5 µg/kg once a week | Subcutaneous | Dependent on response and genotype | | Chronic hepatitis B | IFN-α2b 10 million units 3x/week | IM, Subcutaneous | 16 weeks |

Question 44

What are the seven stages of the HIV life cycle?

Answer 44

1. **Binding/Attachment**: Viral envelope glycoprotein binds to host receptors (CD4) and coreceptors (CCR5 or CXCR4). 2. **Fusion**: HIV envelope and host cell membrane fuse, allowing viral capsid entry. 3. **Reverse Transcription**: Viral reverse transcriptase converts HIV RNA into double-stranded DNA. 4. **Integration**: Viral integrase integrates viral DNA into host DNA. 5. **Replication**: HIV protein chains and RNA are produced using host cell machinery. 6. **Assembly**: Newly replicated proteins and RNA move to the host cell surface and assemble into immature virions. 7. **Budding and Maturity**: Newly formed virion buds out of the host cell, releasing protease that breaks up viral protein chains, resulting in mature virions.

Question 45

What are the recommended conditions for initiating antiretroviral therapy (ART) in HIV-infected individuals?

Answer 45

ART is recommended for all HIV-infected individuals and should be initiated soon after diagnosis. Conditions that increase urgency for therapy include: 1. **Pregnancy** 2. **Presence of HIV-related complications** 3. **Opportunistic infections** 4. **Chronic hepatitis B and C infection** 5. **Acute symptomatic HIV infection** 6. **CD4 ≤ 200 cells/μL**, rapidly declining CD4 counts, and higher viral loads (>100,000 copies/mL).

Question 46

What is the recommended action when initial suppression of HIV is not achieved or is lost?

Answer 46

Rapidly change to a new regimen with at least 2 active drugs.

Question 47

What is the typical time frame for viral load reduction to below limits of assay detection in an ART-naive patient?

Answer 47

Viral load reduction usually occurs within the first 12 to 24 weeks of therapy.

Question 48

What are some factors that may predispose individuals to adverse effects of antiretroviral therapy (ARV)?

Answer 48

Factors include: - Concomitant use of medications with overlapping and additive toxicities - Comorbid conditions that increase the risk of or exacerbate adverse effects - Drug-drug interactions that may lead to an increase in drug toxicities - Genetic factors that predispose patients to abacavir (ABC) hypersensitivity reaction.

Question 49

What are the two types of prophylaxis mentioned for HIV prevention?

Answer 49

1. Preexposure Prophylaxis (PrEP) 2. Postexposure Prophylaxis

Question 50

What is a key consideration regarding drug interactions in antiretroviral therapy?

Answer 50

Pharmacokinetic (PK) drug-drug interactions between antiretroviral (ARV) drugs and concomitant medications may lead to changes in drug exposure.

Question 51

What is the mechanism of action of Maraviroc?

Answer 51

Maraviroc selectively binds to the human chemokine receptor CCR5 on the cell membrane, preventing the interaction of HIV-1 gp120 and CCR5 necessary for CCR5-tropic HIV-1 to enter cells.

Question 52

What are the side effects and precautions associated with Enfuvirtide?

Answer 52

Enfuvirtide can cause mucocutaneous side effects such as local injection site reactions, induration, erythema, nodules, and cysts. Other side effects include gastrointestinal upset and an increased risk of bacterial pneumonias.

Question 53

What are the side effects associated with Abacavir?

Answer 53

Abacavir can cause fatal hypersensitivity reactions, particularly in patients with the HLA-B*5701 allele, who are at a higher risk.

Question 54

What are the common side effects of Emtricitabine?

Answer 54

Emtricitabine can cause fat redistribution, leading to an increased amount of fat in the upper back and neck ('buffalo hump'), breast, and around the trunk. It may also cause hyperpigmentation primarily of palms and/or soles, and various types of rash including hypersensitivity reactions.

Question 55

What are the side effects of Didanosine?

Answer 55

Didanosine can cause rash, pruritus, xerostomia, alopecia, lipodystrophy, SJS, vasculitis, pancreatitis, and peripheral neuropathy.

Question 56

What are the side effects of Lamivudine?

Answer 56

Lamivudine can cause alopecia, rash, pruritus, fat redistribution, and neutropenia.

Question 57

What are the side effects of Tenofovir?

Answer 57

Tenofovir can cause rash (including macular, papular, pustular, vesiculobullous, or urticarial), pruritus, diaphoresis, headache, and nausea. It can also elevate didanosine levels and lower atazanavir levels.

Question 58

A patient with HIV is experiencing hypersensitivity reactions characterized by rash and organ dysfunction. Which drug is likely responsible?

Answer 58

Abacavir is likely responsible. The HLA-B*5701 allele increases the risk of hypersensitivity reactions.

Question 59

A patient with HIV is prescribed maraviroc. What is its mechanism of action?

Answer 59

Maraviroc selectively binds to the CCR5 receptor, preventing HIV-1 entry into cells. Major side effects include hepatotoxicity and mucocutaneous reactions like Stevens-Johnson syndrome.

Question 60

A patient with HIV is prescribed enfuvirtide. What is its mechanism of action?

Answer 60

Enfuvirtide mimics a portion of glycoprotein 41, preventing viral fusion with the host cell membrane. Common side effects include local injection site reactions.

Question 61

A patient with HIV is experiencing severe hypersensitivity reactions. Which genetic test should be performed before initiating therapy?

Answer 61

The HLA-B*5701 test should be performed to assess the risk of abacavir hypersensitivity.

Question 62

What are the side effects associated with Zidovudine?

Answer 62

- **Lipodystrophy** - Skin/nail pigmentation changes (blue) - Stevens–Johnson syndrome - Toxic epidermal necrolysis - Urticaria and morbilliform eruption - Bone marrow suppression - GI intolerance - **Mitochondrial toxicity**: may manifest as hepatic steatosis, peripheral neuropathy, pancreatitis, dyslipidemia, fat maldistribution, and lipoatrophy. - Lamivudine + didanosine + nelfinavir may cause onset of bullous pemphigoid.

Question 63

What is the mechanism of action of Non-Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NNRTIs)?

Answer 63

NNRTIs bind near the catalytic site of reverse transcriptase and alter the enzymes’ ability to change conformation, which increases enzyme rigidity and prevents normal polymerization function, thereby reducing the viral replication rate.

Question 64

What are the side effects and precautions associated with Etravirine?

Answer 64

- **Self-limiting rash** (19%) - **Teratogenic** effects - Requires acidic environment for absorption; must not be given with H2 blockers.

Question 65

What are the side effects of Raltegravir?

Answer 65

- Severe, potentially life-threatening and fatal skin reactions (e.g., SJS, hypersensitivity reaction, TEN).

Question 66

What is the mechanism of action of Integrase Strand Transfer Inhibitors (INSTIs)?

Answer 66

INSTIs inhibit HIV integrase, preventing the integration of HIV-1 DNA into host genomic DNA, which blocks the formation of the HIV-1 provirus and propagation of the viral infection.

Question 67

What are the common side effects of Protease Inhibitors (PIs)?

Answer 67

- **Lipodystrophy**: most common side effect, may relate to inhibition of ZMPSTE24. - Other mucocutaneous side effects include: - Morbilliform rash - Generalized erythema - SJS - Striae - Paronychia - Ingrown toenails - Pruritus - Xerosis - Desquamative cheilitis - Icterus (especially with atazanavir)

Question 68

What is the role of Ritonavir in the treatment of HIV?

Answer 68

Ritonavir is used for its good oral bioavailability, but side effects limit the dose. It is also metabolized via the hepatic cytochrome P450 (CYP) system and is often used to boost the effects of other protease inhibitors.

Question 69

A patient with HIV is experiencing severe lipodystrophy. Which class of drugs is most likely responsible?

Answer 69

Nucleoside reverse transcriptase inhibitors (NRTIs) are most likely responsible. The hallmark toxicity is mitochondrial toxicity, which can manifest as hepatic steatosis and lipoatrophy.

Question 70

A patient with HIV is on a protease inhibitor regimen and develops lipodystrophy. What is the likely mechanism behind this side effect?

Answer 70

Lipodystrophy may be related to the inhibition of ZMPSTE24, an enzyme involved in removing the farnesylated tail of prelamin.

Question 71

A patient with HIV is experiencing severe skin reactions, including Stevens-Johnson syndrome. Which class of drugs is most likely responsible?

Answer 71

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are most likely responsible, particularly nevirapine.

Question 72

A patient with HIV is on a regimen including dolutegravir. What is the mechanism of action of this drug?

Answer 72

Dolutegravir inhibits HIV integrase, preventing viral DNA integration into the host genome. Side effects include hypersensitivity reactions and liver injury.

Question 73

A patient with HIV is experiencing peripheral neuropathy and hepatic steatosis. Which class of drugs is responsible?

Answer 73

Nucleoside reverse transcriptase inhibitors (NRTIs) are responsible. The underlying mechanism is mitochondrial toxicity.

Question 74

A patient with HIV is experiencing severe anemia and bone marrow suppression. Which drug is likely responsible?

Answer 74

Zidovudine is likely responsible. It is primarily used as a nucleoside reverse transcriptase inhibitor in HIV therapy.

Question 75

A patient with HIV is experiencing severe rash and systemic symptoms. Which drug is likely responsible?

Answer 75

Raltegravir is likely responsible. The recommended action is immediate discontinuation of the drug.

Question 76

A patient with HIV is experiencing severe GI intolerance and nail pigmentation changes. Which drug is likely responsible?

Answer 76

Zidovudine is likely responsible.

Question 77

A patient with HIV is experiencing severe fat redistribution. Which drug class is responsible?

Answer 77

Protease inhibitors are responsible. Manifestations include increased fat in the upper back and neck, breast, and trunk.

Question 78

A patient with HIV is experiencing severe lactic acidosis. Which drug class is responsible?

Answer 78

Nucleoside reverse transcriptase inhibitors (NRTIs) are responsible. The underlying mechanism is mitochondrial toxicity.

Question 79

What is the mechanism of action of the entry inhibitor drug AMD-070?

Answer 79

AMD-070 is a selective, reversible, small molecule CXCR4 chemokine co-receptor antagonist.

Question 80

How does the drug Cabotegravir function in the context of HIV treatment?

Answer 80

Cabotegravir prevents viral DNA integration into the host genome.

Question 81

What is the role of the drug Doravirine in HIV treatment?

Answer 81

Doravirine acts as a noncompetitive inhibitor of HIV-1 reverse transcriptase.

Question 82

What is the function of the maturation inhibitor BMS-955176?

Answer 82

BMS-955176 binds to HIV-1 Gag, inhibiting the final protease-mediated cleavage event.

Question 83

What is the purpose of the gene therapy product SB-728-T in HIV treatment?

Answer 83

SB-728-T aims to provide HIV-infected individuals with a reproducible pool of CD4 T cells that are permanently resistant to HIV entry, potentially improving immune restoration and functional control of HIV.

Question 84

What is the risk of progression to liver cirrhosis in patients with untreated acute HCV infection?

Answer 84

The risk of progression to liver cirrhosis is approximately 15% to 30% within 20 years for patients with untreated acute HCV infection.

Question 85

What are the stages of the HCV life cycle?

Answer 85

The stages of the HCV life cycle include: 1. **Attachment**: Binding of HCV particles onto hepatocytes. 2. **Cell entry**: Clathrin-mediated endocytosis.

Question 86

What are the stages of the HCV life cycle?

Answer 86

The stages of the HCV life cycle include: 1. **Attachment**: Binding of HCV particles onto hepatocytes. 2. **Cell entry**: Clathrin-mediated endocytosis allows HCV particles to enter early endosomes. 3. **Fusion**: pH-dependent membrane fusion releases the HCV genome into the cytosol. 4. **Translation and Replication**: Viral genome is translated into a polyprotein, cleaved into mature viral proteins. 5. **Assembly**: Dependent on cellular lipid metabolism and viral proteins. 6. **Release**: HCV virions are released as lipoviral particles essential for infectivity.

Question 87

What are the currently approved direct-acting antivirals (DAAs) for HCV treatment?

Answer 87

Currently approved DAAs include: 1. **Protease (NS3/4A) inhibitors**: paritaprevir, simeprevir, elbasvir, grazoprevir. 2. **NS5A inhibitors**: daclatasvir, ledipasvir, ombitasvir. 3. **Polymerase (NS5B) inhibitors**: sofosbuvir (nucleot(s)ide analog), dasabuvir (nonnucleoside analog).

Question 88

What is the primary efficacy endpoint for HCV treatment?

Answer 88

The primary efficacy endpoint for HCV treatment is the **Sustained Virologic Response (SVR)**, defined as undetectable HCV RNA levels at a specified end point after completion of therapy, with SVR at 12 weeks being the adopted standard.

Question 89

What are the side effects associated with PEG-IFN-alpha and Ribavirin combination therapy?

Answer 89

Side effects associated with PEG-IFN-alpha and Ribavirin combination therapy include: - **Localized injection site reactions**: erythema, tenderness, pruritus, rashes, cutaneous necrosis. - **Other reactions**: blistering reactions, granulomatous dermatitis, lupus-like reactions, embolia cutis medicamentosa, localized alopecia. - **Alopecia**: occurs in 28% to 36% of patients. - **Skin rash**: occurs in 21%, often as eczematous dermatitis. - **Other adverse effects**: flulike symptoms, fatigue, bone marrow suppression/cytopenias, mood disturbances, and "black box" warnings for hemolytic anemia and teratogenicity for Ribavirin.

Question 90

What are the side effects and precautions associated with boceprevir and telaprevir?

Answer 90

- **Boceprevir**: anemia, neutropenia, dysgeusia. - **Telaprevir**: rash, pruritis, anorectal discomfort, diarrhea, anemia. - Rash: 50% of cases occurred within the first 4 weeks of therapy; mostly Grade 1 or 2 and did not progress; may cause drug rash with eosinophilia and systemic symptoms (DRESS) and SJS.

Question 91

What are the side effects of Simeprevir and Sofosbuvir when used in combination with other treatments?

Answer 91

- **Simeprevir (Olysio)**: rash within 4 weeks, photosensitivity, pruritis, nausea, transient hyperbilirubinemia. - **Sofosbuvir (Sovaldi)**: - Used with PEG-IFN-α + ribavirin: fatigue, nausea, anemia, neutropenia. - Used with ribavirin: fatigue, headache, nausea, pruritis.

Question 92

What are the common side effects of Ledipasvir and Sofosbuvir (Harvoni)?

Answer 92

- **Common side effects**: fatigue, headache, nausea, diarrhea. - **Rash**: occurs in 7% of patients, pruritis in 1% to 2%.

Question 93

What are the key characteristics of NRTIs used for treating Hepatitis B?

Answer 93

- **NRTIs**: commonly used to treat Hepatitis B virus (HBV) infection. - Administered orally once daily, with dose adjustments for renal impairment (creatinine clearance <50 mL/min). - Inhibit polymerase activity of HBV. - **Black Box warning**: includes risk of mitochondrial toxicity and associated conditions such as myopathy, peripheral neuropathy, hepatic steatosis, pancreatitis, dyslipidemia, lipoatrophy, and lactic acidosis.

Question 94

Which agents are preferred for the treatment of Hepatitis B?

Answer 94

- **Preferred agents**: entecavir or tenofovir. - **Other NRTIs approved for treatment of HBV** include: - lamivudine - adefovir - telbivudine.

Question 95

A patient with chronic hepatitis C is being treated with sofosbuvir and ledipasvir. What is the goal of this therapy, and what are common side effects?

Answer 95

The goal is sustained virologic response (SVR), defined as undetectable HCV RNA levels 12 weeks after therapy. Common side effects include fatigue, headache, and nausea.

Question 96

A patient with hepatitis C is being treated with a combination of sofosbuvir and ribavirin. What are the common side effects of this regimen?

Answer 96

Common side effects include fatigue, headache, nausea, and pruritus.

Question 97

A patient with hepatitis C is being treated with daclatasvir and sofosbuvir. What is the goal of this therapy, and what are common side effects?

Answer 97

The goal is sustained virologic response (SVR). Common side effects include fatigue, headache, and nausea.

Question 98

A patient with hepatitis C is being treated with simeprevir. What are the common side effects, and what is its indication?

Answer 98

Common side effects include rash, photosensitivity, and pruritus. It is indicated for use in combination with sofosbuvir or PEG-IFN-α plus ribavirin.

Question 99

A patient with hepatitis C is being treated with sofosbuvir and velpatasvir. What is the goal of this therapy, and what are common side effects?

Answer 99

The goal is sustained virologic response (SVR). Common side effects include headache, fatigue, and nausea.

Question 100

What are the adverse effects associated with Tenofovir?

Answer 100

**Adverse effects of Tenofovir** include: - Nephrotoxicity - Fanconi syndrome - Rashes (including maculopapular, urticarial, vesiculobullous, pustular, and lichenoid rashes)

Question 101

What is the only effective treatment for persons with HDV coinfection?

Answer 101

**PEG-IFNα** is the only effective treatment for persons with HDV coinfection.

Question 102

What are the indications for initiation of treatment in patients with hepatitis B?

Answer 102

**Indications for initiation of treatment include:** 1. ALF or decompensated cirrhosis (NRTIs only) 2. Significant liver injury or fibrosis, indicated by elevated ALT levels or biopsy-proven inflammation and/or fibrosis plus active HBV viremia. 3. Immunosuppressive therapy.

Question 103

What are the adverse effects of Oseltamivir and Peramivir?

Answer 103

**Adverse effects:** | Drug | Adverse Effects | |--------------|------------------------------------| | Oseltamivir | SJS, EM | | Peramivir | SJS, EM, urticaria, maculopapular rash |

Question 104

What is the duration of treatment for patients treated with PEG-IFNα?

Answer 104

Patients treated with **PEG-IFNα** are typically treated for **48 weeks**.

Question 105

A patient with hepatitis B and HIV coinfection requires treatment. Which drugs are preferred, and why?

Answer 105

Preferred drugs include tenofovir, entecavir, and lamivudine because they are active against both HBV and HIV.

Question 106

A patient with severe influenza is prescribed oseltamivir. What is the mechanism of action of this drug, and what are its potential adverse effects?

Answer 106

Oseltamivir is a neuraminidase inhibitor that prevents the release of new viral particles. Adverse effects include Stevens-Johnson syndrome (SJS) and erythema multiforme (EM).

Question 107

A patient with chronic hepatitis B is being treated with entecavir. What is the mechanism of action of this drug, and what are its adverse effects?

Answer 107

Entecavir inhibits HBV polymerase activity. Adverse effects include nephrotoxicity and rashes.

Question 108

A patient with chronic hepatitis B is being treated with tenofovir. What are its major adverse effects?

Answer 108

Major adverse effects include nephrotoxicity and Fanconi syndrome.

Question 109

What is the effectiveness time frame for initiating Acyclovir for varicella and herpes zoster?

Answer 109

Acyclovir is most effective when initiated within __ hours for varicella and __ hours for herpes zoster.

Question 110

What is the effectiveness time frame for initiating Valacyclovir after first diagnosis and recurrent episodes?

Answer 110

Valacyclovir is most effective when initiated within __ hours of first diagnosis and __ hours of onset of recurrent episode.

Question 111

What side effect is associated with the medication mentioned in the content?

Answer 111

This medication has a side effect of **symmetrical intertriginous and flexural exanthem**.

Question 112

Which medication is available in a 1% ophthalmic aqueous solution for the treatment of HSV conjunctivitis?

Answer 112

The medication available in 1% ophthalmic aqueous solution for treatment of HSV conjunctivitis is **Acyclovir**.

Question 113

What are the first-line ART recommendations for HIV among different populations?

Answer 113

First-line ART of HIV among adults, pregnant/breastfeeding individuals, adolescents, and children varies and needs to be specified.

Question 114

What are the recommended regimens for HIV preexposure and postexposure prophylaxis?

Answer 114

HIV preexposure prophylaxis regimen and postexposure prophylaxis (for adults and children) need to be specified.

Question 115

What is the hallmark toxicity of NRTIs that may manifest as hepatic steatosis and peripheral neuropathy?

Answer 115

The hallmark toxicity of NRTIs that may manifest as **hepatic steatosis** and **peripheral neuropathy** needs to be specified.

Question 116

What are the preferred agents for HBV treatment?

Answer 116

The preferred agents for HBV treatment need to be specified.