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Antiretrovirals for HIV/AIDS - CCR5 Antagonists, Fusion Inhibitors, and Attachment Inhibitors: Nursing Pharmacology

Notes

Notes

ANTIRETROVIRALS for HIV/AIDS: CCR5 ANTAGONISTS, FUSION INHIBITORS, and ATTACHMENT INHIBITORS, PART 1/2
DRUG NAME
maraviroc (Selzentry)
*High Alert Medication*

enfuvirtide (Fuzeon)
*High Alert Medication*

CLASS
CCR5 Antagonists
Fusion inhibitors
MECHANISM of ACTION
Blocks CCR5 coreceptor → prevents CCR5-tropic HIV entry
Binds to gp41 → prevents viral fusion
INDICATIONS
Multi-drug resistant HIV or AIDS
ROUTE(S) of ADMINISTRATION
PO
SubQ
SIDE EFFECTS
  • Respiratory tract infections
  • Bronchospasm
  • Cardiac ischemia
  • Orthostatic hypotension
  • Visual disturbances
  • Gastrointestinal disturbances
  • Joint pain
  • Muscle cramps
  • Immune reconstitution syndrome
  • Boxed warning: hepatotoxicity
  • Injection site reactions
  • Fatigue
  • Insomnia
  • Gastrointestinal disturbances 
  • Bacterial pneumonia
  • Hypersensitivity reactions
  • Immune reconstitution syndrome

CONTRAINDICATIONS & CAUTIONS
  • Impaired renal function
  • Pregnancy
  • Breastfeeding
  • Children
  • Elderly clients
  • Cardiac or hepatic disease 
  • Drug interactions: CYP2A inducers and inhibitors
  • Pregnancy
  • Breastfeeding
  • Coagulation disorders or taking anticoagulants
  • Drug interactions: orlistat, protease inhibitors 

ANTIRETROVIRALS for HIV/AIDS: CCR5 ANTAGONISTS, FUSION INHIBITORS, and ATTACHMENT INHIBITORS, PART 2/2
DRUG NAME
fostemsavir (Rukobia)
*High Alert Medication*

ibalizumab (Trogarzo)
*High Alert Medication*

CLASS
Attachment inhibitors
Post-attachment inhibitors
MECHANISM of ACTION
Prodrug → temsavir → binds to gp120 → prevents viral attachment
Binds to CD4 T cells → prevents viral entry
INDICATIONS
Multi-drug resistant HIV or AIDS
ROUTE(S) of ADMINISTRATION
PO
IV
SIDE EFFECTS
  • Prolonged QT interval
  • Hepatotoxicity
  • Elevated liver enzymes
  • Gastrointestinal disturbances
  • Dizziness
  • Drowsiness
  • Headaches
  • Peripheral neuropathy
  • Immune reconstitution syndrome
  • Infusion reactions
  • Dizziness
  • Immune reconstitution syndrome

CONTRAINDICATIONS & CAUTIONS
  • Pregnancy
  • Breastfeeding
  • Children
  • Elderly clients
  • Coinfection with hepatitis B or C
  • Drug interactions: medications that prolong QT interval, strong CYP3A inducers
None
NURSING CONSIDERATIONS for ANTIRETROVIRALS for HIV/AIDS: CCR5 ANTAGONISTS, FUSION INHIBITORS, AND
ATTACHMENT INHIBITORS
ASSESSMENT & MONITORING
Assessment and monitoring: maraviroc

Assessment
  • Current symptoms: fever, fatigue, and mental status changes; presence of opportunistic infection; nutrition status, weight loss
  • Vital signs
  • Laboratory test results: tropism test to document the presence of the CCR5 receptor; HIV RNA level, CD4 T-cell count, hepatic and renal function

Monitoring
  • Side effects
  • Evaluate for the therapeutic effect: increased CD4 T-cell count, decreased HIV RNA, improved immune function and quality of life
CLIENT EDUCATION
  • Purpose of medication: prevents HIV replication
  • Does not cure HIV or prevent them from infecting others
    • Notify sexual partners about their diagnosis
    • Take precautions to prevent transmission
  • Take their medication consistently, twice daily, without or without food, with an eight ounce glass of water
  • For missed dose: take the medication as soon as they remember if the next dose is less than six hours
  • Develop schedule for taking multiple prescribed medications
  • Side effects
    • Dizziness, orthostatic hypotension: make position changes slowly
    • Notify healthcare provider 
      • Infection: fever, chills, sore throat, cough, or increased sputum production
      • Hepatotoxicity: fatigue, anorexia, dark urine, or yellowing of their skin or eyes
      • Cardiotoxicity: chest pain or pressure or shortness of breath
      • Hypersensitivity reaction: unusual rash, blistering, or the presence of mouth, throat, or nasal sores
Transcript

Antiretrovirals are medications used to treat infections caused by retroviruses. This is a group of RNA viruses that includes human immunodeficiency virus, or HIV, which can cause acquired immunodeficiency syndrome, or AIDS. Now, antiretrovirals include different classes of medications, such as CCR5 antagonists, fusion inhibitors, and attachment inhibitors.

The only medication of the CCR5 antagonist class is maraviroc. It is administered orally in combination with other antiretroviral medications for adult clients infected with an HIV strain that’s resistant to other antiretrovirals. Once administered, maraviroc works by blocking the CCR5 coreceptor on the CD4+ T cells, which is used by the CCR5-tropic HIV to enter these cells. Unfortunately, if the virus uses a CXCR4 coreceptor instead of CCR5, this medication will have no therapeutic effect.

Common side effects of maraviroc include dizziness, fever, cough, abdominal pain, and a skin rash or hypersensitivity reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug rash with eosinophilia with systemic symptoms or DRESS. In addition, maraviroc can cause serious side effects like upper and lower respiratory tract infections or pneumonia, bronchospasm, and cardiac ischemia.

Clients might also experience visual disturbances, as well as orthostatic hypotension, and gastrointestinal disturbances like dyspepsia, diarrhea, or constipation. Some clients on maraviroc may experience musculoskeletal side effects like joint pain or muscle cramps, and an excessive inflammatory response called immune reconstitution syndrome, that can also cause flare-ups of a previously known infection like tuberculosis. Finally, maraviroc has a boxed warning for hepatotoxicity!

Regarding contraindications, maraviroc is contraindicated in clients with impaired renal function. Precaution should be taken during pregnancy and breastfeeding, as well as with children or elderly clients. Additionally, maraviroc should be used cautiously in clients with cardiac and hepatic disease.

Regarding interactions, maraviroc should not be combined with CYP2A inhibitors or inducers, since it is metabolized by the cytochrome P450 system, more specifically its CYP2A subgroup. Therefore, the dose of maraviroc needs to be adjusted when combined with CYP2A inducer medications, such as barbiturates, dexamethasone, or phenytoin; or CYP2A inhibitors like amiodarone, and some anti-infective medications.

Moving on to fusion inhibitors, the only medication in this group is called enfuvirtide, which is administered subcutaneously in combination with other antiretrovirals to treat clients with resistant HIV strains. Once administered, enfuvirtide works by binding to the envelope protein of the HIV called glycoprotein 41, or gp 41 for short, which prevents the HIV from fusing with the cell membrane of the CD4+ T cells, and therefore prevents it from entering and infecting the cell.

Now, clients on enfuvirtide can often present with side effects like injection site reactions, as well as fatigue, insomnia, and gastrointestinal disturbances like anorexia, abdominal pain, nausea, and diarrhea. Serious side effects include increased risk for bacterial pneumonia. Finally, some clients might experience severe hypersensitivity reactions, as well as immune reconstitution syndrome.

When it comes to contraindications, enfuvirtide should be used with caution during pregnancy and breastfeeding, as well as in clients with coagulation disorders or taking anticoagulants, since there’s an increased risk of bleeding at the injection site. Regarding interactions, combining enfuvirtide with medications like orlistat may decrease the blood levels of enfuvirtide; while combination with protease inhibitors may increase the blood levels of enfuvirtide.

Attachment inhibitors include fostemsavir, which is administered orally in combination with other antiretrovirals to adult clients with the resistant HIV strains. Fostemsavir is a prodrug, so once administered, it converts to its active form called temsavir, which binds to another envelope protein of the HIV called gp 120, and ultimately prevents the virus from attaching to CD4+ T cells and infecting them.

Now, clients taking fostemsavir may present with side effects like a prolonged QT interval. In addition, this medication may cause hepatotoxicity and elevated liver enzymes, especially in clients coinfected with hepatitis B or C. Clients can also experience gastrointestinal side effects like nausea, vomiting, and diarrhea; as well as neurologic side effects like dizziness, drowsiness, headaches, and peripheral neuropathy. Other important side effects include immune reconstitution syndrome.