Antiretrovirals for HIV/AIDS - CCR5 antagonists, fusion inhibitors, and attachment inhibitors: Nursing pharmacology

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.