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Antiretrovirals for HIV/AIDS - NRTIs & NNRTIs: Nursing Pharmacology



zidovudine (Retrovir),
didanosine, stavudine,
lamivudine (Epivir),
abacavir (Ziagen),
emtricitabine (Emtriva)
*High Alert Medications*

efavirenz (Sustiva),
nevirapine (Viramune),
rilpivirine (Edurant),
etravirine (Intelence)
*High Alert Medications*

Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)
Compete with naturally occurring nucleosides → interfere with DNA synthesis → decrease viral replication
Bind and inhibit reverse transcriptase → interfere with DNA synthesis → decrease viral replication
Combination therapy for the treatment of HIV infection
  • PO
  • IV: zidovudine
  • PO
  • Fever, headache, dizziness, insomnia, anxiety, depression, asthenia, peripheral neuropathy
  • Nausea, vomiting, diarrhea, anorexia, constipation, abdominal pain
  • Myalgia, arthralgia
  • Dyspnea, cough
  • Hepatotoxicity 
  • Hypersensitivity reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis
  • Lactic acidosis, hepatomegaly, steatosis (boxed warning for zidovudine, didanosine, stavudine, and emtricitabine)
  • Zidovudine: bone marrow suppression, lipodystrophy, myopathy, hematologic toxicity
  • Didanosine and stavudine: bone marrow suppression, pancreatitis (boxed warning) 
  • Lamivudine, tenofovir, and emtricitabine: hepatitis B exacerbations in clients coinfected with HIV and HBV (boxed warning) 
  • Tenofovir: osteomalacia
  • Emtricitabine: skin hyperpigmentation, immune reconstitution syndrome
  • Abacavir: increased risk of myocardial infarction, immune reconstitution syndrome, severe hypersensitivity reactions (boxed warning) 
  • Cushingoid fat redistribution
  • Efavirenz: immune reconstitution syndrome, neurotoxicity, psychological reactions
  • Delavirdine and rilpivirine: immune reconstitution syndrome 
  • Nevirapine: neutropenia, increased blood cholesterol, severe and potentially fatal hepatotoxicity and hypersensitivity reactions (boxed warning)
  • Pregnancy and breastfeeding
  • Children
  • Hepatic or renal disease
  • Abacavir: hepatic impairment, HLA-B*5701 allele

Drug interactions:
  • Didanosine: other antiretrovirals like stavudine and tenofovir
  • Abacavir: ribavirin (increase the risk of fatal lactic acidosis and pancreatitis)
  • Efavirenz: hepatic impairment, hepatitis B or C infection, consuming alcohol
  • Nevirapine: moderate to severe hepatic impairment

Drug interactions:
  • Efavirenz: elbasvir or grazoprevir
  • Delavirdine: rifampin, midazolam, or ergot alkaloids
  • Rilpivirine: phenytoin, phenobarbital, rifampin, dexamethasone, or proton pump inhibitors
Assessment and monitoring: abacavir
  • Current symptoms: fatigue fever, and mental status changes
  • Presence of opportunistic infection
  • Weight
  • Vital signs
  • Laboratory test results, HIV RNA level, CD4+ count, liver and renal function tests, CBC, glucose, triglycerides; HLA-B5701 gene

  • Side effects
  • Evaluate for the therapeutic effect of improvement in their CD4 T-cell count, decreased HIV RNA, improved immune function and quality of life
  • Purpose of medication: helps prevent HIV replication
  • Does not cure HIV or prevent them from infecting others
    • Notify sexual partners about their diagnosis
    • Take precautions to prevent transmission
  • Take consistently, twice daily, without or without food, with an eight ounce glass of water
  • Develop schedule for taking multiple prescribed medications
  • Side effects
    • Headache, loss of appetite, malaise, or insomnia
      • Contact healthcare provider if persistent
    • Gastrointestinal side effects
      • Typically improve within 2–4 weeks of treatment
      • Take medication with food; eat smaller, frequent meals during the day
    • Report
      • Changes in body fat distribution
      • Hepatotoxicity: fatigue, anorexia, dark urine, yellowing of their skin or eyes
      • Nephrotoxicity: decreased urine output, blood in the urine, edema, or weight gain
      • Lactic acidosis: tachycardia, tachypnea, shortness of breath, vomiting, feeling dizzy or very tired
      • Severe hypersensitivity reaction: unusual rash, blistering, or the presence of mouth, throat, or nasal sores 

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, among which some of the most commonly used are nucleoside reverse transcriptase inhibitors, or NRTIs, and non-nucleoside reverse transcriptase inhibitors, or NNRTIs. NRTIs include zidovudine, didanosine, stavudine, lamivudine, abacavir, and emtricitabine. On the other hand, NNRTIs include efavirenz, delavirdine, nevirapine, rilpivirine, and etravirine.

Both NRTIs and NNRTIs are taken orally, while the NRTI zidovudine can also be administered intravenously. Once administered, these medications inhibit the viral enzyme reverse transcriptase. More specifically, NRTIs compete with naturally occurring nucleosides and bind to the viral RNA chain. On the other hand, NNRTIs directly bind to and inhibit the reverse transcriptase. Ultimately, both NRTIs and NNRTIs prevent this enzyme from reverse-transcribing the viral RNA into proviral DNA, thus interfering with viral replication.

Unfortunately, clients taking NRTIs or NNRTIs may experience a wide range of side effects, and many of them can be serious. These medications often cause fever, headache, dizziness, insomnia, and anxiety or depression, as well as asthenia and peripheral neuropathy. Gastrointestinal side effects like nausea, vomiting, diarrhea, anorexia, constipation and abdominal pain are also common, as well as myalgia, arthralgia, and dyspnea or cough. Although more rarely, they can lead to hepatotoxicity and hypersensitivity reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis. All NRTIs can also cause lactic acidosis, hepatomegaly, and steatosis, which is a boxed warning for zidovudine, didanosine, stavudine, and emtricitabine. In addition, zidovudine, didanosine, and stavudine can cause bone marrow suppression, and zidovudine may also cause lipodystrophy, myopathy, and hematologic toxicity. Didanosine and stavudine have a boxed warning for pancreatitis. On the other hand, lamivudine, tenofovir, and emtricitabine have a boxed warning for causing hepatitis B exacerbations in clients coinfected with HIV and HBV. Clients taking tenofovir may also develop osteomalacia; while emtricitabine may cause skin hyperpigmentation, especially involving palms and soles, and could expand to the lips and tongue. Abacavir may cause increased risk of myocardial infarction, especially in clients with coronary artery disease; and it has a boxed warning for causing severe hypersensitivity reactions. Lastly, both emtricitabine and abacavir may lead to an excessive inflammatory response called immune reconstitution syndrome, that can also cause flare-ups of a previously known infection like tuberculosis; this side effect can also occur in clients taking certain NNRTIs like efavirenz, delavirdine, and rilpivirine. NNRTIs may also lead to cushingoid fat redistribution, which typically involves peripheral wasting, along with truncal obesity, and the development of a fat pad on the base of the neck. Efavirenz can lead to neurotoxicity, potentially causing encephalopathy and ataxia. Clients taking efavirenz may also experience psychological reactions, such as impaired concentration, aggressiveness, delusions, paranoia, and even suicidal thoughts or behaviors; especially clients with mental health disease or a history of drug abuse. On the other hand, clients taking nevirapine may present with neutropenia and increased blood cholesterol. In addition, nevirapine has boxed warnings for severe and potentially fatal hepatotoxicity and hypersensitivity reactions. Finally, it’s important to note that etravirine carries a higher risk for hypersensitivity reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

Regarding contraindications, NRTIs and NNRTIs should be used cautiously during pregnancy and breastfeeding, as well as in children, and in clients with hepatic or renal disease. In particular for NRTIs, abacavir is contraindicated in clients with hepatic impairment, as well as in those with the HLA-B*5701 allele, since they are at increased risk of developing a hypersensitivity reaction. Regarding interactions, clients should not combine didanosine with other antiretrovirals like stavudine and tenofovir, or combine abacavir with ribavirin, since these combinations increase the risk of fatal lactic acidosis and pancreatitis. Regarding NNRTIs, efavirenz should be used with caution in clients with hepatic impairment or hepatitis B or C infection, and clients should avoid consuming alcohol. Nevirapine is contraindicated in clients with moderate to severe hepatic impairment, for whom hepatotoxicity may be fatal. Regarding interactions, efavirenz shouldn’t be combined with the medications elbasvir or grazoprevir. On the other hand, delavirdine should not be combined with medications like rifampin, midazolam, or ergot alkaloids. Finally, rilpivirine should not be combined with phenytoin, phenobarbital, rifampin, dexamethasone, or proton pump inhibitors.

Alright, when caring for a client prescribed an NRTI like abacavir as part of their antiretroviral regimen for HIV, start your assessment by asking your client about symptoms such as fatigue, fever, and mental status changes. Also, assess for the presence of opportunistic infection, and review their nutrition status to determine if they have any nutritional deficiencies or weight loss. In addition, be sure to obtain their weight and vital signs; and review their most recent laboratory test results, including CD4 T-cell count, HIV RNA levels, glucose, triglycerides, and their hepatic and renal function. Lastly, confirm that your client has been tested for the HLA-B5701 gene, and that the results are available prior to treatment. If your client is positive for this gene, do not administer abacavir, contact the healthcare provider, and ensure it is documented in their medical record as a medication hypersensitivity.

Moving on to client education, explain that the medication works along with the other medications in their antiretroviral regimen to help prevent HIV replication. Remind them that their antiretroviral regimen won’t cure their HIV infection, and that it won't prevent them from infecting others, so they should notify sexual partners about their diagnosis, and be sure to take precautions to prevent transmission, like using condoms. Next, instruct your client to take their medication consistently, twice daily, without or without food, and with an 8 ounce glass of water. Be sure to promote adherence to their medication regimen by assisting your client to develop a schedule for taking multiple prescribed medications.