Chapter 46 Drugs Treating HIV Infection and AIDS

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Physiology
CD4 cells are necessary for normal immune function. The CD4 cell recognizes foreign antigens and infected cells and helps activate the antibody-producing B lymphocytes. CD4 cells also induce cell-mediated immunity. Human immunodeficiency virus HIV is like all other viruses in structure. The HIV virus is called a retrovirus. The difference between a virus and a retrovirus is in the genetic material.

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CD4 T-Cell Function

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Pathophysiology
HIV infection begins when gp120 binds to cells that have a CD4+ protein receptor site. These cells include CD4 cells, monocytes, macrophages, and certain nerve cells. Once the virus is bound to the cell, the viral envelope and the plasma membrane fuse. In the cell, viral RNA is transcribed into a single strand of viral DNA. The HIV virus has an affinity for CD4 cells.

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Diagnosis of HIV Infection

Diagnosis of HIV infection is initially made by a screening test followed by a confirmatory assay. Screening tests are highly sensitive, whereas confirmatory assays are highly specific. The combination use of these two types of tests produces results that are highly accurate.

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Nucleoside/Nucleotide Reverse Transcriptase Inhibitors

The nucleoside reverse transcriptase inhibitors (NRTIs) are the first class of drugs approved by the FDA to treat HIV infection and AIDS. NRTIs are chemically similar to human nucleosides or nucleotides, which are considered the building blocks of DNA. To be effective, all of the NRTIs must convert to their active forms. These drugs inhibit reverse transcriptase, an enzyme critical to HIV replication (see Figure 46.3). Prototype drug: zidovudine (AZT, ZDV, Retrovir).

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Zidovudine: Core Drug Knowledge

Pharmacotherapeutics Epstein-Barr virus, hepatitis B virus & HIV infection. Pharmacokinetics Administered: parenterally or orally. Metabolism: liver. Excreted: kidneys. Pharmacodynamics

Inhibits the synthesis of DNA by reverse transcriptase.

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Zidovudine: Core Drug Knowledge (cont.)

Contraindications and precautions Hypersensitivity, breastfeeding, and lactic acidosis Adverse effects GI symptoms, headache, seizures, somnolence, and hematologic toxicities Drug interactions

Ganciclovir, acetaminophen, interferon beta-1b, probenecid, rifampin, trimethoprim, and valproic acid

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Zidovudine: Core Patient Variables

Health status Assess for hypersensitivity and pregnancy status. Life span and gender Assess pregnancy and lactation. Lifestyle, diet, and habits Assess understanding of HIV transmission.

Environment
Assess environment where drug will be given.

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Zidovudine: Nursing Diagnoses and Outcomes

Acute Pain related to headache from drug effects Desired outcome: the patient will self-medicate with analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs). Ineffective Protection related to anemia and granulocytopenia Desired outcome: the patient will remain free of opportunistic diseases related to blood dyscrasias.

Disturbed Sleep Pattern: Insomnia related to CNS adverse effects

Desired outcome: the patient will obtain adequate sleep throughout drug therapy.

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Zidovudine: Planning & Interventions

Maximizing therapeutic effects Administer zidovudine 1 hour before meals. Make sure the patient is on a low-fat diet. Minimizing adverse effects Intramuscular injections should not be administered to patients receiving zidovudine.

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Zidovudine: Teaching, Assessment & Evaluations

Patient and family education Explain the importance of adhering to the therapeutic regimen. It is important to advise patients about potential adverse effects, especially the Black Box warnings. Ongoing assessment and evaluation Perform a physical examination at each encounter with the patient who is taking zidovudine. Laboratory data should be obtained every 2 to 4 weeks.

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Question
What are the absolute contraindications to the use of zidovudine? A. Hypersensitivity

B. Breastfeeding
C. Existing lactic acidosis D. A & C

E. All of the above

Answer : E.
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Nonnucleoside Reverse Transcriptase Inhibitors (NNRTIs)

The nonnucleoside reverse transcriptase inhibitors (NNRTIs) comprise the second class of drugs used to treat HIV infection. NNRTIs affect only HIV-1; they do not inhibit reverse transcriptase in HIV-2. They inhibit a specific site on the reverse transcriptase that is required to carry out the process of DNA synthesis. Prototype drug: efavirenz (Sustiva).

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Efavirenz: Core Drug Knowledge

Pharmacotherapeutics HIV-1 infection. Pharmacokinetics Administered: oral. Protein bound. Metabolism: liver. Excreted: urine and feces. Pharmacodynamics

Inhibits HIV reverse transcriptase.

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Efavirenz: Core Drug Knowledge (cont.)

Contraindications and precautions Hypersensitivity Adverse effects Dizziness, impaired concentration, insomnia, abnormal dreams, and hallucinations Drug interactions

Interacts with drugs that are metabolized by P-450 CYP3A4

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Efavirenz: Core Patient Variables

Health status Assess medical history. Life span and gender Pregnancy category D. Lifestyle, diet, and habits Assess ability to take drug as prescribed. Environment

Assess environment where drug will be given.

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Efavirenz: Nursing Diagnoses and Outcomes

Risk for Injury related to CNS adverse effects Desired outcome: the patient will remain free from injury and contact the healthcare provider if symptoms should occur.

Disturbed Thought Processes related to CNS adverse effects

Desired outcome: the patient will remain oriented and able to communicate effectively with others. Ineffective Protection related to drug-related rash

Desired outcome: the patient will report any rash to the prescriber.

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Efavirenz: Planning & Interventions

Maximizing therapeutic effects Administer efavirenz once a day, preferably at bedtime.

For missed doses, it is important that the patient take the drug as soon as remembered unless it is time for the next dose.
Minimizing adverse effects Administer efavirenz on an empty stomach.

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Efavirenz: Teaching, Assessment & Evaluations

Patient and family education Explain the importance of adherence to drug therapy. Advise patients experiencing depression, anxiety, behavior changes, and those feeling paranoid or manic to contact the health care provider immediately. Ongoing assessment and evaluation Coordinate periodic examinations and blood monitoring in patients receiving efavirenz.

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Question
Efavirenz is a pregnancy category ____ drug. A. A B. B C. C D. D E. X Answer: D. ( teratogenic during all trimesters)
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Protease Inhibitors
Protease inhibitors (PIs) are the third major class of drugs used in treating HIV infection and AIDS. Their arrival has changed the opinion of experts as to the ultimate fatality of HIV and AIDS. The PIs represent the most potent anti-HIV drugs. Prototype drug: saquinavir (Invirase).

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Saquinavir: Core Drug Knowledge

Pharmacotherapeutics Treating HIV infection in adults. Pharmacokinetics Administered: oral. Poor bioavailability. Excreted in feces and urine. Pharmacodynamics

Competitive inhibitor of HIV protease, an enzyme required for HIV replication.

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Saquinavir: Core Drug Knowledge (cont.)

Contraindications and precautions Hypersensitivity and children under age 16 Adverse effects Nausea, diarrhea, stomach discomfort, insomnia, and headache Drug interactions

Interacts with drugs that are metabolized by P-450 CYP3A4

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Saquinavir: Core Patient Variables

Health status

Assess the patient for hypersensitivity.

Life span and gender

Assess the patient for pregnancy or lactation.

Lifestyle, diet, and habits

Assess the patients ability and willingness to adhere to drug therapy.

Environment

Assess environment where drug will be given.

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Saquinavir: Nursing Diagnoses and Outcomes

Acute Pain related to headache from adverse drug effect Desired outcome: the patient will self-medicate with analgesics such as acetaminophen. Desired outcome: the patient will remain oriented and able to communicate effectively with others. Desired outcome: the patient will avoid dehydration and report persistent diarrhea to the prescriber. Desired outcome: the patient will recognize the symptoms of hepatoxicity and contact the healthcare provider immediately.
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Disturbed Thought Processes related to adverse CNS effects

Diarrhea related to adverse GI effects

Risk for injury related to hepatoxicity.

Saquinavir: Planning & Interventions

Maximizing therapeutic effects Administer saquinavir tablets or capsules within 2 hours after eating a full meal.

Administer ritonavir with each dose of saquinavir.

Minimizing adverse effects Give small, frequent meals if GI distress is problematic.

Administer acetaminophen for complaints of headache.

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Saquinavir: Teaching, Assessment & Evaluation

Patient and family education Explain the importance of periodic clinical and blood monitoring.

Teach patients the signs and symptoms of diabetes.

Ongoing assessment and evaluation Patients who take saquinavir should have periodic examinations and blood monitoring.

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Question
Due to the poor bioavailability of saquinavir given alone, what medication is given in combination with saquinavir to increase bioavailability? A. Ritonavir B. Zidovudine C. Efavirenz D. Enfuvirtide

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Rationale
Due to the poor bioavailability of saquinavir given alone, what medication is given in combination with saquinavir to increase bioavailability? A. Ritonavir Saquinavir is only about 4% bioavailable after dosing. Saquinavir is always combined with ritonavir because ritonavir significantly inhibits saquinavir's metabolism.

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Entry Inhibitors
Entry inhibitors are also known as fusion inhibitors. This new class of drugs inhibits the HIV virus from binding to, fusing with, and entering the human cell.

Prototype drug: enfuvirtide (Fuzeon).

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Enfuvirtide: Core Drug Knowledge

Pharmacotherapeutics Managing HIV infection in patients who have experienced treatment failure.

Pharmacokinetics
Administered: subcutaneously. Pharmacodynamics

Binds to the gp41 protein on the surface of HIV.

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Enfuvirtide: Core Drug Knowledge (cont.)

Contraindications and precautions Hypersensitivity Adverse effects Injection site reaction, anorexia, nausea, weight loss, fatigue, anxiety, headache, insomnia, peripheral neuropathy, and infections Drug interactions Drugdrug interactions have not yet been identified

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Enfuvirtide: Core Patient Variables

Health status Review the patients HIV history and treatment plan carefully.

Life span and gender

Pregnancy category B. Lifestyle, diet, and habits Teach the patient to avoid risk factors that predispose them to infection. Environment Assess environment where drug will be given.

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Enfuvirtide: Nursing Diagnoses and Outcomes

Pain related to injection site reactions and headache Desired outcome: the patient will self-medicate with analgesics such as acetaminophen. Risk for Infection related to drug adverse effect Desired outcome: the patient will recognize symptoms associated with infections. Risk for Injury related to insomnia and peripheral neuropathy

Desired outcome: the patient will remain injury free throughout therapy.

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Enfuvirtide: Planning & Interventions

Maximizing therapeutic effects Reconstitute the enfuvirtide with sterile water, and then allow the solution to sit for 10 minutes to ensure that the powder dissolves completely. Minimizing adverse effects Use aseptic technique when reconstituting or administering enfuvirtide.

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Enfuvirtide: Teaching, Assessment & Evaluation

Patient and family education Emphasize the importance of aseptic technique when reconstituting and administering enfuvirtide.

Explain the potential for injection-site reactions.

Ongoing assessment and evaluation Assess the patient taking enfuvirtide for signs of infectious disorders, such as pneumonia, sinusitis, herpes simplex, influenza, and conjunctivitis.

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Question
The major adverse effect of enfuvirtide is: A. Seizures B. Respiratory distress C. Injection site reaction D. Hepatic failure Answer: C.

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