HIV Therapy: Anesthetic Interactions

Introduction

• Many anesthetic agents, opioids and sedatives are metabolized by CYP₃A₄ and preventing the most clinically significant perioperative DDIs and managing chronic ARVD-related side effects is the main priority in patients being treated for HIV infection.³
• PIs (atazanavir, lopinavir, darunavir) especially when boosted with the potent CYP₃A₄ inhibitors ritonavir or cobicistat, decrease the metabolic clearance of midazolam, diazepam, fentanyl, alfentanil and lidocaine.⁴
• Coadministration of boosted PIs and lidocaine can increase systemic lidocaine levels due to CYP₃A₄ inhibition leading to cardiac arrythmias.³
• Nonnucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine and efavirenz can induce CYP₃A₄ and CYP₂B₆, increasing the metabolism of propofol and the volatile agents leading to subtherapeutic plasma concentrations requiring higher or more frequent dosing of these anesthesia agents.¹

Pharmacodynamic Interactions and Drug Toxicity

• Cardiovascular: HIV and ARVD (especially PIs and older NRTIs) can worsen coronary artery disease, cause dilated cardiomyopathy or precipitate pulmonary hypertension.
• Neurological: NRTIs often cause a dose-dependent and painful peripheral neuropathy which should be documented prior to any regional anesthesia techniques.
• Mitochondrial toxicity: NRTIs can cause mitochondrial dysfunction, leading to lactic acidosis, myopathy or pancreatitis.
• Renal and hepatic function: ARVDs such as tenofovir are nephrotoxic and PIs and NNRTIs can be hepatotoxic requiring dose adjustments or avoidance of renally or hepatically cleared anesthetic drugs.

Anesthetic Management Strategies

Preoperative Assessment

• Cardiopulmonary evaluation should include chest radiography to screen for tuberculosis or other pulmonary opportunistic infections, while electrocardiography and echocardiography are helpful to identify an underlying cardiomyopathy.
• Laboratory investigations should include a complete blood count, clotting function and coagulation studies, and biochemical tests (glucose, electrolytes, renal and liver function) as well as a viral load test within the previous 6 months or CD₄ count within the previous 12 months.
• If the viral load is less than 200 copies/mL and the CD₄ count is more than 200 cells/mm3, proceed as with a patient who does not have HIV.⁴
• Interrupting ARVDs for elective surgery risks viral load rebound and rapid development of drug resistance.

Intraoperative Considerations

• Volatile agents: volatile gases are generally unaffected.
• Intravenous agents: etomidate, cisatracurium, atracurium and remifentanil are preferred as their metabolism is independent of the hepatic cytochrome P₄₅₀ system.
• Opioids and sedatives: fentanyl and midazolam are metabolized by CYP₃A₄ and, for patients on boosted PIs, anticipate a reduction in metabolism and significantly reduce initial doses (often by 50–75%) to prevent toxicity.
• Regional anesthesia: regional techniques are generally safe and preferred as they avoid systemic DDIs. Documenting the presence and severity of pre-existing peripheral neuropathy is essential.
• Obstetrical considerations: epidural blood patch for post dural puncture headache has been shown to be a safe treatment option in HIV-seropositive patients.⁵
• Infection control: strict universal precautions are required for all healthcare personnel to prevent both occupational exposure and the transmission of opportunistic infections to the immuno-compromised HIV patient.⁶
• Blood transfusions: allogenic blood transfusions have been shown to demonstrate immunomodulation and result in subsequent increase in HIV viral load in patients with advanced HIV infection.⁷

Postoperative Immunosuppression

• Immunosuppression can occur within 15 minutes of induction of anesthesia and can persist as long as 3-11 days with the risk of postoperative infections and progression of malignant diseases.³