Antivirals

Antivirals

Medication                                                          

Efavirenz (EFV)

Ethnic, Cultural, and Genetic Differences

The effect of ethnicity on EFV exposure can be attributed to genetic underpinnings. The hepatic enzyme CYP2B6 is a key enzyme in the metabolism of efavirenz. The expression and activity of this enzyme vary widely among individuals. Polymorphisms in CYP2B6 are known to alter EFV levels. Identifying mechanisms and factors that might influence CYP2B6 activity is important to the safe and effective use of efavirenz. Environmental factors also contribute to differences in EFV plasma levels and immunologic recovery (Röhrich et al., 2016).

CYP2B6 genetic variants that influence constitutive CYP2B6 expression contribute to interindividual variability in the drug interactions that ensue. At least three CYP2B6 loss-of-function polymorphisms have been consistently associated with increased plasma efavirenz exposure (Röhrich et al., 2016). Greater mean plasma efavirenz through concentration has been reported in populations with African ancestry than those with European ancestry. This is largely explained by differing frequencies of CYP2B6 516G>T polymorphism, which decreases the activity of CYP2B6 (Röhrich et al., 2016).

Mechanism of Action

Efavirenz is a Nonnucleoside reverse transcriptase inhibitor (NNRTI). It is a selective, noncompetitive inhibitor of HIV-1 reverse transcriptase. It binds to HIV reverse transcriptase, inducing a conformational change that results in enzyme inhibition.

Hints for Monitoring

Monitoring hepatic function before and during treatment with efavirenz is recommended. Lab tests (Periodic liver functions and lipid profile) should be conducted in the course of treatment. In addition, monitoring GI status and evaluating the ability to maintain a normal diet are recommended.

Side Effects

• The principal side effects involving the central nervous system (CNS) include drowsiness, dizziness, insomnia, nightmares, and headache.
• Psychiatric symptoms, such as depression, psychosis, and mania, have also been observed.
• Skin rash early in therapy.
• Others include nausea, vomiting, diarrhea, elevated liver enzymes, crystalluria, and an increase in total serum cholesterol by 10–20%

Drug interactions

Efavirenz is both an inducer and an inhibitor of CYP3A4. Coadministration of efavirenz can alter the concentrations of other drugs, and other drugs may alter the concentrations of efavirenz. Efavirenz levels are decreased by saquinavir, rifampin. Lastly, efavirenz levels are increased by ritonavir, fluconazole.

Clinical trial

Clinical trials of Efavirenz (Sustiva), formerly known by the codename DMP 266, have been conducted since December 9, 1996. It was approved for use in the United States for HIV treatment in 1998. A European license was granted in May 1999. It is recommended that the drug must be taken in combination with other antiretroviral drugs.

References

Alcorn, K. (2017, June 01). Efavirenz (Sustiva). Retrieved November 05, 2020, from https://www.aidsmap.com/about-hiv/arv-background-information/efavirenz-sustiva

Röhrich, C. R., Drögemöller, B. I., Ikediobi, O., Merwe, L. V., Grobbelaar, N., Wright, G. E., Warnich, L. (2016). CYP2B6*6 and CYP2B6*18 Predict Long-Term Efavirenz Exposure Measured in Hair Samples in HIV-Positive South African Women. AIDS Research and Human Retroviruses, 32(6), 529-538. doi:10.1089/aid.2015.0048

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Antivirals

Antivirals

• Select a medication and discuss the ethnic, cultural, or genetic differences in the uses for the treatment of a viral infection.
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• In addition, share a clinical trial that supports the use of this agent.
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