Pharmacokinetic Enhancers

Reviewed by: HU Medical Review Board | Last reviewed: 5/31/22

Pharmacokinetic enhancers are a class of drugs used in the treatment of HIV. When pharmacokinetic enhancers are used in combination with other HIV-fighting medications the treatment regimen is referred to as antiretroviral therapy (ART).

It’s important to note that pharmacokinetic enhancers do not directly treat HIV. Instead, they function to increase the effectiveness of other drugs used in an ART treatment regimen, typically drugs that belong to the integrase inhibitor or protease inhibitor classes.

HIV life cycle

Viruses like HIV need human host cells to replicate. They cannot multiply on their own without human cells. When HIV particles called virions enter the body after a transmission event, the next main steps of the HIV lifecycle are as follows:

  1. Binding
  2. Fusion
  3. Reverse transcription
  4. Integration
  5. Replication
  6. Assembly
  7. Budding1

The first two steps of the life cycle focus on HIV getting into a human CD4 cell, or T cell, which is its target cell. Once inside, it needs to disassemble itself and begin the replication process. The next three steps represent the replication process of the virus’s genetic material. The virus’ RNA (its original genetic material) gets converted to DNA through a process called reverse transcriptase. This newly formed viral DNA gets inserted into human host cell DNA so that it can continue to be replicated. The integration of viral DNA into human DNA is carried out by an enzyme HIV carries around with it called integrase.1

The last two steps of the process involve HIV re-assembling itself into new, mature virions that can be released from the CD4 cell and enter the bloodstream where they can go on to infect new cells. Fully formed HIV carries around with it its viral RNA (its genetic material) and several enzymes, including the reverse transcriptase enzyme, the integrase enzyme (both involved in replication), and the protease enzyme. An HIV virion is not considered complete and able to infect more CD4 cells without all of these components.1

Pharmacokinetic enhancers’ mechanism of action

As mentioned, pharmacokinetic enhancers don’t directly target and treat HIV. Instead, they inhibit an enzyme in the human body called cytochrome P450 3A4, also called CYP3A4. Normally, CYP3A4 helps break down drugs and other molecules in the body so that they can be eliminated. Drugs that get broken down, or metabolized, by this enzyme are prevented from staying in the body for too long.

However, when CYP3A4 is inhibited by a pharmacokinetic enhancer, it allows for the normal drug targets of this enzyme to continue to exist and work in the body beyond what’s normal. By preventing the breakdown enzyme from doing its job, the concentration and efficacy of other drugs may be increased.

Not all drugs are broken down by this enzyme. There are many different enzymes involved in the breakdown and excretion of drugs and other molecules in the body. However, some HIV drugs, including certain integrase inhibitors and protease inhibitors are broken down by CYP3A4. Medications like the integrase inhibitor elvitegravir, and the protease inhibitors atazanavir and darunavir can be used with a pharmacokinetic enhancer and potentially have their efficacy improved. Pharmacokinetic enhancers used in HIV treatment are also called CYP3A4 inhibitors.2

Examples of pharmacokinetic enhancers

Common pharmacokinetic enhancers include, but may not be limited to:

  • Cobicistat (COBI)
  • Ritonavir (RTV)2,3

Side effects and drug interactions

Pharmacokinetic enhancers may cause yellowing of the skin or whites of the eyes. Because pharmacokinetic enhancers impact the way some drugs are broken down, they may have significant drug interactions, and should not be taken alongside certain medications.

Your doctor or healthcare provider will provide you with information on what issues you may be at risk for based on what pharmacokinetic enhancer you are taking, and what other medications you should avoid. Some individuals may develop kidney issues, or a worsening in previous kidney problems when a pharmacokinetic enhancer is taken with specific medications.

Pharmacokinetic enhancers may also impact the way other things like vitamins, supplements, and herbal products are broken down. It is important to tell your healthcare provider if you currently use, or are planning to use, any of these products before starting a pharmacokinetic enhancer.4

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