Pharmacokinetic Enhancers

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

It’s important to note that PK 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

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

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

How do PK enhancers work?

PK enhancers don’t directly target and treat HIV. Instead, they block 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 they can be eliminated. Drugs that get broken down by this enzyme are prevented from staying in the body for too long.^2-4

But when CYP3A4 is blocked by a PK 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.^2-4

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. Drugs like the integrase inhibitor elvitegravir and the protease inhibitors atazanavir and darunavir can be used with a PK enhancer and potentially have their efficacy improved. PK enhancers used in HIV treatment are also called CYP3A4 inhibitors.^2-4

Examples of PK enhancers

PK enhancers used in HIV treatment include:^2-4

• Tybost^® (cobicistat/COBI)
• Norvir^® (ritonavir/RTV)

PK enhancers are also available in several combination therapies.

What are the possible side effects?

Side effects can vary depending on the specific drug you are taking. The most common side effects of PK enhancers include:^5,6

• Yellowing of the skin or whites of the eyes
• Nausea, vomiting
• Diarrhea
• Stomach (abdominal) pain
• Tingling feeling or numbness in hands or feet or around the lips
• Rash
• Feeling weak or tired

These are not all the possible side effects of PK enhancers. Talk to your doctor about what to expect when taking a PK enhancer. You also should call your doctor if you have any changes that concern you when taking a PK enhancer.

Other things to know

Before starting treatment with a PK enhancer, tell your doctor if you have:^5,6

• Kidney problems
• Liver problems, including hepatitis B or C
• Heart problems
• High blood sugar (diabetes)
• Bleeding problems or hemophilia
• Any other medical conditions

There is not enough data to know if PK enhancers are safe to take while pregnant or breastfeeding. Before starting treatment with a PK enhancer, tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. They can help you decide if a PK enhancer drug is right for you.^5,6

PK enhancers can interact with other medicines and cause serious side effects. Before beginning treatment for HIV, tell your doctor about all your health conditions and any other drugs, vitamins, or supplements you are taking. This includes over-the-counter drugs.