Integrase Inhibitors

Integrase inhibitors are a class of drugs used to suppress HIV in the body. When integrase inhibitors are used in combination with other HIV-fighting drugs, the treatment regimen is referred to as antiretroviral therapy (ART).¹

INSTIs act on the integration portion of the HIV life cycle, where the newly formed viral DNA gets inserted into host cell DNA for HIV to carry out the rest of its replication process. Integrase inhibitors are sometimes called integrase strand transfer inhibitors.¹

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:^2,3

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

Figure 1. Integrase inhibitors target integration in the HIV life cycle

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. Normally, our body converts the information in our DNA to RNA (transcription), and then RNA to proteins. DNA and RNA are both forms of genetic material. The HIV virus is able to go backward through this process to become DNA. This process is called reverse transcription. HIV carries around a special enzyme called reverse transcriptase, which allows it to move backward from RNA to DNA. This special property of HIV is why it is classified as a retrovirus.^2,3

The newly formed viral DNA can then be inserted into the host cell’s DNA using the enzyme integrase. HIV carries around its own integrase just like it carries its own reverse transcriptase. This integration step is important in allowing HIV to continue to be replicated in its original form with the rest of our normal DNA. Once HIV replicates itself, it can then reassemble into new virion particles that get released out of the cell and back into the bloodstream to infect new CD4 cells.^2,3

How do integrase inhibitors work?

Integrase inhibitors can be used to block the integrase enzyme and prevent the further integration of HIV DNA into our host cells. If HIV’s DNA cannot be inserted into our host cells’ genome, the virus cannot continue to be replicated, assembled into mature virus particles, and released into the blood to continue infecting other cells.^1,4

Examples of integrase inhibitors

Integrase inhibitors approved to treat HIV include:^1,4

• Bictegravir (Biktarvy®)
• Cabotegravir (Vocabria)
• Dolutegravir (Tivicay, Tivicay PD)
• Raltegravir (Isentress)

What are the possible side effects of integrase inhibitors?

The most common side effects of integrase inhibitors include:^1,4

• Diarrhea
• Nausea
• Fatigue
• Headache
• Insomnia
• Dizziness

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

Other things to know

Before starting treatment with an integrase inhibitor, tell your doctor if you have:^1,4

• Liver problems
• Kidney problems
• Hepatitis B or C infection
• Any other medical conditions

There is not enough data to know if integrase inhibitors are safe to take while pregnant or breastfeeding. Before starting treatment with an integrase inhibitor, tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding. They can help you decide if an integrase inhibitor is right for you.^1,4

Integrase inhibitors may 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.^1,4