Types of antiretroviral medications

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Key points

  • There are more than 30 antiretroviral medications in six drug classes; these are listed below.
  • Each class of drug attacks HIV in a different way.

There are six main types (‘classes’) of antiretroviral drugs.

Each class of drug attacks HIV in a different way. Generally, drugs from two (or sometimes three) classes are combined to ensure a powerful attack on HIV.

Most people start HIV treatment on two drugs from the nucleoside/nucleotide reverse transcriptase inhibitors class combined with either one integrase inhibitor, one non-nucleoside reverse transcriptase inhibitor, or one protease inhibitor – hence, ‘triple therapy’.

Nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs)

Nucleoside reverse transcriptase inhibitors (NRTIs), and nucleotide reverse transcriptase inhibitors (NtRTIs), often all referred to as NRTIs, work by targeting the action of an HIV protein called reverse transcriptase.

After the HIV virus releases its genetic material into a host cell, reverse transcriptase converts the viral RNA into DNA, a process known as ‘reverse transcription’. NRTIs disrupt the construction of a new piece of proviral DNA, thereby stopping the reverse transcription process and halting HIV replication.

This class of medications is sometimes referred to as the ‘backbone’ of a first-line HIV treatment combination. It includes the following drugs:

Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) also target reverse transcriptase, but in a different way to NRTIs.

NNRTIs interfere with the reverse transcriptase enzyme by binding directly to it, blocking the reverse transcription process.

Integrase inhibitors

Integrase inhibitors target a protein in HIV called integrase which is essential for viral replication.

Integrase is responsible for inserting viral genomic DNA into the host chromosome. The integrase enzyme binds to host cell DNA, prepares an area on the viral DNA for integration, and then transfers this processed strand into the host cell’s genome.

Glossary

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

generic

In relation to medicines, a drug manufactured and sold without a brand name, in situations where the original manufacturer’s patent has expired or is not enforced. Generic drugs contain the same active ingredients as branded drugs, and have comparable strength, safety, efficacy and quality.

receptor

In cell biology, a structure on the surface of a cell (or inside a cell) that selectively receives and binds to a specific substance. There are many receptors. CD4 T cells are called that way because they have a protein called CD4 on their surface. Before entering (infecting) a CD4 T cell (that will become a “host” cell), HIV binds to the CD4 receptor and its coreceptor. 

non-nucleoside reverse transcriptase inhibitor (NNRTI)

Non-nucleoside reverse transcriptase inhibitor, the family of antiretrovirals which includes efavirenz, nevirapine, etravirine, doravirine and rilpivirine. Non-nucleoside reverse transcriptase inhibitors (NNRTIs) bind to and block HIV reverse transcriptase (an HIV enzyme), preventing HIV from replicating.

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

Integrase inhibitors stop the virus from inserting itself into the DNA of human cells.

Entry inhibitors

Entry inhibitors stop HIV from entering human cells. There are two types: CCR5 inhibitors and fusion inhibitors.

In order to enter a host cell, HIV must bind to two separate receptors on the cell’s surface: the CD4 receptor and a co-receptor (CCR5 or CXCR4). Once HIV has attached to both, its envelope can fuse with the host cell membrane and release viral components into the cell. CCR5 inhibitors prevent HIV from using the CCR5 co-receptor by binding to it, blocking viral entry.

CCR5 inhibitors won’t work in everyone and are very rarely used for first-line treatment. You would have a test to see if this type of treatment would be effective before starting on it. One CCR5 inhibitor is licensed in Europe:

A fusion inhibitor (enfuvirtide) is used only for people who have no other treatment options. It works by stopping the fusion of the HIV envelope protein with the CD4 cell.

Protease inhibitors (PIs)

Protease inhibitors (PIs) block the activity of the protease enzyme, which HIV uses to break up large polyproteins into the smaller pieces required for assembly of new viral particles. While HIV can still replicate in the presence of protease inhibitors, the resulting virions are immature and unable to infect new cells.

  • Atazanavir may be marketed under the name Reyataz, but generic versions are also available. Atazanavir is included in the combination tablet Evotaz.
  • Darunavir may be marketed under the name Prezista, but generic versions are also available. Darunavir is included in the combination tablets Rezolsta and Symtuza.
  • Lopinavir is only available in the combination tablet Kaletra.

Post-attachment inhibitors

Post-attachment inhibitors bind to the CD4 receptor on T-cells. They prevent the HIV gp120 protein from changing its shape to engage with co-receptors after it engages with the CD4 receptor. One post-attachment inhibitor is available.

Booster drugs

Booster drugs are used to ‘boost’ the effects of protease inhibitors. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

Single-tablet regimens

There are some fixed-dose pills that combine two or three antiretroviral drugs from more than one class into a single pill that is taken once a day. Find out more about these on our page Single-tablet regimens.

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