Integraseremmers

Integraseremmers, or integrase inhibitors, are a class of antiretroviral drugs used to treat HIV-1 infection by blocking the integrase enzyme that inserts viral DNA into the host genome. By preventing this integration, they stop the replication cycle of the virus and reduce viral load when used as part of combination antiretroviral therapy.

Mechanism of action: Integrase inhibitors block the strand transfer step carried out by HIV integrase, preventing the viral DNA from becoming part of the host cell’s genome. This leads to the production of unintegrated viral DNA and markedly lowers the generation of new virions.

Clinical use: These drugs are typically used in combination with other antiretrovirals, often in first-line regimens due to strong efficacy and favorable tolerability. They are commonly prescribed with nucleoside reverse transcriptase inhibitors (NRTIs) such as tenofovir/emtricitabine or abacavir/lamivudine, in single-tablet regimens or as part of standard multi-drug therapies.

Examples and approvals: Raltegravir (Isentress) was the first approved integrase inhibitor (2007), followed by elvitegravir (EVG) in 2012, dolutegravir (DTG) in 2013, and bictegravir (BIC) in 2018. These drugs are used in various fixed-dose combinations with NRTIs and boosters, depending on the regimen.

Pharmacokinetics and interactions: Most integrase inhibitors are taken orally, but absorption can be reduced by concurrent intake of polyvalent cations (calcium, magnesium, iron). Dosing may need to be separated from such supplements. Dolutegravir and bictegravir are mainly metabolized by UGT1A1 and have relatively few drug interactions; raltegravir is primarily cleared by glucuronidation. Attention is required with certain enzymes inducers or inhibitors, and in pregnancy, guidelines should be consulted.

Resistance and safety: Resistance can arise through mutations in the integrase gene, sometimes with cross-resistance among agents. Dolutegravir generally has a higher barrier to resistance. Common side effects include headache, insomnia, and nausea; rare hypersensitivity reactions occur. Overall tolerability is favorable for many patients.