HIV Integrase Inhibitors
Examples
- Dolutegravir
- Elvitegravir
- Raltegravir
Indications
HIV infection
HIV treatment is very complex and should be undertaken by a specialist. Most regimes include a combination of drug from different classes.
Contraindications
Contraindications
- Pregnancy
- Elderly
- Hepatic impairment
- Psychiatric illness
- Pre-existing risk factors for myopathy or rhabdomyolysis
Mechanism
These inhibitors act on HIV integrase which results in the blocking of the strand transfer step of retroviral DNA integration into the host genome which is essential for the HIV replication cycle.
Administration
Oral (for all drugs)
Adverse Reactions
- GI disturbances (abdominal pain, diarrhoea, dyspepsia, nausea)
- Insomnia
- Hepatitis
- Osteonecrosis
Interactions
Not as big of an issue as some the other HIV drug classes. However, they still interact with some other medicines;
- Antiepileptics (carbamazepine, phenytoin)- Can reduce the exposure to the integrase inhibitors.
- Mineral supplementation (calcium chloride, ferrous sulphate)- Can decrease the absorption of integrase inhibitors.
- Metformin- Dolutegravir can moderately increase the exposure to metformin.
- Rifampicin- Can decrease the exposure to integrase inhibitors.
Education
Treatment regimes for HIV are no longer as complex as they once were, however patient education about compliance is still important.
Pharmacokinetics
Given orally and absorbed in the gastrointestinal tract. Metabolised by the liver via glucuronidation and excreted in the urine and faeces.
