Raltegravir integrase strand transfer inhibitors

It is the first of a new class of antiretroviral drugs known as integrase inhibitors. Raltegravir specifically inhibits the final step in integration of strand transfer of the viral DNA into our own host cell DNA. Raltegravir has a half-life of approximately 9 hours and is, therefore, dosed twice daily. The route of metabolism is UGT1A1-mediated glucuronidation and, therefore, drug interactions with CYP450 inducers, inhibitors, or substrates do not occur. Raltegravir is well tolerated, with nausea, headache, and diarrhea as the most common side effects. More serious side effects reported include elevated CK (creatine kinase) with muscle pain and rhabdomyolysis and possible depression with suicidal ideation. In combination with other antiretroviral agents, raltegravir is approved for both initial therapy of both treatment-naïve patients as well as treatment-experienced patients with evidence of viral replication despite ongoing antiretroviral drug therapy Raltegravir is a pyrimidine derivative that binds integrase, an enzyme essential to replication of both HIV-1 and HIV-2, inhibiting strand transfer. As a result, integration of reverse-transcribed HIV DNA into host cell chromosomes is inhibited. The drug has been used mainly in treatment-naïve HIV patients, usually in combination regimens. The drug is metabolized by glucuronidation and is not affected by agents that induce or inhibit hepatic cytochromes P450. However, if used with rifampin, which induces UDP-glucuronosyltransferase, the dose of raltegravir should be doubled. Adverse effects include nausea, dizziness, and fatigue. An increase in creatinine kinase has been reported, with potential for myopathy or rhabdomyolysis. Dolutegravir and elvitegravir are similar.