[Integrase inhibitors - new challenges for the treatment of HIV-1 infections].

Abstract

Integrase inhibitors are a promising new group of antiretroviral drugs that suppress the integrase yielded by human immunodeficiency viruses (HIV) via inhibiting the ,,integration" of the viral deoxyribonucleic acid (DNA) into the hosts' DNA genome. In 2007, raltegravir was the first integrase inhibitor that has been approved for the treatment of HIV-1 infections in antiretroviral-pretreated (-experienced) and antiretroviral-naive patients. Recently, elvitegravir, as a fixed coformulation with cobicistat, tenofovir und emtricitabine, has been approved for the treatment of HIV-1-infected antiretroviral-naive patients. InAugust of 2013, dolutegravir, a third integrase inhibitor, has been approved by the US Food and Drug Adiministation (FDA) for the treatment of HIV-1 infections in adults and children aged 12 years and older. Raltegravir has to be applied twice daily without a boosting agent. Elvitegravir and dolutegravir are applied once daily in the presence of a booster (elvitegravir) or unboosted (dolutegravir). In contrast to raltegravir and elvitegravir, dolutegravir shows a high genetic barrier to resistance, and is also applicable for the treatment of several HIV-1 infections with raltegravir and elvitegravir-resistant HIV variants. During the last years, raltegravir, elvitegravir and dolutegravir have been proven and established in the antiretroviral treatment of HIV-1 infections as effective, safe and well-tolerated agents. However, reliable statement forecasts of long-term toxicity of these substances can not yet be made.

• Authors: Ingo Stock
• Journal: Medizinische Monatsschrift fur Pharmazeuten (Med Monatsschr Pharm) Vol. 36 Issue 12 Pg. 448-59; quiz 461-2 (Dec 2013) ISSN: 0342-9601 [Print] Germany
• Vernacular Title: Integrase-lnhibitoren-neue Wege für die Therapie der HIV-l-lnfektion.
• PMID: 24450269 (Publication Type: Journal Article, Review)

Chemical References

• Anti-HIV Agents
• Heterocyclic Compounds, 3-Ring
• Integrase Inhibitors
• Oxazines
• Piperazines
• Pyridones
• Pyrrolidinones
• Raltegravir Potassium
• dolutegravir

Topics

• Anti-HIV Agents (pharmacology)
• Contraindications
• Drug Resistance, Viral
• HIV Infections (drug therapy)
• HIV-1 (drug effects)
• Heterocyclic Compounds, 3-Ring (pharmacology, therapeutic use)
• Humans
• Integrase Inhibitors (pharmacokinetics, pharmacology, therapeutic use)
• Oxazines
• Piperazines
• Pyridones
• Pyrrolidinones (pharmacology, therapeutic use)
• Raltegravir Potassium
• United States