İnsan İmmünoyetmezlik Virüsü-1 HIV-1 İntegraz İnhibitörleri

Year 2017, Issue: 1, 29 - 51, 01.01.2017

Pınar Erkekoğlu Nida Koyuncu

Abstract

İnsan immünoyetmezlik virüsü-1 HIV-1 replikasyon için proteaz, revers transkriptaz ve integraza IN ihtiyaç duyar. Son yıllarda, insan immünoyetmezlik sendromunun AIDS tedavisinde HIV-1 IN, antiviral tedavi için önemli bir hedef olarak popülarite kazanmıştır. IN’ye odaklanarak önemli çalışmalar yapılmıştır ve üç yeni ilaç raltegravir, elvitegravir ve dolutegravir Gıda ve İlaç Dairesi’nden FDA onay almıştır. Bu ilaçlar tek veya HIV DNA kopya sayısında daha iyi düşüşler sağlamak için kombine doz rejimleri şeklinde kullanılabilir. Birçok çalışma ile bu ilaçların etkinliği ve güvenliliği hep daha önce tedavi görmemiş, hem de daha önce tedavi gören HIV hastalarında belirlenmiştir. Son zamanlardaki uygulama kılavuzlarına göre IN inhibitörü ilaç rejimleri daha önce tedavi görmemiş hastalarda ilk basamak tedavi olarak kabul edilmektedir. Henüz geliştirilmekte olan birçok IN inhibitörü de doğal veya sentetik bulunmaktadır. Bu maddelerin de etkinlikleri ve yan etkileri farklı çalışmalar ile araştırılmaktadır. Bu çalışmaların en önemli hedefleri etkinliği arttırarak, rezistans profillerini geliştirmek ve ilaç uygulama sıklığını ve yan etkilerini azaltmaktır. Bu derlemede, kullanımda olan ve yeni bulunan IN inhibitörlerinin farmakolojik ve toksikolojik etkilerinden söz edilecektir.

Keywords

HIV, AIDS, integraz, raltegravir, diketo asitler

Human Immunodeficiency Virus-1 HIV-1 Integrase Inhibitors

Abstract

Human immunodeficiency virus-1 HIV-1 requires protease, reverse transcriptase and integrase IN for replication. In the last decades, HIV-1 IN is gaining popularity as a target for the antiviral therapy of acqired immunodeficiency syndrome AIDS . Substantial work focusing on IN has been performed and three new drugs raltegravir, elvitegravir and dolutegravir received approval from Food and Drug Administration FDA . These drugs can be used in single or combined dose regimens to obtain better reduction in HIV DNA copies. The efficacy and safety of these three drugs in treatment-naïve and experienced HIV-infected patients have been established by multiple studies. Based on the current practice guidelines, IN inhibitor-based drug regimens are considered as one of the first-line therapies for treatment-naïve HIV-infected patients. There are also several new IN inhibitors natural or synthetic in development. These efficiancies and side effects of these substances are now being investigated by different studies. The most important goals of these studies are to increase the efficacy, to improve the resistance profiles and to decrease the frequency of drug administration and side effects. This review will focus on the pharmacology and toxicology of IN inhibitors in use and the newly discovered IN inhibitors.

Keywords

HIV, AIDS, integrase, raltegravir, diketo acids

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