Review of integrase strand transfer inhibitors for the treatment of human immunodeficiency virus infection

Abstract

Integrase strand transfer inhibitors (INSTIs) are oral antiretroviral agents used against HIV infection. There are three agents available, including raltegravir, elvitegravir and dolutegravir, some of which are available as combination medications with other antiretroviral drugs. The efficacy and safety of INSTIs in treatment-naïve and experienced HIV-infected patients have been established by multiple studies. Based on the current practice guidelines, INSTI-based regimens are considered as one of the first-line therapies for treatment-naïve HIV-infected patients. There are new INSTIs in development to improve the resistance profile and to decrease the frequency of drug administration.

Keywords:

• dolutegravir
• elvitegravir
• human immunodeficiency virus
• integrase strand transfer inhibitor
• raltegravir

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Integrase strand transfer inhibitors (INSTIs) are proven safe and effective for treatment-naïve and treatment-experienced, HIV-1–infected patients.

• Currently available INSTIs include raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG), some of which are also available as combination products.

• RAL has been studied recently as a sparing agent replacing other antiretroviral drugs, which demonstrated promising results.

• RAL is well tolerated with creatine phosphokinase elevation observed in some patients.

• A fixed-dose combination product of EVG is proven efficacious in treatment-naïve patients and as a sparing agent for virologically suppressed patients who cannot tolerate other antiretroviral drugs.

• EVG should be avoided in patients with creatinine clearance <70 ml/min, otherwise it is considered well tolerated.

• The efficacy of DTG is supported by various clinical trials with minimal adverse effects.

• DTG may be considered an appropriate option for patients who have resistance to RAL and/or EVG. However, DTG has reduced efficacy in patients with Q148 substitutions plus two or more INSTI resistance substitution.

• Based on current guidelines, INSTIs are considered as the first-line therapy for treatment-naïve, HIV-1–infected patients regardless of the pre-treatment viral load.

• Newer INSTI compounds are being developed that may demonstrate high barrier to resistance, no cross-resistance to other INSTIs, and less-frequent dosing schedule. The integrase enzyme target will be further developed extending the benefits for patients with HIV-1 infection in the future.