In the HIV life cycle, the HIV-1 integrase enzyme plays a vital role to insert the
HIV-1 proviral DNA into the host chromosome. It is a rational target to design inhibitors
for HIV treatment and prevention. This chapter focuses on three FDA approved HIV-1
integrase strand transfer inhibitors (INSTIs); raltegravir, elvitegravir and dolutegravir.
Raltegravir is the first approved HIV-1 integrase inhibitor. It blocks HIV-1 replication by
inhibiting the strand-transfer activities of integrase with a rapid absorption (Tmax ~ 4 h).
With twice daily dosing, approximately 83% of raltegravir is bound to human plasma
proteins and its terminal elimination half-life is approximately 9 hours. For raltegravir, no
adjustment of dosing is necessary for food, gender, age, body mass index, or hepatic and
renal function. It has significant anti-HIV potency in both antiretroviral treatment-naïve and
treatment-experienced patients. As the second approved HIV-1 integrase inhibitor,
elvitegravir is absorbed rapidly with the Tmax being 3-4 h. The absorption of elvitegravir
increased up to three folds when it was administered with food. It was approved to be used
once daily as part of a fixed-dose combination, known as stribild, which is a complete
regimen for the treatment of adults with antiretroviral treatment-naïve HIV-1 infection.
Dolutegravir is a second-generation integrase inhibitor that has more rapid and sustained
virologic suppression than raltegravir and elvitegravir. It is time to the maximum plasma
concentration (Tmax) is 1 h. The terminal elimination half-life of dolutegravir is 13 ~ 14 h.
Clinically, dolutegravir is a commonly used antiretroviral regiment for both treatmentnaïve
and treatment-experienced patients. In summary, HIV-1 integrase inhibitors are a
novel class of antiretroviral drug, which provide a tremendous advancement in AIDS
treatment options.
Keywords: Administration, adverse effects, catalytic mechanism, clinical
trials, DNA, dolutegravir, drug interactions, elvitegravir, function, HIV-1
integrase, inhibitors, pharmacodynamics, pharmacokinetics, raltegravir,
resistance, structure.
