A recent Phase 1-2a study conducted by Shionogi-GlaxoSmithKline Pharmaceuticals evaluated the pharmacokinetics, safety, and antiviral activity of investigational integrase inhibitor (INI), or S/GSK1265744, in healthy and HIV-infected individuals. Data showed a decrease in viral load in HIV-infected patients and positive pharmacokinetic and safety reports in both healthy and HIV-infected individuals. Pharmacokinetics is the study of a drug and its effect on the body, including absorption mechanisms, distribution, rate and duration of effects, chemical changes in the body and the drug’s method of excretion.

Integrase inhibitors belong to a class of anti-HIV drugs that work by inhibiting HIV replication, thereby preventing viral DNA from invading the genetic material of T-cells (healthy immune cells). Because integrase inhibitors have a different mechanism of action from other anti-HIV drugs, patients will have more options for viral suppressants, thereby making their treatment more effective and less vulnerable to developing resistance.

The study was a double-blind, randomized, placebo-controlled study of INI divided into three parts: single (Part A) and multiple (Part B) oral dose of increasing increments in 48 healthy subjects and a multiple oral dose study (Part C) in 11 HIV-infected patients.

In Part A, two groups were given alternating doses of INI suspension or placebo. In Part B, three groups were given INI suspension or placebo once daily for 14 days. In Part C, subjects were given six 5mg INI tablets or placebo once daily for 10 days.

Results in Part C showed a reduction in viral load of HIV infected patients. Additionally, 88 percent of the subjects receiving INI were able to reach undetectable levels of HIV in their level (below 50 copies/mL) by Day 14. Pharmacokinetic data from healthy subjects and INI-naïve HIV subjects showed that INI has a long plasma half-life of 30 hours (how long INI is able to stay in the plasma), lower variability, was able to reach therapeutic concentrations with a low dosage.

Overall, INI was well tolerated in both healthy and HIV-infected subjects, with mild side effects reported, the most common being headaches. Additional studies are needed in order to determine the safety and efficacy of INI as an anti-viral medication for HIV-patients.

For more information, please see Shionogi-GlaxoSmithKline Pharmaceuticals’ press release.