Experimental integrase inhibitor GSK-572 looks good in early studies

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A second-generation integrase inhibitor - GlaxoSmithKline's S/GSK1349572, or GSK-572 for short - demonstrated very good anti-HIV activity in a 10-day monotherapy study, researchers reported on Tuesday at the Fifth International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Cape Town, South Africa.

Laboratory studies and early human trials showed that GSK-572 has a potent anti-HIV effect and reached high and stable levels in the body, making it suitable for once-daily dosing without the need for ritonavir boosting.

Investigators then evaluated the safety and efficacy of the drug used alone in HIV-positive individuals never previously treated with an integrase inhibitor.


integrase inhibitors (INI, INSTI)

A class of antiretroviral drugs. Integrase strand transfer inhibitors (INSTIs) block integrase, which is an HIV enzyme that the virus uses to insert its genetic material into a cell that it has infected. Blocking integrase prevents HIV from replicating.


A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

phase II

The second stage in the clinical evaluation of a new drug or intervention, in which preliminary data on effectiveness and additional information about safety is collected among a few hundred people with the disease or condition.

clinical trial

A research study involving participants, usually to find out how well a new drug or treatment works in people and how safe it is.

treatment failure

Inability of a medical therapy to achieve the desired results. 

In a multicentre controlled Phase 2a clinical trial, 35 participants were randomly assigned to receive GSK-572 at one of three doses (2 mg, 10 mg, or 50 mg), or else a placebo. All of the participants were men and most were white.

None of the participants had previously taken another integrase inhibitor, but otherwise they could be either treatment-experienced or new to antiretroviral therapy. The experimental drug was taken for ten days and patients took no other anti-HIV medications drugs during this period

After 10 days of treatment, average HIV viral load fell between 1.51 and 2.46 log10 copies/ml across the three 572 treatment arms. This contrasted with a 0.5 log10 copies/ml increase in viral load amongst patients taking the placebo.

The investigators described the nearly 2.5 log10 copies/ml decrease in the 50 mg group as "unprecedented." The 10 mg dose produced a viral load reduction of about 2 log10 copies/ml, similar to the decreases seen with other integrase inhibitors and potent drugs in other classes.

When the researchers analysed viral load in patients who received the 50mg dose of GSK-572, they found that 70% achieved a lowest viral load below 50 copies/ml, whilst 90% had less than 400 copies/ml. In the 2 mg and 10mg dose groups, however, although about 60% had a lowest viral load below 400 copies/ml, few reached a level below 50 copies/ml.

CD4 count rose by 15 to 106 cells/mm3 in patients who took GSK-572, whilst falling in the placebo group, but the clinical effect of CD4 cell changes over such a short period is unclear.

Overall, GSK-572 was generally well tolerated. No serious adverse events were reported and no patients withdrew from the trial due to side-effects or for any other reason.

The most commonly reported adverse events were diarrhoea, fatigue and headache, usually mild or moderate in severity. Most side-effects occurred more often in the placebo group, but headache was more common amongst people who took the highest dose of GSK-572. The investigators did not find evidence that GSK-572 caused any laboratory or heart abnormalities.

HIV susceptibility to GSK-572 remained the same from baseline to the end of the study period. No participants developed mutations associated with resistance to GSK-572 or other integrase inhibitors.

The S/GSK1349572 research team also presented four posters describing preclinical laboratory studies and early trials in humans. In test tube studies, 572 was active against HIV from patients experiencing treatment failure with the approved integrase inhibitor raltegravir (Isentress), suggesting it may be active against raltegravir-resistant virus.

In a study of HIV-negative volunteers, GSK-572 had stable and consistent pharmacokinetics (how the drug is processed in the body), could be taken with or without food, and did not have a tendency to interact with other drugs.

A Phase 2b clinical trial is starting this month to study the 50 mg dose of GSK-572 in a tablet form in a larger number of patients.