MK-0518 is an integrase inhibitor under development by Merck & Co. Integrase inhibitors block the incorporation of HIV’s genetic material into the host cell’s DNA, a necessary step for the virus’s life-cycle.

MK-0518 has shown promising results in a phase II study in 35 HIV-positive patients who had not taken anti-HIV therapy previously. The patients were given one of four doses of the drug (100, 200, 400 or 600mg) or placebo twice a day for ten days.

Viral loads fell by between 1.7 and 2.2 log₁₀ from a baseline of over 5000 copies/ml across all of the MK-0518 groups, compared to a reduction of 0.2 log₁₀ in the placebo group. This resulted in at least 50% of the patients having viral loads below 400 copies/ml by day 10. The commonest side-effects were headache, tiredness and dizziness^[1].

The drug has also shown promising results a study of highly treatment-experienced patients. One hundred and sixty-seven patients were randomised to take 200, 400 or 600mg MK-0518 twice daily or placebo. After 16 weeks, between 56 and 72% of those taking MK-0518 had viral loads below 50 copies/ml, compared to 8% of the patients taking placebo. All of the patients started treatment with viral loads above 5000 copies/ml and resistance to the three major classes of anti-HIV drugs: 50% had no active drugs in addition to MK-0518 and 98% were resistant to all protease inhibitors.

The commonest side-effects were diarrhoea, nausea, tiredness, headache, flushing, injection site reactions from T-20 (enfuvirtide, Fuzeon) and itching, but none of the side-effects were more common in the MK-0518 arm than the placebo arm, and they were unrelated to MK-0518 dose^[2].

MK-0518 is currently being tested in a 96-week study in comparison with efavirenz (Sustiva) in combination with other anti-HIV drugs in patients who have not taken anti-HIV therapy before. Preliminary 24-week results from this studdy suggest that MK-0518 is as effective in reducing viral loads and increasing CD4 cell counts as efavirenz, with between 85 and 95% of patients achieving a viral load below 50 copies/ml at all four doses studies: 100, 200, 400 and 600mg twice a day^[3].

MK-0518 is not metabolised through the CYP3A enzyme, so is unlikely to have important interactions with other anti-HIV drugs.

Merck announced in August 2006 that MK-0518 will be made available through a wordwide expanded access scheme for adult patients with HIV who have run out of other drugs and who are at risk of clinical illness or deterioration of the immune system.