MK-0518 integrase inhibitor effective in treatment-naive patients

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Merck’s new integrase inhibitor, MK-0518, is as effective as efavirenz (Sustiva) when given as part of potent antiretroviral therapy, according to preliminary findings presented at the Sixteenth International AIDS Conference in Toronto on Thursday, August 17th.

Integrase is an HIV enzyme that allows the virus to insert its genetic material into the DNA of human T-cells. By blocking this step in the viral life-cycle, researchers hope that integrase inhibitors will prevent the virus from replicating.

Investigators from Merck, in collaboration with researchers in the United States, Peru, Thailand, and Canada, enrolled 198 HIV-positive participants receiving antiretroviral therapy for the first time. At study entry, patients had viral loads above 5000 copies/ml and CD4 cell counts greater than 100 cells/mm3. Participants were randomly assigned to receive one of four doses of MK-0518 (100, 200, 400, or 600mg twice a day) or 600mg efavirenz once a day. All of the patients also took tenofovir (Viread) and 3TC (lamivudine, Epivir). Baseline patient characteristics were similar across all arms. Some participants were continuing from an earlier 10-day monotherapy stage of the study, while others were newly enrolled.



A protein which speeds up a chemical reaction.

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.


In HIV, an individual who is ‘treatment naive’ has never taken anti-HIV treatment before.

phase III

The third and most definitive stage in the clinical evaluation of a new drug or intervention, typically a randomised control trial with the new intervention compared to an existing therapy or a placebo, in large numbers of participants (typically hundreds or thousands). Trial results are used to evaluate the overall risks and benefits of the drug and provide the information needed for regulatory approval.


An antibiotic that works by stopping the growth of bacteria. It is used with other medications to treat active tuberculosis (TB) infections, and on its own to prevent active TB in people who may be infected with the bacteria without showing any symptoms (latent TB). 

The researchers presented data from patients who had been treated for 24 weeks. After 24 weeks of combination therapy, all four groups of patients taking MK-0518 had similar rates of HIV suppression to those taking efavirenz, with an average decline of greater than 2 log10.

Depending on dose, 85-95% of patients taking MK-0518 achieved viral loads below 50 copies/ml, compared with 92% of those taking efavirenz. The differences in the rates of viral suppression across the five arms were not statistically significant. Viral load fell more rapidly in patients taking MK-0518, but by week 4, most participants in all arms had undetectable viral load.

CD4 cell counts rose by similar amounts, between 75 and 135 cells/mm3 in all arms.

MK-0518 was well tolerated. The most common side-effects across all arms were nausea, dizziness, and headache. A total of eight severe adverse events were reported, with similar numbers in the MK-0518 and efavirenz arms, but these were not considered drug-related. Abnormal laboratory tests were common, but mostly mild-to-moderate. One patient taking the highest dose of MK-0518 stopped taking the drug after experiencing an elevation in the liver enzyme aspartate aminotransferase (AST); this individual was also taking the anti-tuberculosis drug isoniazid, which can cause liver toxicity.

The researchers concluded that in this preliminary analysis, “MK-0518 with tenofovir/3TC at all doses studied had potent antiretroviral activity and was generally well-tolerated in antiretroviral therapy-naive patients.”

Researchers previously reported that MK-0518 is also active against HIV in treatment-experienced patients with resistant virus. Another study presented at the AIDS conference found that MK-0518 demonstrated activity against virus with a wide range of resistance mutations.

The treatment-naive study will continue through 96 weeks, and a phase III trial is also underway. The same day these results were presented, Merck announced that it was starting an MK-0518 expanded access program for individuals who are unable to take part in the trials.


Markowitz M et al. Potent antiviral effect of MK-0518, novel HIV-1 integrase inhibitor, as part of combination ART in treatment -naïve HIV-1 infected patients. Sixteenth International AIDS Conference, Toronto, abstract THLB0214, 2006

Miller M et al. Biochemical and antiviral activity of MK-0518, a potent HIV integrase inhibitor. Sixteenth International AIDS Conference, Toronto, abstract 4758, 2006