Results of an Initial Phase II Study Showed That MK-0518, an Investigational Integrase Inhibitor, Provided Superior Reduction in HIV Viral RNA vs. Placebo in Treatment-Naive HIV-infected Patients

Initial phase ll clinical trial results presented at the EuropeanAIDS Clinical Society meeting today showed that the investigationalHIV-1 integrase inhibitor MK-0518 tablet had potent reduction in viralload over a 10-day course as monotherapy. Significant viral loadreduction (p=0.001) versus placebo was shown across all doses studiedin previously untreated HIV-infected patients (n=28), according tostudy authors. CD4 count was not significantly different frombaseline.

MK-0518, developed by Merck Sharp & Dohme (MSD), could be thefirst in a new class of investigational anti-retroviral therapy (ART)called integrase inhibitors that may inhibit the integrase enzyme frominserting HIV viral DNA into the human gene*. Inhibiting integrasefrom performing this essential function blocks the ability of thevirus to replicate and infect new cells.

"This study further demonstrated proof-of-concept for theantiviral activity of HIV integrase inhibitors as a new and excitingclass of anti-retroviral agents," said Robin Isaacs, MD, ExecutiveDirector, Infectious Disease and HIV Vaccine Clinical Research, MSD.

"MK-0518 was generally well tolerated and demonstrated potentshort-term viral load reduction as monotherapy in this small, earlytrial."

In the multi-center, double-blinded, randomized trial, 35ART-naive (previously untreated) patients were given one of four dosesof MK-0518 as monotherapy (100 mg, 200 mg, 400 mg, 600 mg) or placebotwice daily for 10 days. Patients at baseline (MK0518: 28, placebo: 7)had HIV-RNA of at least 5000 copies/mL and CD4 counts of at least 100cells/uL. Primary endpoints of the study were the safety andtolerability profiles of MK-0518 and the reduction from baseline inHIV-RNA. Patients undergoing immunosuppressive therapy or withdiagnosed acute hepatitis, chronic liver disease or renal disease wereexcluded from the trial(1).

Results demonstrated a 1.7 to 2.2 log10 copies/mL reduction inHIV-RNA across all MK-0518 treatment groups (a decline of 98 percentfrom baseline) and a 0.2 log10 copies/mL reduction for placebo (pless than 0.001). In addition, at least 50 percent of patients in eachMK-0518 group achieved an HIV-RNA of less than 400 copies/mL by Day10(1).

MK-0518 therapy was generally well tolerated. The most commonadverse experiences (AEs) were headache, fatigue and dizziness; thesewere similar between the MK-0518 and the placebo groups. There were nodiscontinuations due to AEs and no serious AEs(1).

Based on these results, a 48-week dose-ranging trial of MK-0518versus efavirenz - a non-nucleoside reverse transcriptase inhibitor -in combination therapy has been initiated in treatment-naive patients.Additional studies are necessary to evaluate the efficacy and safetyprofile of this investigational drug over a longer period of time andin a larger number of patients.

HIV resistance to drugs increases

It is estimated that up to 78 percent of patients treated withanti-retroviral drugs have developed resistance to more than onetherapeutic class of these medicines. The problem of resistance alsohas increased substantially in drug-naive patients. The proportion oftreatment-naive patients who carried resistant virus has grown to morethan 20 percent today from eight percent in 1999(2).

Despite the availability of drugs to treat HIV/AIDS, the epidemiccontinues. An estimated 40 million people are currently infectedworldwide. AIDS is now the largest infectious disease cause ofmortality worldwide, responsible for three million deaths eachyear(2).

MSD's leadership in developing breakthrough treatments and avaccine against HIV/AIDS has been underway for more than 15 years andcontinues today. MSD was the first to elucidate integrase strandtransfer inhibition and to define the mechanism of action. MSD wasalso the first to demonstrate the mechanism of action in vitro and invivo.

*Inside the host cell, the virus turns its RNA into DNA withanother enzyme, reverse transcriptase. Integrase is one of three HIVenzymes required by the virus to reproduce.

About Merck

Merck & Co., Inc., which operates in many countries as Merck Sharp& Dohme, (MSD), is a global research-driven pharmaceutical companydedicated to putting patients first.

Established in 1891, Merck discovers, develops, manufactures andmarkets vaccines and medicines in more than 20 therapeutic categories.The company devotes extensive efforts to increase access to medicinesthrough far-reaching programs that not only donate Merck medicines buthelp deliver them to the people who need them. Merck also publishesunbiased health information as a not-for-profit service. For moreinformation, visit www.merck.com.

Forward-looking statement

This press release contains "forward-looking statements" as thatterm is defined in the Private Securities Litigation Reform Act of1995. These statements involve risks and uncertainties, which maycause results to differ materially from those set forth in thestatements. The forward-looking statements may include statementsregarding product development, product potential or financialperformance. No forward-looking statement can be guaranteed, andactual results may differ materially from those projected. Merckundertakes no obligation to publicly update any forward-lookingstatement, whether as a result of new information, future events, orotherwise. Forward-looking statements in this press release should beevaluated together with the many uncertainties that affect Merck'sbusiness, particularly those mentioned in the cautionary statements inItem 1 of Merck's Form 10-K for the year ended Dec. 31, 2004, and inits periodic reports on Form 10-Q and Form 8-K, which the companyincorporates by reference.(1) Morales-Ramirez JO, Teppler H, Kovacs C, Steigbigel RT, Cooper D, Liporace RL, Schwartz R, Wenning L, Zhao J, Gilde L, Isaacs R, Nguyen B-Y; Antiretroviral Effect of MK-0518, a Novel HIV-1 Integrase Inhibitor, in ART-Naive HIV-infected Patients. EACS presentation, Dublin, Ireland, November 2005.(2) Data available on file, MSD.

NOTE TO EDITORS: The 10 in "log10" is a subscript. This symbol maynot appear properly in some systems.