To optimize treatment, Merck initiated the OnceMRK Trial, a Merck HIV clinical trial designed to evaluate whether Raltegravir 1200 mg once daily could be as effective as the standard Raltegravir 400 mg twice daily regimen. This trial provided critical insights into the potential of raltegravir high-dose therapy and helped shape modern HIV management.

1. Background on Raltegravir and Isentress HD

Raltegravir, sold under the brand name Isentress HD, was first approved in 2007. It became a cornerstone of HIV therapy due to its potency, tolerability, and ability to rapidly reduce viral load.

• Mechanism of action: It blocks HIV integrase, an enzyme the virus needs to insert its genetic material into host DNA.

• Formulations: Initially available as Raltegravir 400 mg twice daily, which required patients to take two doses per day.

• New development: Raltegravir 1200 mg once daily formulation, designed for better convenience and adherence.

2. Purpose of the OnceMRK Trial

The OnceMRK Trial was launched to determine if the once-daily dosing strategy could maintain the same level of efficacy and safety as the traditional twice-daily regimen.

The trial specifically compared:

• Raltegravir 1200 mg once daily vs. Raltegravir 400 mg twice daily

• Virological suppression rates in treatment-naïve HIV patients

• Long-term safety and resistance profiles

3. Design of the Merck HIV Clinical Trial

The Merck HIV clinical trial (OnceMRK Trial) was a randomized, double-blind, active-controlled study that enrolled treatment-naïve adults with HIV-1 infection.

Key Features:

• Participants: Adults with HIV who had not yet started antiretroviral therapy.

• Groups: One group received Raltegravir 400 mg twice daily, while the other received Raltegravir 1200 mg once daily (raltegravir high-dose).

• Duration: Results were measured at Week 48 and extended to long-term follow-up.

• Combination therapy: Both regimens were given with background therapy (usually tenofovir and emtricitabine).

4. Results of the OnceMRK Trial

The OnceMRK Trial demonstrated that Raltegravir 1200 mg once daily was non-inferior to the standard Raltegravir 400 mg twice daily regimen.

Primary Outcomes:

• Virologic suppression: Both groups achieved similar rates of viral load suppression below 50 copies/mL at Week 48.

• CD4 cell count recovery: Improvements in immune system markers were equivalent in both groups.

• Safety and tolerability: Both regimens were well tolerated, with low discontinuation rates due to adverse events.

Significance:

The results confirmed that a raltegravir high-dose once-daily regimen could simplify HIV treatment without compromising effectiveness.

5. Advantages of Raltegravir High-Dose (Once-Daily)

• Improved adherence: Patients find it easier to remember a once-daily pill.

• Quality of life: Simplified dosing reduces treatment fatigue.

• Equivalent efficacy: No compromise in viral suppression compared to twice-daily dosing.

• Fewer pills: Fits into the trend toward single-tablet regimens.

6. Clinical Implications for HIV Management

The success of the OnceMRK Trial and the approval of Isentress HD (raltegravir high-dose) added flexibility in HIV treatment planning. For patients unable to use other integrase inhibitors (such as dolutegravir or bictegravir), Raltegravir 1200 mg once daily provides a safe and effective alternative.

Moreover, the trial reinforced Merck’s role as a leader in HIV clinical trials and paved the way for continued innovation in antiretroviral therapy.

7. Limitations of the OnceMRK Trial

While the trial demonstrated non-inferiority, some limitations should be noted:

• Population studied: Focused on treatment-naïve patients; less data for heavily treated patients with resistance.

• Once-daily absorption: Requires co-formulation with other drugs to ensure convenience in multi-drug regimens.

• Competition from other drugs: Newer integrase inhibitors (dolutegravir, bictegravir) are now preferred in guidelines due to resistance profiles.

8. The Role of Merck HIV Clinical Trials in the Future

The Merck HIV clinical trial program continues to explore next-generation treatments. Beyond raltegravir, Merck is investigating long-acting injectables, combination therapies, and potential curative strategies.

The OnceMRK Trial is a landmark because it showed how dosing convenience can directly influence patient outcomes. It remains an example of how pharmaceutical innovation, such as Isentress HD, can improve adherence and quality of life for people living with HIV.

Conclusion

The OnceMRK Trial was a pivotal Merck HIV clinical trial comparing Raltegravir 1200 mg once daily with Raltegravir 400 mg twice daily. Its results proved that a raltegravir high-dose regimen could provide equivalent viral suppression with the added benefit of simplified dosing.

The trial not only established Isentress HD as a modern treatment option but also reinforced the importance of ongoing innovation in HIV care. By reducing pill burden and improving adherence, this breakthrough helps people living with HIV achieve better long-term health outcomes.

References

1. Cahn P, et al. Raltegravir 1200 mg once daily versus 400 mg twice daily: Week 96 results from the OnceMRK trial. J Int AIDS Soc. 2018.
   https://onlinelibrary.wiley.com/doi/full/10.1002/jia2.25119

2. Merck & Co. – Isentress HD (raltegravir) prescribing information.
   https://www.merck.com/product/usa/pi_circulars/i/isentress_hd/isentress_hd_pi.pdf

3. NIH – Integrase Inhibitors in HIV Treatment Guidelines.
   https://clinicalinfo.hiv.gov

4. Gatell JM, et al. Efficacy and safety of once-daily raltegravir: results from the ONCEMRK trial. HIV Medicine. 2019.

5. AIDSMap – Raltegravir high-dose: once-daily treatment results.
    https://www.aidsmap.com