Once-Daily, Fixed-Dose Combination Tablet Containing Doravirine Achieved HIV-1 Viral Suppression

MedicalResearch.com Interview with:

Dr. Kathleen Squires MD Professor and Director of Infectious Diseases Thomas Jefferson University Philadelphia, PA 

Dr. Squires

Dr. Kathleen Squires MD
Professor and Director of Infectious Diseases
Thomas Jefferson University
Philadelphia, PA 

MedicalResearch.com: What is the background for this study? What are the main findings?

  • The pivotal Phase 3 DRIVE-AHEAD study evaluated the safety and efficacy of a once-daily, single tablet, fixed-dose combination containing doravirine, an investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) for the treatment of HIV-1 infection, compared to a fixed-dose combination containing efavirenz.
    • After 48 weeks of treatment, 84 percent of the 364 treatment-naïve patients taking once-daily DOR/3TC/TDF achieved levels of HIV-1 RNA <50 copies/mL compared to 81 percent of the 364 patients taking once-daily EFV/FTC/TDF, with an estimated treatment difference of 3.5 percent.
    • Increases in mean CD4+ T-cell counts from baseline for the DOR/3TC/TDF and EFV/FTC/TDF groups were 198 and 188 cells/mm3, respectively, with an estimated treatment difference of 10.1.
    • In addition, comparable efficacy was observed across both treatment groups among individuals with high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, which consisted of 69 patients in the DOR/3TC/TDF group and 73 patients in the EFV/FTC/TDF group (Observed Failure approach).
      • Of those patients with a high viral load (HIV-1 RNA >100,000 copies/mL) at baseline, 81 percent in the DOR/3TC/TDF group and 81 percent in the EFV/FTC/TDF group achieved the study’s primary endpoint of <50 copies/mL of HIV-1 RNA, with a treatment difference of 1.0 percent.
    • The study also met its primary safety endpoint, showing that treatment with DOR/3TC/TDF resulted in fewer patients reporting events of several pre-specified neuropsychiatric adverse events compared to EFV/FTC/TDF by Week 48, including dizziness (8.8 percent versus 37.1 percent); sleep disorders and disturbances (12.1 percent versus 25.5 percent); and inability to think clearly or concentrate (4.4 percent versus 8.2 percent).

MedicalResearch.com: What should readers take away from your report?

  • The DRIVE-AHEAD study results are encouraging, as the findings demonstrate that a once-daily, fixed-dose combination tablet containing doravirine was shown to be safe and effective, achieving viral suppression in HIV-1 infected, treatment-naïve adults, comparable to a fixed-dose combination containing efavirenz. Based on these results, doravirine may offer physicians a new, single-tablet treatment option for some patients.
  • Additionally, through 48 weeks of treatment, the fixed dose, single tablet combination containing doravirine resulted in statistically significantly fewer patients reporting pre-specified neuropsychiatric adverse events, including dizziness, sleep disorders and disturbances; and inability to think clearly or concentrate. These safety findings are important because such effects on the central nervous system are commonly reported adverse events for other drugs within the NNRTI class. For this reason, we, the study investigators, closely followed any reports of these events in the DRIVE-AHEAD study.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

  • Clinicians strive to individualize antiretroviral therapy for their patients, recognizing that co-morbidities with the requirements for concomitant medications, specific life requirements such as life/work requirements and patient’s desires regarding pill size, number of medications, etc., are crucial to selection of the optimal regimen for an individual patient. It will be important to define which patients may benefit from this novel agent.

MedicalResearch.com: Is there anything else you would like to add? Any disclosures?

  • Received research grants from Gilead Sciences, and has served on advisory boards for BMS, Gilead Sciences, Janssen, MSD, and ViiV.
  • I’m excited to report that I will be joining Merck in August 2017; and look forward to working with the company to continue advancing HIV research.

Citation:

Findings from the ongoing DRIVE-AHEAD Phase 3 trial were featured as part of a late-breaking oral presentation session at the 9th International Conference on HIV Science (IAS 2017) taking place in Paris, France, from July 23-26, 2017.

http://investors.merck.com/news/press-release-details/2017/Mercks-Investigational-NNRTI-Doravirine-Meets-Primary-Efficacy-Endpoint-of-Non-Inferiority-to-Efavirenz-Both-in-Combination-with-Other-Antiretroviral-Agents-in-Pivotal-Phase-3-Trial-for-Treatment-of-HIV-1-Infection/default.aspx

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

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