Raltegravir 1200 mg Once Daily vs 400 mg Twice Daily, With Emtricitabine and Tenofovir Disoproxil Fumarate, for Previously Untreated HIV-1 Infection: Week 96 Results From ONCEMRK, a Randomized, Double-Blind, Noninferiority Trial.

Abstract

BACKGROUND:

Raltegravir 1200mg (2×600mg tablets) once daily (QD) demonstrated noninferior efficacy and similar safety to raltegravir 400mg twice daily (BID) at week 48 of the ONCEMRK trial. Here, we report the week 96 results from this study.

METHODS:

ONCEMRK is a phase 3, multicenter, double-blind, noninferiority trial comparing raltegravir 1200mg QD with raltegravir 400mg BID in treatment-naive HIV-1-infected adults. Participants were assigned (2:1) to raltegravir 2×600mg QD or 400mg BID, both with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) for 96 weeks. Randomization was stratified by screening HIV-1 RNA and hepatitis B/C status. Efficacy was assessed as the proportion of participants with HIV-1 RNA <40 copies per milliliter (Food and Drug Administration Snapshot approach); the noninferiority margin was 10 percentage points.

RESULTS:

Of the 797 participants who received study therapy (84.6% were men, 59.3% were white, and mean age was 35.9 years), 694 completed 96 weeks of treatment (87.6% QD; 84.4% BID), with few discontinuations because of lack of efficacy (1.1% for both groups) or adverse events (1.3% QD; 2.3% BID). At week 96, 81.5% (433/531) of QD recipients and 80.1% (213/266) of BID recipients achieved HIV-1 RNA <40 copies per milliliter (difference 1.4%, 95% confidence interval: -4.4 to 7.3). CD4 T-cell counts increased >260 cells/mm from baseline in both groups. Resistance to raltegravir was infrequent, occurring in 0.8% of each treatment group through week 96. Adverse event rates were similar for the 2 regimens.

CONCLUSIONS:

In HIV-1-infected treatment-naive adults receiving FTC/TDF, raltegravir 1200mg QD demonstrated noninferior efficacy to raltegravir 400mg BID that was durable to week 96, with a safety profile similar to raltegravir 400mg BID.

• Authors: Pedro Cahn, Paul E Sax, Kathleen Squires, Jean-Michel Molina, Winai Ratanasuwan, Mohammed Rassool, Mark Bloch, Xia Xu, Yan Zhou, Brenda Homony, Deborah Hepler, Hedy Teppler, George J Hanna, Bach-Yen Nguyen, Wayne Greaves, ONCEMRK Study Group
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 78 Issue 5 Pg. 589-598 (08 15 2018) ISSN: 1944-7884 [Electronic] United States
• PMID: 29771789 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• 9-(2-((bis(pivaloyloxymethoxy)phosphinoyl)methoxy)propyl)adenine
• Anti-HIV Agents
• Phosphorous Acids
• Placebos
• RNA, Viral
• Raltegravir Potassium
• Emtricitabine
• Adenine

Topics

• Adenine (administration & dosage, analogs & derivatives, therapeutic use)
• Adult
• Anti-HIV Agents (administration & dosage, therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Drug Therapy, Combination
• Emtricitabine (administration & dosage, therapeutic use)
• Female
• HIV Infections (drug therapy)
• HIV-1 (genetics, isolation & purification)
• Humans
• Male
• Phosphorous Acids (administration & dosage, therapeutic use)
• Placebos
• RNA, Viral (blood)
• Raltegravir Potassium (administration & dosage, therapeutic use)