DRIVE AHEAD DOR-TDF-3TC vs. EFV-TDF-FTC as Initial Therapy DRIVE - - PowerPoint PPT Presentation

DOR-TDF-3TC vs. EFV-TDF-FTC as Initial Therapy

DRIVE AHEAD

DOR-TDF-3TC vs. EFV-TDF-FTC as Initial Therapy

DRIVE AHEAD: Design

Source: Orkin C, et al. Clin Infect Dis. 2019:68:535-44.

DOR-TDF-3TC

(n = 364)

EFV-TDF-FTC

(n = 364)

DRIVE AHEAD: Study Design

• Background: Randomized, double-blind, active-

controlled, phase 3 study evaluating the efficacy and safety of doravirine-tenofovir DF-lamivudine (DOR-TDF-3TC) versus efavirenz-tenofovir DF- emtricitabine (EFV-TDF-FTC) for treatment-naïve individuals

• Inclusion Criteria
• Age ≥18
• Antiretroviral-naïve
• HIV RNA ≥1,000 copies/mL
• No resistance to any study drug
• Chronic HBV or HCV allowed
• Regimens
• Doravirine-TDF-3TC (100/300/300 mg)
• Efavirenz-TDF-FTC (600/300/200 mg)

DOR-TDF-3TC vs. EFV-TDF-FTC as Initial Therapy

DRIVE AHEAD: Results

Week 48 Virologic Response (Observed Failure)

Source: Orkin C, et al. Clin Infect Dis. 2019:68:535-44.

88.7 90.6 81.2 88.8 91.1 80.8

20 40 60 80 100 All ≤100,000 copies/mL >100,000 copies/mL HIV RNA <50 copies/mL (%) Baseline HIV RNA Doravirine-Tenofovir DF-Lamivudine Efavirenz-Tenofovir DF-Emtricitabine

307/346 294/331 251/277 235/258 56/69 59/73

DOR-TDF-3TC vs. EFV-TDF-FTC as Initial Therapy

DRIVE AHEAD: Results

Week 48 Virologic Response (FDA Snapshot: All missing data= Failure)

Source: Orkin C, et al. Clin Infect Dis. 2019:68:535-44.

84.3 10.7 80.8 10.2

20 40 60 80 100 HIV RNA ≤50 copies/mL HIV RNA >50 copies/mL Response (%) Doravirine-Tenofovir DF-Lamivudine Efavirenz-Tenofovir DF-Emtricitabine

307/364 294/364 39/364 37/364

DOR-TDF-3TC vs. EFV-TDF-FTC as Initial Therapy

DRIVE AHEAD: Results

Source: Orkin C, et al. Clin Infect Dis. 2019:68:535-44.

Treatment Emergent Adverse Events in DRIVE AHEAD Through Week 48 DOR/TDF/3TC

(n = 364)

EFV/TDF/FTC

(n = 364)

Drug-related AE’s, % 31 63 Discontinued due to drug-related AE, % 3 7 Headache, % 13 12 Diarrhea, % 11 13 Nausea, % 8 11 Vomiting, % 4 7 Abnormal Dreams, % 5 12 Rash, % 5 12

DOR-TDF-3TC vs. EFV-TDF-FTC as Initial Therapy

DRIVE AHEAD: Results

Proportion with Pre-Defined Neuropsychiatric Side Effects at Week 48

Source: Orkin C, et al. Clin Infect Dis. 2019:68:535-44.

8.8 12.1 4.4 4.1 37.1 25.5 8.2 6.6 10 20 30 40 50 Dizziness Sleep disorder, disturbance Altered sensorium Depression, suicide, self-injury Percent of Participants Doravirine-Tenofovir DF-Lamivudine Efavirenz-Tenofovir DF-Emtricitabine

p < 0.05 p < 0.05 p < 0.05

• 2.0
• 1.6

1.9

• 12.4

21.8 8.7 8.5 22.0

• 20
• 10

10 20 30 Cholesterol LDL Cholesterol HDL Cholesterol Triglycerides

Change from Baseline, mg/dL

Doravirine-Tenofovir DF-Lamivudine Efavirenz-Tenofovir DF-Emtricitabine

DOR-TDF-3TC vs. EFV-TDF-FTC as Initial Therapy

DRIVE AHEAD: Results

Change in Baseline Fasting Lipids at Week 48

Source: Orkin C, et al. Clin Infect Dis. 2019:68:535-44.

DOR-TDF-3TC vs. EFV-TDF-FTC as Initial Therapy

DRIVE AHEAD: Summary

Source: Orkin C, et al. Clin Infect Dis. 2019:68:535-44.

Conclusions: “In HIV-1 treatment-naive adults, doravirine/lamivudine/tenofovir DF demonstrated non-inferior efficacy to efavirenz/emtricitabine/tenofovir DF at week 48 and was well tolerated, with significantly fewer neuropsychiatric events and minimal changes in LDL-C and non-HDL-C compared with efavirenz/emtricitabine/tenofovir DF.”

Acknowledgment

The National HIV Curriculum is an AIDS Education and Training Center (AETC) Program supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) as part of an award totaling $800,000 with 0% financed with non-governmental sources. This project is led by the University of Washington’s Infectious Diseases Education and Assessment (IDEA) Program.

The content in this presentation are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by HRSA, HHS, or the U.S. Government.