TY - JOUR
T1 - Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus–1 Infection
T2 - Week 48 Results of the DRIVE-AHEAD Trial
AU - Orkin, Chloe
AU - Squires, Kathleen E
AU - Molina, Jean-Michel
AU - Sax, Paul E
AU - Wong, Wing-Wai
AU - Sussmann, Otto
AU - Kaplan, Richard
AU - Rodgers, Anthony
AU - Nguyen, Bach-Yen
AU - Hwang, Carey
AU - Hanna, George J
AU - Lin, Gina
AU - Lupinacci, Lisa
AU - Sklar, Peter
AU - Kumar, Sushma
AU - Xu, Xia
AU - Martin, Elizabeth A
AU - DRIVE-AHEAD Study Group
A2 - Nielsen, Henrik Ib
PY - 2019/2/1
Y1 - 2019/2/1
N2 - Background. Doravirine (DOR), a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI), is active against wild-type Human Immunodeficiency Virus (HIV)-1 and the most common NNRTI-resistant variants, and has a favorable and unique in vitro resistance profile. Methods. DRIVE-AHEAD is a phase 3, double-blind, non-inferiority trial. Antiretroviral treatment.naive adults with .1000 HIV-1 RNA copies/mL were randomized (1:1) to once-daily, fixed-dose DOR at 100 mg, lamivudine at 300 mg, and tenofovir disoproxil fumarate (TDF) at 300 mg (DOR/3TC/TDF) or to efavirenz at 600 mg, emtricitabine at 200 mg, and TDF at 300 mg (EFV/ FTC/TDF) for 96 weeks. The primary efficacy endpoint was the proportion of participants with 50 HIV-1 RNA copies/mL at week 48 (Food and Drug Administration snapshot approach; non-inferiority margin 10%). Results. Of the 734 participants randomized, 728 were treated (364 per group) and included in the analyses. At week 48, 84.3% (307/364) of DOR/3TC/TDF recipients and 80.8% (294/364) of EFV/FTC/TDF recipients achieved 50 HIV-1 RNA copies/mL (difference 3.5%, 95% CI, -2.0, 9.0). DOR/3TC/TDF recipients had significantly lower rates of dizziness (8.8% vs 37.1%), sleep disorders/disturbances (12.1% vs 25.2%), and altered sensorium (4.4% vs 8.2%) than EFV/FTC/TDF recipients. Mean changes in fasting low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) were significantly different between DOR/3TC/TDF and EFV/FTC/TDF (.1.6 vs +8.7 mg/dL and .3.8 vs +13.3 mg/dL, respectively). Conclusions. In HIV-1 treatment-naive adults, DOR/3TC/TDF demonstrated non-inferior efficacy to EFV/FTC/TDF at week 48 and was well tolerated, with significantly fewer neuropsychiatric events and minimal changes in LDL-C and non.HDL-C compared with EFV/FTC/TDF. Clinical Trials Registration. NCT02403674.
AB - Background. Doravirine (DOR), a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI), is active against wild-type Human Immunodeficiency Virus (HIV)-1 and the most common NNRTI-resistant variants, and has a favorable and unique in vitro resistance profile. Methods. DRIVE-AHEAD is a phase 3, double-blind, non-inferiority trial. Antiretroviral treatment.naive adults with .1000 HIV-1 RNA copies/mL were randomized (1:1) to once-daily, fixed-dose DOR at 100 mg, lamivudine at 300 mg, and tenofovir disoproxil fumarate (TDF) at 300 mg (DOR/3TC/TDF) or to efavirenz at 600 mg, emtricitabine at 200 mg, and TDF at 300 mg (EFV/ FTC/TDF) for 96 weeks. The primary efficacy endpoint was the proportion of participants with 50 HIV-1 RNA copies/mL at week 48 (Food and Drug Administration snapshot approach; non-inferiority margin 10%). Results. Of the 734 participants randomized, 728 were treated (364 per group) and included in the analyses. At week 48, 84.3% (307/364) of DOR/3TC/TDF recipients and 80.8% (294/364) of EFV/FTC/TDF recipients achieved 50 HIV-1 RNA copies/mL (difference 3.5%, 95% CI, -2.0, 9.0). DOR/3TC/TDF recipients had significantly lower rates of dizziness (8.8% vs 37.1%), sleep disorders/disturbances (12.1% vs 25.2%), and altered sensorium (4.4% vs 8.2%) than EFV/FTC/TDF recipients. Mean changes in fasting low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) were significantly different between DOR/3TC/TDF and EFV/FTC/TDF (.1.6 vs +8.7 mg/dL and .3.8 vs +13.3 mg/dL, respectively). Conclusions. In HIV-1 treatment-naive adults, DOR/3TC/TDF demonstrated non-inferior efficacy to EFV/FTC/TDF at week 48 and was well tolerated, with significantly fewer neuropsychiatric events and minimal changes in LDL-C and non.HDL-C compared with EFV/FTC/TDF. Clinical Trials Registration. NCT02403674.
KW - Doravirine
KW - Efavirenz
KW - HIV-1
KW - Randomized controlled trial
KW - Treatment-naive
UR - http://www.scopus.com/inward/record.url?scp=85055461749&partnerID=8YFLogxK
U2 - 10.1093/cid/ciy540
DO - 10.1093/cid/ciy540
M3 - Journal article
C2 - 30184165
SN - 1058-4838
VL - 68
SP - 535
EP - 544
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 4
ER -