DOR/3TC/TDF is Non-Superior to EFV/FTC/TDF for Reducing HIV-1 RNA Copies at 48 Weeks

A treatment comprised of DOR/3TC/TDF was non-superior to EFV/FTC/TDF for primary efficacy but resulted in fewer adverse events.

A treatment regimen comprised of doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF) was non-inferior to a regimen comprised of efavirenz/emtricitabine/TDF/tenofovir disoproxil fumarate (EFV/FTC/TDF) in achieving <50 HIV-1 RNA copies/mL at week 48 in antiretroviral treatment-naive HIV patients presenting with ≥1000 HIV-1 RNA copies/mL, according to a study published in Clinical Infectious Diseases.

“Physicians must consider a number of factors when assessing an appropriate treatment regimen for patients,” study researcher Elizabeth Anne Martin, PhD, told Contagion ®. “Having multiple therapeutic options is important for physicians and patients, especially for treating a chronic condition such as HIV. The DRIVE-AHEAD study demonstrates that DELSTRIGO (DOR/3TC/TDF) does not have the same adverse event or efficacy limitations of other drugs in the same class.”

In the non-inferiority, phase 3 trial, investigators enrolled a total of 728 antiretroviral treatment—naïve adult patients with ≥1000 HIV-1 RNA copies/mL. Participants were randomized to receive either once-daily DOR/3TC/TDF (n = 364) at 100 mg, 300 mg, 300 mg doses, respectively, or to receive EFV/FTC/TDF (n = 364) at 600 mg, 200 mg, and 300 mg, respectively. Additionally, both groups took a matching placebo with their assigned once-daily treatment regimen.

Study treatment ran for up to 96 weeks. The primary efficacy endpoint was comprised of the percentage of patients achieving <50 HIV-1 RNA copies/mL at 48 weeks of treatment. Additionally, the investigators compared treatments in regard to adverse events.

At 48 weeks, a similar proportion of patients in both groups achieved <50 HIV-1 RNA copies/mL (84.3% vs 80.8%, respectively; difference 3.5%, 95% CI, -2.0-9.0). Overall, response rates favored EFV/FTC/TDF in patients ≤31 years old and DOR/3TC/TDF in individuals >31 years of age. At each follow-up, both groups demonstrated similar rates of virologic response.

From baseline to 48 weeks, the mean CD4+ T cell count change was also similar between the DOR/3TC/TDF and EFV/FTC/TDF treatment arms (198 vs 188 cells/mm3, respectively; difference, 10.1; 95% CI -16.1-36.3).

Patients receiving DOR/3TC/TDF experienced lower adverse event rates, including 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%) compared with those who received EFV/FTC/TDF. Additionally, treatment with DOR/3TC/TDF resulted in significantly greater and more favorable changes in mean fasting low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol (1-sided P <.0001) compared with the other treatment group.

While response appeared similar across the majority of subgroups, several of these subgroups were comprised of a small proportion of patients, including women (15.4%), Blacks/African Americans (18.5%), and patients with high baseline viral loads (>100000 copies/mL, 21.3%), low CD4+ T-cell counts (≤200/mm3 , 12.4%), or hepatitis B/C co-infections (2.7%).

“We believe DELSTRIGO is a promising new treatment option for adults with HIV-1 infections as it is a once-daily fixed dose combination with few drug-drug interactions and without the adverse event or efficacy limitations of other NNRTIs,” Dr. Martin concluded. “The favorable safety profile of DELSTRIGO may reduce the likelihood of non-compliance and treatment discontinuation.”