fumarates and doravirine

Doravirine (DOR) is a nonnucleoside reverse-transcriptase inhibitor. In the phase 3 DRIVE-AHEAD trial in treatment-naive adults with human immunodeficiency virus type 1 (HIV-1) infection, DOR demonstrated noninferior efficacy compared with efavirenz (EFV) and superior profiles for neuropsychiatric tolerability and lipids at 48 weeks. We present data through week 96.. DRIVE-AHEAD is a phase 3, multicenter, double-blind, noninferiority trial in antiretroviral treatment-naive adults with HIV-1 RNA ≥1000 copies/mL. Participants were randomized to a daily fixed-dose tablet of DOR (100 mg), lamivudine (3TC; 300 mg) and tenofovir disoproxil fumarate (TDF; 300 mg) (DOR/3TC/TDF) or EFV (600 mg), emtricitabine (FTC; 200 mg) and TDF (300 mg) (EFV/FTC/TDF). The efficacy end point of interest at week 96 was the proportion of participants with HIV-1 RNA levels <50 copies/mL (Food and Drug Administration Snapshot Approach) with a predefined noninferiority margin of 10% to support week 48 results. Safety end points of interest included prespecified neuropsychiatric adverse events and the mean change in fasting lipids at week 96.. Of 734 participants randomized, 728 received study drugs and were included in analyses. At week 96, HIV-1 RNA <50 copies/mL was achieved by 77.5% of DOR/3TC/TDF vs 73.6% of EFV/FTC/TDF participants, with a treatment difference of 3.8% (95% confidence interval, -2.4% to 10%). Virologic failure rates were low and similar across treatment arms, with no additional resistance to DOR observed between weeks 48 and 96. Prespecified neuropsychiatric adverse events and rash were less frequent in DOR/3TC/TDF than in EFV/FTC/TDF participants through week 96. At week 96, fasting low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol (HDL-C) levels increased in the EFV/FTC/TDF group but not in the DOR/3TC/TDF group; the mean changes from baseline in total cholesterol/HDL-C ratio were similar.. NCT02403674.

Topics: Adult; Alkynes; Anti-HIV Agents; Benzoxazines; Cyclopropanes; Emtricitabine; Fumarates; HIV Infections; HIV-1; Humans; Lamivudine; Pyridones; Tenofovir; Treatment Outcome; Triazoles

HIV post- exposure prophylaxis (PEP) is a prevention tool for individuals with a recent potential exposure to HIV. Doravirine has been available since 2019 in combination with tenofovir disoproxil fumarate and lamivudine and has not been evaluated as a PEP. DOR/3TC/TDF is our department's most commonly prescribed PEP treatment since 2021. This study evaluates the completion rate of the DOR/3TC/TDF as compared to EVG/c/FTC/TAF for PEP, which was the regimen prescribed until 2020 in our hospital.This retrospective observational study was conducted between January 2020 and September 2021. The subjects included consecutively were adults who consulted for an HIV sexual exposure accident and for whom DOR/3TC/TDF in 2021 or EVG/c/FTC/TAF in 2020 was prescribed. The outcomes were the completion rate to the end of treatment (28 days), the seroconversion rate, and the description of side effects.During the study period, 311 people were included: 140 treated with DOR/3TC/TDF and 171 treated with EVGc/FTC/TAF. Considering subjects with a follow-up visit, the completion rate was 96.8% (90/93) in the DOR/3TC/TDF group, and 94.6% (123/130) in the EVG/c/FTC/TAF group (p-value: 0.53). The number of people lost to follow-up was nearly equivalent in both groups: 27.1% (38/140) in the DOR/3TC/TDF group and 23.4% (40/171) in the EVG/c/FTC/TAF group (p-value: 0.45). A side effect was described for 38% (36/94) in the DOR/3TC/TDF group, and 29.7% (38/128) in the EVG/c/FTC/TAF group. No cases of seroconversion were observed.DOR/3TC/TDF appears to have a similar safety profile to EVG/c/FTC/TAF. Due to its lower cost, it seems to be a treatment option for consideration in the context of HIV-exposure accidents.

Topics: Adult; Anti-HIV Agents; Cobicistat; Drug-Related Side Effects and Adverse Reactions; Emtricitabine; Fumarates; HIV Infections; Humans; Lamivudine; Tenofovir

Topics: Alopecia; Anti-HIV Agents; Anti-Retroviral Agents; Emtricitabine; Fumarates; HIV Infections; Humans; Lamivudine; Male; Middle Aged; Pyridones; Tenofovir; Triazoles; Viral Load

Topics: Acquired Immunodeficiency Syndrome; Anti-HIV Agents; Emtricitabine; Fumarates; HIV Infections; Humans; Hypertriglyceridemia; Lamivudine; Tenofovir

Doravirine is a non-nucleoside reverse transcriptase inhibitor for treatment of human immunodeficiency virus type 1 (HIV-1) infection. A population pharmacokinetic (PK) model for treatment-naive participants in doravirine clinical studies was updated with data from switch participants in the DRIVE-SHIFT trial and used to estimate individual

Topics: Anti-HIV Agents; Emtricitabine; Fumarates; HIV Infections; HIV-1; Humans; Lamivudine; Pyridones; Tenofovir; Triazoles