Delstrigo (doravirine/lamivudine/tenofovir disoproxil fumarate) / Merck (MSD) - LARVOL DELTA

Opti-DOR: A Randomised, Phase 3 Non-inferiority Study of DOR/3TC/TDF Compared to DTG/TAF/FTC in Participants Infected With HIV-1 Starting First-line Antiretroviral Therapy (clinicaltrials.gov) - P3 | N=600 | Active, not recruiting | Sponsor: Professor Francois Venter | Recruiting ➔ Active, not recruiting

Enrollment closed • Human Immunodeficiency Virus • Infectious Disease

ELDORADO: DORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living with HIV-1 Infection (clinicaltrials.gov) - P3 | N=610 | Recruiting | Sponsor: ANRS, Emerging Infectious Diseases | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

META-D: The Effect on Lipid Profile of Switching to Delstrigo in HIV Positive Patients (clinicaltrials.gov) - P4 | N=18 | Terminated | Sponsor: Chelsea and Westminster NHS Foundation Trust | N=60 ➔ 18 | Trial completion date: Jul 2024 ➔ Nov 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2024 ➔ Nov 2024; The CI, sponsor and funder jointly made the decision to end the trial due to lack of recruitment, as well as due to delays it was felt value of the primary endpoint had lessened to a point where its scientific value was questioned.

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Human Immunodeficiency Virus • Infectious Disease • Inflammation

Three‐ versus two‐drug doravirine‐based regimens: a multicentre observational study (HIV-Glasgow 2024) - "Characteristics of PWH on DOR/3TC/TDF versus DOR/3TC DOR/3TC/TDF (n = 171) DOR/3TC (n = 47) p-value Age (years), median (IQR) 50.9 (31.2−68.6) 55.9 (32.4−74.5) 0.0199 Males, n (%) 117 (68.0) 35 (74.5) 0.271 Ethnicity, n (%) 0.001 Caucasian 132 (77.2) 43 (91.5) African 28 (16.4) 0 (0) Asiatic 7 (4.1) 0 (0) Other 4 (2.33) 4 (8.5) Time since HIV diagnosis (years), median (IQR) 15.1 (2.4−34.2) 18.2 (5.4−37.1) 0.011 HIV mode of acquisition, n (%) 0.037 Heterosexual 73 (42.7) 19 (40.4) MSM 76 (44.4) 14 (29.8) Other 22 (12.9) 13 (27.7) CD4 nadir, median (IQR) 287 (25−773) 240 (31−501) 0.223 HIV RNA zenith (copies/ml), median (IQR) 63,150 (2800−1,699,328) 30,200 (5100−500,000) 0.914 AIDS, n (%) 46 (29.3) 11 (26.8) 0.460 Time since ART initiation (years), median (IQR) 12.0 (1.8−26.4) 17.5 (3.5−29.6) 0.009 Duration VS pre-switch (months), median (IQR) 104 (1−228) 105 (21−180) 0.549 Previous regimen, n (%) 3DR 151 (88.3) 24 (51.0) 0.000 TXF 139 (81.3) 22 (46.8) 0.000 DOR 3 (1.8) 5..."

Clinical • Observational data • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • CNS Disorders • Diabetes • Diabetic Nephropathy • Dyslipidemia • Human Immunodeficiency Virus • Hypertension • Infectious Disease • Mental Retardation • Metabolic Disorders • Nephrology • Osteoporosis • Psychiatry • Renal Disease • Rheumatology • CD4 • CD8

Profile of people with HIV (PWH) switching prior antiretroviral treatment (ART) to a doravirine (DOR)‐ based regimen in the real‐world clinical setting in Greece: the DORAVITO study (HIV-Glasgow 2024) - "Key demographic, disease and treatment characteristics Overall (N = 110) DOR/3TC/TDF fixed dose combination (N = 96) DOR single agent combined with other ARV(s) (N = 14) Switch to DOR in the second line (N = 37) Switch to DOR in the >second line (N = 71)a Demographic characteristics at baseline Age, mean (SD), years 49.3 (10.8) 48.6 (10.5) 54.6 (11.5) 43.1 (11.2) 52.0 (8.2) Male sex assigned at birth, % 90.9 91.7 85.7 86.5 93.0 Greek ethnic origin, % 75.5 75.0 78.6 59.5 83.1 Clinical, virological and immunological characteristics at baseline HIV clinical stage, % Asymptomatic 88.2 87.5 92.9 91.9 85.9 HIV clinical stage, % Symptomatic (without AIDS-defining conditions) 8.2 8.3 7.1 5.4 9.9 HIV clinical stage, % AIDS 3.6 4.2 − 2.7 4.2 Available virological suppression status (HIV-load <50 copies/ml)b, n n = 89 n = 75 n = 14 n = 33 n = 54 Virologically suppressed among evaluable pts, % 86.5 86.7 85.7 84.8 90.7 Available immunological testing in the last 6 months, n n =..."

Clinical • Real-world • Real-world evidence • Cardiovascular • Congestive Heart Failure • Dyslipidemia • Heart Failure • Hepatitis B • Hepatitis C • Hepatology • Human Immunodeficiency Virus • Hypertension • Infectious Disease • Inflammation • CD4

Evaluation of changes in Systematic Coronary Risk Evaluation 2 (SCORE2) in experienced people with HIV switching to DOR/3TC/TDF: real‐world data from DOROTEA multicentre cohort (HIV-Glasgow 2024) - "The amelioration observed in the lipid profile and in SCORE2 risk estimation at 48 weeks provide further evidence that DOR/3TC/TDF is a suitable option for dyslipidaemic PWH with a high risk of CVD."

Clinical • Real-world • Real-world evidence • Cardiovascular • Diabetes • Human Immunodeficiency Virus • Hypertension • Infectious Disease • Metabolic Disorders • CD4

Discontinuation rates of doravirine/lamivudine/tenofovir‐DF due to neuropsychiatric adverse effects (HIV-Glasgow 2024) - "Due to high costs, NHS England antiretroviral commissioning policies [2] encouraged to consider switching away from rilpivirine/emtricitabine/tenofovir-DF (RPV/F/TDF) in people living with HIV offering generic formulation switches. Rates of NPAE leading to discontinuation of DOR/L/TDF when switching from RPV/F/TDF in this small cohort are higher than described in large randomized studies and ongoing vigilance is justified. Importantly, all patients were involved in their ART decision-making and regular screening of adverse effects is required."

Adverse events • Human Immunodeficiency Virus • Infectious Disease • Insomnia • Pain • Psychiatry • Sleep Disorder

Viral blips in the doravirine phase III clinical trials DRIVE‐FORWARD and DRIVE‐AHEAD (HIV-Glasgow 2024) - "Summary of viral blips in DRIVE-FORWARD and DRIVE-AHEAD DRIVE-FORWARD (1439-018) DRIVE-AHEAD (1439A-021) Double-blind phase (day 1–week 96) DOR + 2NRTIs, n (%) DRV/r + 2NRTIs, n (%) DOR/3TC/TDF, n (%) EFV/FTC/TDF, n (%) Participants in population 342 338 336 322 Total # of blips 42 56 54 46 Participants with blips 38/42 (11.1) 52/338 (15.4) 40/336 (11.9) 39/322 (12.1) With 1 blip 35 (92.1) 48 (92.3) 28 (70.0) 35 (89.7) With 2 blips 2 (5.3) 4 (7.7) 10 (25.0) 3 (7.7) With 3 or more blips 1 (2.6) 0 (0.0) 2 (5.0) 1 (2.6) Months to first blip, median (IQR)a 11.2 (5.4−16.6) 8.5 (5.5−16.7) 13.9 (6.2−18.3) 11.1 (8.3−16.6) Virological failure after blip 8/342 (2.3) 7/338 (2.1) 5/336 (1.5) 3/322 (0.9) Open-label extension (week 100–192) Continued DOR + 2NRTIs Switched to DOR + 2NRTIs Continued DOR/3TC/TDF Switched to DOR/3TC/TDF Participants in population 253 225 286 265 Total # of blips 14 22 20 24 Participants with blips 14/253 (5.5) 17/225 (7.6) 19/286 (6.6) 21/265 (7.9) With 1..."

Clinical • P3 data • Human Immunodeficiency Virus • Infectious Disease • CD4

Cardiovascular Safety of Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate in Virologically Suppressed PLWHIV: A Comparative Analysis of CVD Scores. (PubMed, AIDS Res Hum Retroviruses) - "After 96 weeks, we registered a significant reduction in total cholesterol (-19 mg/dL, p < .001). DOR/3TC/TDF has shown a favorable metabolic profile, with a significant reduction in 10Y-CD, independently from the use of lipid-lowering drugs."

Journal • Cardiovascular • Human Immunodeficiency Virus • Infectious Disease

ELDORADO: DORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living With HIV-1 Infection (clinicaltrials.gov) - P3 | N=610 | Not yet recruiting | Sponsor: ANRS, Emerging Infectious Diseases | Trial completion date: Apr 2027 ➔ Nov 2027 | Initiation date: Apr 2024 ➔ Nov 2024 | Trial primary completion date: Apr 2026 ➔ Nov 2026

Head-to-Head • Trial completion date • Trial initiation date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

DORASPEP: "Observational Study on Tolerability and Observance of Post-exposure Prophylaxis With Doravirine in HIV Viral Risk" (clinicaltrials.gov) - P=N/A | N=226 | Completed | Sponsor: Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

DORA: 48-week weight and metabolic changes in Black women with HIV, in a phase IIIb switch study from dolutegravir- or efavirenz- to doravirine-based first-line antiretroviral therapy. (PubMed, HIV Med) - "Our findings suggest that a switch to doravirine from efavirenz or dolutegravir is safe and effective in Black women, with significant improvement in lipid profiles, but does not arrest progressive weight gain."

Journal • P3 data • Human Immunodeficiency Virus • Infectious Disease

TLATOANI: Change in Body Weight and BMI in PWH with DOR/3TC/TDF Compared with INSTI (clinicaltrials.gov) - P4 | N=108 | Recruiting | Sponsor: Instituto Mexicano del Seguro Social

New P4 trial • Human Immunodeficiency Virus • Infectious Disease

Treatment Experienced People Living With HIV switching to DOR/3TC/TDF in Outpatient Setting: Real-World Data on Tolerability and Cost Savings From an Italian Multicenter Cohort. (PubMed, J Acquir Immune Defic Syndr) - No abstract available

HEOR • Journal • Real-world • Real-world evidence • Human Immunodeficiency Virus • Infectious Disease

DeLiTE: Can INSTI-associated Weight Gain be Halted or Reversed With a Switch to Doravirine/Lamivudine/Tenofovir DF? (clinicaltrials.gov) - P4 | N=4 | Terminated | Sponsor: University Health Network, Toronto | N=25 ➔ 4 | Trial completion date: Dec 2024 ➔ Mar 2024 | Enrolling by invitation ➔ Terminated | Trial primary completion date: Aug 2024 ➔ Mar 2024; enrollment futility

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Human Immunodeficiency Virus • Infectious Disease • CD4

DORASPEP: "Observational Study on Tolerability and Observance of Post-exposure Prophylaxis With Doravirine in HIV Viral Risk" (clinicaltrials.gov) - P=N/A | N=226 | Active, not recruiting | Sponsor: Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba | Recruiting ➔ Active, not recruiting | Trial completion date: Mar 2024 ➔ Jun 2024 | Trial primary completion date: Dec 2023 ➔ Jun 2024

Enrollment closed • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

Bidirectional pharmacokinetics of doravirine, tenofovir, and feminizing hormones in transgender women (IDentify): A randomized crossover trial. (PubMed, Clin Transl Sci) - "Volunteers were randomized 1:1 into two sequences containing three treatment groups (DOR, lamivudine [3TC], and TDF alone; estradiol, spironolactone, and placebo; and DOR/3TC/TDF, estradiol, and spironolactone). There is not a clinically significant impact of FHT on DOR/TFV PKs. Similarly, there is no observed impact on estradiol PKs and total testosterone following use of DOR/3TC/TDF."

Journal • PK/PD data

Effects of Switching From ATRIPLA™ (Efavirenz, Tenofovir, Emtricitabine) to MK-1439A (Doravirine, Tenofovir, Lamivudine) in Virologically-Suppressed Participants (MK-1439A-028) (clinicaltrials.gov) - P2 | N=86 | Completed | Sponsor: Merck Sharp & Dohme LLC | Active, not recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

META-D: The Effect on Lipid Profile of Switching to Delstrigo in HIV Positive Patients (clinicaltrials.gov) - P4 | N=60 | Recruiting | Sponsor: Chelsea and Westminster NHS Foundation Trust | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease • Inflammation

ELDORADO: DORAvirine Versus DOlutegravir Based Antiretroviral Regimens in Treatment-naïve People Living With HIV-1 Infection (clinicaltrials.gov) - P3 | N=610 | Not yet recruiting | Sponsor: ANRS, Emerging Infectious Diseases

Head-to-Head • New P3 trial • Human Immunodeficiency Virus • Infectious Disease

Effects of Switching From ATRIPLA™ (Efavirenz, Tenofovir, Emtricitabine) to MK-1439A (Doravirine, Tenofovir, Lamivudine) in Virologically-Suppressed Participants (MK-1439A-028) (clinicaltrials.gov) - P2 | N=86 | Active, not recruiting | Sponsor: Merck Sharp & Dohme LLC | Phase classification: P2b ➔ P2

Phase classification • Human Immunodeficiency Virus • Infectious Disease

DoraDO: Doravirine Dose Optimisation in Pregnancy (clinicaltrials.gov) - P4 | N=76 | Recruiting | Sponsor: University of Liverpool

Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease

DoraDO: Doravirine Dose Optimisation in Pregnancy (clinicaltrials.gov) - P4 | N=76 | Recruiting | Sponsor: University of Liverpool | Not yet recruiting ➔ Recruiting

Enrollment open • Human Immunodeficiency Virus • Infectious Disease

Opti-DOR: A Randomised, Phase 3 Non-inferiority Study of DOR/3TC/TDF Compared to DTG/TAF/FTC in Participants Infected With HIV-1 Starting First-line Antiretroviral Therapy (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Professor Francois Venter | Not yet recruiting ➔ Recruiting

Enrollment open • Head-to-Head • Human Immunodeficiency Virus • Infectious Disease

Efficacy and safety of doravirine-based regimens by sex and race: long-term results from three phase 3 clinical trials (EACS 2023) - P3 | "In DRIVE-FORWARD and DRIVE-AHEAD extensions, participants randomized to DOR+2 NRTIs or DOR/3TC/TDF continued these regimens (DOR continued group); participants randomized to comparators (DRV/r+2 NRTIs or EFV/FTC/TDF) switched to DOR-based regimens (DOR switch group). Conclusions : Participants who continued or switched to DOR-based regimens had mostly comparable efficacy and safety outcomes across sex and race subgroups, but rates of virological suppression were lower among Black participants, consistent with previous studies. Future studies should enroll greater gender and racial diversity to investigate potential factors leading to outcome disparities."

Clinical • P3 data • Human Immunodeficiency Virus • Infectious Disease • CD4