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

Doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/ TDF) treatment in people living with HIV: A single-center real-world experience from Belgrade, Serbia. (PubMed, Germs) - "In routine care in Belgrade, once-daily DOR/3TC/TDF was well tolerated and effective: naïve patients achieved rapid suppression with CD4 gains, and switch patients maintained high rates of undetectable viral load without adverse lipid shifts. These findings support DOR/3TC/TDF as a practical option in the Serbian setting."

Journal • Real-world evidence • Human Immunodeficiency Virus • Infectious Disease • CD4

Factors Associated With Weight Change After Continuing or Switching to a Doravirine-based Regimen. (PubMed, Open Forum Infect Dis) - P3 | "Participants were randomized to first-line therapy with doravirine or darunavir/ritonavir, each given with 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) (DRIVE-FORWARD) and to doravirine/lamivudine/tenofovir disoproxil fumarate (TDF) or efavirenz/emtricitabine/TDF (DRIVE-AHEAD); after 96 weeks, participants continued (n = 466) or switched to (n = 423) doravirine for 96-week open-label extensions. More research in historically underrepresented groups may help explain these findings. NCT02275780, NCT02403674, NCT02397096."

Clinical • Journal • Human Immunodeficiency Virus • Infectious Disease

Changes in cardiovascular and metabolic risk scores after switching to DOR/3TC/TDF, DTG/3TC or BIC/FTC/TAF: results from a multicenter Italian cohort (EACS 2025) - "Finally, regarding METS-IR, after 48 weeks we observed a significant decrease in the DOR group (-0.9, p=0.024), while there were no significant changes with DTG and an increase of +0.3 with BIC (p=0.013). Conclusions : We found that switching to DOR/3TC/TDF was associated with more favorable changes in SCORE-2, METS-IR and BMI compared to DTG/3TC and BIC/FTC/TAF."

Clinical • Infectious Disease

Improved body weight, lipid and immune profile and adipose tissue gene expression after a 48-week switch from an INSTI regimen to DOR/3TC/TDF in persons with HIV with INSTI-associated weight gain: The ADDORE study (EACS 2025) - "Conclusions : Switching PWH with INSTI-associated body weight increase to DOR/3TC/TDF for 48 weeks improved weight, lipid profile, allowed a partial reversal of INSTI-induced altered adipose gene expression associated with fat hypertrophy and inhibition of beiging together with changes in lymphoid and myeloid immune responses favoring a less inflammatory profile. ADDORE was granted by MSD"

IO biomarker • Human Immunodeficiency Virus • Infectious Disease • B3GAT1 • CD8 • GDF15 • IL10 • IL18 • LEP • PD-1 • PD-L1 • PPARG • PRDM16

Two versus three-drug Doravirine based regimens in real life: a multicentric observational study (EACS 2025) - "Purpose : To evaluate reasons for switching, effectiveness and durability of a two-drug (2DR) doravirine (DOR)-based combination, DOR+3TC, versus a DOR-based three-drug regimen (3DR), DOR/3TC/TDF. Conclusions : DOR/3TC/TDF and DOR+3TC were comparable in effectiveness and durability. DOR+3TC may be viable for people with complex metabolic profiles and treatment intolerance histories, if full susceptibility is confirmed and adherence reinforced."

Clinical • Observational data • Human Immunodeficiency Virus • Infectious Disease

Effectiveness of switching to bictegravir/emtricitabine/tenofovir alafenamide from NNRTI-based ART in virologically suppressed people with HIV (PWH): a retrospective analysis (DRIVE-SWITCH study) (EACS 2025) - "Purpose : Large real-world data in people with HIV (PWH) switching from non-nucleoside reverse transcriptase inhibitors (NNRTIs), especially from rilpivirine (RPV)-based regimens to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) are lacking...Results : Overall, 250 PWH were included: median age 59 years (interquartile range, IQR 51-65); 65 (26%) females at birth, 213 (85%) Italian natives; 141 (56%) switched from RPV/FTC/TAF, 7 (2.8%) from RPV/FTC/TDF, 96 (38.4%) from EFV/FTC/TDF, 3 (1.2%) from NVP+TDF/FTC, 2 (0.8%) from DOR/3TC/TDF, 1 (0.4%) from NVP+TAF/FTC...Treatment discontinuations were rare events. No resistance mutations detected."

Retrospective data • Human Immunodeficiency Virus • Infectious Disease

Changes in weight and BMI associated with switching to doravirine/lamivudine/tenofovir disoproxil fumarate vs. continuing an integrase inhibitor- or protease inhibitor-based regimen- an observational prospective case-control study (EACS 2025) - "Switching to doravirine/lamivudine/tenofovir disoproxil fumarate vs. continuing an INSTI-based regimen was associated with significantly more weight loss compared to continuing a PI-based regimen post-switch (-0.55 kg/month vs. +0.18 kg/month respectively, p=0.032) through Week 24. Conclusions : At Week 24, switching to doravirine/lamivudine/tenofovir disoproxil fumarate was associated with significantly lower weight gain post-switch among overweight and obese adults compared to continuing an INSTI or PI-based regimen."

Clinical • Observational data • Infectious Disease

The efficacy and safety of doravirine/lamivudine/tenofovir disoproxil fumarate in treatment-naïve and treatment-experienced patients with HIV. (PubMed, Ann Med) - "Twenty-seven patients (32.5%) were treatment-naïve PWH, and 56 patients (67.5%) were treatment-experienced PWH, the most common switch was from integrase inhibitors (37/56) to DOR, followed by efavirenz (18/56) and nevirapine (1/56). In addition, anxiety, depression and sleep disorders improved in those patients who switched regimens from efavirenz to DOR. We provide a short-term observational report of the efficacy and safety of DOR/3TC/TDF in routine clinical practice, further supporting its use in PWH."

Journal • Retrospective data • CNS Disorders • Depression • Human Immunodeficiency Virus • Infectious Disease • Mood Disorders • Psychiatry • Sleep Disorder • CD4

No evidence of an effect of the M184I/V on the doravirine/lamivudine/tenofovir switch efficacy in people living with HIV. (PubMed, AIDS) - "Among PLWHIV with antiretroviral experience, there was no evidence that switching to doravirine + lamivudine plus tenofovir affected short-term treatment response in individuals harboring HIV M184I/V mutations."

Journal • Human Immunodeficiency Virus • Infectious Disease

DORAVIPEP: Evaluation of (Doravirine / Lamivudine / Tenofovir Disoproxil Fumarate) (Delstrigo®) as a New Strategy for Non-occupational Post Exposure Prophylaxis, a Prospective Open Label Study (clinicaltrials.gov) - P4 | N=399 | Completed | Sponsor: Hospital Clinic of Barcelona | Recruiting ➔ Completed

Trial completion • Human Immunodeficiency Virus • Infectious Disease

Acute rhabdomyolysis in a woman living with HIV - antiretroviral treatment is not always to blame. (PubMed, Int J STD AIDS) - "As we suspected a drug-related cause, Dovato® was changed for tenofovir disoproxil fumarate, lamivudine and doravirine (Delstrigo®) without improvement. The outcome was favorable after treatment with corticosteroids followed by methotrexate. Dovato® was subsequently re-prescribed without recurrence of symptoms or rhabdomyolysis."

Journal • Dermatomyositis • Human Immunodeficiency Virus • Immunology • Infectious Disease • Musculoskeletal Pain • Myositis • Pain

COATL: DOR/TDF/3TC COmpared With BIC/FTC/TAF in ART-Naïve People Living With HIV and Overweight or Obesity (clinicaltrials.gov) - P3 | N=306 | Recruiting | Sponsor: Instituto Mexicano del Seguro Social

New P3 trial • Genetic Disorders • Human Immunodeficiency Virus • Infectious Disease • Obesity

DOR/TDF/3TC Switch With M184V/I in People With Controlled HIV (Drive Off-Road) (clinicaltrials.gov) - P2 | N=32 | Recruiting | Sponsor: University Hospital, Caen | Not yet recruiting ➔ Recruiting | Trial completion date: May 2025 ➔ May 2026 | Trial primary completion date: Apr 2024 ➔ Apr 2026

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

Simultaneous Quantification of Doravirine, Lamivudine, and Tenofovir Disoproxil Fumarate in Human Plasma by UPLC-MS/MS: Method Development and Validation. (PubMed, Turk J Pharm Sci) - "A novel, high-throughput liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technique has been developed that uses Etravirine (ETR) as the internal standard (IS) to simultaneously quantify Doravirine (DOR), Lamivudine (LAM), and Tenofovir Disoproxil Fumarate (TDF) in human plasma. The developed bioanalytical method, validated in accordance with ICH M10 guidelines, demonstrated high accuracy, precision, and reproducibility for the simultaneous quantification of DOR, LAM, and TDF. Its streamlined design and reliable performance make it a valuable tool for routine analysis."

Journal

Effectiveness of switching to doravirine-based antiretroviral therapy: A real-world study in Germany. (PubMed, HIV Med) - "DOR-based ART is effective in maintaining virological suppression without evidence of ART-related weight increase in a switch population of individuals with a high prevalence of comorbidities."

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

Efficacy and safety of doravirine/lamivudine/tenofovir disoproxil fumarate in HIV treatment: a real-world single-center study in China. (PubMed, Front Med (Lausanne)) - "Among patients with central nervous system (CNS) symptom, both the Pittsburgh Sleep Quality Index (PSQI) and the Hospital Anxiety and Depression Scale (HADS) scores, as well as the proportion of patients with scores greater than 7 points, decreased significantly post-switch (p < 0.05). We provided an observational report on the effectiveness and safety of the short-term use of DOR/3TC/TDF in routine clinical practice."

Journal • Real-world evidence • CNS Disorders • Depression • Human Immunodeficiency Virus • Infectious Disease • Mood Disorders • Psychiatry • CD4

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