Efficacy and Safety of Doravirine in the Rapid Initiation (RapiDO)

Efficacy and Safety of Doravirine in the Rapid Initiation of Highly Active Antiretroviral Therapy (HAART) in HIV-1positive Patients Without Prior Treatment

Protocol title: "Efficacy and safety of doravirine in the rapid initiation of highly active antiretroviral therapy (HAART) in HIV-1positive patients without prior treatment."

Study Overview

• Status: Not yet recruiting
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Doravirine / lamivudine/ Tenofovir Disoproxil Oral Tablet

Detailed Description

Protocol number: FH-96

Primary objective: To evaluate the antiviral activity of DOR/3TC/TDF at week 48 in HIV.

Secondary objectives:

1. To evaluate the antiviral activity of DOR/3TC/TDF at < 200 coIPes/mL at week 48, using the intention-to-treat analysis (FDA snapshot analysis) for the exposed population (ITT-E). 2. To evaluate the antiviral activity of DOR/3TC/TDF at week 48 using an observed analysis (only including patients with available virological data).

3. To evaluate the antiviral activity of DOR/3TC/TDF in the subgroup of participants with baseline ITINN mutations that do not confer resistance to doravirine, (according to the list of mutations defined in the exclusion criteria) by calculating the proportion of patients with viral load <200 coIPes/mL and <50 coIPes/mL at week 48.

4. To evaluate the antiviral activity of DOR/3TC/TDF at <200 coIPes/mL and <50 coIPes/mL at week 24.

5. To evaluate the safety and tolerability of DOR/3TC/TDF. 6. To evaluate the antiviral activity of DOR/3TC/TDF at week 48 in patients with a baseline viral load >100,000 coIPes/mL.

7. Immune response: to evaluate immune recovery (CD4, CD8 and CD4/CD8 T-cell counts at weeks 24 and 48.

8. To evaluate the development of HIV-1 resistance in patients experiencing virological failure while undergoing treatment with DOR/3TC/TDF.

9. To assess changes in weight, BMI, and liIPd profile (total cholesterol, HDL, LDL and triglycerides) at weeks 24 and 48.

Study population: Subjects will be HIV-1 infection patient without ARV experience (naïve) within 30 days of diagnosis, willing to start ARV therapy in a rapid initiation setting, with ≥ 18 years of age, and who meet all inclusion criteria and do not meet any of the exclusion criteria.

Study design: Phase IV, multicenter, non-randomized, single-arm, open-label study describing the antiviral efficacy, safety, and tolerability of DOR/3TC/TDF therapy as rapid initiation therapy in subjects with HIV-1 infection who have not received prior treatment.

Regimens: Doravirine 100 mg; Lamivudine 300 mg; Tenofovir disoproxil 245 mg. Thirteen bottles. (Trade name: DELSTRIGO - MSD). Duration: 48 weeks.

Sample size: 100 subjects

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: María I Figueroa, MD; Phone Number: 2007 1121209999; Email: maria.figueroa@huesped.org.ar
• Study Contact Backup: Name: Pedro E Cahn, MD; Phone Number: 2007 1121209999; Email: pedro.cahn@huesped.org.ar

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1202ABB
    • Fundación Huésped
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina, C1405CKC
      • Fundacion IDEAA -Infectologia de atencion ambulatoria
      • Contact: Ezequiel Cordova, MD; Phone Number: 011 49017133; Email: dr_ecordova@hotmail.com
      • Contact: Norma Porteiro, MD; Phone Number: 011 49017133; Email: normaporteiro@yahoo.com.ar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject has to voluntarily signed and dated an informed consent form, approved by an institutional ethics committee.
2. ≥18 years of age.
3. Not previously exposed to ARV (naïve). Subject may have received oral PrEP and PEP within the last 6 months and injectable PrEP and PEP within the last year.

4. Have a received an HIV diagnosis within 30 days prior to selection. Defined as: Having confirmed HIV-1 infection. HIV-1 positive result is considered if the HIV1 RNA in plasma is ≥ 1000 copies/mL or two HIV antibody tests (using two different tests) are positive.

   NOTE: Participants may be included without knowing their baseline viral load. If baseline viral load results are less than 1000 copies/mL, the volunteer's participation will be suspended and they will be considered to have failed the screening test. A viral load brought by the subject may be considered if it was performed within the last 30 days prior to the SCR visit.

5. CD4+ T-cell count: No limit.
6. Subjects able to meet the protocol requirements.

Exclusion Criteria:

1. History of hypersensitivity to doravirine, tenofovir, or lamivudine.
2. Severe hepatic impairment (Child-Pugh C).
3. Active HCV infection requiring specific treatment during study participation at the time of eligibility assessment. If HCV is diagnosed during the study and the participant requires treatment, the decision on whether to continue in the study will be at the investigator's discretion.

4. A woman may be eligible to enter and participate in the study if she is not pregnant (confirmed by a negative urine pregnancy test at the time of screening/baseline). If the baseline visit is scheduled on a different day than the SCR, the urine pregnancy test will be repeated) or breastfeeding and if at least one of the following conditions applies:

   1. Women without reproductive capacity, defined as premenopausal women with tubal ligation or hysterectomy, or documented bilateral oophorectomy; or as postmenopausal women with 12 months of spontaneous amenorrhea, and women ≥ 45 years of age without hormone replacement therapy.
   2. Women with reproductive capacity who agree to adopt one of the contraceptive options in Appendix 2 for at least 30 days after the last dose of study medication and/or completion of the follow-up visit.

   The chosen contraceptive method must be used consistently, according to the approved product label. All study participants must be advised on safer sex practices, including the use of effective barrier methods, and the choice of effective contraceptive method must be documented in the eCRF (Electronic Case Report Form).

5. The subject's general health status, in the investigator's oIPnion, interferes with the requirements of the study.
6. Has a diagnosis of an active opportunistic infection defining AIDS or a malignant neoplasm within 30 days prior to evaluation (except Kaposi's sarcoma with fewer than 10 skin lesions).
7. Is participating or has participated in a clinical study in the last 6 months.
8. Creatinine clearance (CrCl) ≤50 mL/min according to the Cockcroft-Gault equation.
9. Any verified Grade 4 abnormality (except liIPds: HDL, LDL, total cholesterol, triglycerides).
10. History or presence of allergy to study drugs or their components, or to drugs in their class.
11. Subjects taking any medication during the study, including over-the-counter medications and herbal preparations, without the approval of the study physician.
12. Mutations resistant to doravirine, 3TC, or TDF, according to the list described below:

DOR mutations (INNTI):

Doravirine (INNTI) Primary: the presence of one or more ART-resistant mutations will be grounds for exclusion.

Mutations: V106A/M, F227C/V, L234I, Y188L, Y318F, M230I/L. Secondary: the presence of one or more RAMs will be grounds for exclusion. Mutations: A98G, V108I, G190E, H221Y, P225H, F227L, P236L. Others: the presence of five or more RAMs will be grounds for exclusion. Mutations: V90I, L100I, K101E/H/P, K103N/R/S, V106I, I135T, Y181C/I/V, E138A/G/K/Q/R, V170F/T, G190A/Q/S, Y188C/H, F227I, V245E, K311R.

NRTI (TDF) Relevant mutations: Presence of one or more RAM Mutations: K65R, insertion 69, K70R/E, Q151M,

NRTI (3TC) Relevant mutation Presence of IM184V

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Doravirine /Lamivudine/ Tenofovir Disoproxil; Doravirine 100 mg/Lamivudine 300 mg/Tenofovir disoproxilo245 mg	Drug: Doravirine / lamivudine/ Tenofovir Disoproxil Oral Tablet; Pharmaceutical form: Oral tablets Unit dose concentration/dose level(s): 100/300/245 mg Administration instructions: Take one tablet once a day; Other Names: Delstrigo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the antiviral activity of DOR/3TC/TDF at week 48 in HIV patients without prior antiretroviral treatment, in a rapid initiation setting.	Proportion of patients with a viral load < 50 copies/mL at week 48, as determined by an intention-to-treat analysis (FDA snapshot analysis) of the exposed population (ITT-E)	48 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the antiviral activity of DOR/3TC/TDF at < 200 copies/mL at week 48, using the intention-to-treat analysis (FDA snapshot analysis) for the exposed population (ITT-E).	Proportion of patients with a viral load < 200 copies/mL at week 48, using intention-to-treat analysis (FDA snapshot analysis) for the exposed population (ITT-E).	48 Weeks
Evaluate the antiviral activity of DOR/3TC/TDF at week 48 using an observed analysis (only including patients with available virological data).	Proportion of patients who achieved HIV-1 RNA levels <50 copies/mL at week 48, in those with available data (observed analysis)	48 Weeks
Evaluate the antiviral activity of DOR/3TC/TDF in the subgroup of participants with baseline ITINN mutations that do not confer resistance to doravirine, by calculating the proportion of patients with viral load <200 c/mL and <50 c/mL at week 48.	Proportion of patients with viral load < 200 copies/mL and viral load < 50 copies/mL at week 48 in the subgroup of participants with baseline ITINN mutations that do not confer resistance to doravirine, according to the list of mutations defined in the exclusion criteria.	48 Weeks
Evaluate the antiviral activity of DOR/3TC/TDF at <200 copies/mL and <50 copies/mL at week 24.	Proportion of patients with viral load < 200 copies/mL and viral load < 50 copies/mL at week 24, using intention-to-treat analysis (FDA snapshot analysis) for the exposed population (ITT-E).	24 Weeks
Evaluate the safety and tolerability of DOR/3TC/TDF.	Frequency, type, severity, and seriousness of adverse events and laboratory abnormalities, and proportion of patients who discontinued treatment with DOR/3TC/TDF due to adverse events or death	52 Weeks
Evaluate the antiviral activity of DOR/3TC/TDF at week 48 in patients with a baseline viral load >100,000 copies/mL.	Proportion of patients with a baseline HIV-1 RNA level >100,000 c/mL who achieve virological suppression below 50 copies/mL at week 48 (ITT-E analysis).	48 Weeks
Immune response: evaluate immune recovery (CD4, CD8 and CD4/CD8 T-cell counts at weeks 24 and 48.	Changes in CD4 T-cell count, CD8 T-cell count, and CD4/CD8 ratio between baseline and weeks 24 and 48.	24 and 48 Weeks
Evaluate the development of HIV-1 resistance in patients experiencing virological failure while undergoing treatment with DOR/3TC/TDF	Number and type of resistance mutations in cases of virological failure.	48 Weeks
Assess changes in weight and BMI, at weeks 24 and 48.	Changes in weight and BMI between baseline and weeks 24 and 48. Weight and height will be combined to calculate BMI in kg/m^2. Weight will be measured at all visits and height only at the baseline visit.	24 and 48 Weeks
Assess changes in lipid profile (total cholesterol, HDL, LDL and triglycerides) at weeks 24 and 48.	Changes in lipid profile (total cholesterol, HDL, LDL and triglycerides) between baseline and weeks 24 and 48.	24 and 48 Weeks

Collaborators and Investigators

• Sponsor: Fundación Huésped
• Collaborators: MSD Pharmaceuticals LLC; Fundacion IDEAA

Study record dates

Study Major Dates

• Study Start (Estimated): July 13, 2026
• Primary Completion (Estimated): January 13, 2028
• Study Completion (Estimated): January 13, 2028

Study Registration Dates

• First Submitted: January 12, 2026
• First Submitted That Met QC Criteria: January 20, 2026
• First Posted (Actual): January 22, 2026

Study Record Updates

• Last Update Posted (Actual): January 22, 2026
• Last Update Submitted That Met QC Criteria: January 20, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Efficacy; Doravirine; Rapid initiation of highly active antiretroviral therapy
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Purines; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Organophosphorus Compounds; Nucleosides; Deoxyribonucleosides; Organophosphonates; Adenine; Dideoxynucleosides; Zalcitabine; Tenofovir; Lamivudine; doravirine
• Other Study ID Numbers: FH-96

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: It will be shared upon request, 6 months after last patient´s last visit. URL not yet available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No