Dolutegravir/Lamivudine Dual Therapy for ART-naïve People With HIV and TB Receiving Rifampin-based TB Treatment (DOVETAIL)

Dolutegravir Plus Lamivudine (DTG/3TC) Dual Therapy Versus Dolutegravir With TDF-lamivudine (DTG + TDF/3TC) Among Antiretroviral naïve People With HIV and TB Receiving Rifampin-based TB Treatment

This will be a Phase IIIb Clinical Trial, an international multicenter, randomized, three-arm, non-comparative trial of efficacy, safety, and tolerability of the dual therapy regimen dolutegravir plus lamivudine either twice daily or DTG/3TC ( Dovato) in the morning +dolutegravir (DTG) in the evening, versus standard of care (SOC) twice-daily dolutegravir plus 2 once-daily Nucleoside reverse-transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate /lamivudine (TDF/3TC), among antiretroviral therapy (ART)-nave individuals with HIV-1 receiving rifampin-based TB therapy

Study Overview

• Status: Recruiting
• Conditions: HIV; Tuberculosis
• Intervention / Treatment: Drug: Dolutegravir 50mg Tab; Drug: Dolutegravir plus Tenofovir disoproxil fumarate (TDF)/ lamivudine (3TC); Drug: Dolutegravir/Lamivudine 50 MG-300mg Oral Tablet [DOVATO]

Detailed Description

Tuberculosis (TB) is the most common cause of death in people with HIV worldwide. Among patients with HIV, the incidence of TB per year is about 5-10%. The two diseases are now always treated concurrently in co-infected individuals, as there is a survival benefit for starting antiretroviral therapy (ART) soon after TB treatment initiation. Current Brazilian guidelines suggest that for patients with a cluster of differentiation 4 (CD4) < 50, ART should be started within 2 weeks of starting TB treatment; for patients with a CD4>50, ART should be started within 2 months of starting TB treatment. World Health Organization guidelines suggest ART initiation within 2 weeks of TB diagnosis regardless of CD4 count (provided there are no signs of TB meningitis), but most programs defer ART until 6-8 weeks in patients with CD4 >50 to reduce the risk of immune reconstitution inflammatory syndrome (IRIS).

The option of dual therapy for HIV (i.e., complete regimens to treat HIV composed of only 2 drugs) is of increasing interest and can lower costs for patients, payors, and programs while lowering cumulative lifetime exposure to ART (with potential resultant lessened burden of cumulative toxicities) and maintaining high antiviral efficacy. Based on the GEMINI, TANGO, and SALSA clinical trials, a regimen of 50 milligram (mg) DTG combined with 300mg lamivudine (3TC) has been shown to be a highly effective stand-alone option for the treatment of HIV-1 in ART treatment-naïve or virologically suppressed individuals through 48 weeks (SALSA) and 144 weeks (GEMINI and TANGO).

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Beatriz M Kohler, RN; Phone Number: 410 614 3812; Email: bkohler@jhmi.edu
• Study Contact Backup: Name: Kate Boehner, RN; Email: kboehne1@jh.edu

Study Locations

• Brazil
  • Amazonas
    • Manaus, Amazonas, Brazil, 69040-000
      • Recruiting
      • Instituto Tropical de Doenças Infecciosas Manaus
      • Contact: Marcus Lacerda, MD, PhD; Phone Number: +55 92 99114-7633; Email: marcuslacerda.br@gmail.com
      • Contact: Marcelo Cordeiro,,MD, PhD; Phone Number: +55 92 98533-3533
      • Principal Investigator: Marcus Lacerda, MD,PhD
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 40110-160
      • Recruiting
      • Universidade Federal da Bahia
      • Principal Investigator: Carlos Brites, MD, PhD
      • Contact: Carlos Brites, MD, PhD; Phone Number: +55 71 992329552; Email: crbrites@gmail.com
  • Rio Grande do Norte
    • Natal, Rio Grande do Norte, Brazil, 59.025-050
      • Recruiting
      • CePClin - Center for Studies and Research in Infectious Diseases Ltda
      • Contact: Mônica Bay B Bay, MD; Phone Number: +55 84 994141921; Email: monibay@gmail.com
      • Contact: Sibele F Araújo; Email: sibelearaujo@cpclinrn.com.br
  • Rio de Janeiro
    • Rio de Janeiro, Rio de Janeiro, Brazil, 21040-360
      • Recruiting
      • FIOCruz
      • Contact: Valeria Rolla, MD; Phone Number: +55 21 99490-4251; Email: valeria.rolla@ini.fiocruz.br
      • Contact: Aline Benjamin, PhD; Email: alinebenjaminipec@gmail.com
      • Principal Investigator: Valeria Rolla, MD
    • Rio de Janeiro, Rio de Janeiro, Brazil, 26210-190
      • Recruiting
      • Hospital Geral de Nova Iguaçu
      • Contact: Aline Ramalho, MD; Phone Number: +55 22 996107788; Email: alineramalhopesquisa@gmail.com
      • Principal Investigator: Aline Ramalho, MD
  • São Paulo
    • São Paulo, São Paulo, Brazil, 04037-030
      • Recruiting
      • RDSS- Ricardo Diaz Solucoes Cientificas
      • Contact: Ricardo S Diaz, MD; Phone Number: +55 21 99799 4412; Email: rsdiaz@ricardodiaz.com.br
      • Principal Investigator: Ricardo S Diaz, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Documentation of HIV-1 status: HIV-1 infection, documented by any licensed rapid HIV test or HIV-1 enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, or plasma HIV 1 RNA viral load. Two or more HIV-1 RNA viral loads of >1,000 copies/mL are also acceptable as documentation of HIV-1 infection.
• CD4+ cell count ≥50 cells/mm3 obtained within 30 days prior to study entry
• HIV-1 viral load ≥1000 copies/mL
• ART-naïve.
• Documentation of pulmonary TB

Exclusion Criteria:

• Pregnant, or plans to become pregnant.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 2: DTG 50 mg/ 3TC 300mg (Dovato®) once daily (QD) in the morning with DTG 50 mg in the evening; Arm 2: DTG 50mg/300mg FDC tablet plus DTG 50mg at night during TB treatment and for 2 weeks after, then DTG 50 mg/ 3TC 300 mg FDC tablet (Dovato®) once daily to week 52	Drug: Dolutegravir 50mg Tab; Participants will receive Dolutegravir 50mg; Other Names: TIVICAY 50 mg; TIVICAY PD; Drug: Dolutegravir/Lamivudine 50 MG-300mg Oral Tablet [DOVATO]; Participants will receive Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO]
Active Comparator: Arm 3: Standard of Care 3-drug ART (DTG+ TDF/3TC) plus DTG 50mg in the evening.; Arm 3: Local Standard of Care 3-drug ART (DTG 50mg + TDF/3TC) plus DTG 50 mg at night during TB treatment and for 2 weeks after, then DTG 50 mg + TDF/3TC FDC tablet once daily to week 52	Drug: Dolutegravir plus Tenofovir disoproxil fumarate (TDF)/ lamivudine (3TC); Participants will receive Dolutegravir plus Tenofovir disoproxil fumarate (TDF)/ lamivudine (3TC)
Experimental: Arm 1: DTG 50 mg/ 3TC 300mg (Dovato®) twice daily (BID); Arm 1: DTG 50mg/3TC 300 mg fixed-dose-combination (FDC) tablet (Dovato®) twice daily during TB therapy and for 2 weeks after, then DTG 50mg/3TC 300 mg FDC tablet (Dovato®) once daily to week 52	Drug: Dolutegravir/Lamivudine 50 MG-300mg Oral Tablet [DOVATO]; Participants will receive Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet [DOVATO]

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Among treatment-naïve participants with HIV-1 who are taking rifampin-based regimens for TB, determine the proportion with HIV-1 virologic suppression (via FDA snapshot algorithm) at 28 weeks of HIV treatment, by arm	To Compare the proportion of participants with HIV-1 virologic suppression at 28 weeks of HIV treatment by arm.	28 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
1.3.2 Number of patients with HIV-1 virologic suppression at 48 weeks, in the combined DTG/3TC arms (Arm 1 + Arm 2)	To compare the proportion of patients with HIV-1 virologic suppression at 48 weeks, in the combined DTG/3TC arms (Arm 1 + Arm 2)	48 weeks
1.3.3 Change from baseline in CD4 over 28 weeks and 48 weeks of HIV treatment, by arm	To compare the changes from baseline over 28 weeks and 48 weeks of HIV treatment by the arm.	28 weeks, 48 weeks
1.3.4 Concentration of the PK of DTG	Concentration of DTG when given twice daily as a 50 mg/ 300 mg DTG/3TC FDC with RIF-containing TB treatment, X DTG 50 mg/ 3TC 300 mg FDC given once daily without RIF among the same participants after completing TB treatment.	2years
1.3.5 Compare Grade 3 or 4 adverse events, by arm	To compare the Grade 3 & 4 adverse events by arm	2 years
1.3.1 Number of patients with HIV-1 virologic suppression (via FDA snapshot algorithm) at 48 weeks, in each arm	To compare the proportion in each arm above DTG protein adjusted 90% inhibitory concentration (IC90) (64 ng/mL) at each PK sampling.	48 weeks
1.3.4 Proportion of participants with DTG Cmin above target DTG trough of 158 ng/mL	1-To estimate the pharmacokinetics (PK) of DTG when given twice daily as a 50 mg/ 300 mg DTG/3TC FDC with rifampicin (RIF)-containing TB treatment, X DTG 50 mg/ 3TC 300 mg FDC given once daily without RIF among the same participants after completing TB treatment.	2years

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: ViiV Healthcare
• Investigators: Principal Investigator: Ethel M Weld, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2029

Study Registration Dates

• First Submitted: July 4, 2024
• First Submitted That Met QC Criteria: July 4, 2024
• First Posted (Actual): July 11, 2024

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; 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; dolutegravir
• Other Study ID Numbers: IRB00441778

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No