Clinical trial NCT06497465: Dolutegravir/Lamivudine Dual Therapy for ART-naïve People With HIV and TB Receiving Rifampin-based TB Treatment
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Tuberculosis
HIV
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: ViiV Healthcare
First posted: 2024-07-11
Enrollment: 150
Sex: ALL
Minimum age (years): 15
Maximum age (years): 99
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Arm 1(n=50): DTG 50mg/3TC 300 mg FDC tablet (Dovato®) twice daily during TB therapy and for 2 weeks after, then Dolutegravir (DTG) 50mg / lamivudine (3TC) 300 mg fixed dose combination (FDC) tablet (Dovato®) once daily to week 52

Arm 2(n=50): 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

Arm 3(n=50): 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 Dolutegravir (DTG) 50 mg + Tenofovir disoproxil fumarate (TDF)/ lamivudine (3TC) FDC tablet once daily to week 52
Primary purpose: TREATMENT

Brief summary: 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

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).

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 28 weeks
Secondary outcomes:
measure: 1.3.1 Number of patients with HIV-1 virologic suppression (via FDA snapshot algorithm) at 48 weeks, in each arm
timeFrame: 48 weeks
measure: 1.3.2 Number of patients with HIV-1 virologic suppression at 48 weeks, in the combined DTG/3TC arms (Arm 1 + Arm 2)
timeFrame: 48 weeks
measure: 1.3.3 Change from baseline in CD4 over 28 weeks and 48 weeks of HIV treatment, by arm
timeFrame: 28 weeks, 48 weeks
measure: 1.3.4 Proportion of participants with DTG Cmin above target DTG trough of 158 ng/mL
timeFrame: 2years
measure: 1.3.4 Concentration of the PK of DTG
timeFrame: 2years
measure: 1.3.5 Compare Grade 3 or 4 adverse events, by arm
timeFrame: 2 years
Other outcomes:
Locations:
city: Manaus
country: Brazil
facility: Instituto Tropical de Doenças Infecciosas Manaus
state: AM
city: Salvador
country: Brazil
facility: Universidade Federal da Bahia
state: BA
city: Rio De Janeiro
country: Brazil
facility: FIOCruz
state: RJ
city: Rio De Janeiro
country: Brazil
facility: Hospital Geral de Nova Iguaçu
state: RJ
city: São Paulo
country: Brazil
facility: RDSS- Ricardo Diaz Solucoes Cientificas
state: SP
Study officials:
affiliation: Johns Hopkins University
name: Ethel M Weld, MD
role: PRINCIPAL_INVESTIGATOR
References: