Tuberculosis, HIV
Conditions
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).
Interventions
Participants will receive Dolutegravir 50mg
DRUGDolutegravir/Lamivudine 50 MG-300mg Oral Tablet [DOVATO]
Participants will receive Dolutegravir/Lamivudine 50 MG-300 MG Oral Tablet \[DOVATO\]
DRUGDolutegravir plus Tenofovir disoproxil fumarate (TDF)/ lamivudine (3TC)
Participants will receive Dolutegravir plus Tenofovir disoproxil fumarate (TDF)/ lamivudine (3TC)
Sponsors
ViiV Healthcare
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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
Eligibility
Sex/Gender
ALL
Age
15 Years to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 28 weeks | To Compare the proportion of participants with HIV-1 virologic suppression at 28 weeks of HIV treatment by arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 1.3.2 Number of patients with HIV-1 virologic suppression at 48 weeks, in the combined DTG/3TC arms (Arm 1 + Arm 2) | 48 weeks | To compare the proportion of patients with HIV-1 virologic suppression at 48 weeks, in the combined DTG/3TC arms (Arm 1 + Arm 2) |
| 1.3.3 Change from baseline in CD4 over 28 weeks and 48 weeks of HIV treatment, by arm | 28 weeks, 48 weeks | To compare the changes from baseline over 28 weeks and 48 weeks of HIV treatment by the arm. |
| 1.3.1 Number of patients with HIV-1 virologic suppression (via FDA snapshot algorithm) at 48 weeks, in each arm | 48 weeks | To compare the proportion in each arm above DTG protein adjusted 90% inhibitory concentration (IC90) (64 ng/mL) at each PK sampling. |
| 1.3.4 Concentration of the PK of DTG | 2years | 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. |
| 1.3.5 Compare Grade 3 or 4 adverse events, by arm | 2 years | To compare the Grade 3 & 4 adverse events by arm |
| 1.3.4 Proportion of participants with DTG Cmin above target DTG trough of 158 ng/mL | 2years | 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. |
Countries
Brazil
Contacts
Primary ContactBeatriz M Kohler, RN
Backup ContactKate Boehner, RN
Outcome results
None listed