D2ARLING: Efficacy of Dolutegravir Plus Lamivudine in HIV-1-infected Treatment-naïve Adults Without a Baseline Genotyping Test
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy of DTG + 3TC versus DTG + TDF/FTC over 48 weeks in HIV-1 naive patients in a real life setting with no baseline HIV genotypic resistance testing available.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Detailed Description
This is a 48-week, Phase IV, randomized, open-label, to assess the non-inferior antiviral activity (VL < 50 c/ml) of 2DR DTG+3TC versus 3DR TDF/FTC + DTG over 48 weeks in HIV1 naïve adult patients without baseline GT available at Day 1 visit. Subjects will be stratified by screening HIV-1 RNA (≤100,000 c/mL or >100,000 c/mL) and Screening CD4+ cell count (≤ or >200 cells/mm3).
The study will comprise:
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a 28-day Screening Phase (which may be extended to 35 days to allow receipt of all Screening assessment results).
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an Open-label Randomized Phase (Day 1 to Week 48).
Approximately 200 HIV-1 naïve adult patients will be randomized 1:1 to receive 2DR DTG+3TC versus 3DR TDF/FTC + DTG for 48 weeks.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dolutegravir + lamivudine Dolutegravir 50 mg, 1 tablet QD plus lamivudine 300 mg, 1 tablet QD |
Drug: Lamivudine 300 MG
Experimental arm
Other Names:
|
| Active Comparator: Dolutegravir + emtricitabine/tenofovir (FTC/TDF) Dolutegravir 50 mg, 1 tablet QD plus FTC/TDF 200/300 mg, 1 coformulated tablet QD |
Drug: Emtricitabine / Tenofovir Disoproxil Pill
Active Comparator
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Virologic Efficacy [48 weeks]
To demonstrate the non-inferior antiviral activity (VL < 50 c/ml) of 2DR DTG+3TC versus 3DR TDF/FTC + DTG over 48 weeks in HIV-1 naïve adult patients without baseline genotypic resistance testing available. Endpoint: Proportion of subjects with plasma HIV-1 RNA <50 copies/mL (c/mL) at Week 48 using the FDA Snapshot algorithm [Missing, Switch or Discontinuation = Failure (MSD=F)] for the intent-to-treat exposed (ITT-E) population.
Secondary Outcome Measures
- Genetic barrier [48 weeks]
To assess the selection / emergence of viral resistance in subjects meeting confirmed virologic withdrawal (CVW) criteria. Endpoint: incidence of treatment-emergent genotypic resistance to DTG and 3TC or TDF/FTC in subjects meeting CVW criteria.
- Efficacy in presence of any major resistanceassociated mutation al baseline [48 weeks]
To evaluate the antiviral activity of DTG + 3TC compared to DTG + TDF/FTC over time in patients with pre-existing viral resistance based on the presence of any major resistanceassociated mutation (IAS-USA 2019). Endpoint: Proportion of subjects with plasma HIV-1 RNA <50 copies/mL (c/mL) at Week 48 using the FDA Snapshot algorithm and The proportion of participants with HIV-1 RNA <50 or <200 copies/mL using the observed algorithm (excluding participants with missing data) in patients with pre-existing viral resistance based on the presence of any major resistance-associated mutation (IAS-USA 2019).
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subject should be antiretroviral naïve (defined as <=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV 1 infection).
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Age ≥ 18 years
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Screening plasma HIV-1 RNA ≥1000 c/mL
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CD4 cell count nadir: any value
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Effective contraception for women of childbearing potential.
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Informed consent form signed by patient and investigator
Exclusion Criteria:
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History of suicide ideation, intention or action.
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Evidence of HBV infection based on the results of testing at Screening* for HBV surface antigen (HBsAg), HBV core antibody (anti-HBc), HBV surface antibody (antiHBs or HBsAb), and HBV DNA as follows: Subjects positive for HBsAg are excluded; Subjects negative for anti-HBs and HBsAg but positive for anti-HBc and positive for HBV DNA are excluded.
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Anticipated need for any HCV therapy during the first 48 weeks of the study.
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Acute symptomatic HIV Infection.
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Any active Opportunistic Infection (category C, CDC 2014).
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Current pregnancy or breastfeeding.
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No effective contraception for the women of childbearing.
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Any verified Grade 4 laboratory abnormality. A single repeat test is allowed during the Screening period to verify a result.
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ALT (Alanine Aminotransferase) ≥ 5 x upper limit of normal value (ULN) or AST (Aspartate Aminotransferase) ≥ 3 x ULN and bilirubinemia ≥ 1.5 x ULN (with 35% direct bilirubinemia).
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Unstable liver disease (ascitis, encephalopathy, coagulopathy, hypoalbuminemia, oesophageal or gastric varices or persistent jaundice).
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Creatinine clearance of <50 mL/min/1.73 m2 (Cockroft-Gault method).
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History or presence of allergy to the trial drugs or their components.
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Severe hepatic insufficiency (Child Pugh Class C).
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Any available historical resistance test result.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Fundacion IDEAA | Buenos Aires | Argentina | 1405 |
Sponsors and Collaborators
- Fundacion IDEAA
- ViiV Healthcare
Investigators
- Principal Investigator: Ezequiel Cordova, MD, Fundacion IDEAA
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- IDEAA 002