A Phase 3b Study Comparing Dolutegravir/Lamivudine to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Antiretroviral-Naive Adults with HIV

The primary objective of this study is to demonstrate the **non-inferior antiviral activity** of the combination of dolutegravir/lamivudine (DTG/3TC) compared to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in antiretroviral-naïve persons living with **HIV**. This is clinically relevant as it evaluates the efficacy of a two-drug regimen against a three-drug regimen, potentially offering a simpler treatment option with fewer drugs for patients.

Secondary objectives include:

• To demonstrate the antiviral and immunologic effects, and the incidence of disease progression, including HIV-associated conditions, AIDS, and death, with the use of DTG/3TC compared to BIC/FTC/TAF.
• To evaluate the time to virologic suppression with DTG/3TC compared to BIC/FTC/TAF in antiretroviral-naïve persons living with HIV.
• To assess the development of viral resistance in participants experiencing confirmed virologic failure.
• To evaluate renal (in urine and blood) and bone (in blood) biomarkers in participants treated with DTG/3TC compared to BIC/FTC/TAF.

The clinical trial involves a total of **130 participants** diagnosed with **Human immunodeficiency virus (HIV)**. The study population includes both male and female adults aged 18 years and older, with no prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection. Participants are required to be antiretroviral-naïve, ensuring that the study evaluates the antiviral activity of the treatment in individuals who have not previously received such therapies. The trial includes a vulnerable population, indicating that special considerations are in place to protect these participants. The selection process ensures that all participants are capable of providing informed consent, and for those enrolled in France, affiliation with a social security category is mandatory. The trial does not specify any particular lifestyle considerations such as diet or physical activity, focusing instead on the medical condition and treatment history of the participants.

The clinical trial is a **Phase 3b**, multi-center, randomized, parallel-group, open-label, non-inferiority study designed to evaluate the efficacy, safety, and tolerability of oral **dolutegravir/lamivudine** once-daily as a first-line regimen compared to oral **bictegravir/emtricitabine/tenofovir alafenamide** once daily for virologic suppression and maintenance in antiretroviral therapy-naive adults living with **Human Immunodeficiency Virus (HIV)**. The trial aims to demonstrate the non-inferior antiviral activity of the two-drug regimen compared to the three-drug regimen in antiretroviral-naïve participants with HIV.

The trial is expected to commence recruitment on January 15, 2024, and is estimated to conclude by May 28, 2027. Participants will be involved in the study for a maximum treatment period of 96 weeks. The study will include several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor efficacy and safety, and an end-of-study visit to assess the final outcomes. The primary endpoint is the proportion of participants with plasma HIV-RNA <50 copies/mL at Week 48, while secondary endpoints include virologic suppression at Week 96, changes in HIV-1 RNA and CD4+ cell count, and the occurrence of disease progression through Week 96.

Participants must meet specific inclusion criteria, such as being 18 years or older, antiretroviral-naïve, and capable of providing informed consent. Female participants must not be pregnant or lactating. Conditions for early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial is not classified as low intervention and involves oral administration of the investigational products, which are film-coated tablets. The study is conducted under the authorization of relevant regulatory bodies, ensuring adherence to ethical and scientific standards.

The clinical trial involves the administration of two experimental medications, **Dovato** and **Biktarvy**, both of which are utilized in the treatment of HIV. **Dovato** is a combination of **lamivudine** and **dolutegravir sodium**, provided in the form of film-coated tablets. Each tablet contains 50 mg of dolutegravir sodium and 300 mg of lamivudine. The medication is administered orally once daily. The maximum treatment period for Dovato is 96 weeks. The study-specific labeling is applied to the product, and participant compliance is monitored through regular assessments.

**Biktarvy** is another experimental medication used in this trial, consisting of **emtricitabine**, **tenofovir alafenamide**, and **bictegravir**. It is also provided as film-coated tablets, with each tablet containing 50 mg of bictegravir, 200 mg of emtricitabine, and 25 mg of tenofovir alafenamide. Similar to Dovato, Biktarvy is administered orally once daily, with a maximum treatment period of 96 weeks. The product is labeled specifically for the study, and adherence to the dosing schedule is closely monitored to ensure participant compliance.

Both medications are chemical in origin and are not classified as orphan drugs. The trial is designed to evaluate the efficacy, safety, and tolerability of these medications in antiretroviral therapy-naive adults living with HIV. The study aims to demonstrate the non-inferior antiviral activity of Dovato compared to Biktarvy. No non-experimental treatments, such as standard-of-care therapy or placebo, are used in this study. The trial is conducted under open-label conditions, allowing for direct comparison of the two treatment regimens.

The efficacy of the clinical trial will be assessed by evaluating the **antiviral activity** of the treatment regimens in antiretroviral-naïve adults living with HIV. The primary endpoint for efficacy is the proportion of participants achieving plasma HIV-RNA levels of less than 50 copies/mL at Week 48, as determined by the Snapshot algorithm. Secondary endpoints include the proportion of participants with plasma HIV-1 RNA levels below 50 copies/mL at Week 96, the proportion of participants with HIV-RNA levels greater than or equal to 50 copies/mL at Weeks 48 and 96, and changes from baseline in HIV-1 RNA (log10 copies/mL), CD4+ cell count, and CD4/CD8 ratio over time through Weeks 48 and 96. Additionally, the occurrence of disease progression, including HIV-associated conditions, AIDS, and death, will be monitored through Weeks 48 and 96.