Maintenance therapy with dolutegravir and lamivudine versus bictegravir, emtricitabine, and tenofovir alafenamide in people with HIV (PASO-DOBLE): 48-week results from a randomised, multicentre, open-label, non-inferiority trial.

Background: Although single-tablet, oral bictegravir, emtricitabine, and tenofovir alafenamide or dolutegravir and lamivudine are preferred regimens in several major guidelines and are widely used in many countries, they have not been compared in a fully powered trial. This study aimed to prospectively compare the 48-week results of dolutegravir and lamivudine versus bictegravir, emtricitabine, and tenofovir alafenamide as maintenance therapies for people with HIV.

Methods: PASO-DOBLE is a randomised, multicentre, open-label, non-inferiority trial done over 48 weeks at 30 sites in Spain. Adults (aged ≥18 years) with HIV-1, without previous viral failure, who had reached virological suppression on oral regimens containing at least one pill a day, cobicistat, efavirenz, or tenofovir disoproxil fumarate and no previous use of dolutegravir or bictegravir, and plasma HIV-1 RNA <50 copies per mL for at least 24 weeks were eligible. Participants were randomly assigned (1:1) to switch regimens to dolutegravir 50 mg and lamivudine 300 mg or bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg once daily, using random block permutation, stratified by tenofovir alafenamide presence at baseline and sex assigned at birth. The primary endpoint was the proportion of participants with HIV RNA ≥50 copies per mL at week 48 in the intention-to-treat exposed population (ie, all participants who received at least one dose of study medication). The primary and safety analysis was done in the intention-to-treat exposed population. The non-inferiority margin was 4%. This trial is registered with ClinicalTrials.govNCT04884139 and is incomplete.

Findings: Between July 14, 2021, and March 24, 2023, 553 participants initiated dolutegravir and lamivudine (n=277) or bictegravir, emtricitabine, and tenofovir alafenamide (n=276). The difference in the proportion of participants with HIV RNA ≥50 copies per mL between the dolutegravir and lamivudine group (six [2%] of 277) and bictegravir, emtricitabine, and tenofovir alafenamide group (two [1%] of 276) was 1·4% (95% CI -0·5 to 3·4; p=0·16), showing non-inferiority. The most common adverse events occurring in at least 10% of participants in either group were infections, musculoskeletal, gastrointestinal, metabolic, and psychiatric events. Adverse events were usually mild or moderate and considered unrelated to the study drugs. More grade 3-4 adverse events occurred in the bictegravir group (ten [3%]) than in the dolutegravir group (three [1%]; p=0·049). Very few participants discontinued dolutegravir and lamivudine (n=1) or bictegravir, emtricitabine, and tenofovir alafenamide (n=2) due to adverse events. There were no deaths in either group.

Interpretation: These results provide further evidence that might be useful in shared decision-making between physicians and people living with HIV regarding switching oral antiretroviral therapy.

Funding: ViiV Healthcare, CIBER de Enfermedades Infecciosas (CIBERINFEC), and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS).

Translation: For the Spanish translation of the abstract see Supplementary Materials section.