Dolutegravir plus lamivudine vs dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): Week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials
The Lancet Jan 12, 2019
Cahn P, et al. - Researchers compared a two-drug regimen to a three-drug regimen with respect to efficacy and safety in the treatment of HIV-1 infection in antiretroviral therapy (ART)-naive adults. They observed that, compared to a guideline-recommended three-drug regimen, the dolutegravir plus lamivudine regimen displayed non-inferior efficacy and similar tolerability profile at 48 weeks in ART-naive adults. Dolutegravir plus lamivudine can be used as initial therapy for patients with HIV-1 infection.
- At 192 centres in 21 countries, two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2, were conducted including subjects (≥18 years) with HIV-1 infection and a screening HIV-1 RNA of 500 000 copies per mL or less, and who were naive to ART.
- In a random manner (1:1), a once-daily two-drug regimen of dolutegravir (50 mg) plus lamivudine (300 mg) or a once-daily three-drug regimen of dolutegravir (50 mg) plus tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) was administered orally to participants.
- Treatment assignment was done masking participants and investigators: dolutegravir was administered as single-entity tablets (similar to its commercial formulation, except with a different film colour), and lamivudine tablets and tenofovir disoproxil fumarate and emtricitabine tablets were over-encapsulated to visually match each other.
- They used Snapshot algorithm and a non-inferiority margin of −10%, to assess the proportion of participants with HIV-1 RNA of less than 50 copies per mL at week 48 in the intention-to-treat-exposed population (primary endpoint).
- Safety analyses including the safety population were carried out.
- Either the two-drug regimen (n=719) or three-drug regimen (n=722) was received randomly by 1,441 participants across both studies between July 18, 2016, and March 31, 2017.
- At week 48, plasma HIV-1 RNA of less than 50 copies per mL was achieved in 320 (90%) of 356 participants receiving the two-drug regimen and 332 (93%) of 358 receiving the three-drug regimen in the GEMINI-1 intention-to-treat-exposed population (adjusted treatment difference −2·6%, 95% CI −6·7 to 1·5), and 335 (93%) of 360 in the two-drug regimen and 337 (94%) of 359 in the three-drug regimen in the GEMINI-2 (adjusted treatment difference −0·7%, 95% CI −4·3 to 2·9), demonstrating non-inferiority at a −10% margin in both studies (pooled analysis: 655 [91%] of 716 in the two-drug regimenvs 669 [93%] of 717 in the three-drug regimen; adjusted treatment difference −1·7%, 95% CI −4·4 to 1·1).
- Numerically, the three-drug regimen vs the two-drug regimen was associated with more occurrence of drug-related adverse events (169 [24%] of 717 vs 126 [18%] of 716); discontinuation attributed to adverse events was seen in few participants (16 [2%] in the three-drug regimen and 15 [2%] in the two-drug regimen).
- In the two-drug regimen group of GEMINI-2, the occurrence of 2 deaths was reported, but neither was considered to be associated with the study medication.
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