- The meta-analysis supports the paradigm shift from 3-drug antiretroviral therapy (ART) regimens to a 2-drug regimen in treatment-naive patients with HIV-1.
- The analysis shows that a 2-drug regimen with dolutegravir and lamivudine (DTG+3TC) was similar to traditional 3-drug regimens in terms of virologic suppression, change in CD4+ cell count from baseline and safety at week 48.
- Results were also confirmed in the subgroup of difficult-to-treat patients with high baseline viral load (>100,000 RNA copies/ml).
Combination ART traditionally comprises a 3-drug regimen, two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) and a non-NRTI core agent. Since ART agents are associated with long-term risk, a 2-drug regimen based on DTG and 3TC is actually recommended by guidelines. Indeed, this regimen was found to have favourable efficacy and safety in treatment-naive patients with HIV-1 in two single-arm, pilot studies. Further, two large phase III randomised controlled trials demonstrated noninferiority of DTG+3TC relative to DTG+tenofovir disoproxyl fumarate/emtricitabine (TDF/FTC).
In order to compare the efficacy and safety of DTG+3TC regimen with traditional 3-drug regimens, authors performed a network meta-analysis, including 14 double-blind randomised controlled trials (10,043 patients).
The analysis of efficacy (the primary outcome) showed that DTG+3TC was better than efavirenz+TDF/FTC (mean difference: -7.3% [95% CrI: -13.8, -0.8]), and similar to all other 3-drug regimens investigated in term of virologic suppression at week 48.
Results were consistent in the subgroup of patients with baseline viral load over 100,000 RNA copies/ml. With only two exceptions, for which subgroup data were not available, the proportion of patients achieving virologic suppression at week 48 with DTG+3TC was relative to virologic suppression seen with 3-drug regimens, in the overall population.
Further, in the overall population, DTG+3TC induced similar increases in CD4+ cell count between baseline and week 48 compared with all 3-drug regimens investigated, except for DTG+tenofovir alafenamide/FTC.
With regard to safety (the secondary outcome that included adverse events, serious adverse events and drug-related adverse events at 48 weeks), DTG+3TC was broadly similar to all regimens analysed, with few exceptions.
This study demonstrates comparable efficacy and safety outcomes over 48 weeks with the 2-drug regimen DTG+3TC compared with traditional 3-drug antiretroviral therapy regimens and supports its use in treatment-naive patients with HIV-1. In addition, 2-drug regimens can improve patient adherence and reduce costs.
Limitations: Not all studies reported all of the efficacy and safety outcomes or subgroup data.