Dolutegravir/lamivudine vs triple ART have similar efficacy in advanced HIV infection with CD4 100,000 | HTB

Dolutegravir/lamivudine vs triple ART have similar efficacy in advanced HIV infection with CD4 <200 and viral load >100,000

The dual combination of dolutegravir/lamivudine is already included as one of the four recommended as first-line ART in UK guidelines.

This is based on several randomised studies (including GEMINI) showing similar efficacy to triple combinations based on second-generation integrase inhibitors.

However, current UK guidelines do not recommend dolutegravir/lamividine if baseline CD4 and viral load are <200 cells/mm³ or higher than 500,000 copies/mL.

An oral presentation at HIV Glasgow 2024 added further data supporting similar efficacy and safety results to triple therapy in participants with advanced HIV and CD4 counts <200 cells/mm³, irrespective of baseline CD4 and viral load.

Week 48 results from the open-label DOLCE study in 230 treatment-naive participants in Brazil and Argentina with advanced HIV were presented by Pedro Cahn from Fundacion Huesped, Buenos Aires.

Participants were randomised 2:1 to DTG/3TC (single pill) or DTG + TDF/XTC (two pills) and results were stratified by baseline viral load >100,000 copies/mL.

Baseline characteristics included median CD4 count and viral load of 116 cells/mm³ (IQR: 53 to 188) and 151,000 copies/mL (IQR: 49,027–446,947), respectively. Notably, 22% (n=35) had baseline viral load >500,000 and 10% (n=16) were >1 million copies/mL.

Median age was 35 years (IQR: 28 to 47), 77% male/23% female, and just under half were gay and bisexual men. Approximately 17% were Black, 8% Indigenous South American, 43% Spanish/Latino and 34% white.

At week 48, the primary analysis of viral load <50 copies/mL by ITT analysis was 82% (125/152) vs 80% (62/77), in the dual vs triple ART arms, adjusted difference: 2% (95% CI −8.7 to +12.8%). These results suggested non-inferiority in an exploratory post-hoc analysis (p=0.016), but were not presented as a formal conclusion.

Similar responses were reported in participants with baseline viral load >100,000 copies/mL: 80% vs 76%, adj. difference 5.1% (95% CI: −10.1 to +20.3%). Overall suppression rates were lower in participants with the highest baseline levels: 72% when >500,000 and 61% when >1 million – although these were reported as being close to <50 copies/mL.

Protocol defined failures (7% vs 8%, with median viral load at 144 copies/mL) and missing data (11% vs 12%) were also similar. No resistance was detected in the 11 participants with protocol defined failure.

CD4 count increases were +200 vs +177 cells/mm³ in the dual vs triple ART arms, respectively, also superimposable.

IRIS was reported in 10 participants: 6/153 (3.9%) vs 4/77 (5.2%) and severe adverse events (n=27) were reported in 17/153 (11.1%) vs 10/77 (12.9%) participants, both in the dual vs triple ART arms respectively.