Dolutegravir knocks down HIV faster than bictegravir

A first-line antiretroviral regimen containing dolutegravir reduces a high viral load faster than one containing bictegravir, and the effect was especially noticeable in people with the highest viral load, French researchers reported on Tuesday at the 26th International AIDS Conference (AIDS 2026) in Rio de Janeiro.

The findings have implications for the choice of first-line regimen in people with a high viral load, and may also be important for preserving immune function and restricting the size of the HIV reservoir, Dr Antoine Chéret of the University of French West Indies told the conference.

High viral load at treatment initiation (above 100,000 copies/ml) raises the risk of treatment failure, the development of drug resistance and onward transmission before viral suppression is achieved. Data on the virological efficacy of bictegravir in people with a high viral load are limited and early drug development studies showed that dolutegravir treatment resulted in significantly faster viral suppression than bictegravir when the two drugs were dosed on their own.

The study

French researchers looked at the rates and speed of viral suppression in previously untreated people with a high viral load starting treatment with a three-drug regimen containing dolutegravir (n=703) or bictegravir (n=1,826) in the national DAT’AIDS observational cohort between 2009 and 2023.

People starting dolutegravir or bictegravir were similar in most respects; the median age at treatment initiation was around 38, approximately 80% were male and approximately 40% were born outside France. Viral load at treatment initiation was slightly higher in the dolutegravir group and people were more likely to start dolutegravir than bictegravir during acute HIV infection (27% vs 17%), but there was no significant difference in viral load between groups among the subset who started treatment during the acute phase of HIV infection.

Results

People in the dolutegravir group achieved viral suppression below 50 copies/ml significantly faster than the bictegravir group. By 24 weeks after treatment initiation, 74.9% of people taking dolutegravir had a viral load below 50, compared to 69.1% of those taking bictegravir.

The difference in viral suppression was more pronounced in people with acute HIV infection (81.8% vs 72.7%) and people with viral loads above 5.7log₁₀ (501,000 copies/ml) (68.7% vs 58.7%).

In each case, the difference between groups was statistically significant in a Kaplan-Meier time to viral suppression analysis. This difference persisted in a Cox model using propensity scores estimated from age, sex, acute HIV infection, CD4 cell count, and baseline viral load. In a time-dependent Cox analysis that accounted for treatment switches, the superiority of dolutegravir in speed of viral suppression was increasingly pronounced at higher baseline viral loads.

Although the study found no difference in CD4 count recovery after treatment initiation, there was a small but significant difference in CD4/CD8 ratio at week 5 after treatment initiation (p=0.024) but not at later points, suggesting a slight advantage to dolutegravir in immune function. Dr Chéret said that more rapid viral load reduction might also be expected to restrict the size of the HIV reservoir.

Dolutegravir two-drug regimen matches three-drug bictegravir regimen

A second study presented at AIDS 2026 this week, the randomised In VOGUE trial, showed that dolutegravir / lamivudine (Dovato) was non-inferior to bictegravir / tenofovir alafenamide / emtricitabine (Biktarvy) in previously untreated adults with HIV.

Two previous clinical trials, GEMINI 1 & 2, showed that dolutegravir / lamivudine was non-inferior to dolutegravir / tenofovir disoproxil (TDF) / emtricitabine. As a result, dolutegravir / lamivudine has been recommended as a first-line treatment option in Europe since 2019. In VOGUE is the first study to compare dolutegravir / lamivudine with Biktarvy, the most commonly prescribed first-line combination in the United States and Europe in 2025.

In VOGUE had no viral load or CD4 count restrictions on eligibility to join the study, reproducing everyday clinical practice, and participants began treatment before the results of genotypic drug resistance tests were available, again following clinical practice in many settings. The study excluded people with active hepatitis B.

The study recruited 509 people with a median age of 33 years; 84% were male, and 17% were non-White. Almost half (44%) of participants had baseline viral loads above 100,000, including 16% of study participants witha viral load above 500,000. The median CD4 cell count was 378; 16% of participants had a CD4 count below 200.

The primary endpoint of the study was viral suppression below 50 at week 48. Dolutegravir / lamivudine was non-inferior to bictegravir / tenofovir alafenamide / emtricitabine (Biktarvy) at week 48 (89% vs 92%), an adjusted difference of -3% (95% confidence interval -8, 2). The non-inferiority margin in this study was -10%.

Participants were stratified at randomisation between viral load above and below 100,000 copies/ml and CD4 count above and below 200 cells/mm3. Dolutegravir / lamivudine achieved similar levels of viral suppression to bictegravir / tenofovir alafenamide / emtricitabine at higher viral loads or lower CD4 counts.

CD4 cell count recovery was similar between the two study arms (+232 cells vs +236 cells) at week 48.

Seven participants in the dolutegravir arm and six in the bictegravir arm experienced virologic rebound (two consecutive viral load measurements above 200 copies/ml). One bictegravir recipient did not achieve viral suppression during the study. None developed drug resistance.

No drug-related serious adverse events occurred during the study and no new hepatitis B infections or reactivations were observed. There was no substantial difference in weight gain between the study arms (+3.6kg vs +4kg at week 48).

Dr Jade Ghosn of Bichat University Hospital, Paris, said that the findings of In VOGUE reinforce the use of dolutegravir / lamivudine as an effective, two-drug, first-line option for a broad population when used as part of a test-and-treat approach.