HIV reservoir, inflammatory markers appear similar 48 weeks after treatment simplification

In virally suppressed people living with HIV, switching to a two-drug antiretroviral regimen (dolutegravir/lamivudine) did not result in a greater viral reservoir, HIV transcription, or worse inflammatory markers compared to a standard three-drug regimen after 48 weeks, a small study in Belgium found. Metabolic outcomes were also similar between the two regimens.

About This Study

“In-depth Analysis of the HIV Reservoir Confirms Effectiveness and Safety of Dolutegravir/Lamivudine in a Phase 4 Randomized Controlled Switch Trial (RUMBA)” was published online on Sept. 3, 2024, in The Journal of Infectious Diseases. The lead author is Marie-Angélique De Scheerder, M.D., of the Department of Internal Medicine at Ghent University Hospital in Ghent, Belgium. The study was supported by ViiV Healthcare, the manufacturer of the study drug; a disclaimer stated that ViiV was not involved in study design or analysis, nor did it take part in writing the published manuscript.

Key Research Findings

This single-site prospective randomized controlled trial, conducted in 2020 and 2021, analyzed the viral reservoir and markers of inflammation in 89 people living with HIV who were randomized to switch from a three-drug regimen to dolutegravir/lamivudine and in 45 participants who were randomized to switch to or remain on bictegravir/emtricitabine/tenofovir alafenamide. At baseline, 80 participants were on bictegravir/emtricitabine/tenofovir alafenamide, 49 participants were on abacavir/dolutegravir/lamivudine, and one participant was on dolutegravir + emtricitabine/tenofovir alafenamide.

Median participant age was 47 years, 118 participants were men, and 102 participants were of European ancestry. Everyone was virally suppressed (viral load <50 copies/mL) prior to study start. After 48 weeks, 98% of participants remained virally suppressed.

Baseline median body mass index was 25 kg/m² in the three-drug arm versus 26 kg/m² in the two-drug arm. Forty-eight weeks later, participants in the three-drug arm gained an estimated 4% fat from baseline and those in the two-drug arm gained 2% fat. Of the 49 participants who had not taken tenofovir alafenamide at baseline, 9% on the bictegravir regimen gained fat vs. 2% fat on the dolutegravir regimen.

By study end, the adjusted estimate of intact HIV DNA copies/million CD4 cells increased by 10% in the two-drug arm and by 43% in the three-drug arm, with no significant mean relative difference between the two arms. HIV transcription and inflammatory markers were also similar between the arms.

Discussion Highlights and Implications for Practice

Study limitations reported included the small sample size, limiting the study’s power, as well as a lack of tissue samples and no randomization by body mass index. The study was intended to generate a hypothesis that needs to be confirmed in larger randomized controlled trials.

Results show that switching to dolutegravir/lamivudine is safe in the short term, study authors concluded. Longer-term data is being collected to determine whether the results continue to hold for 240 weeks.

By Barbara Jungwirth