Virological and metabolic outcomes after switching to dolutegravir or rilpivirine in virologically suppressed adults with HIV in Thailand: an open-label, randomised, controlled, non-inferiority trial.

BACKGROUND

Dolutegravir (DTG)-based antiretroviral therapy is widely recommended; however, weight gain and metabolic effects remain a concern. Rilpivirine (RPV) is a potential switch option for virologically suppressed individuals with HIV receiving efavirenz (EFV)-based treatment. We aimed to compare the virological and metabolic outcomes after switching from TDF/FTC/EFV to TDF/3TC/DTG or TDF/FTC plus RPV.

METHODS

In this randomised, open-label, parallel-group, non-inferiority trial at Maharat Nakhon Ratchasima Hospital, Thailand, adults with HIV-1 RNA below 50 copies per mL for at least 6 months on TDF/FTC/EFV were randomly assigned 1:1 to once-daily TDF/3TC/DTG or TDF/FTC plus RPV. The primary outcome was virological non-suppression, defined as HIV-1 RNA 50 copies per mL or higher at week 48. Non-inferiority of RPV was concluded if the lower bound of the 95% CI for the risk difference (DTG minus RPV) was greater than -8 percentage points. Secondary outcome included changing in body weight, LDL cholesterol, HbA1c, and estimated glomerular filtration rate (eGFR) over 48 weeks. This study was registered with the Thai Clinical Trial Registry (TCTR20211229003).

FINDINGS: Between March 2022 and November 2023, 267 participants were randomly assigned to receive DTG (n = 133) or RPV (n = 134). In the per-protocol population, virological non-suppression occurred in three (3%) of 118 participants in the DTG group and five (4%) of 122 participants in the RPV group (risk difference -1.56%, 95% CI -6.08 to 2.97). Non-inferiority of RPV was demonstrated in all prespecified analysis populations using the -8% margin. Weight gain was greater with RPV than with DTG (2.3 kg vs. 1.4 kg; p = 0.035). LDL cholesterol decreased in both groups without significant between-group differences, while eGFR declined more in the DTG group.

INTERPRETATION: Switching to RPV was non-inferior to DTG for virological outcomes at 48 weeks. RPV represents an alternative for patients in whom DTG is unsuitable or not preferred. Although between-group differences in metabolic outcomes and weight gain were minimal, larger, longer-term trials are warranted to confirm these findings.

FUNDING: This work was supported by The Royal College of Physicians of Thailand, (to R.K.). APC fee was supported by Faculty of Tropical Medicine, Mahidol University and Mahidol University (to T.N.).