DTG/3TC tied to lower steatotic liver disease rates in PLWH

Switching to dolutegravir/lamivudine (DTG/3TC) was associated with a significantly lower rate of steatotic liver disease (SLD) compared with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among people living with HIV (PLWH), according to a subgroup analysis of the PASO DOBLE trial presented at CROI 2026.

“SLD is common in PLWH and is associated with overweight and its related metabolic disorders. Both INSTIs* and TAF have been linked to weight gain in clinical trials and real-life studies,” said study author Dr Juan Pineda from Hospital Universitario Virgen de Valme in Sevilla, Spain.

“However, conflicting results have been reported regarding their effect on SLD,” he noted.

The PASO DOBLE subgroup consisted of 111 virologically suppressed adults with HIV (median age 51 years) recruited from centres equipped with VCTE** devices for measuring the Controlled Attenuation Parameter (CAP). Participants were switched to either DTG/3TC (n=58) or BIC/FTC/TAF (n=53), with CAP values assessed at baseline and at week 96.

At week 96, the proportion of patients with SLD, defined as a CAP value of ≥248 dB/m, was significantly lower in the DTG/3TC group than in the BIC/FTC/TAF group (29 percent vs 49 percent; p=0.033). [CROI 2026, abstract 598]

From baseline to week 96, fewer DTG/3TC-treated patients experienced weight gain (≥5 percent of baseline body weight) compared with BIC/FTC/TAF-treated patients (21 percent vs 32 percent; p=0.173).

In turn, the median CAP decreased significantly by 19 dB/m in the DTG/3TC group, while it increased by 14 dB/ in the BIC/FTC/TAF group (p=0.027), with SLD occurring at a significantly lower rate in the DTG/3TC group (17 percent vs 76 percent; p=0.002).

This finding aligns with the earlier sub-study at 48 weeks, which demonstrated that the prevalence of SLD increased significantly from baseline in the BIC/FTC/TAF arm, but not in the DTG/3TC arm, among PLWH who had gained weight. [Pineda et al, CROI 2025]

Among individuals who gained <5 percent of their baseline weight, no significant difference in median CAP value was observed between the DTG/3TC and BIC/FTC/TAF groups (32 percent vs 36 percent; p=0.740).

After adjusting for relevant baseline variables, including age, sex, assigned treatment, triglycerides, weight gain, and NRTIs in the prior regimen, the CAP increase was found to be independently associated with the assigned treatment (B=23.026; p=0.050).

This 96-week PASO DOBLE subanalysis contributes to the robust clinical and real-world data for DTG/3TC, highlighting the differences between the two‑drug regimen (DTG/3TC) and the three‑drug regimen (BIC/FTC/TAF) in metabolic health outcomes, according to a press release.

Overall, in virologically suppressed PLWH, the significantly lower SLD frequency with DTG/3TC vs BIC/FTC/TAF, especially those with ≥5 percent weight gain, underscores the association between metabolic changes and liver health, as noted by the researchers.

These findings enable healthcare providers and PLWH to make informed decisions concerning long-term HIV treatment, including metabolic health, they added.