Dual noninferior to triple ART in maintaining viral suppression among PLWH

Switching to maintenance dual antiretroviral therapy (ART) with DTG+3TC* or ATV/r+3TC** was noninferior to continuing triple current ART with TDF+3TC+EFV*** or DTG+3TC+TDF⁺ in maintaining virologic suppression for up to 96 weeks among people living with HIV (PLWH), according to the MODERATO trial presented at IAS 2025.

“Switching to a two-drug [ART] regimen has shown long-term noninferior efficacy compared with a three-drug regimen and is recommended in guidelines from Northern countries, but not in WHO recommendations, [current ART regimens], at the time of planification of this study,” said study author Dr Fatoumata Fadiga from Programme PAC-CI-PRISME, Abidjan, Côte d'Ivoire.

“The MODERATO trial was the first RCT at week 96 in West and Central Africa that supported dual maintenance therapy as a therapeutic option in Sub-Saharan African countries,” she added.

This study involved 480 individuals (median age 50 years, 70 percent female) with HIV-1 infection and a detectable viral load of <50 copies/mL who were virologically suppressed for ≥2 years. Participants were randomized to receive dual maintenance therapy with DTG+3TC or ATV/r+3TC once daily (n=320) or triple reference therapy with TDF+3TC+EFV or DTG+3TC+TDF once daily (n=160).

In the overall population, 95 percent (n=304) of those who switched to dual therapy and 97.5 percent (n=156) of those who continued triple therapy maintained virologic suppression (HIV-1 RNA <50 copies/mL) at week 96. As a result, the criteria for noninferiority were met, according to Fadiga. [IAS 2025, abstract 5282]

Only 3.1 percent and 2.5 percent of individuals in the dual and triple therapy groups, respectively, had virologic failure (HIV-1 RNA ≥50 copies/mL) at week 96.

In terms of safety, the DTG+3TC and ATV/r+3TC arms experienced 19 and 22 grade 3/4 adverse events (AEs), respectively, while 15 AEs were reported in the TDF+3TC+EFV and DTG+3TC+TDF arms.

However, the mean body weight significantly increased by 3.73 kg in the DTG+3TC arm and by 2.59 kg in the ATV/r+3TC arm (p<0.001 for both) at week 96, whereas it remained stable in the TDF+3TC+EFV arm.

Metabolic parameters such as blood glucose, cholesterol, and triglycerides levels remained unchanged in all treatment groups, Fadiga noted.

“Overall, switching to dual therapy with DTG+3TC or ATV/r+3TC is as effective as continuing triple therapy, the current ART regimen, … with a favourable safety profile at week 96,” Fadiga concluded.