TOPLINE

Treatment-naive adults living with HIV initiating dolutegravir/lamivudine (DTG/3TC) demonstrated no significant differences in CD4 to CD8 ratio recovery compared with those starting an integrase strand transfer inhibitor (INSTI)-based three-drug regimen (3DR) over 3 years, suggesting that regimen complexity does not affect medium-term immune recovery.

METHODOLOGY

• Researchers used a target trial emulation framework to evaluate treatment-naive adults in a Spanish HIV cohort who initiated antiretroviral therapy between June 2015 and November 2024.
• They analyzed data to compare CD4 to CD8 ratio recovery over a 3-year follow-up period between adults initiating the two-drug regimen (2DR) of DTG/3TC (n = 805) and propensity score-matched adults initiating an INSTI-based 3DR (n = 1302).
• Three outcomes were assessed: CD4 to CD8 ratio normalization at 3 years using one of three predefined cutoffs (≥ 0.4, ≥ 1.0, or ≥ 1.5), representing thresholds ranging from those associated with non-AIDS morbidity and mortality to full ratio normalization (with a ratio > 1 considered a marker of successful immune reconstitution).
• Virologic failure was defined as two consecutive HIV-RNA measurements > 50 copies/mL after suppression, whereas a viral blip was defined as an isolated HIV-RNA measurement > 50 copies/mL not followed by virologic failure.

TAKEAWAY

• Adults initiating a 3DR had higher rates of viral blips (17.8% vs 7.8%; P < .001) and virologic failure (5.0% vs 1.0%; P < .001) as well as lower baseline CD4 counts and CD4 to CD8 ratios than those initiating a 2DR.
• At 3 years, 83% of adults achieved a CD4 to CD8 ratio > 0.4, 45% achieved a ratio > 1.0, and 17% achieved a ratio > 1.5.
• No significant differences were observed in the probability of achieving a CD4 to CD8 ratio ≥ 0.4, ≥ 1.0, or ≥ 1.5 between the 2DR and 3DR treatment strategies at 3 years.

IN PRACTICE

“These findings suggest that within second-generation INSTI-based regimens, the number of antiretroviral agents does not appear to be associated with major differences in CD4/CD8 ratio recovery over three years,” the authors wrote.

SOURCE

This study was led by Roser Navarro-Soler, Hospital Ramón y Cajal, IRYCIS, CIBERINFEC, Madrid, Spain. It was published online on June 20, 2026, in Open Forum Infectious Diseases.

LIMITATIONS

Residual confounding could not be entirely excluded, and the findings should be interpreted as indicating no detected difference rather than evidence of immunologic equivalence. Although the CD4 to CD8 ratio is a well-established surrogate marker of immune recovery, direct clinical endpoints such as non-AIDS events were not assessed. The cohort’s demographic homogeneity limits the generalizability of the findings to women, older adults, and other key populations.

DISCLOSURES

This study was supported by CIBER, Instituto de Salud Carlos III, and others. Several authors disclosed receiving personal fees, nonfinancial support, research grants, or support for attending meetings and travel from or having other financial ties with multiple sources.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.