TOPLINE:

Lamivudine/dolutegravir demonstrated real-world effectiveness as first-line therapy for HIV infection, with a 3-year rate of treatment failure less than 6%. Patients with a viral load of more than 100,000 copies/mL, those with a CD4 count of 200 or fewer cells/mm³, and older adults had a higher risk for treatment failure.

METHODOLOGY:

• Researchers conducted a real-world study across 61 centers in Italy to assess the effectiveness and failure rate of first-line lamivudine/dolutegravir in antiretroviral therapy (ART)-naive people with HIV infection (PWH).
• Data were gathered from the Icona Foundation Study cohort including 446 PWH (median age, 37 years; 15% women) who initiated lamivudine/dolutegravir as first-line therapy between 2016 and 2024 and were followed up for a median of 22 months.
• The primary endpoint was the time to treatment failure, defined as treatment discontinuation due to toxicity, lack of virologic control, nonadherence, virologic failure (> 50 copies/mL), or death from any cause.
• Secondary endpoints evaluated the time to pure treatment discontinuation regardless of the reason and pure virologic failure with a threshold of more than 50 copies/mL.

TAKEAWAY:

• The overall cumulative probability of treatment failure was 2.2% (95% CI, 0.7%-3.7%) at 1 year, 4.2% (95% CI, 1.9%-6.4%) at 2 years, and 5.8% (95% CI, 2.9%-8.7%) at 3 years.
• Patients who initiated treatment with an HIV RNA level of more than 100,000 copies/mL, those with a CD4 count of 200 or fewer cells/mm³, foreign-born individuals, and those older than 50 years had a higher risk for treatment failure.
• A total of 9.4% of patients discontinued treatment, with a cumulative probability of treatment discontinuation for any reason of 13.4% (95% CI, 9.1%-17.6%) at 3 years. No significant association was found between CD4 count, baseline HIV RNA level, age, or country of birth and discontinuation.
• The risk for pure virologic failure by 3 years was 2.3% (95% CI, 0.19%-4.4%).

IN PRACTICE:

“In conclusion, lamivudine/dolutegravir appears to be a safe and effective first-line regimen with good tolerability,” the authors wrote.

“Nevertheless, our findings underline the fact that clinicians should exercise special caution when starting ART in these vulnerable subgroups to prevent suboptimal adherence or discontinuations that could result in treatment failure,” they added.

SOURCE:

This study was led by Alessandra Vergori, National Institute for Infectious Diseases, Lazzaro Spallanzani IRCCS, Rome, Italy. It was published online on September 23, 2025, in the Journal of Antimicrobial Chemotherapy.

LIMITATIONS:

This study was limited by the low prevalence of key exposure factors such as low CD4 count and high viral load. The small sample size and low statistical power may have affected the ability to draw conclusive results. Additionally, as in all real-world data analyses, residual and unmeasured confounding could not be ruled out.

DISCLOSURES:

This study was supported by an unrestricted grant from ViiV Healthcare. The Icona Foundation is supported by unrestricted grants from Gilead Sciences, ViiV Healthcare, and Merck Sharpe & Dohme Italia. Several authors reported receiving financial aid and serving as a paid consultant to various pharmaceutical companies.

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