TOPLINE:

Factors such as younger age, lower BMI for age, and lower CD4% were associated with a higher risk for treatment failure in children living with HIV at initiation of first-line dolutegravir-based antiretroviral therapy (ART), with a steeper increase in risk among the youngest children.

METHODOLOGY:

• Researchers combined data from two ODYSSEY first-line cohorts, including 381 children living with HIV (median age, 10.5 years; 52% girls) who were on ART, to identify risk factors for treatment failure.
• Children were randomly assigned to receive either dolutegravir-based regimens (n = 189) or standard-of-care (SOC) regimens (n = 192), with 91% of children aged 3 years or older (n = 314) starting efavirenz and 79% of children younger than 3 years (n = 67) starting lopinavir.
• The primary endpoint was treatment failure by 96 weeks, defined as insufficient virologic response (viral load decline < 1 log10 by week 24 or viral load ≥ 50 copies per mL at week 24 if baseline viral load was < 500 copies per mL, followed by ART switch for treatment failure), and virologic failure (two consecutive viral loads ≥ 400 copies per mL, with the first at or after week 36).
• They also assessed incidence of a new or recurrent World Health Organization (WHO) stage IV or severe WHO stage III event, or death from any cause.

TAKEAWAY:

• By 96 weeks, 75 children (20%) experienced treatment failure: 24 in the dolutegravir-based regimen group and 51 in the SOC group. Among these failures, 75% were due to virologic failure, 15% due to new or recurrent WHO stage IV events, 8% due to death, and 3% due to insufficient virologic response.
• The risk for treatment failure was lower in the dolutegravir-based regimen group than in the SOC group (adjusted hazard ratio [aHR], 0.47; P = .002). A lower BMI-for-age z score (aHR, 0.82 per unit increase; P = .01) was an independent predictor of treatment failure.
• At a CD4% of 20%, the risk for treatment failure was 140% (95% CI, 1.58-3.65) higher at 1 year of age, 84% (95% CI, 1.38-2.47) higher at 2 years of age, and 30% (95% CI, 1.15-1.48) higher at 5 years of age than at 10 years of age.
• In 1-year-old children, compared with a CD4% of 20%, a CD4% of 15% was associated with a 39% higher risk for treatment failure (aHR, 1.39; P = .002), whereas a CD4% of 30% was associated with a 48% lower risk (aHR, 0.52; 95% CI, 0.36-0.75). By the age of 10 years, the relationship was much weaker.

IN PRACTICE:

“Screening for and prevention of opportunistic infections such as tuberculosis should be routine in children starting ART and nutritional support should be considered. Baseline CD4% (preferably by point of care) would help identify those at highest risk of treatment failure and should be retained for ART initiation assessments,” the authors wrote.

SOURCE:

This study was led by James Wyncoll, Institute of Clinical Trials and Methodology, London, England. It was published online on April 10, 2026, in Clinical Infectious Diseases. 

LIMITATIONS:

The analysis used clinical trial data, possibly limiting the generalizability of the findings to routine care. Data on caregiver, household, and social factors — potentially important predictors of treatment failure in young children — were not collected. The composition of the ODYSSEY population should be considered when generalizing findings to real-world settings.

DISCLOSURES:

This study was supported by the Penta Foundation, ViiV Healthcare, and the UK Medical Research Council. One author reported being co-chair of the WHO-led Paediatric Antiretroviral Working Group, trial clinician for the ODYSSEY trial and a member of the Penta ID scientific steering committee.

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