Hydroxyurea Does Not Increase Infection Risk in Sickle Cell Anaemia

HYDROXYUREA infection risk was not increased among children with sickle cell anaemia receiving treatment in the international REACH trial, with infection rates declining as treatment progressed to the maximum tolerated dose (MTD). 

The retrospective cohort analysis included 606 children aged 1–10 years who had sickle cell anaemia and were enrolled in REACH across hospitals in Angola, the Democratic Republic of the Congo, Kenya and Uganda. Children underwent screening before receiving a fixed dose of oral hydroxyurea for six months, followed by dose escalation to the MTD. 

Across 5,638 person-years of observation, 5,493 clinically diagnosed infections occurred, corresponding to an overall incidence rate of 97.4 per 100 person-years. 

Infection Rates Declined During Treatment 

Among non-malarial infections, incidence decreased from screening to the fixed-dose phase (adjusted incidence rate ratio [IRR]: 0.81; 95% CI: 0.67–0.98) and declined further by the MTD phase (adjusted IRR: 0.51; 95% CI: 0.43–0.61; p<0.0001). 

Declines were also observed across several infection categories. For upper respiratory tract infections, the adjusted IRR reached 0.64 during the MTD phase, while the corresponding figure for lower respiratory tract infections was 0.45. 

Bacterial skin or nail infections declined to an adjusted IRR of 0.31 at MTD, while non-specific infectious syndromes fell to 0.39. The analysis also found a significant reduction in grade 3 or higher infections across treatment phases (p=0.0006). 

Findings Support Hydroxyurea Safety 

The results did not indicate that hydroxyurea increased the incidence or severity of clinically diagnosed infections in children with sickle cell anaemia living in sub-Saharan Africa. 

The authors concluded that the findings provide reassurance regarding hydroxyurea infection risk, including when treatment is escalated to the MTD. The findings therefore support the continued use of hydroxyurea without evidence from this cohort of an increased risk of infection-related illness or death. 

Reference 

Williams TN et al. Incidence of clinically diagnosed infections in children with sickle cell anaemia treated with oral hydroxyurea in Angola, DR Congo, Kenya, and Uganda: a retrospective cohort study from the REACH trial. Lancet Haematol. 2026;DOI: 10.1016/S2352-3026(26)00246-2.