HIV status and the risk of typhoid fever and iNTS: a systematic review and meta-analysis

Objectives: The WHO recommends prioritising people living with HIV (PLHIV) for typhoid vaccination, but evidence for increased typhoid fever risk is inconsistent. We aimed to evaluate whether HIV infection alters the risk of blood culture-confirmed typhoid fever.

Methods: We systematically searched four databases from inception to 30 November 2023 for studies reporting Salmonella Typhi bacteraemia with documented HIV status. Where available, we also extracted data on invasive non-typhoidal Salmonella (iNTS) bacteraemia. We used random-effects meta-analysis to pool odds ratios (ORs) and assessed effect modification by ART era, age, and CD4 count.

Results: Seventeen studies met inclusion criteria, comprising 10,117 PLHIV and 53,289 HIV-negative individuals from Africa and Asia. PLHIV had lower odds of typhoid fever (OR 0.53, 95% CI 0.30–0.92), but higher odds of iNTS disease (OR 4.06, 2.23–7.39). Apparent protection against typhoid was most evident in adults with CD4 counts <200 cells/µl and was not significant after ART rollout.

Conclusions: Advanced HIV infection may reduce the risk of typhoid fever. While altered clinical presentations or healthcare-seeking behaviours could contribute, the contrasting increase in iNTS risk within the same populations suggests a genuine difference in susceptibility. These findings support re-evaluating WHO guidance that prioritises PLHIV for typhoid vaccination.