Incidence of neonatal sepsis among HIV exposed neonates of mothers on integrase strand transfer inhibitors in sub-Saharan Africa: a systematic review and meta-analysis.

INTRODUCTION: Human immunodeficiency virus (HIV)-exposed infants face elevated risks of neonatal sepsis, influenced by maternal antiretroviral therapy (ART) regimens. Dolutegravir (DTG), a widely used integrase transfer inhibitor (INSTI), and the preferred first line drugs for management of HIV in pregnancy, has shown potential adverse effects such as hyperglycaemia, which may impact neonatal outcomes including risk of neonatal sepsis. We estimated the pooled incidence of neonatal sepsis among neonates exposed to INSTIs in utero compared to non-INSTIs-based ART regimens. METHODS AND ANALYSIS: A systematic review and meta-analysis were conducted following written as per the PRISMA guidelines. Databases including PubMed/MEDLINE, Embase, Cochrane Library, CINAHL, Global Health and Global Index Medicus were searched for studies published between January 2013 and September 2025. Eligible studies included clinical trials and cohort studies comparing INSTI-based ART regimens with non-INSTI regimens among pregnant women living with HIV. Data were extracted using Covidence software, Cochrane risk of bias (RoB) and Newcastle-Ottawa Scale (NOS) were used to assessed for quality of randomised clinical trials and observational studies, respectively. The certainty of the evidence was assessed using the Grading, Recommendation, Assessment, Development and Evaluation (GRADE) framework. RESULTS: A total of 714 studies were identified and screened based on their titles and abstracts, of which 63 articles underwent full-text review. Ultimately, four studies, comprising 7,636 participants, met the predefined eligibility criteria and were included in the analysis. The pooled odds ratio (OR) for neonatal sepsis among infants exposed to INSTIs was 0.44 (95% confidence interval [CI]: 0.15-1.30, p = 0.137). The test for subgroup difference was not significant (p = 0.358): the pooled OR for dolutegravir was 0.27 (95% CI 0.06-1.23, p = 0.090) and for the single raltegravir study was 0.73 (95% CI 0.16-3.30, p = 0.681). CONCLUSION: INSTI-based ART was not associated with a significant difference in neonatal sepsis risk compared with non-INSTI regimens. However, the low number of events limited the precision of the estimates, highlighting the need for further research. REGISTRATION: This review has been registered with the PROSPERO at https://www.crd.york.ac.uk/PROSPERO/view/CRD420251178411 , registration number CRD420251178411.