Project Details

Prevalence of antimicrobial resistance and effects on gut health among children who are HIV-exposed but uninfected

Emily Begnel, PhD, MPH

Summary

BACKGROUND: Cotrimoxazole (CTX) prophylaxis to reduce opportunistic infections among HIV-exposed children has been recommended for several decades. However, as pediatric HIV declines, recent data suggest CTX prophylaxis may no longer reduce morbidity in children who are HIV-exposed and remain uninfected (CHEU); instead, prolonged exposure to this broad-spectrum antibiotic may increase antimicrobial resistance (AMR), which is rising globally and threatens public health by decreasing the effectiveness of antibiotics. GAP: No study has compared the prevalence and co-occurrence of CTX-associated antimicrobial resistance genes (ARG) and enteric pathogens among CHEU born to women receiving optimized antiretroviral therapy (ART) versus children who are HIV-unexposed (CHU) from the same population. Enteric pathogens carry ARG and are a major source of infant morbidity, but it is unclear how early pathogen colonization affects acquisition of ARG or whether ARG contribute to morbidity by increasing intestinal inflammation. HYPOTHESIS: Compared to CHU, CHEU will have higher prevalence of ARG but lower prevalence of enteric pathogens due to receiving CTX. ARG will be associated with higher levels of gut inflammation in both CHEU and CHU. METHODS: This study is nested in a Nairobi, Kenya-based cohort of CHEU born to women who initiated optimized ART before or in early pregnancy and CHU with similar clinical and sociodemographic characteristics; 95% of CHEU received CTX. Infant stool samples will be tested by PCR for CTX-associated ARG and inflammatory bacterial pathogens, and existing cohort data for intestinal inflammation will be leveraged for analyses. RESULTS: Pending. IMPACT: Results will provide context to whether CTX-associated ARG and enteric pathogen prevalence among healthy CHEU differs from the background prevalence experienced by their CHU peers in the current era of optimized ART. Findings will inform new research and policy decisions about prophylactic CTX use and seed new directions of investigation.