Antiretrovirals also shaped gut ecology. In Uganda & Botswana, efavirenz was linked to Prevotella loss. Computational & in vitro experiments showed that efavirenz may inhibit bacterial reverse transcriptases involved in antiphage defense, disrupting non-Western Prevotella-rich ecosystems.

Although taxa varied by region, shifts in microbial functions were shared across HIV cohorts: reduced carbohydrate-utilization and motility/sporulation genes, and enriched mannose PTS transporters—pointing to a shift toward mucosal colonizers in an inflamed gut.

At taxonomic level, we observed both geography-specific shifts (e.g. Uganda→Botswana→US gradient in Prevotella) as well as shared alterations (e.g. depletion of Faecalibacterium prausnitzii across cohorts with HIV), which also helped predict HIV status across sites.