Impact of prolonged co-trimoxazole prophylaxis on colonization with antibiotic resistant bacteria in persons newly diagnosed with HIV-infection: CoTrimResist-a randomized placebo-controlled trial

Objective To assess whether prolonged co-trimoxazole prophylaxis for people with HIV in sub-Saharan Africa increases colonization with antibiotic-resistant bacteria. Methods The CoTrimResist trial (NCT03087890) randomized newly diagnosed Tanzanian adults with HIV and CD4 counts >350/µL to daily co-trimoxazole or placebo for 1 year. Clinical data, rectal and nasopharyngeal/nasal swabs were collected at enrolment, 2 weeks, 6 months, and 1 year. Primary outcomes were carriage of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) and Klebsiella species (ESBL-K), methicillin-resistant Staphylococcus aureus (MRSA), and penicillin-non-susceptible pneumococci (PNSP). Results Among 537 participants (median age 37 years; 77% female), 259 received co-trimoxazole, and 278 placebo. Co-trimoxazole temporarily reduced nasal S. aureus carriage at 2 weeks (risk difference −7.3%; 95% confidence interval [CI] −12.0% to −2.6%) and 6 months (−7.6%; 95% CI −13.9% to −1.3%), and MRSA at 2 weeks (−4.5%; 95% CI −8.0% to −1.1%). ESBL-EC colonization increased more rapidly with co-trimoxazole. At 1 year, there were no between-group differences in colonization rates, mortality or serious adverse events. Intercurrent use of other antibiotics was associated with increased carriage of ESBL-EC. Conclusion Prolonged co-trimoxazole prophylaxis leads to transient reductions in S. aureus and MRSA and early increase in ESBL-EC, but shows no persistent effect on colonization with antimicrobial-resistant bacteria at 1 year.