Clinical Scorecard: Effect of Extended Co-trimoxazole Prophylaxis on Antibiotic-Resistant Bacterial Colonization in People Newly Diagnosed with HIV: The CoTrimResist Randomized, Placebo-Controlled Trial

At a Glance

Key Highlights

• CoTrimResist randomizes 537 participants to daily co-trimoxazole (259) or matching placebo (278) for 1 year.

• Target organisms include extended-spectrum beta-lactamase-producing E. coli and Klebsiella species, methicillin-resistant Staphylococcus aureus (MRSA), penicillin-nonsusceptible pneumococci, and vancomycin-resistant enterococci.

• Co-trimoxazole temporarily reduces S. aureus carriage at 2 weeks and 6 months and MRSA carriage at 2 weeks.

• ESBL-producing E. coli carriage increases more rapidly in the co-trimoxazole group, but the primary analysis does not show a significant treatment effect. Baseline imbalances and regression to the mean may explain this pattern.

• At 1 year, colonization rates do not differ significantly between groups. Mortality and serious adverse events also show no significant between-group differences.

Guideline-Based Recommendations

Diagnosis

• The article does not establish new HIV diagnostic recommendations. Trial eligibility requires a first HIV-positive test during routine screening and CD4 assessment.

Management

• European and US guidance described in the article recommends primary prophylaxis against Pneumocystis jirovecii pneumonia below CD4 counts of 200 cells/µL, with discontinuation after counts remain stably above 100 or 200 cells/µL, respectively, with appropriate antiretroviral therapy.

• The article describes WHO recommendations supporting prolonged prophylaxis in settings with a high burden of malaria and bacterial infections.

• The trial does not establish a survival benefit from prolonged prophylaxis in this study population.

Monitoring & Follow-up

• Trial assessments occur at baseline, 2 weeks, 6 months, and 1 year, including clinical review, medication adherence, other antibiotic use, and microbiological sampling.

• This research schedule does not establish a routine clinical monitoring recommendation.

Risks

• Potential selection for antibiotic resistance remains a concern. Temporary reductions in S. aureus and MRSA carriage do not persist through 1 year.

• Suboptimal adherence and incomplete follow-up limit interpretation; 74% of participants attend the 1-year visit.

Patient & Prescribing Data

Eligibility includes nonpregnant adults older than 18 years with newly diagnosed HIV and CD4 counts ≥350 cells/µL. Known co-trimoxazole allergy is an exclusion criterion. Participants have a median age of 37 years, and 77% are women.

Participants receive one tablet daily containing 80 mg trimethoprim and 400 mg sulfamethoxazole, or matching placebo, for 1 year.

Clinical Best Practices

• Interpret findings within the trial’s selected population and 1-year follow-up.

• Consider baseline carriage imbalances, self-reported adherence, and loss to follow-up when evaluating the results.

• The authors emphasize strengthening infection control and antibiotic stewardship in HIV care: other antibiotic use is associated with ESBL-producing E. coli carriage, and intercurrent hospitalization is associated with ESBL-producing Klebsiella carriage.

• Trial safeguards include written informed consent, concealed allocation, double blinding, and independent safety monitoring.

Related Resources & Content

European AIDS Clinical Society. EACS Guidelines. Version 13. European AIDS Clinical Society; 2025.

World Health Organization. Guidelines on co-trimoxazole prophylaxis for HIV-related infections among children, adolescents and adults. World Health Organization; 2006.

Laurens MB, Mungwira RG, Nampota N, et al. Revisiting Co-trimoxazole prophylaxis for African adults in the era of antiretroviral therapy: a randomized controlled clinical trial. Clin Infect Dis. 2021;73:1058–1065.

Anywaine Z, Levin J, Kasirye R, et al. Discontinuing cotrimoxazole preventive therapy in HIV-infected adults who are stable on antiretroviral treatment in Uganda (COSTOP): a randomised placebo controlled trial. PLoS One. 2018;13:e0206907.