Impact of Cotrimoxazole Use in Immunocompetent HIV Patients on Carriage of Antimicrobial Resistant Bacteria
Status:
Completed
Trial end date:
2019-07-25
Target enrollment:
Participant gender:
Summary
Cotrimoxazole preventive therapy (CPT) is recommended for prevention of morbidity and
mortality due to Pneumocystis pneumonia and other infections in HIV positive patients with
low immunity. Common clinical practice is to start CPT in any patient with CD4 counts below
200/µL, and, conversely, to stop CPT when immunity has been restored by antiretroviral
treatment to CD4 counts above 200/µL or when viral suppression has been documented for 3
months. However, the latest WHO guidelines widely expands the indication for CPT by
advocating for settings with high prevalence of malaria and bacterial infections, that all
patients with HIV start CPT regardless of CD4 counts and clinical stage. Furthermore, WHO
recommends these patients to continue CPT indefinitely regardless of evidence of immune
restoration (The recommendation is for settings with high prevalence of malaria and bacterial
infections, not for high-income countries). There is limited scientific evidence to recommend
prolonged CPT, as studies have shown it is associated with modestly reduced morbidity due to
pneumonia, meningitis and malaria, but no corresponding reduction in mortality. The impact of
such a large increase in antibiotic use on the emergence of antimicrobial resistance has not
been thoroughly considered. Our previous studies in Tanzania showed that multidrug-resistant
bacteria frequently cause bloodstream infections with resultant very high case-fatality
rates. As genes encoding for multiple antibiotic resistance traits are transferred by
plasmids together with resistance towards cotrimoxazole, prolonged CPT will likely favor the
selection of carriage of multidrug-resistant gut bacteria. The proposed randomized clinical
trial is designed to assess whether prolonged CPT in HIV-positive patients results in
increased fecal carriage of multi-drug resistant gut microbes or increased nasal carriage of
methicillin-resistant Staphylococcus aureus (MRSA). Secondary endpoints are morbidity
(clinical events, hospitalizations) and mortality. Stool specimens, nasal swabs and clinical
data will be collected from persons attending voluntary counseling and testing facilities and
HIV-clinics in Dar es Salaam, Tanzania. The study results may have important impact on public
health in terms of assisting development of rational recommendations for CPT use, and may
help prevent emerging antibiotic resistance.
Phase:
Phase 4
Details
Lead Sponsor:
University of Bergen
Collaborators:
Haukeland University Hospital Helse Vest Muhimbili University of Health and Allied Sciences
Treatments:
Sulfamethoxazole Trimethoprim Trimethoprim, Sulfamethoxazole Drug Combination