Impact of Cotrimoxazole Use in Immunocompetent HIV Patients on Carriage of Antimicrobial Resistant Bacteria

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.

Conditions

• HIV-1-infection
• Pneumocystis Pneumonia
• Opportunistic Infections
• Preventive Therapy
• Antibiotic Side Effect

Interventions

DRUG

Cotrimoxazole

Patients will receive preventive treatment with 2 tablets cotrimoxazole (80 mg trimethoprim, 400mg sulfamethoxazole) daily for 48 weeks

DRUG

Placebo

Patients will receive 2 tablets placebo daily for 48 weeks

Sponsors & Collaborators

• Haukeland University Hospital

  collaborator OTHER

• Muhimbili University of Health and Allied Sciences

  collaborator OTHER

• Helse Vest

  collaborator OTHER

• University of Bergen

  lead OTHER

Principal Investigators

• Joel Manyahi, MD · Muhimbili University of Health and Allied Sciences

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2017-03-30

Primary Completion

2019-07-25

Completion

2019-07-25

Countries

• Tanzania

Study Locations