Withholding primary PcP prophylaxis in virologically suppressed HIV patients: An emulation of a pragmatic trial in COHERE.
- Atkinson A Dept. of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
- Zwahlen M Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
- Barger D Univ. Bordeaux, ISPED, Inserm Bordeaux Population Health, team MORPH3EUS, UMR 1219, Bordeaux, France.
- d'Arminio Monforte A Institute of Infectious Diseases, Department of Health Sciences, University of Milan, Italy.
- De Wit S Dept. of Infectious Diseases, Saint Pierre University Hospital, Université Libre de Bruxelles, Brussels, Belgium.
- Ghosn J APHP.Nord-Université de Paris, Service des Maladies Infectieuses et Tropicales, Hôpital Bichat, Paris, France.
- Girardi E Clinical Epidemiology Unit, National Institute for Infectious Diseases L. Spallanzani-IRCCS, Rome, Italy.
- Svedhem-Johansson V Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden.
- Morlat P Univ Bordeaux, ISPED, Inserm Bordeaux Population Health, team MORPH3EUS, UMR 1219, Bordeaux, France.
- Mussini C Clinic of Infectious Diseases, University of Modena and Reggio Emilia, Italy.
- Noguera-Julian A Malalties Infeccioses i Resposta Inflamatòria Sistèmica en Pediatria, Unitat d´Infeccions, Servei de Pediatria, Institut de Recerca Pediàtrica Hospital Sant Joan de Déu, Barcelona, Spain.
- Stephan C Infectious Diseases Unit at Medical Center no., Frankfurt University Hospital, Goethe University, Frankfurt, Germany, for Frankfurt HIV Cohort Study.
- Touloumi G Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National & Kapodistrian University of Athens, Athens, Greece.
- Kirk O CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark.
- Mocroft A Centre for Clinical Research, Epidemiology, Modelling and Evaluation (CREME), Institute for Global Health, UCL, Rowland Hill St, London, UK.
- Reiss P HIV Monitoring Foundation, Meibergdreef, AZ Amsterdam, Netherlands.
- Miro JM Infectious Diseases Service, Hospital Clinic - IDIBAPS, University of Barcelona, Barcelona, Spain.
- Carpenter JR Dept. of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK.
- Furrer H Dept. of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland.
- 2020-05-26
Published in:
- Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. - 2020
English
BACKGROUND
Using data from the COHERE collaboration, we investigated whether primary prophylaxis for Pneumocystis Pneumonia (PcP) might be withheld in all patients on antiretroviral therapy with suppressed plasma HIV RNA (≤ 400c/mL) irrespective of CD4 count.
METHODS
We implemented an established causal inference approach whereby observational data is used to emulate a randomised trial. Patients taking PcP prophylaxis were eligible for the emulated trial if their CD4 count was ≤ 200 cells/µL in line with existing recommendations. We compared the following two strategies for stopping prophylaxis: i.) when CD4 count was above 200 cells/µL for more than 3 months, or ii.) when the patient was virologically suppressed (two consecutive HIV RNA ≤ 400c/mL). Patients were artificially censored if they did not comply with these stopping rules. We estimated the risk of primary PcP in patients on ART, using the hazard ratio to compare the stopping strategies by fitting a pooled logistic model, including inverse probability weights to adjust for the selection bias introduced by the artificial censoring.
RESULTS
4'813 patients (10'324 person years) complied with eligibility conditions for the emulated trial. With primary PcP diagnosis as endpoint, the adjusted hazard ratio (aHR) indicated a slightly lower, but not statistically significant, different risk for the strategy based on viral suppression alone compared to the existing guidelines (aHR 0.8 with 95% CI [0.6, 1.1], p = 0.2).
CONCLUSIONS
The study suggests that primary PcP prophylaxis might be safely withheld in confirmed ART-virologically suppressed patients, regardless of their CD4 count.
Using data from the COHERE collaboration, we investigated whether primary prophylaxis for Pneumocystis Pneumonia (PcP) might be withheld in all patients on antiretroviral therapy with suppressed plasma HIV RNA (≤ 400c/mL) irrespective of CD4 count.
METHODS
We implemented an established causal inference approach whereby observational data is used to emulate a randomised trial. Patients taking PcP prophylaxis were eligible for the emulated trial if their CD4 count was ≤ 200 cells/µL in line with existing recommendations. We compared the following two strategies for stopping prophylaxis: i.) when CD4 count was above 200 cells/µL for more than 3 months, or ii.) when the patient was virologically suppressed (two consecutive HIV RNA ≤ 400c/mL). Patients were artificially censored if they did not comply with these stopping rules. We estimated the risk of primary PcP in patients on ART, using the hazard ratio to compare the stopping strategies by fitting a pooled logistic model, including inverse probability weights to adjust for the selection bias introduced by the artificial censoring.
RESULTS
4'813 patients (10'324 person years) complied with eligibility conditions for the emulated trial. With primary PcP diagnosis as endpoint, the adjusted hazard ratio (aHR) indicated a slightly lower, but not statistically significant, different risk for the strategy based on viral suppression alone compared to the existing guidelines (aHR 0.8 with 95% CI [0.6, 1.1], p = 0.2).
CONCLUSIONS
The study suggests that primary PcP prophylaxis might be safely withheld in confirmed ART-virologically suppressed patients, regardless of their CD4 count.
- Language
-
- English
- Open access status
- hybrid
- Identifiers
-
- DOI 10.1093/cid/ciaa615
- PMID 32448894
- Persistent URL
- https://sonar.ch/global/documents/253
Statistics
Document views: 22
File downloads:
- Full-text: 0