No need for secondary Pneumocystis jirovecii pneumonia prophylaxis in adult people living with HIV from Europe on ART with suppressed viraemia and a CD4 cell count greater than 100 cells/µL
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Introduction: Since the beginning of the HIV epidemic in resource-rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS-defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV-RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. Methods: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time-updated CD4 counts, HIV-RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV-RNA was stratified as low (<400), medium (400 to 10,000) or high (>10,000copies/mL). Results: There were 373 recurrences of PjP during 74,295 person-years (py) in 10,476 patients. The PjP incidence in the different plasma HIV-RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV-RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). Conclusions: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | e25726 |
| Tidsskrift | Journal of the International AIDS Society |
| Vol/bind | 24 |
| Udgave nummer | 6 |
| ISSN | 1758-2652 |
| DOI | |
| Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:
The COHERE study group has received unrestricted funding from: Agence Nationale de Recherches sur le SIDA et les H?patites Virales (ANRS), France; HIV Monitoring Foundation, The Netherlands; and the Augustinus Foundation, Denmark. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under EuroCoord grant agreement no 260694. A list of the funders of the participating cohorts can be found at www.COHERE.org. Research reported in this publication was supported by the Swiss National Science Foundation (grant number 324730_149792, PI: H. Furrer), specifically for H. Furrer and A. Atkinson. A. Atkinson is also employed by the University Children?s Hospital in Basel. S. De Wit received grants from Gilead, Janssen, MSD, & ViiV, all paid to his institution. C. Mussini has participated in advisory boards and received study grants and/or speaker honoraria from Abbvie, Gilead Sciences, Viiv Healthcare, Janssen, Angelini, BMS and Merck Sharp & Dohme. C. Stephan received honoraria and travel support from Giliad, MSD and Janssen-Cilag, outside of the submitted work. E. Girardi received unrestricted research grants from Gilead Sciences and Mylan, a travel grant from Gilead sciences, honoraria from Gilead sciences, ViiV, Janssen, Mylan and Angelini, outside the submitted work. O. Kirk has received consulting honoraria and travel support for conferences from Gilead, MSD, Janssen, Merck and Viiv, outside the submitted work. A. Mocroft has received honoraria from Gilead, ViiV and A. Craig Eiland PC outside of the submitted work.
Funding Information:
The COHERE study group has received unrestricted funding from: Agence Nationale de Recherches sur le SIDA et les Hépatites Virales (ANRS), France; HIV Monitoring Foundation, The Netherlands; and the Augustinus Foundation, Denmark. The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007‐2013) under EuroCoord grant agreement no 260694. A list of the funders of the participating cohorts can be found at www.COHERE.org . Research reported in this publication was supported by the Swiss National Science Foundation (grant number 324730_149792, PI: H. Furrer), specifically for H. Furrer and A. Atkinson. A. Atkinson is also employed by the University Children’s Hospital in Basel. S. De Wit received grants from Gilead, Janssen, MSD, & ViiV, all paid to his institution. C. Mussini has participated in advisory boards and received study grants and/or speaker honoraria from Abbvie, Gilead Sciences, Viiv Healthcare, Janssen, Angelini, BMS and Merck Sharp & Dohme. C. Stephan received honoraria and travel support from Giliad, MSD and Janssen‐Cilag, outside of the submitted work. E. Girardi received unrestricted research grants from Gilead Sciences and Mylan, a travel grant from Gilead sciences, honoraria from Gilead sciences, ViiV, Janssen, Mylan and Angelini, outside the submitted work. O. Kirk has received consulting honoraria and travel support for conferences from Gilead, MSD, Janssen, Merck and Viiv, outside the submitted work. A. Mocroft has received honoraria from Gilead, ViiV and A. Craig Eiland PC outside of the submitted work. P. Reiss reports grants from Gilead Sciences, ViiV Heakthcare, Merck & Co and Janssen Pharmaceutica, and other honoraria from Gilead Sciences, ViiV Healthcare, Merck, and Teva, outside the submitted work. J. M. Miro received a personal 80:20 research grant from Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain, during 2017 to 2021, and has received consulting honoraria and/or research grants from AbbVie, Angelini, Contrafect, Cubist, Genentech, Gilead Sciences, Jansen, Medtronic, MSD, Novartis, Pfizer, and ViiV Healthcare, outside of the submitted work. H Furrer reports grants to the institution from ViiV, Gilead, MSD, Abbvie and Sandoz, outside the submitted work. All other authors report no competing interests.
Publisher Copyright:
© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.
ID: 302048562