Withholding Primary Pneumocystis Pneumonia Prophylaxis in Virologically Suppressed Patients With Human Immunodeficiency Virus: An Emulation of a Pragmatic Trial in COHERE
Authors: Atkinson Andrew , Zwahlen Marcel , Barger Diana , d’Arminio Monforte Antonella , De Wit Stephane , Ghosn Jade , Girardi Enrico , Svedhem Veronica , Morlat Philippe , Mussini Cristina , Noguera-Julian Antoni , Stephan Christoph , Touloumi Giota , Kirk Ole , Mocroft Amanda , Reiss Peter , Miro Jose M , Carpenter James R , Furrer Hansjakob ,   for the Opportunistic Infections Project Working Group of the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord, Judd Ali , Zangerle Robert , Touloumi Giota , Warszawski Josiane , Meyer Laurence , Dabis François , Krause Murielle Mary , Ghosn Jade , Leport Catherine , Wittkop Linda , Reiss Peter , Wit Ferdinand , Prins Maria , Bucher Heiner , Gibb Diana , Fätkenheuer Gerd , Del Amo Julia , Obel Niels , Thorne Claire , Mocroft Amanda , Kirk Ole , Stephan Christoph , Pérez-Hoyos Santiago , Hamouda Osamah , Bartmeyer Barbara , Chkhartishvili Nikoloz , Noguera-Julian Antoni , Antinori Andrea , d’Arminio Monforte Antonella , Brockmeyer Norbert , Prieto Luis , Rojo Conejo Pablo , Soriano-Arandes Antoni , Battegay Manuel , Kouyos Roger , Mussini Cristina , Casabona Jordi , M. Miró Jose , Castagna Antonella , Konopnick Deborah , Goetghebuer Tessa , Sönnerborg Anders , Torti Carlo , Sabin Caroline , Teira Ramon , Garrido Myriam , Haerry David , M. Miró Jose , Costagliola Dominique , d’Arminio-Monforte Antonella , Castagna Antonella , del Amo Julia , Mocroft Amanda , Raben Dorthe , Chêne Geneviève 
Published: May 2020

Abstract

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 (ART) with suppressed plasma human immunodeficiency virus (HIV) RNA (≤400 copies/mL), irrespective of CD4 count.

Methods
We implemented an established causal inference approach whereby observational data are used to emulate a randomized 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 2 strategies for stopping prophylaxis: (1) when CD4 count was &gt;200 cells/µL for &gt;3 months or (2) when the patient was virologically suppressed (2 consecutive HIV RNA ≤400 copies/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 (HR) 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
A total of 4813 patients (10 324 person-years) complied with eligibility conditions for the emulated trial. With primary PcP diagnosis as an endpoint, the adjusted HR (aHR) indicated a slightly lower, but not statistically significant, different risk for the strategy based on viral suppression alone compared with the existing guidelines (aHR, .8; 95% confidence interval, .6–1.1; P = .2).

Conclusions
This study suggests that primary PcP prophylaxis might be safely withheld in confirmed virologically suppressed patients on ART, regardless of their CD4 count.