Withholding primary PcP prophylaxis in virologically suppressed HIV patients: An emulation of a pragmatic trial in COHERE. Clinical Infectious Disease
Atkinson et al. for the Opportunistic Infections Project Working Group of the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord 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.
The author group implemented an established causal inference approach whereby observational data were 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. They compared the following 2 strategies for stopping prophylaxis: (1) when CD4 count was >200 cells/ μL for >3 months or (2) when the patient was virologically suppressed (2 consecutive HIV RNA ≤400 copies/mL).
A total of 4’813 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).
In conclusion, this study indicated that HIV replication measured as plasma HIV RNA is a major contributor to the risk of developing primary PcP. In virologically suppressed patients on ART, irrespective of CD4 levels, the risk of PcP is marginally lower using viral suppression alone, compared with when prophylaxis is taken based on the CD4 count threshold according to current guidelines. The study suggests that primary PcP prophylaxis might be safely withheld in patients on ART with confirmed plasma viral suppression, regardless of their CD4 count.