Pneumocystis jirovecii risk high among those with low CD4+ counts at HIV diagnosis

Although combination antiretroviral therapy (cART) has reduced the overall burden of Pneumocystis jirovecii pneumonia (PJP) in patients with HIV, PJP continues to pose a significant risk during the first year of treatment for those with low CD4⁺ cell counts, according to a study published in Open Forum Infectious Diseases.

Pneumocystis pneumonia is associated with high risk for morbidity and mortality among patients with an immunosuppressed status. Although the introduction of combination antiretroviral therapy (cART) has led to declines in PJP and other opportunistic infections in patients with HIV, it remains unclear whether the risk of developing PJP within the first year of HIV diagnosis has also decreased over time.

Investigators conducted a nationwide, population-based cohort study using data from the Danish HIV Cohort Study and other Danish databases. They assessed risk for PJP and PJP-related mortality in individuals (N=4882) diagnosed with HIV between 1995 and 2021. The investigators also examined PJP incidence (per 1000 patient-years) on the basis of time after HIV diagnosis, calendar time, time on cART, and time with a low CD4⁺ (<200 cells/μL) count. Poisson regression was used for statistical analysis.

Among patients included in the analysis, 76.4% were men and 76.1% were White. At HIV diagnosis, the median age was 37.0 (IQR, 30.0-46.0) years, 74.3% of the patients had no comorbidities, the median viral load was 4.8 (IQR, 4.1-5.4) log₁₀ copies/mL, and the median CD4⁺ count was 322 (IQR, 135-530) cells/μL.

Of individuals with PJP identified by discharge diagnostic codes (n=372) and annual review of patient files (n=336), the median ages at HIV diagnosis were 41.0 (IQR, 34.0-51.0) and 41.0 (IQR, 34.0-50.0) years, 82.8% and 83.0% were men, and median CD4⁺ counts at HIV diagnosis were 40 (IQR, 19-109) and 40 (IQR, 15-100) cells/μL, respectively. Most patients in both groups (85.8% and 88.4%, respectively) had low CD4⁺ counts.

A majority of patients with PJP (76.8%) developed the infection within the first 3 months of HIV diagnosis. The investigators noted the magnitude of risk was associated with baseline CD4⁺ count, as PJP incidence in the first year after HIV diagnosis was higher in patients with (incidence rate [IR], 227; 95% CI, 202-255) vs without (IR, 3.42; 95% CI, 1.89-6.18 ) low baseline counts. However, the overall risk decreased after the first year and was no longer associated with baseline CD4⁺ count (IR, 0.92; 95% CI, 0.68-1.23).

The risk for PJP decreased during the study period, with lower rates observed between 1995 and 1999 (IR, 39; 95% CI, 32-49) than between 2016 and 2021 (IR, 1.63; 95% CI, 1.15-2.32). When stratified by baseline CD4⁺ count, the risk among patients with low counts in the first year after HIV diagnosis was reduced in the later calendar period relative to the earlier calendar period (adjusted incidence rate ratio [aIRR], 0.57; 95% CI, 0.36-0.90). In contrast, no significant change in risk was observed in this group across other calendar periods (2000-2008 and 2009-2015). However, in patients without low baseline CD4⁺ counts within the first year of HIV diagnosis, there was a significant decline in PJP risk over the study period (2016-2021 vs 1995-2000; aIRR; 0.08; 95% CI, 0.02-0.29).

In analysis of PJP risk by immune status, the investigators observed the highest absolute risk among patients with low CD4⁺ counts (<100 cells/mL) and high viral loads (>10,000 copies/mL) in the period before cART initiation (IR, 930; 95% CI, 800-1100).

A total of 96 deaths occurred among patients who developed PJP over 3997 person-years of follow-up, with the greatest peak in mortality observed in the month prior to PJP diagnosis (mortality rate, 626 per 1000 person-years; 95% CI; 95% CI, 389-1008).

Study limitations include insufficient power to determine the influence of immune status time on PJP risk for patients who developed the condition after the first month of HIV diagnosis, as well as changes in the method of PJP diagnosis over the study period.

The study authors concluded, “[D]espite the success of cART in reducing the risk of [pneumocystis pneumonia], it remains a significant problem among late presenters with HIV. This emphasizes the critical importance of early HIV diagnosis and raising awareness among those at risk.”

By Jessica Nye, PhD

References:

Moller AK, Schnoor SB, Petersen I, et al. PCP – is it still a threat among people with HIV? A Danish HIV cohort study. Open Forum Infect Dis. 2025:ofaf289. doi:10.1093/ofid/ofaf289