Can a blood test show if an HIV-positive patient has PCP?

A blood test may be able to show if an HIV-positive patient has the AIDS-defining opportunistic infection, Pneumocystis jirovecii pneumonia, US investigators report in the July 15^th edition of Clinical Infectious Diseases.

Pneumocystis jirovecii was formerly known as pneumocystis carinii pneumonia (PCP), and is still commonly known as PCP. It is an AIDS-defining opportunistic infection and was one of the most frequent causes of death in the era before highly active antiretroviral therapy was introduced in 1996.

PCP typically develops when a patient has a CD4 cell count below 200 cells/mm³. Broncoscopy and induced sputum are the standard tests used to diagnose PCP, but both are uncomfortable for the patient and difficult and expensive to perform.

β-glucan is a component of the wall of many fungi, including Pneumocystiis jirovecii. There are some data suggesting that blood levels of β-glucan are elevated in HIV-positive and HIV-negative patients with PCP.

Dr Paul Sax and colleagues at the Brigham and Women's Hospital in Boston of the newly published study found that β-glucan levels were strongly correlated with HIV-related PCP. Median β-glucan levels were significantly higher among patients with PCP than individuals who did not have this infection.

“Blood levels of β-glucan were strongly associated with the diagnosis of PCP,” comment the investigators, who are hopeful that the test could make diagnosis of the infection easier, avoiding the need for invasive tests such as broncoscopy or induced sputum.

However, the authors of an accompanying editorial are not convinced by the study’s findings, concluding “this serum β-glucan test will not yet allow use to lay down the bronchoscope.”

The study involving 252 individuals who were enrolled in the ACTG A5164 trial, a study of early versus deferred antiretroviral therapy in conjunction with treatment for opportunistic infections.

Plasma samples of β-glucan were obtained at baseline, and results were considered positive if β-glucan levels were above 80 pg/ml.

The patients were recruited to the study between 2003 and 2008. They had advanced immune suppression, and their median baseline CD4 cell count was 26 cells/mm³.

Over two-thirds (69%) of patients had PCP. Other common opportunistic infections were cryptococcal meningitis (14%) and bacterial pneumonia (9%). In addition, 44% of patients had either oral or oesophageal thrush.

For patients with PCP, the median β-glucan level was 408 pg/ml, and 92% had a positive β-glucan test result.

In comparison, the median β-glucan level for patients who did not have PCP was37 pg/ml, and 35% had a positive β-glucan test result.

These differences were significant (p < 0.001).

The β-glucan test had a sensitivity of 92% and a specificity of 65% for PCP.

“This sensitivity compares favourably to that reported for induced sputum examination in some clinical centres,” comment the investigators.

The positive predictive value of the test was 65% and the negative predictive value was 80%.

“The strong association of β-glucan with HIV-related PCP could have significant clinical implications, especially in settings where the induced sputum examination for PCP is unavailable or has low sensitivity,” write the authors.

They add, “β-glucan can be a helpful adjunctive test for PCP… since introducing β-glucan testing at our institution, we have found that β-glucan testing has increased the yield of PCP diagnoses, reduced the number of cases treated empirically, and reduced the need for bronchoscopy.”

However, the authors of the accompanying editorial have reservations about the significance of the study’s findings.

“First, β-glucan is positive with certain other fungi; thus, results are nonspecific,” meaning that patients “might be treated for PCP even though another pathogen was the causative agent.” They also note that β-glucan colonisation is common in HIV-positive patients with a low CD4 cell count even if they do not have lung disease or PCP.

The authors of the editorial were also concerned that the study did not include HIV-negative patients.