The influence of hospitalization and HIV severity on gastrointestinal PCR panel evaluation of HIV-related acute diarrhea in New York City: a retrospective, cross-sectional study

Abstract

Introduction: Diarrhea is common in persons living with HIV (PLWH)/AIDS. With the increasing utilization of multiplex gastrointestinal PCR panel (GI panel) testing, we aimed to characterize the roles of CD4 count and hospitalization in GI panel assessments of PLWH with acute diarrhea. Methods: We performed a cross-sectional study of adult PLWH with acute diarrhea who underwent GI panel testing at two urban academic centers. Demographic, HIV disease, GI panel result, and hospitalization data were collected, and patients were cohorted by CD4 count (CD4 < 200, CD4 200–499, CD4 > = 500). The primary outcome was enteric infection as detected by GI panel, and hospitalization. Results: Of 298 PLWH, 119 (39.9%) had a CD4 count below 200, 195 (65.4%) were hospitalized, and 137 (46.0%) had enteric infection. Bacterial infection correlated with higher CD4 count (41.9% (CD4 > = 500) vs 31.2% (CD4 200–499) vs 25.2% (CD4 < 200), p = 0.041). Hospitalization correlated with poorly controlled HIV and fewer enteric infections (34.4% vs 68.0%, p < 0.001). After adjusting for HIV disease severity, a negative GI panel remained independently associated with hospitalization (adjusted odds ratio (aOR) 5.32, 95% confidence interval (CI) 2.72–10.9), even in patients tested within 72 hours of hospitalization. Despite better HIV control, men who have sex with men (MSM) had more frequent infectious diarrhea, including from E. coli, giardiasis, and multiple pathogens. MSM status independently predicted enteric infection (aOR 1.93, 95% CI: 1.02–3.67). Conclusions: GI panel results vary by HIV disease severity and hospitalization in PLWH. Clinicians – especially in the inpatient setting – should carefully consider these factors when interpreting GI panel results. Further characterization of diarrheal etiology in PLWH with a negative GI panel is needed. Plain Language Summary PCR stool test results are affected by certain factors in HIV-related diarrhea Diarrhea is common in people living with HIV (PLWH) and has a variety of causes, including infections, medications, and HIV itself. Multiplex polymerase chain reaction (PCR) stool testing simultaneously evaluates for a variety of common viral, bacterial, and parasitic infections of the gastrointestinal tract, and is increasingly being used in patients with diarrhea. However, patients with HIV and diarrheal illness may have uncommon infections not typically present in those with normal immune function – and thus not routinely evaluated for in stool testing. It is not known what factors, if any, might affect the results of PCR testing in HIV-related diarrhea. In this study, we examined all PLWH who underwent stool PCR testing for diarrhea over a 4-year period. We separated the patients into groups based on HIV disease severity as measured by CD4 T-cell count, or the count of the immune cells affected by HIV. We examined whether there were differences among groups in infection rates as detected by PCR stool testing. Separately, we studied the role of hospitalization in stool PCR test results. Of 298 PLWH who underwent stool PCR testing for diarrhea, 119 had a CD4 count less than 200 (low CD4 count), 195 were hospitalized at time of testing, and 137 had a positive stool PCR test. Compared to those with a low CD4 count, subjects with less severe HIV disease were more likely to have a bacterial infection on stool PCR testing and less likely to be hospitalized. Hospitalized patients were more likely to have a negative PCR stool test, regardless of CD4 count. Many patients with a low CD4 count had diarrheal etiologies not evaluated by multiplex stool PCR. In PLWH who experience diarrhea, stool PCR testing results vary by CD4 count and hospitalization. Providers should be mindful of these factors when interpreting stool PCR test results.

Risk factors and clinical outcomes associated with multiple as opposed to single pathogens detected on the gastrointestinal disease polymerase chain reaction assay

“…24 In a study of GI PCR testing in patients with HIV, Axelrad et al found that 25% of men who have sex with men patients had multiple gut pathogens regardless of their degree of immunosuppression. 11,25 Our study was not powered to look at specific categories of immunosuppression and it is likely that there was heterogeneity in the degree of immunosuppression within the diverse group of immunosuppressed patients included in the study.…”

“…In individuals with weakened immune systems, such as those with HIV/AIDS or undergoing cancer treatment or organ transplantation, the body's normal defense mechanisms against colonization by gut pathogens are compromised. [6][7][8][9][10][11] Similarly, patients with comorbidities that disrupt the gut microbiome, such as cancer, diabetes, heart failure, chronic kidney disease, or inflammatory bowel disease (IBD), are more prone to enteric infections. 9,[12][13][14][15][16][17][18] We further hypothesized that the presence of multiple pathogens would be associated with measurably-worse clinical outcomes even after adjusting for other factors-i.e., that these patients would have true co-infection which would lead to increased healthcare utilization compared to singly-infected patients.…”