Pulmonary Colonization with Pneumocystis cariniiin Human Immunodeficiency Virus-Negative Patients: Assessing Risk with Blood CD4+ T Cell Counts

Pulmonary colonization with Pneumocystis carinii has traditionally been considered a phenomenon restricted to patients with advanced HIV infection. However, the availability of highly sensitive molecular techniques has revealed its occurrence in HIV-negative individuals, raising questions regarding its clinical relevance and underlying immunological determinants. In a prospective observational study, we investigated 82 consecutive HIV-seronegative adults who underwent bronchoalveolar lavage (BAL) for diagnostic evaluation. BAL specimens were systematically analyzed by cytological methods, immunofluorescence, and heminested PCR targeting the mitochondrial large-subunit rRNA gene of P. carinii. Peripheral CD4+ and CD8+ T-cell counts were retrieved retrospectively. Patients were monitored for up to 12 months to document the occurrence of P. carinii pneumonia (PCP). PCR assays identified P. carinii DNA in 13 of 82 patients (14%) despite negative microscopic findings and absence of PCP at enrollment. Colonization was associated with diverse underlying conditions including hematological malignancies, sarcoidosis, renal transplantation, and chronic corticosteroid therapy. Follow-up demonstrated that, in the absence of prophylaxis, colonized individuals did not progress to PCP, supporting the interpretation of subclinical colonization. Among 48 patients with available lymphocyte data, five harbored P. carinii. Colonization was significantly correlated with CD4+ T-cell counts  × 10^6/L (33.3% vs. 2.8%; RR = 12.0; 95% CI, 1.5–97.2; P = 0.01) and with CD4/CD8 ratios <1 (30.7% vs. 2.8%; RR = 10.8; 95% CI, 1.3–87.7; P = 0.015). The highest risk was observed in patients with both parameters altered, 57.1% of whom were colonized, compared with only 2.4% of those with preserved immunological profiles (RR = 23.4; 95% CI, 3.1–180.1; P < 0.001). These findings demonstrate that pulmonary colonization with P. carinii is not uncommon among HIV-negative individuals with systemic disease and impaired cellular immunity. Quantitative CD4+ T-cell counts and CD4/CD8 ratios emerge as reliable markers for stratifying colonization risk, thereby refining our understanding of the immunological thresholds that permit P. carinii persistence outside the classical HIV-associated context.