Nada Fadul

Treatment-Naïve HIV-Infected Patients Have Fewer Gut-Homing β7 Memory CD4 T Cells than Healthy Controls

Objectives The integrin &agr;4&bgr;7 is the gut-homing receptor for lymphocytes. It also is an important co-receptor for human immunodeficiency virus (HIV) via glycoprotein (gp)120 binding. Depletion of gut cluster of differentiation (CD)4 T cells is linked to chronic inflammation in patients with HIV; however, measuring CD4 cells in the gut is invasive and not routine. As such, establishing a peripheral marker for CD4 depletion of the gut is needed. We hypothesized that &agr;4&bgr;7 CD4 T cells are depleted in the peripheral blood of treatment-naïve patients with HIV compared with healthy controls. Methods The study groups were treatment-naïve patients with HIV and uninfected controls. Subjects were included if they were 18 years or older with no history of opportunistic infections, active tuberculosis, or cancer. We collected peripheral blood and examined on whole blood using flow cytometry for the following cell surface markers: CD4, CD45RO, chemokine receptor type 5, C-X-C chemokine receptor type 4 (CXCR4), and the integrin &bgr;7. We collected demographic information, including age, sex, and ethnicity, as well as viral load (VL) and CD4 count. Two-sample t tests and Fisher exact tests were used to compare the differences between the two groups. Spearman correlation coefficients were calculated between CD4 count and log10− VL and percentage of CD4+/CD45RO+/&bgr;7+ and log10− VL in patients. Results Twenty-two subjects were enrolled in the study (12 patients with HIV and 10 controls). There were no differences in age or sex between the two groups. There were more Hispanics and fewer Asians in the group comprising patients with HIV compared with the control group (7 vs 2 and 0 vs 4, P = 0.05, respectively). Patients infected with HIV had significantly lower frequencies of CD4+/CD45RO+/&bgr;7+ cells (median 12%, range 5–18 compared with uninfected controls: median 20%, range 11–26, P = 0.0007). There was a statistically significant difference in the percentage of CD4+/CD45RO+/C-X-C chemokine receptor type 4+ cells between patients (72%, range 60%–91%) compared with controls (79%, range 72%–94%, P = 0.04). The percentage of CD4+/CD45RO+/chemokine receptor type 5+ did not differ between the group of patients with HIV and the control groups (22%, range 11%–57% vs 27%, range 14%–31%; P = 0.8, respectively). There was no correlation between percentage of CD4+/CD45RO+/&bgr;+ cells and log10− VL as measured by the Spearman correlation coefficient (r = 0.05, P = 0.88) in patients infected with HIV. Conclusions Memory CD4 &bgr;7+ cells are reduced significantly in the peripheral blood of untreated patients infected with HIV, which could be used as a noninvasive indicator of intestinal CD4 T cell loss and recovery. Further studies are needed to examine whether depletion of these CD4+/CD45RO+/&bgr;7+ cells in the peripheral blood parallels depletion in the gut of treatment-naïve patients with HIV and whether levels return to control levels after treatment.

Characteristics and Outcomes of Patients with Pneumocystis jirovecii Pneumonia Who were Initiated on Antiretroviral Therapy While Hospitalized: A Preliminary Study.

Abstract Background Pneumocystis jirovecii pneumonia (PJP) is the most frequent and severe respiratory infection in patients with acquired immunodeficiency syndrome (AIDS) with associated 20% mortality. There have been conflicting data regarding the optimal time to initiate antiretroviral therapy (ART) in these patients with most data suggesting benefit for early initiation. The objectives of this study were to compare patients with PJP and AIDS who were initiated on ART while hospitalized compared with those who were not; and to evaluate the association between inpatient initiation of ART and survival. Methods We conducted a retrospective chart review of patients 18 years or older with PJP and AIDS who were not on ART prior to admission. We collected demographic, laboratory and clinical information. SPSS was used to compare the two groups: those who initiated ART while inpatient (ART) vs.. those who did not (NoART) Results Of the 64 patients included in this study, 25 [39%] were in the ART group, 19 [27%] required intensive care unit (ICU), and 16 [25%] required mechanical ventilation (MV). There were no differences in age, gender, race/ethnicity, and smoking between the ART and NoART groups. A higher percentage of patients in the ART group received corticosteroids (96% vs. 72%; P = 0.020), required MV (48% vs.10%; P = 0.001), and ICU admission (60% vs. 10%; P = 0.000) than in the NoART group respectively. There were no differences in the ART and NoART groups in regards to ICU stay (4 vs. 0.5 days; P = 1.000) and APACHE II scores (15.2 vs. 10.7; P = 0.17). A total of 9 (14%) patients died while in the hospital 6 (24%) in ART vs.. 3 (8%) in NoART (P = 0.137). Conclusion Patients with PJP pneumonia who were initiated on ART while inpatient were more likely to require ICU admission, corticosteroids, and mechanical ventilation. There were no differences in APACHE II scores, CD4 count and mortality between those who initiated ART while inpatients vs. those who did not. Further studies with larger sample size are needed to evaluate the association between inpatient initiation of ART and survival. Disclosures All authors: No reported disclosures.