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The ImmuKnow ICFA reports ex vivo CD4 lymphocyte activation to quantify immunosuppression. Limited organ and age-specific data exist for pediatric heart transplant recipients. We sought to examine their normative values and ICFA's association with rejection/infection. A total of 380 ICFAs from 58 heart transplant recipients (6.5/recipient) were studied retrospectively. The median age at the time of their first ICFA was 5.3 yr (IQR 2.4-12.1 yr). ICFA levels during immunologic stability (n = 311) were a median of 305 (IQR: 172-483) and mean of 353 (s.d. ± 224) ng ATP/mL. ICFA levels trended lower with advancing age. ICFA levels during immunologic stability increased over time from transplant after the first six months but were not correlated with calcineurin inhibitor levels or the type used. There is no association between ICFA values during stability and rejection (median 368 ATP ng/mL; IQR 153-527) or infection (median 293 ATP ng/mL; IQR 198-432). In contrast to the manufacturer's suggested ranges, the immunologic stable ranges in pediatric cardiac recipients were very different. ICFA values during immunologic stability are related to time from transplant in pediatric heart recipients. ICFA's ability to discriminate rejection or infection from immunologic stability was not demonstrated.

Background The global HIV/AIDS pandemic and guidelines for initiating anti-retroviral therapy (ART) and opportunistic infection prophylaxis demand affordable, reliable, and accurate CD4 testing. A simple innovative approach applicable to existing technology that has been successfully applied in resource-challenged settings, PanLeukogated CD4 (PLG), could offer solutions for cost saving and improved precision. Methods Day-old whole blood from 99 HIV+ donors was simultaneously studied in five North-American laboratories to compare the performance of their predicate methods with the dual-platform PLG method. The predicate technology included varying 4-color CD45/CD3/CD4/CD8 protocols on different flow cytometers. Each laboratory also assayed eight replicate specimens of day-old blood from 10 to 14 local donors. Bias and precision of predicate and PLG methods was studied between- and within-participating laboratories. Results Significantly (P < 0.0001) improved between-laboratory precision/coefficient of variation (CV%) was noted using the PLG method (overall median 9.3% vs. predicate median CV 13.1%). Within-laboratory precision was also significantly (P < 0.0001) better overall using PLG (median 4.6% vs. predicate median CV 6.2%) and in 3 of the 5 laboratories. PLG counts tended to be 11% smaller than predicate methods (P < 0.0001) for shipped (median of predicate—PLG = 31) and local specimens (median of predicate—PLG = 23), both overall and in 4 of 5 laboratories (median decreases of 4, 16, 20, and 21% in shipped specimens); the other laboratory had a median increase of 5%. Conclusion Laboratories using predicate CD4 methods similar to those in this study could improve their between-laboratory and their within-laboratory precision, and reduce costs, by switching to the PLG method after adequate training, if a change (usually, a decrease) in CD4 counts is acceptable to their health systems. © 2008 Clinical Cytometry Society

Controversial data regarding the association between immunosuppression and prevalence/ severity of periodontal diseases in HIV infection have been reported. Thus, the aim of this study was to test the hypothesis that lower T CD4 lymphocyte levels are not related to a higher prevalence of chronic periodontitis in HIV-infected Brazilians undergoing highly active anti-retroviral therapy (HAART).Sixty-four HIV-infected patients under HAART were classified as having chronic periodontitis; i.e.,or = three sites with probing depth (PD) and/or clinical attachment level (CAL)or = 5 mm or periodontal healthy (no sites with PD3 mm and/or CAL4 mm). All subjects received conventional periodontal therapy. Bleeding on probing, plaque accumulation, PD, and CAL were registered at six sites/tooth at baseline and 4 months after therapy. Epidemiological features and levels of T CD4 lymphocytes were obtained from medical records. Significance of differences in periodontal clinical parameters within and between groups were determined using Wilcoxon signed-rank and Mann-Whitney or independent sample t tests. Associations between T CD4 levels and clinical parameters were determined using the chi square test.Sixty-one percent of the HIV-infected patients represented AIDS cases, although 69% of them were periodontally healthy. The overall T CD4 lymphocyte mean levels was 333 +/- 254 cells/mm3 and viral load was 12,815 +/- 24,607 copies/mm3. Yet the prevalence of chronic periodontitis was relatively low (36%). In addition, patients with periodontitis presented a moderate disease (mean PD = 2.2 +/- 0.10; mean CAL = 2.6 +/- 0.13) and responded successfully to periodontal therapy. These subjects showed higher levels of T CD4 cells, but lower counts of neutrophils than periodontally healthy patients. Among periodontally healthy and chronic periodontitis patients, 41.7% and 22.9%, respectively, had low levels of T CD4 lymphocytes. No significant differences between periodontal status and epidemiological and immunological parameters were observed.Based on these results, the hypothesis that lower T CD4 lymphocyte levels are not associated with higher prevalence of chronic periodontitis in HIV-infected Brazilians under HAART cannot be rejected.

Objectives To describe the prevalence and risk factors of poor CD4 count rise despite a good virological response on highly active antiretroviral treatment (HAART). Methods The patients from the EuroSIDA study who started HAART with a baseline CD4 count of

Peripheral CD4 T-cell depletion has been observed in human immunodeficiency virus (HIV)-negative patients with pulmonary tuberculosis (TB). To investigate more accurately this alteration, we studied peripheral blood CD45RA+ and CD29high CD4 subsets in 79 TB patients with (HIV+TB+) or without (HIV−TB+) HIV infection, 85 HIV-infected patients without TB (HIV+TB−), and 43 healthy controls, all living in West Africa. The high proportion of CD4+CD29high T cells observed in controls was dramatically decreased in CDC-A stage HIV+TB− patients. CD45RA+ CD4+ T cells were depleted during the CDC-B stage. Both the percentage and the absolute count of CD29highCD4+ T cells were decreased in HIV−TB+ and HIV+TB+ patients versus controls, but CD45RA+CD4+ T cells were not decreased in TB patients without HIV-infection. Although distinct alterations in the CD4+ T-cell homeostasis are involved in TB- versus HIV-infected subjects, our data suggest that the CD29+CD4+ T-cell depletion observed during the early HIV disease contributes to the risk of active TB, by reducing the pool of T cells able to relocalize to the sites of the M. tuberculosis multiplication.

The effects of cessation of i.v. drug use on CD4 lymphocyte count and serum levels of beta2 -microglobulin (beta2 m) and soluble interleukin-2 receptor (sIL-2R) were prospectively investigated in 41 HIV-positive drug users enrolled in a methadone treatment programme. Fifteen HIV-positive matched non-abstainers served as controls. During the follow-up of 12 months the mean CD4 lymphocyte count remained unchanged in the methadone-treated group but fell significantly in controls. beta2 m and sIL-2R values decreased in abstainers at the beginning of the treatment but rose in non-abstaining group. We conclude that cessation of illicit drug abuse and methadone treatment in HIV-infected injecting drug users may exert a beneficial effect on the immune status.

Zusammenfassung. Aus der Sicht 40jahriger Erfahrung auf dem Gebiet der medizinischen Mykologie wird anhand folgender aktueller Themen zur Zustandigkeit des medizinischen Mykologen bei der Beurteilung von Pilzen im Wohn- und Krankenhausmilieu Stellung genommen: 1. Der HIV-Infizierte und das Cr.-neoformans-Biotop; die Disposition fur die Cryptococcose in Abhangigkeit von der CD4-Lymphozytenzahl. 2. Invasive Aspergillose nach Herztransplantation; durch enge Zusammenarbeit von Herzchirurg und medizinischem Mykologen wurde gezeigt, das die gefurchtete invasive Aspergillose nach Herztransplantation verhindert werden kann. 3. Bioabfall und Kompost als derzeit aktuelle Pilzbiotope im Wohnbereich. Auf das mogliche Vorkommen der verschiedenen Pilze in Bioabfall, darunter auch Erreger von Systemmykosen, wird aufmerksam gemacht. Summary. From the viewpoint of 40 years of experience in the field of medical mycology with the help of current topics the competence of the medical mycologist for evaluation of a presence of fungi in the home and hospital environment is commented. The topics considered are as follows: 1. The HIV-infected person and the habitat of Cr. neoformans; the predisposition for cryptococcosis and the CD4 lymphocyte count. 2. Invasive aspergillosis after heart transplantation; by exemplary cooperation between the heart surgeon and the medical mycologist it could be demonstrated that the frequently fatal invasive aspergillosis can be avoided. 3. Attention is drawn to the currently most interesting habitats of fungi in the home environment, i.e., biological waste and compost. It has been shown that among the various fungi, the causative agents of systemic mycoses may also be found.

The Ortho CytoronAbsolute is a flow cytometer designed to provide direct absolute counts of lymphocytes and their subsets from a single instrument. This study was designed to determine the performance of four geographically separated CytoronAbsolute instruments using 24-h-old, shipped, whole blood samples and to compare the results obtained on the CytoronAbsolute to those obtained using combinations of hematology instruments and other flow cytometers. The absolute count feature of the CytoronAbsolutes located at the four sites were cross calibrated and gave across-site coefficients of variation (CVs) of4.0% for absolute count and 8.2% for absolute lymphocyte count. The calibration was stable for at least 2 months. Absolute lymphocyte counts and lymphocyte percentage immunophenotypes were determined on blood from 50 healthy human immunodeficiency virus (HIV)-seronegative donors. There were no significant site-to-site differences (each P.05) in CD3+/CD4+ absolute lymphocyte counts determined on the CytoronAbsolute. In contrast, there was a significant site-to-site difference (P.001) between sites 2 and 3 and sites 3 and 4 in the absolute CD3+/CD4+ lymphocyte counts determined via the conventional method of combining a flow cytometry-derived percentage with a hematology instrument-derived lymphocyte count. There was no significant difference (P = .388) in CD3+/CD4+ lymphocyte percent determinations between the CytoronAbsolute and the FACScan or Profile II flow cytometers used in this study. These results demonstrate that different operators can cross calibrate CytoronAbsolutes for absolute CD3+/CD4+ lymphocyte subset determinations, even over large geographic distances.

Summary Forty-seven HIV-infected haemophilic patients were entered into a hepatitis A vaccination programme. 10 patients (21%) were lgG seropositive for hepatitis A consistent with past exposure. Of the 37 patients offered vaccination, one refused and 31 completed the vaccination course, 17/13 (55%) seroconverted, nine after the second and eight after the third injection, and 14 patients failed to seroconvert. The CD4 lymphocyte counts immediately prior to vaccination were significantly higher in the patients who developed immunity compared to the nonresponders (median CD4 count in the immune group 380 × 106/1 (range 170–1290), median CD4 count in nonimmune group 110 × 106/1 (range 10–590), P== 0.003). No patient with a CD4 count < 170 × 106/1 seroconverted and five patients with well-preserved CD4 counts also failed to seroconvert. We conclude that HIV-infected haemophilic patients, especially those with more advanced disease, have an impaired response to hepatitis A vaccination. Due to the likely failure of response in patients with CD4 counts < 150 × 106/1, it is reasonable not to include these patients in a hepatitis A vaccination programme.

Summary Twenty-six haemophilic patients with advanced HIV infection who had developed resistance or intolerance to zidovudine were treated with didanosine (ddI). 11 patients continue to take ddI at a median time of 14 months from commencement (range 7–18 months). Five of these patients showed an increase in CD4 lymphocyte count, reaching a maximum at a median time of 4 months. Four patients with HIV-related symptoms improved clinically. In general, the CD4 count and clinical improvements were not sustained. 11 patients discontinued ddI after a median of 3 months (range 3 days to 10 months), most commonly due to gastrointestinal side-effects. No case of pancreatitis or peripheral neuropathy was seen. Six patients, all with very advanced HIV disease, died. HIV-infected haemophilic patients who become resistant or intolerant to zidovudine may derive benefit from ddI, although this is usually transient.

Autoimmune disorders such as vitiligo have been previously reported in patients with human immunodeficiency virus (HIV) infection. We describe a case of vitiligo in association with HIV where a rising CD4 lymphocyte count due to highly active antiretroviral therapy (HAART) closely correlated with changes in the skin. This effect, to our knowledge, has not been previously observed.

There is significant need for rapid yet reliable evaluation of promising new interventions for the treatment of patients with cancer or HIV infection. Considerable attention has been given to identifying replacement or 'surrogate' endpoints for the true clinical efficacy endpoints, in order to reduce the cost, size and duration of clinical trials. We discuss issues which affect the validity of surrogate markers. The reliability of the CD4 lymphocyte count marker is carefully considered in clinical trials of anti-retroviral agents in HIV infected individuals. The nature of surrogate markers and their reliability is discussed in cancer prevention, screening and treatment trials. Some suggested uses of marker information are also considered.