These findings suggest a pathogenic role for HIV replication in the development of HIVICK and that ART may improve kidney function in patients who have detectable HIV RNA at the time of HIVICK diagnosis. Our data also suggest that IgA nephropathy should be viewed as a separate entity and not included in the HIVICK spectrum.

Current levels of immunodeficiency and renal function were independent predictors of HIV-associated ARF.

No abstract

To explore the heterogeneity of CD4 responses following highly active antiretroviral therapy, the patterns of CD4 recovery of HIV-1-infected Chinese patients who have been on their first antiretroviral regimen for ≥5 years were analysed. The CD4 trajectories were traced, smoothed and differentiated into three defined profiles. Half (56.3%) were 'satisfactory responders', with CD4 gain of >100 cells/μL and a peak of >350 cells/μL, plateauing before the end of Year 5. Thirty-three (24.4%) were 'continuing responders' whose CD4 rise persisted at Year 4-5. The remaining 26 (19.3%) were 'poor responders'. Presentation with AIDS before therapy was common not just among 'poor' but also paradoxically the 'continuing' responders. While a majority had responded well to antiretroviral therapy, older patients and those with AIDS diagnosis before initiation of therapy may never achieve a satisfactory level even with effective treatment. Categorization of HIV patients by their CD4 trajectory may support the prediction of immunological outcome over time, and ultimately inform treatment choices.

BackgroundThe understanding of early events following TB exposure is limited by traditional tests that rely on detection of an immune response to infection, which is delayed, or on imaging tests with low sensitivity for early disease. We investigated for evidence of lung abnormalities in heavily exposed TB contacts using PET/MRI.Methods30 household contacts of 20 index patients underwent clinical assessment, IGRA testing, chest x-ray and PET/MRI scan using 18-F-FDG. MRI images were examined by a radiology/nuclear medicine dual-qualified physician using a standardised report form, while PET/MRI images were examined independently by another radiology/nuclear medicine dual-qualified physician using a similar form. Standardised uptake value (SUV) was quantified for each abnormal lesion.ResultsIGRA was positive in 40%. PET/MRI scan was abnormal in 30%, predominantly FDG uptake in hilar or mediastinal lymph nodes and lung apices. We did not identify any relationship between PET/MRI findings and degree of exposure or IGRA status.ConclusionPET-based imaging may provide important insights into the natural history following exposure to TB that may not be available from traditional tests of TB immune response or imaging. The clinical significance of the abnormalities is uncertain and merits further investigation in longitudinal studies.

We compared the somatostatin analog radioligand, DOTANOC, with FDG, to determine whether there was increased detection of active or sub-clinical lesions in pulmonary tuberculosis (TB) with DOTANOC. Three groups were recruited: (1) active pulmonary TB; (2) IGRA-positive household TB contacts; (3) pneumonia (non-TB). DOTANOC PET/MRI followed by FDG PET/MRI was performed in active TB and pneumonia groups. TB contacts underwent FDG PET/MRI, then DOTANOC PET/MRI if abnormalities were detected. Quantitative and qualitative analyses were performed for total lung and individual lesions. Eight active TB participants, three TB contacts and three pneumonia patients had paired PET/MRI scans. In the active TB group, median SUVmax [FDG] for parenchymal lesions was 7.69 (range 3.00-15.88); median SUVmax [DOTANOC] was 2.59 (1.48-6.40). Regions of tracer uptake were fairly similar for both radioligands, albeit more diffusely distributed in the FDG scans. In TB contacts, two PET/MRIs had parenchymal lesions detected with FDG (SUVmax 5.50 and 1.82), with corresponding DOTANOC uptake < 1. FDG and DOTANOC uptake was similar in pneumonia patients (SUVmax [FDG] 4.17-6.18; SUVmax [DOTANOC] 2.92-4.78). DOTANOC can detect pulmonary TB lesions, but FDG is more sensitive for both active and sub-clinical lesions. FDG remains the preferred ligand for clinical studies, although DOTANOC may provide additional value for pathogenesis studies. Tuberculosis (TB) disease affects 10 million people worldwide every year, and is the leading cause of death from an infectious disease 1. New TB biomarkers are required for a variety of applications, including detection of subclinical disease for early intervention to prevent disease progression; detection of new active TB cases; and for monitoring of treatment response in clinical practice or in clinical trials of new TB therapies. Positron emission tomography (PET) imaging in combination with structural imaging may have value as a biomarker for detecting subclinical TB disease, active disease where the diagnosis is problematical, and an outcome measure in clinical trials 2-7. The standard PET ligand, [18F]fluoro-2-deoxy-2-d-glucose (FDG), accumulates in cells with high levels of glucose metabolism, and is a non-specific marker of inflammation. There may be additional value in using alternatives to FDG, if these have higher sensitivity or specificity for TB-infected cells 8. Somatostatin analog PET radiotracers are useful in evaluating neuro-endocrine tumours 9-11 and other cancers' cells 12-15 that have upregulated cell surface somatostatin receptors (SSTRs). These receptors are also overexpressed on activated macrophages 16,17 , which are a key cell population infected by TB, residing within granulomas 18,19. Over-expression of somatostatin receptors in granulomas within lymph nodes of TB patients have been visualised using in vitro autoradiography 20 , and SSTR-positive cells have been detected using immunohistochemistry analysis in granulomas from multiple granulomatous conditions 21,22 including pulmon...

COX-2 inhibition may be of benefit in the treatment of tuberculosis (TB) through a number of pathways including efflux pump inhibition (increasing intracellular TB drug levels) and diverse effects on inflammation and the immune response. We investigated celecoxib (a COX-2 inhibitor) alone and with standard anti-tuberculosis drugs in the whole-blood bactericidal activity (WBA) model. Healthy volunteers took a single dose of celecoxib (400 mg), followed (after 1 week) by a single dose of either rifampicin (10 mg/kg) or pyrazinamide (25 mg/kg), followed (after 2 or 7 days respectively) by the same anti-tuberculosis drug with celecoxib. WBA was measured at intervals until 8 hours post-dose (by inoculating blood samples with Mycobacterium tuberculosis and estimating the change in bacterial colony forming units after 72 hours incubation). Celecoxib had no activity alone in the WBA assay (cumulative WBA over 8 hours post-dose: 0.03 ± 0.01ΔlogCFU, p = 1.00 versus zero). Celecoxib did not increase cumulative WBA of standard TB drugs (mean cumulative WBA −0.10 ± 0.13ΔlogCFU versus −0.10 ± 0.12ΔlogCFU for TB drugs alone versus TB drugs and celecoxib; mean difference −0.01, 95% CI −0.02 to 0.00; p = 0.16). The lack of benefit of celecoxib suggests that efflux pump inhibition or eicosanoid pathway-related responses are of limited importance in mycobacterial killing in the WBA assay.

Faropenem is not active when used alone, possibly due to inadequate plasma levels relative to MIC. However, there was a suggestion of modest synergy with rifampicin that may merit further testing in clinical trials.