Lidia Gazzola

Spoligotyping and Mycobacterium tuberculosis

Speed of spoligotyping could be a benefit in the clinical setting.

Association between peripheral T-Lymphocyte activation and impaired bone mineral density in HIV-infected patients

BackgroundHIV-infected patients display an increased and early incidence of osteopenia/osteoporosis. We investigated whether bone metabolism disorders in HIV-infected patients are related to immune hyperactivation and premature immune senescence.MethodsBone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA): low BMD (LBMD) was defined as T-score or z-score < -1. CD4+/CD8+ phenotype (CD38/HLA-DR, CD127, CD28/CD57), and circulating IL-7, TNF-α, RANKL, OPG were measured. The variables with p < .05 were evaluated by multivariate logistic regression.Results78 patients were enrolled: 55 were LBMD. LBMD patients showed increased activated HDLADR + CD4+ and CD8+ (p = .03 and p = .002, respectively). Interestingly, no differences in senescent CD28-CD57 + CD4+/CD8+ T-cells were observed between groups. However, LBMD patients displayed a decreased CD4 + CD28- phenotype (p = .04) at the advantage of the CD28+ pool (p = .03), possibly reflecting heightened apoptosis of highly differentiated CD28-negative cells.Activated HLADR + CD4+/CD8+ and CD28 + CD4+ cells were independently associated with impaired BMD (AOR = 1.08 for each additional HLADR + CD4+ percentage higher; CI 95%,1.01-1.15; p = .02; AOR = 1.07 for each additional HLADR + CD8+ percentage higher; CI 95%,1.01-1.11; p = .01; AOR = 1.06 for each additional CD28 + CD4+ percentage higher; CI 95%,1.0-1.13; p = .05).ConclusionsHeightened T-cell activation in HIV-infected patients independently predicts BMD disorders, suggesting a critical role of immune activation in the pathogenesis of osteopenia/osteoporosis, even in patients achieving full viral suppression with HAART.

MYCOBACTERIUM LENTIFLAVUM INFECTION IN IMMUNOCOMPETENT PATIENT

Mycobacterium lentiflavum is a recently described nontuberculous mycobacterium that has mainly clinical importance in young children with cervical lymphadenitis and in immunocompromised patients. We describe a case of chronic pulmonary infection in an immunocompetent patient. Our observation confirms clinical, diagnostic, and treatment difficulties in the management of M. lentiflavum infection.

Skewed T-cell maturation and function in HIV-infected patients failing CD4+ recovery upon long-term virologically suppressive HAART.

Objective:Analysis of functionally defined T-cell differentiation in HIV-infected patients with low CD4+ on virologically suppressive HAART is crucial to design clinically efficacious treatments. Methods:We cross-sectionally investigated the maturation (CD45RA/CCR7, CD7) and function [antigen-specific enzyme-linked immunosorbent spot assay (ELISPOT), interleukin-2 (IL-2)/interferon-γ-producing cells] of CD4+ and CD8+ T cells in 34 HIV-infected immunological nonresponders (INRs): CD4+ cell count less than or equal to 200 cells/μl, HIV-RNA 50 copies/ml or less, as compared to 20 full responders (CD4+ > 500 cells/μl, HIV-RNA < 50 copies/ml). Results:We describe skewed T-cell maturation in INRs with outgrowth of effector memory CD45RA−CCR7− CD4+/CD8+ and Th2-committed CD7−CD4+, and reduced unprimed-naive T cells (P = 0.001). Functionally, INRs display reduced Gag-specific ELISPOT (P = 0.04) and IL-2-secreting CD8+ (P = 0.08) while showing CMV-specific responses comparable to full responders. Conclusion:CD4 lymphopenia on HAART results in skewed, senescent T-cell maturation profile, inefficient T-helper function and poor HIV-specific CD8+ response. This delineates a functional/phenotypic T-cell pattern that correlates to unfavourable clinical outcome.

Assessment of radiological vertebral fractures in HIV‐infected patients: clinical implications and predictive factors

The aim of this study was to evaluate the clinical impact of including lateral spine X‐ray in the screening of bone diseases in HIV‐positive patients.

Rhodococcus equi infection in a patient with spinocellular carcinoma of unknown origin

A Rhodococcus equi pulmonary infection in a 63-year-old man receiving chemotherapy and radiotherapy for spinocellular carcinoma is described. The patient, a knife-grinder, was promptly treated with levofloxacin plus amikacin followed by rifampicin for 2 months, and he is still in good clinical condition after an 8-month follow-up.

Efficacy and Safety of Darunavir/Ritonavir Plus Etravirine Dual Regimen in Antiretroviral Therapy–Experienced Patients: A Multicenter Clinical Experience

Abstract Objectives: To assess the outcome of a dual regimen combining darunavir/ritonavir plus etravirine in a cohort of antiretroviral therapy (ART)–experienced patients. Methods: A retrospective analysis was performed on all ART-experienced patients starting a darunavir/ritonavir plus etravirine regimen at the 3 clinics. Patients were stratified according to HIV RNA detectability (≥40 copies/mL) at baseline. Two efficacy endpoints were evaluated by Kaplan-Meier and Cox multivariable models: virological failure (confirmed HIV RNA ≥40 copies/mL after 6 months) and therapeutic failure (including virological failure and treatment discontinuation for any reason). Results: Sixty-eight patients were included in the study. They had a median of 10.8 years on ART and 5 previous ART regimens; 61.3% showed primary protease inhibitor (PI) mutations and 70% showed previous non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure. HIV RNA was detectable in 34 (50%) patients. The median observation period was 21 (interquartile range [IQR], 11.9–25.1) months. After 24 months, 75.1% of the patients were still on the study regimen and 88.8% remained free from virological failure. Although a higher therapeutic failure rate was reported in patients with detectable viremia at baseline, only the immunological status revealed an independent predictive role. No differences in virological failure were observed according to HIV RNA detectability at baseline; a higher number of previous ART regimens was the only predictor. Discontinuation due to adverse events occurred in 5.9%. Conclusions: Darunavir/ritonavir plus etravirine regimen proved virological efficacy and safety in heavily pretreated patients with a high rate of virological success, even in patients who switched during virological failure.

The usefulness of PCR assay in diagnosing disseminated mycobacterial infection in AIDS patients

Disseminated mycobacterial infections (DMI), caused by Mycobacterium tuberculosis (MTB) and M. avium (MAC), are common complications of late-stage human immunodeficiency virus (HIV) infection [1]. Although the use of highly active antiretroviral therapy (HAART) has substantially reduced DMI incidence [2], disease diagnosis still remains a critical problem for physicians. Both pathologies have non-specific clinical features, unhelpful in the differential diagnosis [3, 4], and microbiological isolation and identification are characterised by long turnaround time and uncertain sensitivity that often oblige clinicians to commence anti-mycobacterial therapy based solely upon clinical suspect. In light of these premises, we evaluated whether the introduction of a molecular method for mycobacterial DNA detection may represent a suitable approach for diagnosis. After optimizing a polymerase chain reaction (PCR) hybridization technique, based on the amplification of a 16rRNA gene sequence using pan-Mycobacterium primers and on the hybridization to two probes, designed to differentiate between M. tuberculosis and M. avium [5], we estimated its reliability and usefulness on blood specimens and/or bone marrow (BM) aspirates. Between March 1999 and April 2004, all of the episodes of suspected DMI investigated with PCR assay performed on blood specimen [6] and a corresponding blood culture (radiometric Bectec AFB system) [7], and/or with a PCR performed on BM aspirate [6] and a corresponding BM analysis (i.e. histopathologic, microscopic and culture exam) [7] were included in the study. Clinical charts were reviewed to assess the diagnosis of disseminated MTB and MAC disease. We drew up two clinical diagnostic criteria: (1) suggestive signs and symptoms of DMI (fever, drenching night sweats, anaemia and weight loss) [3], in addition to blood or BM culture confirmation; (2) suggestive signs and symptoms of DMI in addition to at least two other minor signs or symptoms (diarrhoea, abdominal pain, lymphadenopathy, hepatomegaly, splenomegaly) and/or histopathologic patterns suggestive for mycobacterial infection in patients responding positively to anti-TB or anti-MAC therapy, whose clinical findings excluded other diseases. Patients without exhaustive data to confirm or rule out a DMI were excluded. Data were classified in two-by-two contingency tables to evaluate sensitivity, specificity, negative predictive value and positive predictive value of culture and PCR assay performed on different samples, compared to clinical diagnosis. PCR assay was successfully performed on 117 samples from 95 patients, 71 blood specimens and 46 BM aspirates. Among these, there were 11 paired BM–blood specimens collected from 11 patients available for complete analysis. Eur J Clin Microbiol Infect Dis (2008) 27:163–166 DOI 10.1007/s10096-007-0407-0

Association between abdominal aortic calcifications, bone mineral density and vertebral fractures in a cohort of HIV-positive patients.

Evidence from HIV‐negative cohorts suggests a link between osteoporosis and cardiovascular disease. We evaluated the presence and distribution of abdominal aortic calcifications (AAC) and its correlation with bone mineral density (BMD) and vertebral fractures (VF) in a cohort of HIV‐positive patients.

Affronto multidisciplinare delle co-morbiditità HIV-correlate: esperienza e casistica di un centro italiano@@@Muldisciplinary approach to HIV-related co-morbidities: clinical experience of an Italian centre

Riassunto Una nuova sfida per i clinici è rappresentata dalla gestione della popolazione HIV positiva che invecchia e che spesso è colpita da severe comorbidità che possono compromettere la tollerabilità ai regime antiretrovirali. In questa popolazione speciale, è indispensabile ottimizzare al meglio la terapia antiretrovirale per non peggiorare le condizioni cliniche sottostanti e raggiungere sia tolleranza che efficacia viro-immunologica. Riportiamo la nostra esperienza nella gestione delle comorbidità dei pazienti con infezione da HIV. Presso il nostro centro, da Febbraio 2010 ad Agosto 2015, 597 pazienti HIV positivi sono stati valutati per comorbidità metaboliche (studio cardiovascolare, osseo e renale), con lo scopo di ottimizzare la HAART e ridurre le tossicità farmaco correlate. articolo originale