Trend of estimated glomerular flitration rate in a large cohort of HIV mother-to -child infected patients, an observational multicenter study from 2010 to 2018

Background: People vertically infected with HIV (PVI-HIV) are a special population, due to exposition since birth to HIV and antiretroviral therapy (ART). Among ART, Tenofovir disoproxil fumarate (TDF) was widely used in recent years, but there are few data on safety in these patients; in particular, data about estimated glomerular filtration rate (eGFR) trend in this population. Aim of our study is to evaluate eGFR trend in a multicentre cohort of PVI-HIV exposed to TDF

Variazioni del filtrato glomerulare (eGFR) in una coorte di pazienti nati con HIV, risultati di uno studio osservazionale dal 2009 al 2018

Introduzione e scopo dello studio I pazienti nati con infezione da HIV rappresentano una popolazione speciale a causa dell\u2019esposizione fin dalla nascita ad HIV e alla terapia antiretrovirale di combinazione (cART). Molti pazienti hanno assunto tenofovir disoproxil fumarato (TDF) per necessit\ue0 anche se i dati in questa coorte sono scarsi. Inoltre vi sono pochi dati in letteratura relativi all\u2019andamento dell\u2019eGFR in questa popolazione. Scopo del nostro studio \ue8 di valutare le variazioni dell\u2019eGFR nei pazienti con infezione da HIV materno-fetale in follow-up nella nostra coorte. Materiali e metodi Studio osservazionale retrospettivo monocentrico nel periodo 2010-2018. Il dato \ue8 stato associato alla cART in corso. Abbiamo arruolato i pazienti con diagnosi di HIV trasmessa alla nascita ed estratto i dati delle cART e degli esami ematici dal sistema informatico ReteligureHIV (www.reteligureHIV.it) per il periodo in analisi. Abbiamo raccolto i dati del peso corporeo e altezza dalle cartelle cliniche. Abbiamo calcolato l\u2019eGFR con la formula di Cockroft-Gault nei pazienti maggiorenni al 2018, con la revised Schwartz equation nei minorenni. Abbiamo stratificato il dato con la cART effettuata (TDF, TAF, inibitore proteasi (PI), analogo non nucleosidico (NNRTI), inibitore integrasi (INI)). Risultati La nostra coorte \ue8 composta da 39 pazienti, di questi ne abbiamo arruolati 34, 5 sono stati esclusi per mancanza di dati. Il tempo di osservazione medio \ue8 di 8,8 anni (range 7-9). Le femmine 18 (53%), et\ue0 media di 18 anni nel 2010 (range 6-28). 30 pazienti (88%) hanno effettuato cART contenente TDF per almeno 1 anno, 19 (55%) hanno associato TDF+PI per almeno 1 anno, 14 (41%) TDF+NNRTI, 12 (35%) TDF+INI. 4 pazienti (12%) non hanno mai assunto TDF. Abbiamo osservato una riduzione mediana dell\u2019eGFR di 1,83 mL/min/anno (16,5 mL/min in 9 anni di studio). La riduzione \ue8 maggiore nel gruppo di pazienti in terapia con TDF+INI (3,7 mL/min/anno), minore per i pazienti in terapia con TDF+NNRTI (2,2 mL/min/anno) e TDF+PI (1,44 mL/min/anno). Abbiamo inoltre osservato un miglioramento dell\u2019eGFR mediano totale di 5 mL/min tra il 2017 e il 2018, anno in cui 23 pazienti (68%) hanno iniziato terapia con TAF. Nel solo gruppo esposto a TDF+INI abbiamo osservato un peggioramento dell\u2019eGFR anche nel 2018 (-5 mL/min). Conclusioni Il nostro studio ha evidenziato un peggioramento progressivo dell\u2019eGFR, come atteso in una popolazione esposta al virus HIV e alla cART. Il miglioramento osservato nel 2018 \ue8 un dato interessante, alla luce dell\u2019arrivo del TAF. Il peggioramento del filtrato con INI potrebbe dipendere dall\u2019associazione con DTG. Il proseguimento del follow-up \ue8 necessario per valutare l\u2019andamento negli anni futuri

Reduced probability of improving viro-immunological state in subjects with vertical transmission of HIV reaching adult age: A multicenter retrospective cohort study

Introduction: Young adults with vertical transmission (VT) of human immunodeficiency virus (HIV) represent a fragile population. This study evaluates factors associated with viro-immunological outcome of these patients. Methods: We performed a multicenter study including HIV-infected subjects with VT ≥ 18 years old from six Italian clinics. Subjects were observed from birth to death, lost to follow-up, or last visit until December 31, 2019. Condition of "optimal viro-immunological status" (OS) was defined as the simultaneous presence of HIV ribonucleic acid (RNA) < 50 copies/mL, CD4+ > 500 cells/mm3 , and CD4+/CD8+ ratio ≥ 1. Results: A total of 126 subjects were enrolled. At 18 years of age, 52/126 (44.4%) had HIV-RNA > 50 copies/mL, 47/126 (38.2%) had CD4+ < 500/mm3 , and 78/126 (67.2%) had CD4+/CD8+ < 1; 28 subjects (23.7%) presented in the condition of OS. Having a CD4+/CD8+ ratio ≥ 1 at 18 years of age was related with an increased probability of shift from suboptimal viro-immunological status (SOS) to OS (HR: 7.7, 95% confidence interval [CI]: 4.23-14.04), and a reduced risk of shift from the OS to the SOS (HR: 0.49, 95% CI: 0.26-0.92). Acquired immunodeficiency syndrome (AIDS) diagnosis significantly reduced the probability of shift from a viro-immunological SOS to OS (HR: 0.09, 95% CI: 0.03-0.30). Subjects who had not achieved an OS at 18 years of age had an increased risk of discontinuation of combination antiretroviral therapy (cART, p = .019). Conclusions: Only a small proportion of subjects with VT of HIV reached the adult age with "OS". Transition to the adult care with a compromised viro-immunological condition represents a negative driver for future optimal infection control, with a higher risk of discontinuation of cART and a reduced probability to improve the immunological status later in the years

Trends in the annual incidence of carbapenem-resistant Klebsiella pneumoniae bloodstream infections: A 8-year retrospective study in a large teaching hospital in northern Italy

BACKGROUND: Bloodstream infections (BSI) due to carbapenem-resistant (C-R) Klebsiella pneumoniae (Kp) are of global concern from both clinical and public health standpoints. This retrospective study aimed to describe C-R Kp BSI epidemiology in a large teaching hospital in northern Italy. METHODS: Between 1 January 2007 and 31 December 2014, annual incidences both of C-R Kp BSI and of carbapenem-susceptible (C-S) Kp BSI were calculated as the number of events per 10,000 patient-days. A Chi square test for linear trend was used to assess the change in the incidence of C-R Kp BSI and C-S Kp BSI over the study period. Crude 30-day mortality rates were provided both for C-R Kp BSI and for C-S Kp BSI. RESULTS: From 2007 to 2014, we observed 511 episodes of Kp BSI, 349 of which were caused by C-R Kp (68.3 %). The incidence of C-R Kp BSI considerably increased from 0.04/10,000 patient-days in 2007 to 1.77/10,000 patient-days in 2014 (Chi square for trend p < 0.001). The highest incidence of C-R Kp BSI was observed in intensive care units (ICUs), with a peak of 22.01 C-R Kp BSI/10,000 patient-days in 2012. A less marked but significant increase of C-S Kp BSI was also observed (Chi square for trend p = 0.004). Crude 30-day mortality was 36.1 % in patients with C-R Kp BSI and 23.5 % in those with C-S Kp BSI. CONCLUSIONS: During the study period, we observed a dramatic increase in the incidence of C-R Kp BSI in our hospital. More concerted infection-control efforts are needed to contain this alarming C-R Kp diffusion

Viremia copy-years and risk of estimated glomerular filtration rate reduction in adults living with perinatal HIV infection

Among people with perinatal HIV infection (PHIV), non-communicable diseases, such as chronic kidney disease, are increasing. Both HIV replication and antiretroviral therapy are recognised causes of renal impairment. Objective of the study is to describe the impact of viremia copy-years (VCY) and antiretroviral therapy on trend of estimated glomerular filtration rate (eGFR) in a cohort of adults with perinatal HIV infection. We conducted a multicentre observational study in sixty adults living with PHIV across a 9-year period, from January 2010 to December 2018. The mean values of eGFR were analysed at the first (T0) and last year of observation (T1). VCY was defined as the area under HIV-RNA curve during the study period. We analysed data according to antiretroviral therapy: tenofovir disoproxil (TDF), non-nucleoside reverse transcriptase inhibitors (NNRTI), boosted protease inhibitors (PI/b), integrase inhibitors (INI). We observed a mean overall eGFR reduction from 126.6 mL/min (95%CI: 119.6-133.5) to 105.0 mL/min (95%CI: 99.55-110.6) (p&lt;0.001). Older age, higher baseline eGFR, higher VCY and longer exposure to INI treatment were associated with eGFR reduction at univariate analysis. In the multivariate model, older age (p= 0.039), baseline eGFR (p&lt;0.001) and VCY (p= 0.069), were retained. We also observed a longer exposure to PI/b and INI in patients with lower control on HIV-RNA, expressed as VCY&gt;2 log(10). Our study outlines a progressive eGFR reduction in young adults with PHIV, related to the lower control on HIV-RNA VCY and related to aging

Efficacy of Convalescent Plasma to Treat Long-Standing COVID-19 in Patients with B-Cell Depletion

The use of antivirals, corticosteroids, and IL-6 inhibitors has been recommended by the WHO to treat COVID-19. CP has also been considered for severe and critical cases. Clinical trials on CP have shown contradictory results, but an increasing number of patients, including immunocompromised ones, have shown benefits from this treatment. We reported two clinical cases of patients with prolonged COVID-19 infection and B-cell depletion who showed rapid clinical and virological recovery after the administration of CP. The first patient in this study was a 73-year-old female with a history of follicular non-Hodgkin lymphoma previously treated with bendamustine followed by maintenance therapy with rituximab. The second patient was a 68-year-old male with chronic obstructive pulmonary disease, bipolar disorder, alcoholic liver disease, and a history of mantellar non-Hodgkin lymphoma treated with rituximab and radiotherapy. After the administration of CP, both patients showed a resolution of symptoms, improvement of their clinical conditions, and a negative result of the nasopharyngeal swab test. The administration of CP might be effective in resolving symptoms and improving clinical and virological outcomes in patients with B-cell depletion and prolonged SARS-CoV2 infections

Long-Term Effectiveness of Rilpivirine-Based Single-Tablet Regimens in a Seven-Year, Two-Center Observational Cohort of People Living with HIV

Data on the long-term durability of rilpivirine (RPV) are still scarce. A two-center retrospective study was performed, including all people living with HIV (PLWH) treated with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC)/RPV or tenofovir alafenamide (TAF)/FTC/RPV in the period January 2013-December 2019. Aims of the study were to assess the rate of discontinuation of the RPV single-tablet regimen (STR) and identify factors associated with the risk of discontinuation according to Cox's regression analysis. A total of 684 PLWH were enrolled. Mean duration of RPV-STR treatment was 192.5 (+/- 99.5) weeks for 123 antiretroviral therapy (ART)-naive participants (18%) and 173.3 (+/- 85.6) weeks for 561 ART-experienced study participants (82%). During the study period, the incidence of discontinuation was 7.7 per 100 person-years. The estimated proportions of discontinuation after 48 and 96 weeks were 5.6% and 13.4%, respectively. Causes of discontinuation were loss to follow-up (30%), side effects (15%), ART optimization (14%), virological failure (VF) (12%), death or transfer to another center (9%), low adherence (7%), drug interactions (6%), simplification to dual therapy (3%), and unknown (3%). No differences were observed in cumulative probability of discontinuation between ART-naive and -experienced PLWH. Heterosexual (hazard ratio [HR] 3.0, 95% confidence interval [CI] 1.4-6.8) and mother-to-child (HR 5.3, 95% CI 1.8-15.3) transmission of HIV infection and history of previous VF (HR 1.7, 95% CI 1.2-2.5) were associated with higher risk of discontinuation. High RPV-STR effectiveness and durability were confirmed in our real-life population of PLWH. Given these data, RPV has the potential to be a drug for life in patients selected according to current guidelines

Desirability of outcome ranking (DOOR) for comparing diagnostic tools and early therapeutic choices in patients with suspected candidemia

Desirability of outcome ranking (DOOR) has been developed for assessing desirability of outcome in interventional studies. However, its possible use in observational studies of the diagnosis and early treatment of infectious diseases has not been explored so far, and it might introduce interesting features in specific scenarios. This was a post hoc analysis of a prospective observational study in intensive care unit patients with sepsis and at risk of candidemia. The probabilities that a randomly selected patient would have a more, less, and equally cost-effective early therapeutic choice following a BDG-based diagnostic strategy rather than the empirical administration of antifungals to all patients were calculated using DOOR methods. The probability of a more cost-effective therapeutic choice following the BDG-based rather than the empirical strategy was 67.81% (95% CI 67.32\u201368.30), whereas the probabilities of a less and equally cost-effective early therapeutic choice were 19.68% (95% CI 19.27\u201320.10) and 12.50% (95% CI 12.16\u201312.85), respectively. The application of DOOR methods to observational studies focused on diagnosis and early treatment is a novel field that could merit further investigation