Search

In a multicentre, open-label, clinical trial, 43 patients virologically suppressed while receiving a standard triple antiretroviral therapy were randomized (1:1:1) to switch to monotherapy with darunavir/ritonavir (DRV/r-MT arm), monotherapy with lopinavir/ritonavir (LPV/r-MT arm) or to continue on the ongoing regimen (cART arm). The proportion (95% CI) of patients with virological success (Snapshot analysis) at week 48 was 73% (48%-90%) in the DRV/r-MT arm, 69% (42%-88%) in the LPV/r-MT arm and 87% (61%-98%) in the cART arm. Virological failure was detected in only one patient receiving LPV/r-MT. The LPV/r-MT arm showed a modest worsening in lipid profile.

Hypovitaminosis D is a very common disorder, regarding both Western and developing countries. A growing amount of data over the last years have shown vitamin D deficiency to be high prevalent among HIV-positive subjects. In addition to "classic" risk factors, such as female sex, low dietary intake, dark skin pigmentation and low sun exposure, HIV-related factors, including immune activation and antiretroviral adverse effects, may affect vitamin D status. Even if both protease inhibitors and non-nucleoside reverse transcriptase inhibitors have been associated with low vitamin D levels, available evidences have failed to univocally associate hypovitaminosis D with specific antiretroviral class effects. Low vitamin D is known to have a negative impact not only on bone health, but also on neurocognitive, metabolic, cardiovascular and immune functions. Similarly to the general population, several studies conducted on HIV-infected subjects have associated hypovitaminosis D with a greater risk of developing osteopenia/osteoporosis and fragility fractures. Analogously, vitamin D deficiency has been described as an independent risk factor for cardiovascular disease and metabolic disorders, such as insulin resistance and type 2 diabetes mellitus. Last EACS guidelines suggest to screen for hypovitaminosis D every HIV-positive subject having a history of bone disease, chronic kidney disease or other known risk factors for vitamin D deficiency. Vitamin D repletion is recommended when 25-hydroxyvitamin D levels are below 10 ng/ml. Furthermore, it may be indicated in presence of 25OHD values between 10 and 30 ng/ml, if associated with osteoporosis, osteomalacia or increased parathyroid hormone levels. The optimal repletion and maintenance dosing regimens remain to be established, as well as the impact of vitamin D supplementation in preventing comorbidities.

BackgroundElectronic health databases are used to identify people at risk of poor outcomes. Using electronic regional health databases (e-RHD), we aimed to develop and validate a frailty index (FI), compare it with a clinically based FI, and assess its association with health outcomes in community-dwellers with SARS-CoV-2.MethodsData retrieved from the Lombardy e-RHD were used to develop a 40-item FI (e-RHD-FI) in adults (i.e., aged ≥18 years) with a positive nasopharyngeal swab polymerase chain reaction test for SARS-CoV-2 by May 20, 2021. The considered deficits referred to the health status before SARS-CoV-2. The e-RHD-FI was validated against a clinically based FI (c-FI) obtained from a cohort of people hospitalized with COVID-19 and in-hospital mortality was evaluated. e-RHD-FI performance was evaluated to predict 30-day mortality, hospitalization, and 60-day COVID-19 WHO clinical progression scale, in Regional Health System beneficiaries with SARS-CoV-2.ResultsWe calculated the e-RHD-FI in 689,197 adults (51.9% females, median age 52 years). On the clinical cohort, e-RHD-FI correlated with c-FI and was significantly associated with in-hospital mortality. In a multivariable Cox model, adjusted for confounders, each 0.1-point increment of e-RHD-FI was associated with increased 30-day mortality (Hazard Ratio, HR 1.45, 99% Confidence Intervals, CI: 1.42–1.47), 30-day hospitalization (HR per 0.1-point increment = 1.47, 99%CI: 1.46–1.49), and WHO clinical progression scale (Odds Ratio = 1.84 of deteriorating by one category, 99%CI 1.80–1.87).ConclusionThe e-RHD-FI can predict 30-day mortality, 30-day hospitalization, and WHO clinical progression scale in a large population of community-dwellers with SARS-CoV-2 test positivity. Our findings support the need to assess frailty with e-RHD.

BacKGrOUnd: Older people hospitalized for cOvid-19 are at highest risk of death. Frailty assessment can detect heterogeneity in risk among people of the same chronological age. We investigated the association between frailty and in-hospital and medium-term mortality in middle-aged and older adults with COVID-19 during the first two pandemic waves. meTHOdS: This study is an observational multicenter study. We recorded sociodemographic factors (age, sex), smoking status, date of symp-tom onset, biological data, need for supplemental oxygen, comorbidities, cognitive and functional status, in-hospital mortality. We calculated a Frailty Index (FI) as the ratio between deficits presented and total deficits considered for each patient (theoretical range 0-1). We also assessed the clinical Frailty Scale (cFS). mortality at follow-up was ascertained from a regional registry. reSULTS: in total, 1344 patients were included; median age 68 years (Q1-Q3, 56-79); 857 (64%) were men. median cFS score was 3 (Q1-Q3 2-5) and was lower in younger vs. older patients. median Fi was 0.06 (Q1-Q3 0.03-0.09) and increased with increasing age. Overall, 244 (18%) patients died in-hospital and 288 (22%) over a median follow-up of 253 days. FI and CFS were significantly associated with risk of death. In two different models using the same covariates, each increment of 0.1 in Fi increased the overall hazard of death by 35% (Hr=1.35, 95%ci 1.23-1.48), similar to the hazard for each increment of cFS (Hr=1.37, 95%ci 1.25-1.50). cOncLUSiOnS: Frailty, assessed with the Fi or cFS, predicts in-hospital and medium-term mortality and may help estimate vulnerability in middle-aged and older cOvid-19 patients.

OBJECTIVES Lymphoproliferative disorders are often observed in HIV-positive patients. Combination antiretroviral treatment (cART) during antineoplastic chemotherapy is beneficial, but little is known about the clinical outcome according to different antiretroviral combinations. The aim of the study was to address this gap in current knowledge. METHODS A retrospective study was conducted in five large Italian centres for the period from 1998 to 2015; HIV-positive patients diagnosed with lymphoma were included and demographic, clinical and therapeutic variables were recorded and associated with clinical outcomes. Bivariate and multivariate analyses were performed, including Cox proportional hazard models for survival. RESULTS A total of 399 patients were included in the study. The most common types of lymphoma were diffuse large B-cell lymphoma (DLCLB; n = 164), Hodgkin lymphoma (HL; n = 99) and Burkitt lymphoma (BL; n = 57), followed by plasmablastic lymphoma (PBL; n = 38), T-cell lymphoma (TCL; n = 17), indolent lymphoma (n = 10) and other less common types (n = 14). cART was given to 327 (out of 387 evaluable) patients: in 216 subjects it was protease inhibitor (PI)-based, in 73 it was nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and in 18 it was integrase strand transfer inhibitor (INSTI)-based (the remaining 20 individuals received other regimens). The 5-year overall survival was 57.5% (52.8% for DLCLB, 67.8% for HL, 42.3% for BL, 60.6% for PBL and 64.7% for TCL). PI-based ART compared with other compounds was associated with worse survival in non-Hodgkin lymphoma (NHL) and HL patients combined (P ≤ 0.001) and in NHL patients alone (P

Background GEPPO is a prospective observational multi-centric cohort including HIV-infected geriatric patients. We hypothesized that the GEPPO cohort may help characterize antiretroviral (ARV) prescribing criteria used in real life by Italian infectious disease (ID) physicians. Methods This was a cross-sectional study describing the current ARV regimen in a geriatric HIV population (≥65 years). Antiretroviral strategies were categorized as follows: (i) multidrug regimens (MDRs), which comprised triple or mega ART combinations; (ii) less drug regimens (LDRs), which comprised fewer than three ART compounds. Multi-morbidity (MM) was defined as the presence of three or more non-communicable diseases, and polypharmacy (PP) as the use of five or more medications in chronic use. Four alternative combinations (MM+PP+, MM+PP-, MM-PP+, MM-PP-) were used in logistic regression analyses. Results A total of 1222 HIV-positive patients were included (median age 70 years). Females composed 16% of the cohort. Median duration of HIV infection was 17 years; 335 population members had been infected for >20 years. MM was present in 64% and PP in 37% of the patients. Treatment consisted of triple therapy in 66.4%, dual therapy in 25.3%, monotherapy in 6.5% and 'mega-ART' with more than three drugs in 1.64% of the patients. In multivariate logistic regression MM and PP were predictive for mono-dual, NRTI-sparing and tenofovir disoproxil fumarate (TDF)-sparing combinations. Female gender and age were predictors of unboosted ARV regimens. Conclusions High prevalence of non-conventional ARV regimens in elderly HIV patients suggests that clinicians try to tailor ARV regimens according to age, HIV duration, MM and PP.

Background: Tat is a key HIV-1 virulence factor, which plays pivotal roles in virus gene expression, replication, transmission and disease progression. After release, extracellular Tat accumulates in tissues and exerts effects on both the virus and the immune system, promoting immune activation and virus spreading while disabling the host immune defense. In particular, Tat binds Env spikes on virus particles forming a virus entry complex, which favors infection of dendritic cells and efficient transmission to T cells via RGD-binding integrins. Tat also shields the CCR5-binding sites of Env rendering ineffective virus neutralization by anti-Env antibodies (Abs). This is reversed by the anti-Tat Abs present in natural infection or induced by vaccination.Findings: Here we present the results of a cohort study, showing that the presence of anti-Tat Abs in asymptomatic and treatment-naïve HIV-infected subjects is associated with containment of CD4+ T-cell loss and viral load and with a delay of disease progression. In fact, no subjects with high anti-Tat Ab titers initiated antiretroviral therapy during the three years of follow-up. In contrast, no significant effects were seen for anti-Env and anti-Gag Abs. The increase of anti-Env Ab titers was associated with a reduced risk of starting therapy only in the presence of anti-Tat Abs, suggesting an effect of combined anti-Tat and anti-Env Abs on the Tat/Env virus entry complex and on virus neutralization.Conclusions: Anti-Tat immunity may help delay HIV disease progression, thus, targeting Tat may offer a novel therapeutic intervention to postpone antiretroviral treatment or to increase its efficacy. © 2014 Bellino et al.; licensee BioMed Central Ltd

Age-related co-morbidities including osteoporosis are relevant in patients responding to combination antiretroviral therapy (cART). Vertebral fractures are common osteoporotic fractures and their diagnosis is useful for managing at-risk individuals. However, there are few data from HIV-infected patients. Therefore, the aim of this study was to determine the prevalence of and factors associated with vertebral fractures in a population of HIV-infected males. A cross-sectional study of 160 HIV-infected patients with available chest X-rays was conducted from 1998 to 2010. One hundred and sixty-three males with comparable age and with no history of HIV infection were recruited as controls. Semi-quantitative evaluation of vertebral heights in lateral chest X-rays and quantitative morphometry assessment of centrally digitized images using dedicated morphometry software were utilized to detect prevalent vertebral fractures. The result showed that the vertebral fractures were detected in 43/160 (26.9%) HIV-infected patients and in 21/163 (12.9%) controls (P = 0.002). In HIV-infected patients with fractures, 27 had two or more fractures and ten patients had severe fractures. The prevalence of any fractures and multiple fractures in HIV-infected patients receiving cART (29.6 and 20.0%) was slightly higher than in HIV-infected patients not exposed to cART (17.1 and 5.7%), but significantly higher than control subjects (12.9 and 3.7%). At multivariable analyses, body mass index and diabetes mellitus were independently correlated with vertebral fractures in HIV-infected patients. We concluded that a significant proportion of HIV-infected males receiving cART showed vertebral fractures. Furthermore, proactive diagnosis of vertebral fragility fractures is particularly relevant in patients who are overweight or suffer from diabetes.