Search

Background Atazanavir and darunavir represent the main HIV PIs recommended in pregnancy, but comparative data in pregnant women are limited. We assessed the safety and activity profile of these two drugs in pregnancy using data from a national observational study. Methods Women with atazanavir or darunavir exposure in pregnancy were evaluated for laboratory measures and main pregnancy outcomes (e.g. preterm delivery, low birthweight, non-elective caesarean section and neonatal gestational age-adjusted birthweight Z-score). Results Final analysis included 500 pregnancies with either atazanavir (n = 409) or darunavir (n = 91) exposure. No differences in pregnancy outcomes, weight gain in pregnancy, drug discontinuations, undetectable HIV-RNA, haemoglobin, ALT, total cholesterol, HDL cholesterol and LDL cholesterol were observed between the two groups. At third trimester, exposure to darunavir was associated with higher levels of plasma triglycerides (median 235.5 versus 179 mg/dL; P = 0.032) and a higher total cholesterol/HDL cholesterol ratio (median 4.03 versus 3.27; P = 0.028) and exposure to atazanavir was associated with higher levels of plasma bilirubin (1.54 versus 0.32 mg/dL; P

Background Transmitted drug-resistance (TDR) remains a critical aspect for the management of HIV-1-infected individuals. Thus, studying the dynamics of TDR is crucial to optimize HIV care. Methods In total, 4323 HIV-1 protease/reverse-transcriptase sequences from drug-naive individuals diagnosed in north and central Italy between 2000 and 2014 were analysed. TDR was evaluated over time. Maximum-likelihood and Bayesian phylogenetic trees with bootstrap and Bayesian-probability supports defined transmission clusters. Results Most individuals were males (80.2%) and Italian (72.1%), with a median (IQR) age of 37 (30-45) years. MSM accounted for 42.2% of cases, followed by heterosexuals (36.4%). Non-B subtype infections accounted for 30.8% of the overall population and increased over time (

Background The aim of our work was to evaluate the potential impact of the European policy of testing for HIV all individuals presenting with an indicator disease, to prevent late diagnosis of HIV. We report on a retrospective analysis among individuals diagnosed with HIV to assess whether a history of certain diseases prior to HIV diagnosis was associated with the chance of presenting late for care, and to estimate the proportion of individuals presenting late who could have been diagnosed earlier if tested when the indicator disease was diagnosed. Methods We studied a large cohort of individuals newly diagnosed with HIV infection in 13 counselling and testing sites in the Lazio Region, Italy (01/01/2004-30/04/2009). Considered indicator diseases were: viral hepatitis infection (HBV/HCV), sexually transmitted infections, seborrhoeic dermatitis and tuberculosis. Logistic regression analysis was performed to estimate association of occurrence of at least one indicator disease with late HIV diagnosis. Results In our analysis, the prevalence of late HIV diagnosis was 51.3% (890/1735). Individuals reporting at least one indicator disease before HIV diagnosis (29% of the study population) had a lower risk of late diagnosis (OR = 0.7; 95%CI: 0.5-0.8) compared to those who did not report a previous indicator disease. 52/890 (5.8%) late presenters were probably already infected at the time the indicator disease was diagnosed, a median of 22.6 months before HIV diagnosis. Conclusions Our data suggest that testing for HIV following diagnosis of an indicator disease significantly decreases the probability of late HIV diagnosis. Moreover, for 5.5% of late HIV presenters, diagnosis could have been anticipated if they had been tested when an HIV indicator disease was diagnosed. However, this strategy for enhancing early HIV diagnosis needs to be complemented by client-centred interventions that aim to increase awareness in people who do not perceive themselves as being at risk for HIV.

Objective We used data from a national study of pregnant women with HIV to evaluate the prevalence of congenital abnormalities in newborns from women with HIV infection. Design Observational study. Setting University and hospital clinics. Population Pregnant women with HIV exposed to antiretroviral treatment at any time during pregnancy. Methods The total prevalence of birth defects was assessed on live births, stillbirths, and elective terminations for fetal anomaly. The associations between potentially predictive variables and the occurrence of birth defects were expressed as odds ratios (ORs) with 95% confidence intervals (95% CIs) for exposed versus unexposed cases, calculated in univariate and multivariate logistic regression analyses. Main outcome measures Birth defects, defined according to the Antiretroviral Pregnancy Registry criteria. Results A total of 1257 pregnancies with exposure at any time to antiretroviral therapy were evaluated. Forty-two cases with major defects were observed. The total prevalence was 3.2% (95% CI 1.9–4.5) for exposure to any antiretroviral drug during the first trimester (23 cases with defects) and 3.4% (95% CI 1.9–4.9) for no antiretroviral exposure during the first trimester (19 cases). No associations were found between major birth defects and first-trimester exposure to any antiretroviral treatment (OR 0.94, 95% CI 0.51–1.75), main drug classes (nucleoside reverse transcriptase inhibitors, OR 0.95, 95% CI 0.51–1.76; non-nucleoside reverse transcriptase inhibitors, OR 1.20, 95% CI 0.56–2.55; protease inhibitors, OR 0.92, 95% CI 0.43–1.95), and individual drugs, including efavirenz (prevalence for efavirenz, 2.5%). Conclusions This study adds further support to the assumption that first-trimester exposure to antiretroviral treatment does not increase the risk of congenital abnormalities.

Skeletochronology has been successfully used to age temperate amphibians, enabling comparisons of longevity and the age at sexual maturity. To date, however, there have been few similar studies conducted using this technique in tropical amphibians. Here we present data on age structure and age at maturity for nine species of Malagasy Mantella frogs: M. baroni, M. bernhardi, M. sp. aff. expectata, M. cowani, M. crocea, M. laevigata, M. nigricans, M. pulchra and M. viridis. The genus Mantella includes some of the most threatened frog species in Madagascar, and also some of the most requested species for the international pet trade. The lack of basic information on the life history of these species in the wild is hindering the development of sustainable collection models. We analysed museum specimens and bone samples of free living individuals collected during several surveys in western and eastern Madagascar. All investigated species showed a comparatively short longevity (0-4 LAGs) and sexual maturity was reached on the 1st or the 2nd year of life.

Aims: As the world population grows older, the co-existence of cancer and cardiovascular comorbidities becomes more common, complicating management of these patients. Here, we describe the impact of a large Cardio-Oncology unit in Southern Italy, characterizing different types of patients and discussing challenges in therapeutic management of cardiovascular complications. Methods and results: We enrolled 231 consecutive patients referred to our Cardio-Oncology unit from January 2015 to February 2020. Three different types were identified, according to their chemotherapeutic statuses at first visit. Type 1 included patients naïve for oncological treatments, Type 2 patients already being treated with oncological treatments, and Type 3 patients who had already completed cancer treatments. Type 2 patients presented the highest incidence of cardiovascular events (46.2% vs. 12.3% in Type 1 and 17.9% in Type 3) and withdrawals from oncological treatments (5.1% vs. none in Type 1) during the observation period. Type 2 patients presented significantly worse 48month-survival (32.1% vs. 16.7% in Type 1 and 17.9% in Type 3), and this was more evident when in the three groups we focused on patients with uncontrolled cardiovascular risk factors or overt cardiovascular disease at the first cardiologic assessment. Nevertheless, these patients showed the greatest benefit from our cardiovascular assessments, as witnessed by a small, but significant improvement in ejection fraction during follow-up (Type 2b: from 50 [20; 67] to 55 [35; 65]; P=0.04). Conclusions: Patients who start oncological protocols without an accurate baseline cardiovascular evaluation are at major risk of developing cardiac complications due to antineoplastic treatments.

Purpose of ReviewOncological treatments are known to induce cardiac toxicity, but the impact of new-onset cancer in patients with pre-existing HF remains unknown. This review focuses on the epidemiology, pathophysiological mechanisms, and clinical implications of HF patients who develop malignancies.Recent FindingsNovel findings suggest that HF and cancer, beside common risk factors, are deeply linked by shared pathophysiological mechanisms. In particular, HF itself may enhance carcinogenesis by producing pro-inflammatory cytokines, and it has been suggested that neurohormonal activation, commonly associated with the failing heart, might play a pivotal role in promoting neoplastic transformation.SummaryThe risk of malignancies seems to be higher in HF patients compared to the general population, probably due to shared risk factors and common pathophysiological pathways. Additionally, management of these patients represents a challenge for clinicians, considering that the co-existence of these diseases significantly worsens patients’ prognosis and negatively affects therapeutic options for both diseases.

PURPOSE: Right ventricular (RV) capacity to adapt to increased afterload is the main determinant of outcome in pulmonary hypertension (PH), a common morbidity seen in systemic sclerosis (SSc). We hypothesized that supine bicycle echocardiography (SBE), coupled with RV longitudinal systolic strain (RVLSS), improves detection of limitations in RV reserve in SSc. METHODS: 56 SSc patients were prospectively studied during SBE with RV functional parameters compared at rest and peak stress. We further dichotomized patients based on resting RV systolic pressure (RVSP) to determine the effects of load on contractile response. RESULTS: Our pooled cohort analysis revealed reduced global RVLSS at rest (−16.2 ± 3.9%) with normal basal contractility (−25.6 ± 7.7%) and relative hypokinesis of the midventricular (−14.1 ± 6.0%) and apical (−8.9 ± 5.1%) segments. With exercise, global RVLSS increased significantly (p=0.0005), however despite normal basal contractility at rest, there was no further augmentation with exercise. Mid and apical RVLSS increased with exercise suggestive of RV contractile reserve. In patients with resting RVSP < 35 mmHg, global and segmental RVLSS increased with exercise. In patients with resting RVSP ≥35 mmHg, global and segmental RVLSS did not increase with exercise and there was evidence of exertional RV dilation. CONCLUSION: Exercise provocation in conjunction with RVLSS identified differential regional contractile response to exercise in SSc patients. We further demonstrate the effect of increased loading conditions on RV contractile response exercise. These findings suggest subclinical impairments in RV reserve in SSc that may be missed by resting noninvasive 2DE-based assessments alone.

Aims In breast cancer (BC) patients treated with anthracyclines-based therapies, we aim at assessing whether adjuvant drugs impact cardiac function differently and whether their cardiotoxicity has a regional pattern. Methods and results In a multicentre study, 146 BC patients (56 ± 11 years) were prospectively enrolled and divided into three groups according to the received treatments: AC/EC-Group (doxorubicin or epirubicin + cyclophosphamide), AC/EC/Tax-Group (AC/EC + taxanes), FEC/Tax-Group (fluorouracil + EC + taxanes). Fifty-six patients of the total cohort also received trastuzumab. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were calculated before starting chemotherapy (T0), at 3 months (T3), at 6 (T6), and 12 months (T12). A ≥10% drop of EF, while remaining within the normal range, was reached at T6 in 25.3% of patients from the whole cohort with an early decrease only in FEC/Tax-Group (P = 0.04). A ≥15% GLS reduction was observed in many more (61.6%) patients. GLS decreased early both in the whole population (P Conclusions The decrease of GLS is more precocious and pronounced in BC patients who received FEC + taxanes. Cardiac function further worsens after 6 months of adjuvant trastuzumab. All LV segments are damaged, with the anterior septum and the apex showing the greatest impairments.

BACKGROUND: Upfront combination therapy with ambrisentan and tadalafil has been reported to improve the condition of patients with pulmonary arterial hypertension (PAH) more than with either drug alone. However, little is known about the long-term associated changes in hemodynamics and risk assessment scores. METHODS: This was a multicenter, retrospective analysis of clinical data in 106 patients with newly diagnosed PAH. Clinical evaluations, including demographics, medical history, World Health Organization (WHO) functional class (FC) and 6-minute walk distance (6MWD), right heart catheterization, and Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk score 2.0, were assessed over 48 months of ambrisentan‒tadalafil therapy. RESULTS: At baseline, 9 patients (9%) showed a low (8) REVEAL risk score. At a median follow-up of 2 years, 45 patients (43%) showed a low, 47 patients (44%) showed an intermediate, and 14 patients (13%) showed a high REVEAL score, along with improvements in WHO FC, 6MWD and a decrease in mean pulmonary artery pressure and N-terminal pro brain natriuretic peptide (all p < 0.001). Pulmonary vascular resistance (PVR) decreased by 37% from 11.5 ± 6.5 to 7.2 ± 4.1 Wood units (p < 0.001). A total of 61 patients (57%) remained in intermediate-risk or high-risk categories. Low-risk patients had either a decrease in PVR of >50% or a stroke volume within the limits of normal. CONCLUSIONS: Initial combination therapy with ambrisentan and tadalafil in PAH improves the REVEAL risk score in proportion to decreased PVR and preserved stroke volume but still insufficiently so in approximately 50% of the patients.

The most important oenological characteristics of high-quality sparkling wines are aromatic aspect, taste persistence, perlage, high levels of acidity and low pH. Due to hot climate and reduced rainfall that characterize Sicily region, white grape varieties such as Grillo cultivar cultivated in this area are characterized by very low concentrations of malic and tartaric acids. Grillo cultivar is characterized by an intense production of raceme grapes with low pH and high content of tartaric and malic acids. These fruits possess the chemical properties useful to increase the amounts of acids in the final wines. With this in mind, the present research was carried out to test the ability of four Saccharomyces cerevisiae strains (CS182, GR1, MSE13 and MSE41) to ferment a raceme must with a pH of 2.9 at two concentrations (14° and 16° Babo degree) of total sugars. The inoculation of the strains was performed after a preadaptation at pH 2.5. The chemical parameters and kinetics of the fermentations were monitored. The experimental sparkling base wines were characterized by a very high total acidity with 16-17 g/L of tartaric acid and 9-10 g/L of malic acids. On the other hand, ethanol was detected at low values in the range 9-10% (v/v). The base wine obtained with GR1differed in their high acidity values, whereas trials inoculated with CS182 showed more intense odors and exotic fruit. Experimental wines produced in this study represent an innovative strategy for "blending wines" to produce sparkling wines in dry Mediterranean climate.

Aims The aim of this study was to investigate prospectively the effect of sacubitril/valsartan in advanced heart failure (HF) patients in waiting list for heart transplantation (HT) and the effect on physical frailty (PF). Methods and results We treated 37 consecutive patients with advanced HF with sacubitril/valsartan. Patients were followed up until HT, device implant, or last follow‐up visit after 2 years of follow‐up. At baseline, mean New York Heart Association (NYHA) class was 3.1 ± 0.4, with 64.9% in NYHA III and 35.1% NYHA IIIB. Left ventricular ejection fraction was 23.5 ± 5.8%, VO2 max was 10.3 ± 2.3 mL/kg/min, cardiac index was 2.3 ± 0.5 L/min/m2, and N‐terminal pro‐brain natriuretic peptide (NT‐pro‐BNP) was 4943.0 ± 5326.8 pg/mL. After a mean follow‐up of 17.1 ± 4.4 months, no deaths were observed, but NYHA class improved significantly with 56.8% in NYHA II, 40.5% in NYHA III, and 2.7% in NYHA IIIB (P < 0.001). VO2 max and 6 min walk test (6MWT) increased, whereas pulmonary systolic blood pressure, E/E′, VE/VCO2 slope, and NT‐pro‐BNP decreased. At right heart catheterization performed after 1 year of follow‐up, cardiac index and pulmonary vascular resistance remained stable, while a decrease in systolic pulmonary artery pressure and pulmonary capillary wedge pressure is observed. Furosemide dosage decrease from 102.7 ± 69.4 to 78.7 ± 66.3 mg (P = 0.040). PF decreased from 3.35 ± 1.0 at baseline to 1.57 ± 1.3 at the end of follow‐up (P < 0.001), with a reduction in all PF domains. Conclusions Our study showed a rapid improvement in PF in HT waiting list patients treated with sacubitril/valsartan. The improvement in all PF domains was paralleled by VO2 and 6MWT increase and together with an NT‐pro‐BNP reduction constant over the follow‐up.

Pulmonary arterial hypertension (PAH) is a heart failure syndrome characterized by right ventricular (RV) to pulmonary circulation uncoupling, counteracted by the sympathetic nervous system activation leading to β

Aim: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus-specific reverse transcriptase-polymerase chain reaction (RT-PCR) represents the diagnostic gold standard. We explored the value of chest ultrasonography to predict positivity to SARS-CoV-2 on RT-PCR in suspected COVID-19 cases. Patients & methods: Consecutive patients with suspect COVID-19 were included if they had fever and/or history of cough and/or dyspnea. Lung ultrasound score (LUSS) was computed according to published methods. Results: A total of 76 patients were included. A 3-variable model based on aspartate transaminase (AST) > upper limit of normal, LUSS >12 and body temperature >37.5°C yielded an overall accuracy of 91%. Conclusion: A simple LUSS-based model may represent a powerful tool for initial assessment in suspected cases of COVID-19., Lay abstract The gold standard for diagnosis of COVID-19 is RT-PCR. During a pandemic emergency, it may be useful to identify suspect symptomatic patients who may safely be observed without undergoing testing for COVID-19. In this work, a simple model based on the findings of lung ultrasound, AST levels and fever showed an overall accuracy of 91% to predict the results of RT-PCR.

BACKGROUND: Carotid dolicoarteriopathies (CDA) are a common finding during the carotid ultrasound or angiography, but their potential role in the development of cerebrovascular diseases is still unclear. Aim of this study is to clarify the possible relationship between CDA and the occurrence of cerebral events. METHODS: We performed a retrospective analysis on 2124 hypertensive patients with high cardiovascular risk that underwent carotid ultrasound from January 2000 to December 2008. Follow-up data on cerebrovascular events (transient ischemic attack and/or stroke occurrence) at 10 years were collected. RESULTS: The global prevalence of CDA in the study population was 12.9% (274/2124), and carotid kinking was more frequent in females and in the left carotid axis. The percentage of cerebrovascular events among hypertensive patients with CDA was similar to those occurred in the group of patients without CDA (10.94% vs. 10.97%, P=NS), with no differences in the number of strokes (8.39% vs. 8.38% P=NS) and TIA (2.55% vs. 2.59% P=NS). CONCLUSIONS: CDA are not associated with a major occurrence of cerebrovascular events in a high-risk population of hypertensives.

Summary: Background: Children with high-risk medulloblastoma are treated with chemotherapeutic protocols which may affect heart function. We aimed to assesscardiovascular events (CVE) in children with medulloblastoma/primitive neuroectodermal tumors (PNET). Methods: We retrospectively collected data from a case series of 22 children with high-risk medulloblastoma/PNET admitted to the Santobono-Pausilipon Hospital, Naples, Italy from 2008 to 2016. All patients received the Milan HART protocol for high-risk brain malignancies as first line treatment (induction phase), followed by a consolidation phase with Thiotepa and hematopoietic stem cells transplantation, except for 1 patient who received the Milan HART as second line therapy. Four patients also received second line treatment, while 4 patients also received maintenance therapy. Patients underwent cardiac examination, including ECG, echocardiography and serum biomarkers, before antineoplastic treatment initiation and then when clinically needed. Six patients developed CVE (CVE group); 16 patients had no CVE (NO-CVE group). Findings: In the CVE group, 3 patients presented acute CVE during chemotherapy (2 patients with left ventricular (LV) dysfunction, 1 patient with arterial hypertension), while 3 patients presented chronic CVE after chemotherapy completion (2 patients with LV dysfunction, 1 patient with ectopic atrial tachycardia). After a 51 months median follow-up, 9 patients died: 4 from the CVE group (in 2 cases heart failure-related deaths) and 5 from the NO-CVE group (progression of disease). Interpretation: A relevant percentage of children treated for medulloblastoma/PNET develops CVE. Heart failure potentially due to chemotherapy may represent a cause of death. Hence, in these patients, strict cardiac surveillance is essential. Funding: No funding was associated with this study.

BACKGROUND: Depression is highly prevalent in Heart Failure (HF). Treatment with sacubitril/valsartan improved quality of life and survival in HF patients. Aim of the study was to investigate prospectively the effect of sacubitril/valsartan on depression in advanced HF patients in waiting list for heart transplant (HT). METHODS: 37 consecutive patients with advanced HF in waiting list for HT were treated with sacubitril/valsartan. We analyzed data derived from the assessment performed the year before the beginning of sacubitril/valsartan, at study entry, and at one year of follow-up. Depression was assessed with Beck Depression Inventory II (BDI) scale. Cognitive function were assessed with Mini-Mental State Examination (MMSE). Functioning was evaluated measuring meters at 6 Minute Walking Test (6MWT) and maximum rate of oxygen consumption (VO2 max). RESULTS: At baseline, 64.9% of HF patients were in NYHA III and 35.1% NYHA IIIB, BDI was 15.2 ± 5.2 with 59.5% of patients with a score > 13. MMSE was 27.8 ± 2.6. After one year of follow-up NYHA class improved significantly, with 56.8% in NYHA II, 40.5% in NYHA III and 2.7% NYHA in IIIB (p 13. MMSE remain stable (28.2 ± 2.1) (p = 0.104). No statistical differences are observed between data collected in the evaluation 1-year before and soon before treatment with sacubitril/valsartan. Multivariate regression analysis demonstrate a relationship between reduction in BDI-II score and improvement in six-minute walking test independently by the effect of sex, age, selective serotonin reuptake inhibitors, VO2 max, NT-proBNP, PAPs, NYHA class differences evaluated at follow-up versus baseline. CONCLUSIONS: Our study showed a reduction in depressive symptomatology in heart transplant waiting list patients treated with sacubitril/valsartan. The improvement in depressive symptomatology was paralleled by 6MWT increase in the follow-up.

Increased left ventricular mass (LVM) is often present in metabolic syndrome (MS), also in the setting of well-controlled blood pressure (BP). Aim of the present study was to evaluate the efficacy of a nutraceutical combination of berberine, red yeast rice extract and policosanol (Armolipid Plus™, AP) in reducing LVM in patients with MS and left ventricular hypertrophy (LVH).In this multicenter, randomized, double-blind, placebo-controlled trial, 158 patients with MS (IDF criteria) and LVH (LVM48 g/mOne-hundred-and-forty-five patients (AP n = 74, placebo n = 71) completed the study. A significant percentage reduction in LVM was observed in AP group vs baseline (-2.7%, p 0.0001), and compared to placebo (-4.1%, p 0.0001), and remained significant after adjustment for age, sex, baseline systolic BP and BMI and their changes during the study period. The proportion of subjects showing LVM reduction was higher in AP group than in the placebo group (57% vs 28%, adjusted p = 0.007). Treatment with AP was associated with improvement of lipid profile.24-week of treatment with AP is associated with a significant reduction in LVM in subjects with MS and LVH, in addition to favourable effects on lipid profile, and could represent an effective strategy aiming at reducing the associated cardiovascular risk. The trial was registered at clinicaltrials.gov with ID NCT02295176.

Background The phase II multicenter, randomized, open label, therapeutic trial (ISS T-002, Clinicaltrials.gov NCT00751595) was aimed at evaluating the immunogenicity and the safety of the biologically active HIV-1 Tat protein administered at 7.5 or 30 μg, given 3 or 5 times monthly, and at exploring immunological and virological disease biomarkers. The study duration was 48 weeks, however, vaccinees were followed until the last enrolled subject reached the 48 weeks. Reported are final data up to 144 weeks of follow-up. The ISS T-002 trial was conducted in 11 clinical centers in Italy on 168 HIV positive subjects under Highly Active Antiretroviral Therapy (HAART), anti-Tat Antibody (Ab) negative at baseline, with plasma viremia

Pulmonary arterial hypertension (PAH) is a rare disease characterized by a dramatic, progressive rise of pulmonary vascular resistance (PVR), leading to elevated pulmonary artery pressures, right ventricular (RV) overload, and, eventually, failure. Current evaluation of PAH is based on invasive hemodynamics (RHC), exercise capacity, echocardiography, and N-terminal pro brain natriuretic peptide (NT-proBNP) levels [1]; although published survival data support a strong clinical role for cardiac magnetic resonance imaging (CMR) of the RV, this technique is still underused [2]. Much research is currently focusing on the exploration of candidate soluble biomarkers of RV dysfunction and prognosis. Soluble ST2 (sST2) is a member of the interleukin 1-receptor family, which increases in response to acute and chronic cardiomyocyte strain [3]; its circulating levels rise in chronic and acutely decompensated heart failure, and the extent of their elevation seems to be especially related to the presence and severity of RV compromise [4,5]. The circulating ligand of sST2, interleukin 33 (IL-33), probably plays a role in several inflammatory states. The aimof the present studywas to assess peripheral serumlevels of sST2 and IL-33 in a group of patients with PAH of different etiology and severity compared with healthy controls, and to explore their possible relation with clinical features and with parameters of RV remodeling and failure as measured by CMR.

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

We describe a new mantellid frog of the subfamily Mantellinae from the karstic Bemaraha Plateau, western Madagascar. The new species belongs to the genus Gephyromantis, subgenus Phylacomantis, which previously included G. azzurrae, G. corvus and G. pseudoasper. Gephyromantis atsingy sp. n. has a snout-vent length of 35–43 mm and is a scansorial frog living among the Tsingy de Bemaraha pinnacles and inside the caves present in the area. A morphological analysis and biomolecular comparison revealed the degree of differentiation between these four species of the Phylacomantis subgenus. The new species seems to be endemic to Tsingy de Bemaraha.