Simulating the development and progression of Chronic Kidney Disease and osteoporosis in people living with HIV

The "chronicization" of HIV infection brings about a growing necessity to attentively evaluate current and potential complications when prescribing the individual therapeutic regimen. Starting from this need, we developed two HIV-comorbidity simulators that, basing on the evidence available in medical literature and starting from the current clinical and demographic features of the individual patient, project and compare the risks of developing and worsening of nephropathy and osteopathy associated with possible ARV regimens. These simulators are embedded in a desktop, user-friendly software thought to be used by the treating physician during prescription discussion with his/her patients, in order to highlight expected clinical outcomes and healthcare resource consumption that may differ according to the therapeutic strategy selected. In this article we present the sources and methods used in developing the mathematical models, alongside a set of examples and the results of cohort-level validation runs

Marked increase in etravirine and saquinavir plasma concentrations during atovaquone/proguanil prophylaxis

The case of a 32-year-old Caucasian female with multi-drug resistant HIV-1 subtype B infection treated with a salvage regimen including maraviroc, raltegravir, etravirine and unboosted saquinavir who started atovaquone/proguanil prophylaxis, is reported. The potential interactions between atovaquone/proguanil and these anti-retroviral drugs are investigated. Pharmacokinetic analyses documented a marked increase in etravirine and saquinavir plasma concentrations (+55% and +274%, respectively), but not in raltegravir and maraviroc plasma concentrations. The evidence that atovaquone/proguanil significantly interacts with etravirine and saquinavir, but not with raltegravir and maraviroc, suggests that the mechanism of interaction is related to cytochrome P450

Genetic divergence of HIV-1 B subtype in Italy over the years 2003\u20132016 and impact on CTL escape prevalence

HIV-1 is characterized by high genetic variability, with implications for spread, and immune-escape selection. Here, the genetic modification of HIV-1 B subtype over time was evaluated on 3,328 pol and 1,152 V3 sequences belonging to B subtype and collected from individuals diagnosed in Italy between 2003 and 2016. Sequences were analyzed for genetic-distance from consensus-B (Tajima-Nei), non-synonymous and synonymous rates (dN and dS), CTL escapes, and intra-host evolution over four time-spans (2003\u20132006, 2007\u20132009, 2010\u20132012, 2013\u20132016). Genetic-distance increased over time for both pol and V3 sequences (P < 0.0001 and 0.0003). Similar results were obtained for dN and dS. Entropy-value significantly increased at 16 pol and two V3 amino acid positions. Seven of them were CTL escape positions (protease: 71; reverse-transcriptase: 35, 162, 177, 202, 207, 211). Sequences with 653 CTL escapes increased from 36.1% in 2003\u20132006 to 54.0% in 2013\u20132016 (P < 0.0001), and showed better intra-host adaptation than those containing 642 CTL escapes (intra-host evolution: 3.0 7 10 123 [2.9 7 10 123\u20133.1 7 10 123] vs. 4.3 7 10 123 [4.0 7 10 123\u20135.0 7 10 123], P[LRT] < 0.0001[21.09]). These data provide evidence of still ongoing modifications, involving CTL escape mutations, in circulating HIV-1 B subtype in Italy. These modifications might affect the process of HIV-1 adaptation to the host, as suggested by the slow intra-host evolution characterizing viruses with a high number of CTL escapes

Haemolytic anaemia in an HIV-infected patient with severe falciparum malaria after treatment with oral artemether-lumefantrine

Intravenous (i.v.) artesunate is now the recommended first-line treatment of severe falciparum malaria in adults and children by WHO guidelines. Nevertheless, several cases of haemolytic anaemia due to i.v. artesunate treatment have been reported. This paper describes the case of an HIV-infected patient with severe falciparum malaria who was diagnosed with haemolytic anaemia after treatment with oral artemether-lumefantrine

Humoral and cellular immune response elicited by mRNA vaccination against SARS-CoV-2 in people living with HIV (PLWH) receiving antiretroviral therapy (ART) according with current CD4 T-lymphocyte count

BACKGROUND: Data on SARS-CoV-2 vaccine immunogenicity in PLWH are currently limited. Aim of the study was to investigate immunogenicity according to current CD4 T-cell count. METHODS: PLWH on ART attending a SARS-CoV-2 vaccination program, were included in a prospective immunogenicity evaluation after receiving BNT162b2 or mRNA-1273. Participants were stratified by current CD4 T-cell count (poor CD4 recovery, PCDR: 500/mm^{3}). RBD-binding IgG, SARS-CoV-2 neutralizing antibodies (nAbs) and IFN-γ release were measured. As control group, HIV-negative healthcare workers (HCWs) were used. FINDINGS: Among 166 PLWH after 1 month from the second dose, detectable RBD-binding IgG were elicited in 86.7% of PCDR, 100% of ICDR, 98.7% of HCDR, and a neutralizing titre ≥1:10 elicited in 70.0%, 88.2% and 93.1%, respectively. Compared to HCDR, all immune response parameters were significantly lower in PCDR. After adjusting for confounders, current CD4 T-cell 500 cell/mm^{3} and HIV-negative controls. A decreased RBD-binding antibody response than HCWs was also observed in PLWH with CD4 T-cell 200-500/mm^{3}, whereas immune response elicited in PLWH with a CD4 T-cell >500/mm^{}3 was comparable to HIV-negative population

Cardiovascular disease in women with HIV-1 infection

Cardiovascular disease is a leading cause of death in women, nevertheless it is often underestimated in female patients without overt risk factors. The chronic infection by Human Immunodeficiency Virus (HIV) is clearly associated, along with the use of certain antiretroviral drugs and traditional risk factors, with an increased risk of cardiovascular diseases. The aim of this manuscript is to review the epidemiology, risk factors, pathogenesis, diagnostic approach, primary and secondary prevention strategies of cardiovascular disease in HIV-negative and HIV-positive female subjects. The ultimate goal is to promote knowledge and development of specific and appropriate clinical interventions and guidelines in this group of high-risk patients, mostly in view of the expected growth of ageing females with HIV

One Extra Gram of Protein to Preterm Infants from Birth to 1800 G: A Single Blinded Randomized Clinical Trial

OBJECTIVE: The aim of the study was to evaluate the effect on growth and neurodevelopment of increasing amino acid (AA) during parenteral nutrition and protein intake during enteral nutrition in extremely low birth-weight infants starting from birth to day of reaching 1800 g body weight. METHODS: We randomized preterm infants with birth weight 500 to 1249 g either to a high AA/protein intake (HiP [high protein]: parenteral nutrition = 3.5 AA, enteral nutrition = 4.6 protein g · kg · day) or to a standard of care group (StP [standard protein]: parenteral nutrition = 2.5 AA, enteral nutrition = 3.6 protein g · kg · day). The primary outcome was weight gain from birth to 1800 g. RESULTS: TWO:: hundred twenty-six patients were screened, 164 completed the study and were analyzed (82 StP and 82 HiP). Cumulative AA/protein intake from birth to 1800 g was 178 ± 42 versus 223 ± 45 g/kg in the StP versus HiP group respectively, P < 0.0001.Blood urea was higher in HiP than in StP group both during parenteral and enteral nutrition (P = 0.004).Weight gain from birth to 1800 g was 12.3 ± 1.6 in StP and 12.6 ± 1.7 g · kg · day in HiP group (P = 0.294). We found no difference in any growth parameters neither during hospital stay nor at 2 years corrected age. Bayley III score at 24 months corrected age was 93.8 ± 12.9 in StP group and 94.0 ± 13.9 in the HiP group, P = 0.92. CONCLUSIONS: Increasing AA/protein intake both during parenteral and enteral nutrition does not improve growth and neurodevelopment of small preterm infants 500 to 1249 g birth weight

Feasibility and safety of endovascular treatment for chronic cerebrospinal venous insufficiency in patients with multiple sclerosis

Objective Chronic cerebrospinal venous insufficiency (CCSVI) is a recently discovered syndrome mainly due to stenoses of internal jugular (IJV) and/or azygos (AZ) veins. The present study retrospectively evaluates the feasibility and safety of endovascular treatment for CCSVI in a cohort of patients with multiple sclerosis (MS). Methods From September 2010 to October 2012, 1202 consecutive patients were admitted to undergo phlebograpy ± endovascular treatment for CCSVI. All the patients had previously been found positive at color Doppler sonography (CDS) for at least two Zamboni criteria for CCSVI and had a neurologist-confirmed diagnosis of MS. Only symptomatic MS were considered for treatment. Percutaneous transluminal angioplasty was carried out as an outpatient procedure at two different institutes. Primary procedures, regarded as the first balloon angioplasty ever performed for CCSVI, and secondary (reintervention) procedures, regarded as interventions performed after venous disease recurrence, were carried out in 86.5% (1037 of 1199) and 13.5% (162 of 1199) of patients, respectively. Procedural success and complications within 30 days were recorded. Results Phlebography followed by endovascular recanalization was carried out in 1999 patients consisting of 1219 interventions. Balloon angioplasty alone was performed in 1205 out of 1219 (98.9%) procedures, whereas additional stent placement was required in the remaining 14 procedures (1.1%) following unsuccessful attempts at AZ dilatation. No stents were ever implanted in the IJV. The feasibility rate was as high as 99.2% (1209 interventions). Major complications included one (0.1%) AZ rupture occurring during balloon dilatation and requiring blood transfusion, one (0.1%) severe bleeding in the groin requiring open surgery, two (0.2%) surgical openings of the common femoral vein to remove balloon fragments, and three (0.2%) left IJV thromboses. The overall major and minor complication rates at 30 days were 0.6% and 2.5%, respectively. Conclusions Endovascular treatment for CCSVI appears feasible and safe. However, a proper learning curve can dramatically lower the rate of adverse events. In our experience, the vast majority of complications occurred in the first 400 cases performed. Copyright © 2013 by the Society for Vascular Surgery

Higher Docosahexaenoic acid, lower Arachidonic acid and reduced lipid tolerance with high doses of a lipid emulsion containing 15% fish oil: A randomized clinical trial

8noBackground & aims: Lipid emulsions containing fish oil, as source of long chain omega 3 fatty acids, have recently became available for parenteral nutrition in infants, but scanty data exist in extremely low birth weight preterms. The objective of this study was to compare plasma fatty acids and lipid tolerance in preterm infants receiving different doses of a 15% fish oil vs. a soybean oil based lipid emulsion. Methods: Preterm infants (birth weight 500-1249 g) were randomized to receive parenteral nutrition with MOSF (30% Medium-chain triglycerides, 25% Olive oil, 30% Soybean oil, 15% Fish oil) or S (S, 100% Soybean oil) both at two levels of fat intake: 2.5 or 3.5 g kg(-1) d(-1), named 2.5Fat and 3.5Fat respectively. Plasma lipid classes and their fatty acid composition were determined on postnatal day 7 and 14 by gas chromatography together with routine biochemistry. Results: We studied 80 infants. MOSF infants had significantly higher plasma phospholipid Docosahexaenoic acid and Eicosapentaenoic and lower Arachidonic acid. Plasma phospholipids, triglycerides and free cholesterol were all significantly higher in the MOSF-3.5Fat group, while cholesterol esters were lower with MOSF than with S. The area under the curve of total bilirubin was significantly lower with MOSF than with S. Conclusions: The use of a lipid emulsion with 15% FO resulted in marked changes of plasma long-chain fatty acids. Whether the benefits of increasing Docosahexaenoic acid outweigh the potential negative effect of reduced Arachidonic acid should be further studied. MOSF patients exhibited reduced lipid tolerance at 3.5 g kg(-1) d(-1) fat intake.reservedmixedD'Ascenzo, Rita; Savini, Sara; Biagetti, Chiara; Bellagamba, Maria P.; Marchionni, Paolo; Pompilio, Adriana; Cogo, Paola E.; Carnielli, Virgilio P.D'Ascenzo, Rita; Savini, Sara; Biagetti, Chiara; Bellagamba, Maria P.; Marchionni, Paolo; Pompilio, Adriana; Cogo, Paola; Carnielli, Virgilio P