The predictive role of NLR and PLR for solid non-AIDS defining cancer incidence in HIV-infected subjects: a MASTER cohort study

Patients’ characteristics according to lost to follow-up at 3-years. Table S2. Distribution of non-AIDS defining cancer. Table S3. Multivariate analysis: time dependent Cox regression model. Variables included in the full model. (DOCX 20 kb

The burden of chronic diseases and cost-of-care in subjects with HIV infection in a Health District of Northern Italy over a 12-year period compared to that of the general population

The increase in life expectancy of HIV-infected patients has driven increased costs due to life-long HIV treatment and concurrent age-related comorbidities. This population-based study aimed to investigate the burden of chronic diseases and health costs for HIV(+) subjects compared to the general population living in Brescia Local health Agency (LHA) over a 12-year period

Trends in methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections: effect of the MRSA "search and isolate" strategy in a hospital in Italy with hyperendemic MRSA

Abstract OBJECTIVE: To evaluate the secular trends in MRSA BSIs after the introduction of a nosocomial MRSA control intervention. DESIGN: Before-after study. SETTING: An 850-bed community hospital with an ICU and vascular surgery, neurosurgery, bone marrow transplantation, and AIDS units. MRSA is endemic at this hospital; the prevalence of methicillin resistance among patients with S. aureus infection is greater than 50%. PATIENTS: Among all inpatients, MRSA BSI was identified, its origin defined, and incidence rates calculated by ward and origin. INTERVENTION: A MRSA control program was implemented based on active surveillance cultures to identify MRSA-colonized patients, followed by isolation using contact precautions. Incidence rates of MRSA BSI during the intervention (i.e., July 1, 1997, to December 31, 2001) and preintervention (i.e., January 1, 1996, to June 30, 1997) periods were compared. RESULTS: Sixty-nine MRSA BSIs were identified. When compared with the preintervention period, the incidence rate of MRSA BSI was reduced from 0.64 to 0.30 per 1000 admissions (RR, 0.46; CI95, 0.25-0.87; P = .02) during the intervention period. The impact was greater in the ICU, with an 89% reduction (RR, 0.11; CI95, 0.01-0.98; P = .03), and for CVC-associated MRSA BSIs, with an 82% decrease (RR, 0.17; CI95, 0.05-0.55; P = .002). Methicillin resistance among S. aureus blood isolates decreased from 46% to 17% (RR, 0.36; CI95, 0.22-0.62; P = .0002). CONCLUSION: A reduction in MRSA bacteremia is achievable through use of the MRSA "search and isolate" intervention even in a hospital with high rates of endemic MRSA

Weight gain, obesity, and the impact of lifestyle factors among people living with HIV: A systematic review

HIV remains a significant health concern, but the advent of antiretroviral therapy (ART) has transformed it into a manageable chronic condition. However, weight gain and obesity pose a substantial challenge for people living with HIV (PLWH). Moreover, the role of lifestyle has not yet been comprehensively investigated. This review aims to provide an updated perspective on the role of lifestyle factors in weight gain and obesity among PLWH. A systematic search was conducted on Medline, Web of Science, Scopus, and ClinicalTrials.gov according to PRISMA guidelines. Overall, 378 articles were identified, of which 22 studies met the inclusion criteria. No article comprehensively addressed all lifestyle factors, and only 8 (36.4%) evaluated 3 or more factors. Addictions (72.7%), food (34.4%), and physical activity (31.8%) were the most analyzed aspects. An absence of concordance was identified among the articles concerning the timing of assessments, methodologies employed in surveys, and the operational definitions utilized for "weight gain," "overweight," and "obesity." Weight gain in PLWH represents a complex phenomenon necessitating a holistic approach to promote well-being in this vulnerable population

Cabotegravir Exposure of Zebrafish (Danio rerio) Embryos Impacts on Neurodevelopment and Behavior

As most new medications, Cabotegravir (CAB) was recently approved as an antiretroviral treatment of HIV infection without in-depth safety information on in utero exposure. Although no developmental toxicity in rats and rabbits was reported, recent studies demonstrated that CAB decreases pluripotency of human embryonic stem cells. CAB exposure effects during development were assessed in zebrafish embryos by the Fish Embryo Toxicity test after exposure at subtherapeutic concentrations up to 25x the human C-max. Larvae behavior was assessed by the light-dark locomotion test. The expression of factors involved in neurogenesis was evaluated by whole-mount in situ hybridization. CAB did not cause gross morphological defects at low doses, although pericardial edema, uninflated swim bladder, decreased heartbeats, growth delay, and decreased hatching rate were observed at the highest concentrations. Decreased locomotion was observed even at the subtherapeutic dose, suggesting alterations of nervous system integrity. This hypothesis was supported by the observation of decreased expression of crucial factors involved in early neuronal differentiation in diencephalic and telencephalic dopaminergic areas, midbrain/hindbrain boundary, and craniofacial ganglia. These findings support CAB effects on neurogenesis in zebrafish embryos and suggest long-term follow-up of exposed infants to provide data on drug safety during pregnancy

Comparison of Efavirenz and Doravirine Developmental Toxicity in an Embryo Animal Model

: In the past, one of the most widely used non-nucleoside reverse transcriptase inhibitors (NNRTI) in first-line antiretroviral therapy (ART) of HIV infection was efavirenz (EFV), which is already used as a cost-effective treatment in developing countries due to its efficacy, tolerability, and availability. However, EFV also demonstrates several adverse effects, like hepatotoxicity, altered lipid profile, neuropsychological symptoms, and behavioral effects in children after in utero exposure. In 2018, another NNRTI, doravirine (DOR), was approved due to its similar efficacy but better safety profile. Preclinical safety studies demonstrated that DOR is not genotoxic and exhibits no developmental toxicity or effects on fertility in rats. Zebrafish (Danio rerio) embryos have been widely accepted as a vertebrate model for pharmacological and developmental studies. We used zebrafish embryos as an in vivo model to investigate the developmental toxicity of DOR compared to EFV. After exposure of the embryos to the drugs from the gastrula stage up to different developmental stages (30 embryos for each arm, in three independent experiments), we assessed their survival, morphology, hatching rate, apoptosis in the developing head, locomotion behavior, vasculature development, and neutral lipid distribution. Overall, DOR showed a better safety profile than EFV in our model. Therapeutic and supra-therapeutic doses of DOR induced very low mortality [survival rates: 92, 90, 88, 88, and 81% at 1, 5, 10, 25, and 50 μM, respectively, at 24 h post fecundation (hpf), and 88, 85, 88, 89, and 75% at the same doses, respectively, at 48 hpf] and mild morphological alterations compared to EFV exposure also in the sub-therapeutic ranges (survival rates: 80, 77, 69, 63, and 44% at 1, 5, 10, 25, and 50 μM, respectively, at 24 hpf and 72, 70, 63, 52, and 0% at the same doses, respectively, at 48 hpf). Further, DOR only slightly affected the hatching rate at supra-therapeutic doses (97, 98, 96, 87, and 83% at 1, 5, 10, 25, and 50 μM, respectively, at 72 hpf), while EFV already strongly reduced hatching at sub-therapeutic doses (83, 49, 11, 0, and 0% at 1, 5, 10, 25, and 50 μM, respectively, at the same time endpoint). Both DOR at therapeutic doses and most severely EFV at sub-therapeutic doses enhanced apoptosis in the developing head during crucial phases of embryo neurodevelopment and perturbed the locomotor behavior. Furthermore, EFV strongly affected angiogenesis and disturbed neutral lipid homeostasis even at sub-therapeutic doses compared to DOR at therapeutic concentrations. Our findings in zebrafish embryos add further data confirming the higher safety of DOR with respect to EFV regarding embryo development, neurogenesis, angiogenesis, and lipid metabolism. Further studies are needed to explore the molecular mechanisms underlying the better pharmacological safety profile of DOR, and further human studies are required to confirm these results in the zebrafish animal model

Dolutegravir and Folic Acid Interaction during Neural System Development in Zebrafish Embryos

: Dolutegravir (DTG) is one of the most prescribed antiretroviral drugs for treating people with HIV infection, including women of child-bearing potential or pregnant. Nonetheless, neuropsychiatric symptoms are frequently reported. Early reports suggested that, probably in relation to folic acid (FA) shortage, DTG may induce neural tube defects in infants born to women taking the drug during pregnancy. Subsequent reports did not definitively confirm these findings. Recent studies in animal models have highlighted the association between DTG exposure in utero and congenital anomalies, and an increased risk of neurologic abnormalities in children exposed during in utero life has been reported. Underlying mechanisms for DTG-related neurologic symptoms and congenital anomalies are not fully understood. We aimed to deepen our knowledge on the neurodevelopmental effects of DTG exposure and further explore the protective role of FA by the use of zebrafish embryos. We treated embryos at 4 and up to 144 h post fertilization (hpf) with a subtherapeutic DTG concentration (1 μM) and observed the disruption of the anterior-posterior axis and several morphological malformations in the developing brain that were both prevented by pre-exposure (2 hpf) and rescued by post-exposure (10 hpf) with FA. By whole-mount in situ hybridization with riboprobes for genes that are crucial during the early phases of neurodevelopment (ntl, pax2a, ngn1, neurod1) and by in vivo visualization of the transgenic Tg(ngn1:EGFP) zebrafish line, we found that DTG induced severe neurodevelopmental defects over time in most regions of the nervous system (notochord, midbrain-hindbrain boundary, eye, forebrain, midbrain, hindbrain, spinal cord) that were mostly but not completely rescued by FA supplementation. Of note, we observed the disruption of ngn1 expression in the dopaminergic regions of the developing forebrain, spinal cord neurons and spinal motor neuron projections, with the depletion of the tyrosine hydroxylase (TH)+ dopaminergic neurons of the dorsal diencephalon and the strong reduction in larvae locomotion. Our study further supports previous evidence that DTG can interfere with FA pathways in the developing brain but also provides new insights regarding the mechanisms involved in the increased risk of DTG-associated fetal neurodevelopmental defects and adverse neurologic outcomes in in utero exposed children, suggesting the impairment of dopaminergic pathways

The impact of antiretroviral therapy on iron homeostasis and inflammation markers in HIV-infected patients with mild anemia

BACKGROUND: Anemia is frequent during HIV infection and is predictive of mortality. Although cART has demonstrated to reduce its prevalence, several patients still experience unresolved anemia. We aimed to characterize iron homeostasis and inflammation in HIV-infected individuals with mild anemia in relation to cART. METHODS: In this retrospective cohort study, HIV-infected patients with mild anemia, CD4+ cells > 200/mm3 at baseline, maintaining virological response for 12 months after cART starting were selected within the Standardized Management of Antiretroviral Therapy Cohort (MASTER) cohort. Several inflammation and immune activation markers and iron homeostasis indexes were measured in stored samples, obtained at cART initiation (T0) and 12 months later (T1). Patients were grouped on the basis of hemoglobin values at T1: group A (> 13 g/dl) and B (< 13 g/dl). Wilcoxon rank sum test was used to compare biomarker values. Pearson correlation coefficients were calculated for all variables. RESULTS: cART improved CD4+ and CD8+ cell counts and their ratio, but this effect was significant only in group A. Only these patients had mild iron deficiency at T0 and showed higher transferrin and lower percentage of transferrin saturation than patients of group B, but differences disappeared with cART. cART decreased inflammation in all patients, but group B had higher levels of all markers than group A, reaching statistical significance only for IL-8 values at T1 (16 vs 2.9 pg/ml; p = 0.017). Hepcidin and IL-6 levels did not show significant differences between groups. Hemoglobin levels both at T0 and T1 did not correlate with any marker. CONCLUSIONS: Baseline mild anemia in HIV-infected patients cannot always be resolved with durable efficient cART, possibly due to residual inflammation or immune activation rather than unbalanced iron homeostasis. Further research is needed on cytokine profiling to understand the mechanisms that induce anemia in HIV with suppressive cART