Alessandro Lazzaro

Background: People with HIV (PWH) are at higher risk of cardiovascular disease (CVD) despite spontaneous or antiretroviral therapy‐induced long‐lasting suppressed viremia. Traditional and HIV‐specific factors have been identified, but CVD incidence and mortality remain high. A microbiome is a community of germs living close to their human host, and bacterial dysbiosis is associated with atherosclerosis and chronic non‐communicable disease development. Methods: We conducted a pilot study designed to analyze the effect of tailored diet intervention on body mass index (BMI), metabolic features and microbiota composition in PWH with suppressed HIV viremia (HIV RNA 3 (398–625). Approximately 75% of participants declared to be adherent to the given dietary recommendations. Participants showed reduced amounts of food intake ( p = 0.022) and, specifically, of saturated fat ( p = 0.007) and cholesterol ( p = 0.011). At M6, most metabolic and inflammatory parameters remained stable. TMAO concentrations were higher at M6 than at baseline (157 vs. 129 ng/mL, p = 0.050). Microbiota alpha and beta diversity did not change over time: yet we observed a significant reduction of Firmicutes ( p = 0.047) and an increase in Proteobacteria ( p = 0.028) relative abundance at M6. Conclusions: In this pilot study assessing a tailored dietary intervention in high CV‐risk PWH, we observed stable metabolic and inflammatory parameters and an unexpected increase in TMAO levels at 6 months. Microbiome composition was marginally affected, and active interventions are probably needed to elicit significant changes over time.

This study examined changes in anti‐Spike (anti‐S) antibodies (Abs) and type I interferon (IFN‐I) following the BNT162b2 vaccine in people living with HIV (PLWH) and analyzed the impact of demographic and immunological factors. In total, 75 PLWH and 28 healthy donors were followed at baseline (T0), at the second dose (T1), after the second dose (T2), and more than 1 year later (T3). Anti‐S Abs were assessed by chemiluminescence and vesicular stomatitis virus (VSV)‐based pseudo virus‐neutralization assay, while IFN‐α2, IFN‐β, and IFN‐ω mRNA levels were measured by RT‐Real Time PCR. PLWH showed an increase in anti‐S Immunoglobulin G (IgG) levels comparable to healthy donors ( p < 0.001) and an induction of anti‐S neutralizing Abs ( p < 0.014 for T2 vs. T3). Age, gender, CD4 ⁺ T cell count, exposure to combined antiretroviral therapy (cART) and IFN‐I levels at T0 did not affect the anti‐S IgG production. IFN‐I gene expression showed temporal changes, with a decrease at T2 ( p < 0.01) and a subsequent increase at T3 ( p < 0.001, for IFN‐α2 and IFN‐ω). A multivariable model revealed no overall change in the IFN‐I response over time, except for IFN‐β, which was lower at T3 than at T1 ( p = 0.032). CD4 ⁺ T cell count was positively correlated with the IFN‐I response ( p < 0.05). These results suggest that mRNA vaccination can elicit an effective anti‐S response and modulate the IFN‐β gene expression in PLWH, with CD4 ⁺ T cell count being a key determinant of vaccine‐induced changes in IFN.

Doravirine (DOR) is a novel antiretroviral agent with a favorable resistance profile and high tolerability. However, evidence is limited on DOR among elderly people living with HIV (PLWH) and whether it might modulate chronic inflammation. We aimed to investigate the efficacy, safety, and tolerability of DOR as a switching strategy among elderly PLWH and its impact on chronic inflammation in a real-life setting. We recruited a cohort of ART-experienced PLWH undergoing a therapeutic switch to a DOR-based regimen under virologic control (defined as HIV-RNA CIs : 91.0%–98.7%) in the per-protocol analysis. After 48 weeks from the switch, we recorded significant reductions in serum fasting glycemia ( P 0.019), triglycerides ( P 0.024), and total cholesterol/HDL ratio ( P 0.017); no clinically significant differences were detected in the body weight and BMI, as long as in immune, hepatic, and renal profiles. A significant reduction in IL-6 ( P 0.019) and hs-CRP ( P 0.019) was observed. DOR is an effective and safe treatment choice for elderly PLWH. The intriguing modulatory effect of DOR-based regimens on chronic systemic inflammation deserves further investigation.

Background: The pathogenesis of HIV-associated neurocognitive (NC) impairment is multifactorial, and antiretroviral (ARV) neurotoxicity may contribute. However, interventional pharmacological studies are limited. Methods: Single-blind, randomized (1:1), controlled trial to assess the change of NC performance (Global Deficit Score, GDS, and domain scores) in PLWH with NC impairment randomized to continue their standard of care treatment or to switch to a less neurotoxic ARV regimen: darunavir/cobicistat, maraviroc, emtricitabine (MARAND-X). Participants had plasma and cerebrospinal fluid HIV RNA< 50 copies/mL, R5-tropic HIV, and were on ARV regimens that did not include efavirenz and darunavir. The change of resting-state electroencephalography was also evaluated. The outcomes were assessed at week 24 of the intervention through tests for longitudinal paired data and mixed-effect models. Results: Thirty-eight participants were enrolled and 28 completed the follow-up. Global Deficit Score improved over time but with no difference between arms in longitudinal adjusted models. Perceptual functions improved in the MARAND-X, while long-term memory improved only in participants within the MARAND-X for whom the central nervous system penetration-effectiveness (CNS penetration effectiveness) score increased by ≥3. No significant changes in resting-state electroencephalography were observed. Conclusions: In this small but well-controlled study, the use of less neurotoxic ARV showed no major beneficial effect over an unchanged regimen. The beneficial effects on the memory domain of increasing CNS penetration effectiveness score suggest that ARV neuropenetration may have a role in cognitive function.

Microbiota plays a crucial role in intestinal maturation in preterm newborns. The clinical manifestation of the immaturity of the gastro-intestinal tract is called feeding intolerance (FI). This condition may resolve spontaneously or dramatically evolve into necrotizing enterocolitis. One of the most challenging tasks for the neonatologist is to identify those neonates that will develop the disease early in order to adequately provide nutrition to these patients, from the very first hours of life. A close interplay between the maturity of the gastro-intestinal tract and gut microbiota has been described; however, in preterm neonates, this relationship is still undefined. We analyzed the bacterial composition of stool samples, collected early in life, from 30 preterm newborns classified as intolerant or tolerant according to the degree of readiness of the gastro-intestinal tract to receive enteral nutrition. The Pielou evenness index was significantly increased in intolerant compared with tolerant newborns. Data corrected for confounding variables confirmed that the occurrence of gut maturation was independently influenced by Pielou evenness at birth. A lower bacterial diversity very early in life is associated with improved feeding tolerance in preterm newborns. The abundance analysis showed that neonates not ready to receive enteral nutrition for feeding intolerance show, after birth, an increased abundance of Proteobacteria, Lachnospiracae, Enterobacter and Acinetobacter. We can argue that those are the taxa that prevent the establishment of pioneer bacteria. A lower alpha-diversity, in the first days of life, may facilitate the seeding of beneficial pioneer bacteria that, in turn, drive healthy microbial colonization during neonatal life.

Given the various clinical manifestations that characterize Coronavirus Disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant proteins A (SP-A) and D (SP-D) are collectins that play a crucial role in ensuring proper alveolar function and an alteration of their serum levels was reported in several pulmonary diseases characterized by Acute Respiratory Distress Syndrome (ARDS) and pulmonary fibrosis. Considering that such clinical manifestations can also occur during Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. In this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n = 51) at admission (T0) and after seven days (T1) and compared with healthy donors (n = 11). SP-D increased in COVID-19 patients compared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. In light of these results, SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia, and the early detection of SP-D serum levels could be crucial for preventive clinical management.

Background: given the various clinical manifestations that characterize coronavirus disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant protein A (SP-A) and D (SP-D) play a crucial role in ensuring proper alveolar function and an alteration of their serum levels have been reported in several pulmonary diseases characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Consid-ering that such clinical manifestations can also occur during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. Methods: in this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n=51) at admission (T0) and after 7 days (T1) and compared with healthy donors (n=11). Results: SP-D increased in COVID-19 patients com-pared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. Conclusions: In the light of these results SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia and the early detection of SP-D serum levels could be crucial for a preventive clinical management.

Background: Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single-tablet regimen for the treatment of people living with HIV (PLWH). We aimed to assess efficacy, safety, and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years. Methods: We recruited an observational retrospective real-life cohort, including all PLWH who underwent a therapeutic switch to BIC/FTC/TAF, independently from the previous treatment regimen (the BICTEL cohort). Longitudinal nonparametric analyses and linear models were built. Results: After 96 weeks of follow-up, 164 PLWH were included, with 106 older than 55. Both the intention-to-treat and the per-protocol analysis showed low rates of virologic failure, independent of the pre-switch anchor drug. At week 96, a significant increase in CD4⁺ T cell count and in CD4⁺/CD8⁺ ratio was observed, inversely correlated with baseline immune status. Fasting serum lipid profile, total body weight, BMI, and hepatic function were not affected by the switch, without new onset of metabolic syndrome or weight gain. Compared to baseline, we observed a renal function worsening which is worthy of further follow-up. Conclusion: BIC/FTC/TAF is an effective, safe, and well-tolerated switching strategy for PLWH, especially among those older than 55.