Francesca Bovis's research while affiliated with Università degli Studi di Genova and other places

Background : Intravenous administration of zidovudine (ZDV) during labour is a key step for vertical HIV transmission (VT) prevention, but there is no evidence of benefit when maternal HIV-RNA at delivery is <50 copies/mL. The aim of this study is evaluating the appropriateness of intrapartum ZDV use in Italy. Methods : Observational study including mother-infant pairs with perinatal HIV exposure during 2002-2019, enrolled in the Italian Register for HIV Infection in Children. Univariable and multivariable logistic regression were used to evaluate factors associated with VT. Results : A total of 3,861 infants, born from 3,791 pregnancies were included. The frequency of ZDV use was 79.9%, 92.1%, 93.7% and 92.8% when HIV-RNA was not available, ≥400 copies, between 50 and 399 copies, and <50 copies/mL. Thirty-three out of 3861 (0.85%) infants were subsequently diagnosed with HIV, 25/3861 (0.6%) of them born to mothers receiving intrapartum ZDV, and 31 (93.9%) to mothers with HIV-RNA ≥50 copies/mL or not available. In women with HIV-RNA < 50 copies/mL, ART discontinuation during pregnancy was the strongest risk factor for VT (odds ratio, OR, 23.1, 95%CI 2.4-219.3), while a higher gestational age (OR 0.6, 95%CI 0.4-0.8) and PEP administration to the newborn (aOR 0.004, 95%CI <0.0001-0.4) were protective factors. Intrapartum ZDV administration did not influence the final outcome in this group. Conclusions : In ART era, more transmission events may occur in utero, limiting value of intrapartum ZDV, particularly for women with suppressed HIV-RNA load. More attention to the HIV-RNA testing of mothers before delivery may avoid unnecessary ZDV use.

The quantification of proviral DNA is raising interest in view of clinical management and functional HIV eradication. Measures of all unintegrated HIV DNA (uDNA) forms in infected reservoir cells provides information on recent replication events that is not found from other proviral DNA assays. To evaluate its actual relevance in a cohort of perinatally-infected adult HIV patients (PHIV), we studied how peripheral blood mononuclear cell uDNA levels correlated with total HIV DNA (tDNA) and with overall replication or innate immune control parameters including NK cell activation/exhaustion and lymphoid turnover. Twenty-two PHIV were included, with successfully controlled HIV (HIV RNA <50 copies/mL) on combined antiretroviral therapy for mean of 8.7 ± 3.9 years. uDNA accounted for 16 [5.2-83.5] copies/µg and was strongly correlated with tDNA (ρ=0.700, p=0.001). Flow cytometric analysis of peripheral NK cells showed that CD69 expression was directly correlated uDNA (p=0.0412), but not with tDNA. Interestingly, CD56⁻CD16⁺NK cells which include newly described inflammatory precursors and terminally differentiated cells were directly correlated with uDNA levels (p<0.001), but not with tDNA, and an inverse association was observed between the proportion of NKG2D⁺ NK cells and uDNA (ρ=-0.548, p=0.015). In addition, CD34⁺DNAM-1brightCXCR4⁺ inflammatory precursor frequency correlated directly with uDNA levels (ρ=0.579, p=0.0075). The frequencies of CD56⁻CD16⁺ and CD34⁺DNAM-1brightCXCR4⁺ cells maintained association with uDNA levels in a multivariable analysis (p=0.045 and p=0.168, respectively). Thus, control of HIV-1 reservoir in aviremic patients on ART is an active process associated with continuous NK cell intervention and turnover, even after many years of treatment. Quantification of linear and circular uDNA provides relevant information on the requirement for ongoing innate immune control in addition to ART, on recent replication history and may help stratify patients for functional HIV eradication protocols with targeted options.

Background: Surgical treatments for snoring and sleep-related symptoms are invasive, may have complications, have inconstant success rates, and may have a significant relapse rate. Methods: We evaluated the effectiveness of a non-surgical, non-invasive outpatient 808 nm diode laser treatment. Forty-five patients with snoring and sleep disorders were treated with an Elexxion-Claros® 50W Diode Laser 808-nm using the specific SNORE3 application. The possible presence of obstructive sleep apnea syndrome in patients was diagnosed with Polysomnography. The Epworth sleepiness scale was reported pre- and post-laser treatments. Patients were classified according to both Friedman tongue position and Mallampati classification. During treatment, the pain reported by patients was measured on a visual analogue scale. Results: The following data improved significantly: visual analogue scale for the loudness of snoring, Epworth sleepiness scale, waking up during sleep because of snoring, dreaming during the night, dry mouth on awakening, daytime sleepiness, tiredness on awakening, Mallampati score, Friedman tongue position and degree of oropharynx at nose, oropharynx, hypopharynx, and larynx classification (p < 0.001). A cessation of choking in 89% of the patients and of restless legs syndrome in 83% of the patients (p ≤ 0.005 and p ≤ 0.025) was also noted after the laser treatments. All of the patients who reported suffering from headaches upon waking (10 subjects) reported the complete cessation of this phenomenon after laser therapy. Conclusions: diode laser treatment is a promising procedure not only in reducing the loudness of snoring, but also in raising the global quality of sleep, a statistically significant reduction of AHI, and a cessation of bothersome phenomenon related to apnea. Results were sustainable at one year post-treatment.

The aim of the present study is to evaluate if an independent association exists between liver enzyme elevations (LEE) and the risk of mortality or intensive care unit (ICU) admissions in patients with COVID-19. This was a single-center observational study, recruiting all consecutive adults with COVID-19. The elevation of aspartate aminotransferase (AST) or alanine aminotransferase (ALT) to the highest level between COVID-19 diagnosis and hospital discharge was categorized according to a standardized toxicity grade scale. In total, 799 patients were included in this study, 39% of which were female, with a mean age of 69.9 (±16.0) years. Of these patients, 225 (28.1%) developed LEE of grade ≥2 after a median of three days (interquartile range (IQR): 0–8 days) from the diagnosis of COVID-19, and they were estimated to have a higher hazard of death or ICU admission (adjusted hazard ratio (aHR): 1.46, 95% confidence interval (CI): 1.14–1.88). The clinical and laboratory variables associated with the development of LEE were male sex, higher respiratory rate, higher gamma glutamyl transpeptidase (GGT) and lower albumin levels at baseline. Among the analyzed treatments, steroids, tocilizumab and darunavir/ritonavir correlated with LEE. In conclusion, LEE were associated with mortality and ICU admission among COVID-19 patients. While the origin of LEE is probably multifactorial, LEE evaluation could add information to the clinical and laboratory variables that are commonly evaluated during the course of COVID-19.

Among people with perinatal HIV infection (PHIV), non-communicable diseases, such as chronic kidney disease, are increasing. Both HIV replication and antiretroviral therapy are recognised causes of renal impairment. Objective of the study is to describe the impact of viremia copy-years (VCY) and antiretroviral therapy on trend of estimated glomerular filtration rate (eGFR) in a cohort of adults with perinatal HIV infection. We conducted a multicentre observational study in sixty adults living with PHIV across a 9-year period, from January 2010 to December 2018. The mean values of eGFR were analysed at the first (T0) and last year of observation (T1). VCY was defined as the area under HIV-RNA curve during the study period. We analysed data according to antiretroviral therapy: tenofovir disoproxil (TDF), non-nucleoside reverse transcriptase inhibitors (NNRTI), boosted protease inhibitors (PI/b), integrase inhibitors (INI). We observed a mean overall eGFR reduction from 126.6 mL/min (95%CI: 119.6–133.5) to 105.0 mL/min (95%CI: 99.55–110.6) (p<0.001). Older age, higher baseline eGFR, higher VCY and longer exposure to INI treatment were associated with eGFR reduction at univariate analysis. In the multivariate model, older age (p = 0.039), baseline eGFR (p<0.001) and VCY (p = 0.069), were retained. We also observed a longer exposure to PI/b and INI in patients with lower control on HIV-RNA, expressed as VCY>2 log10. Our study outlines a progressive eGFR reduction in young adults with PHIV, related to the lower control on HIV-RNA VCY and related to aging.

An unexpected increase in weight gain has recently been reported in the course of integrase strand transfer inhibitors (INSTI) treatment. The possibility of this effect in people who are perinatally infected with HIV (PHIV) and thus exposed to lifelong therapy needs to be explored. This is a retrospective multicenter case-control study. Adults with PHIV followed between 2010 and 2019 in two outpatient services in Northern Italy were included if they had at least two weight measures in two successive years of observation. Patients were considered as cases if they were switched to INSTI (INSTI group), or controls if they were never exposed to INSTI (non-INSTI group). The date of the switch in cases was considered to be the baseline (T0), while it was randomly selected in controls. Mixed effect models were used to assess the weight changes in INSTI and non-INSTI groups. A total of 66 participants, 50.0% women, 92.4% Caucasian, were included. Median follow-up was 9 years (range 2–10): 4 years (range 1–8) before and 3 (range 1–9) after-T0. Mean age at the last study visit was 27.3 (±4.8) years, and mean CD4+ T-cells were 820.8 (±323.6) cells/mm3. Forty-five patients were switched to INSTI during the study, while 21 remained in the non-INSTI group. The INSTI group experienced a mean increase (pre-post T0) in bodyweight of 0.28 kg/year (95% CI − 0.29; 0.85, p = 0.338), while in the non-INSTI group, the mean increase was 0.36 kg/year (95% CI − 0.47; 1.20, p = 0.391), without a significant difference between groups (p for interaction between time and treatment regimen = 0.868). Among patients on INSTI, the weight gain after T0 was higher than pre-T0, amounting to +0.28 kg/year (95% CI − 0.29; 0.85), although this difference did not reach significance (p = 0.337). PHIV switched to an INSTI-based regimen did not experience an excessive weight gain compared to those who were treated with a non-INSTI based regimen in our cohort.

Retrospective multicentre study aiming at analysing the etiology, characteristics and outcome of bloodstream infections (BSI) in people living with HIV (PLWHIV) in an era of modern antiretroviral therapy. Between 2008 and 2015, 79 PLWHIV had at least 1 BSI, for a total of 119 pathogens isolated. Patients were mainly male (72.1%), previous intravenous drug users (55.7%), co-infected with HCV or HBV (58.2%) and in CDC stage C (60.8%). Gram-positive (G+) pathogens caused 44.5% of BSI, followed by Gram-negative (G−), 40.3%, fungi, 10.9%, and mycobacteria, 4.2%. Candida spp. and coagulase-negative staphylococci were the most frequent pathogens found in nosocomial BSI (17% each), while E.coli was prevalent in community-acquired BSI (25%). At the last available follow-up, (mean 3.2 ± 2.7 years) the overall crude mortality was 40.5%. Factors associated with mortality in the final multivariate analysis were older age, (p = 0.02; HR 3.8, 95%CI 1.2–11.7) CDC stage C (p = 0.02; HR 3.3, 95%CI 1.2–9.1), malignancies, (p = 0.004; HR 3.2, 95%CI 1.4–7.0) and end stage liver disease (p = 0.006; HR 3.4, 95%CI 1.4–8.0). In conclusion, the study found high mortality following BSI in PLWHIV. Older age, neoplastic comorbidities, end stage liver disease and advanced HIV stage were the main factors correlated to mortality.

In the originally published article, the name of the first author Isabelle Fini Storchi was labeled incorrectly. The correct name shown below: Given name: Isabelle. Family name: Fini Storchi.

Retention in care is a key feature of the cascade of continuum of care, playing an important role in achieving therapeutic success and being crucial for reduction of HIV transmission. The aim of this study was to evaluate the rate of retention in care in a large referral centre in the North of Italy and to identify predictors associated with failed retention. All new HIV-infected subjects were consecutive enrolled from 1 January 2008 to 31 December 2014. Demographics, immune-virological status, hepatitis co-infection and timing of initiation of combined antiretroviral therapy (cART) data were collected at baseline and at the time of last observation. Failed retention in care was defined as lack of laboratory data, clinical visits and drug dispensation for more than 6 months from the last visit. Cox regression analysis was used. Multivariate analysis of variables with P <0.05 in univariate analysis was performed. We enrolled 269 patients (mean age 46.1 years). Males were 197 (73%), Italian 219 (81%) with mean length of disease of 5.1 years. cART was prescribed for 257 patients (95%). The rate of retention in care was 78.4% and the rate of virological suppression was 75%. Predictors of being loss to follow-up were foreign origin ( P = 0.048), CD4+ count <200/mmc ( P = 0.001) and not being treated for HIV infection ( P = 0.0004). Predictors of cART efficacy were shorter duration of HIV infection and baseline HIV-RNA <100 000 copies/ml. These findings underline the necessity to improve retention in care by identifying groups at increased risk of being loss to follow-up. Retention in care of vulnerable population is crucial to reach 90-90-90 UNAIDS endpoint.

Complete dataset used to perform the statistical analysis. (XLSX)