Long-term outcomes of bictegravir/emtricitabine/tenofovir alafenamide as first-line therapy and as switch strategy in virologically suppressed persons with HIV: data from the ICONA cohort.

OBJECTIVES: To assess the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among people poorly represented in clinical trials and potentially at higher risk of suboptimal response to ART. METHODS: Observational cohort study on persons with HIV (PWH) enrolled in ICONA who started BIC/FTC/TAF as initial therapy or as switching regimen while virologically suppressed. Primary endpoint was time to treatment failure (TF): new AIDS/death or virological failure (VF) or discontinuation for toxicity/failure. Secondary endpoints were time to treatment discontinuation for toxicity (TDT) and to VF. Groups of interest were those aged >50 years, female sex, and advanced HIV disease at first ART start. Probability of the events overall and according to groups and adjusted HR for every endpoint were calculated by Kaplan-Meier curves and Cox regression models. RESULTS: Nine hundred and thirty-three ART-naive and 1655 ART-experienced PWH initiated BIC/FTC/TAF. Over a median follow-up of 69.8 weeks, 89 (9.6%) PWH at their first regimen experienced TF. PWH aged >50 years had 1.83-fold (95% CI: 1.19-2.83) higher risk of TF; PWH with advanced HIV disease had 2.21-fold (95% CI: 1.53-3.82) higher risk; there were no differences in TF according to sex.Over a median follow-up of 146.3 weeks, 109 (6.6%) out of 1655 switching PWH experienced TF; no differences were found in the risk of TF, TDT and VF according to groups of interest. CONCLUSIONS: Overall, BIC/FTC/TAF is well tolerated and virologically effective in the real-world scenario for ART-naive and -experienced PWH. Older ART-naive PWH and those with advanced HIV disease may respond less well as the burden of diseases might compromise treatment efficacy.

Risk of Cardiovascular Events in People with HIV (PWH) Treated with Integrase Strand-Transfer Inhibitors: The Debate Is Not Over; Results of the SCOLTA Study.

Cardiovascular disease (CVD) is common in people with HIV (PWH), and has great impact in terms of morbidity and mortality. Several intertwined mechanisms are believed to play a role in determining the increased risk of CVD, including the effect of certain antiretrovirals; among these, the role of integrase strand-transfer inhibitors (INSTIs) is yet to be fully elucidated. We conducted a multicenter, observational study comprising 4984 PWH evaluating the antiretroviral therapy (ART)-related nature of CVD in real life settings, both in naïve vs. treatment-experienced people. A comparison was conducted between INSTIs vs. either protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) considering demographic, baseline clinical characteristics, incidence of CVD in both 2-year and complete follow-up periods. Among 2357 PWH exposed to INSTIs, 24 people experienced CVD; the corresponding figure was 12 cases out of 2599 PWH exposed to other ART classes. At univariate and multivariate analysis, a tendency towards an increased risk of CVD was observed in the 2-year follow-up period in PWH exposed to INSTIs in the absence, however, of statistical significance. These findings leave open the hypothesis that INSTIs may play a role, albeit minimal, in determining an increased risk of CVD in PWH.

Persistent poor clinical outcomes of people living with HIV presenting with AIDS and late HIV diagnosis - results from the ICONA cohort in Italy, 2009-2022.

OBJECTIVES: Limited data are available on the long-term outcomes in recent years for late HIV diagnosis (LD). METHODS: All subjects with HIV enrolled in the ICONA cohort in 2009-2022 who started antiretroviral treatment (ART) within 4 months from diagnosis were included and divided into: (i) pre-ART CD4 count ≥350/mm3 without AIDS (non-LD), (ii) pre-ART CD4 count <350/mm3 without AIDS (LD asymptomatic), and (iii) with AIDS events pre-ART (LD-AIDS). The estimated probability and independent risk for mortality (all-cause and cause-specific) and treatment failure were evaluated. RESULTS: Of 6813 participants (2448 non-LD, 3198 LD asymptomatic, and 1167 LD-AIDS), 161 (2.4%) died after ART initiation. At survival analysis, a higher probability of all-cause mortality has been identified for LD than non-LD (P <0.001) and within the former, for LD-AIDS over LD asymptomatic (P <0.001). After adjusting for confounders, LD showed a higher risk of all-cause mortality (vs non-LD adjusted hazard ratio (aHR) 5.51, P <0.001) and, in particular, being an AIDS presenter predicted a greater risk of all-cause (aHR = 4.42, P <0.001), AIDS-related (adjusted subhazard ratio [aSHR] = 16.86, P <0.001), and non-AIDS-related mortality (aSHR = 1.74, P = 0.022) than the rest of the late presenters. Among the short-term survivors in the LD-AIDS group, the long-term mortality was mediated by the lack of immune recovery at 2 years. Finally, LD compared with non-LD and, particularly, among the former, LD-AIDS over LD asymptomatic showed a greater risk of treatment failure. CONCLUSIONS: In recent years, LD subjects, particularly, AIDS presenters, remained at a higher risk of poorer outcomes. Public health strategies for early HIV diagnosis are urgently needed to constrain the mortality gap.

People with HIV pioneers of injectable cabotegravir and rilpivirine long acting in Italy: who are they?

Injectable cabotegravir and rilpivirine long-acting therapy is a revolutionary new antiretroviral treatment (ART) option for HIV infection in virologically suppressed adults on a stable ART. The aim of this study from SCOLTA multicenter observational prospective database is to describe the first people living with HIV (PWH) who started this regimen in Italy, assessing adherence to eligibility criteria, describing clinical-epidemiological characteristics compared to registration trials-population and describe early treatment-discontinuations.

Vaccination and Trust in the National Health System among HIV+ Patients: An Italian Cross-Sectional Survey.

BACKGROUND: This study aimed to evaluate the knowledge, attitudes, and practises (KAP) of individuals living with HIV (PLWH) regarding vaccines and their trust in the Italian national health system (NHS). METHODS: A cross-sectional survey was conducted at Amedeo di Savoia Hospital in Turin, Italy, involving 160 HIV-positive patients. Descriptive statistics were utilised to analyse variables such as vaccination status and intention, perceived risk of infection, and disease severity. The infections were categorised into sexually transmitted diseases and other vaccine-preventable diseases. RESULTS: Except for the perceived severity of infection, there were no significant differences in the percentages between the two infection groups for the variables examined. Concerning patients' perception of the Italian NHS, a high percentage of the sample believed in the information provided by healthcare workers (HCWs) (95.6%) and considered HCWs up-to-date on vaccines (93.1%). However, a considerable proportion expressed concerns about insufficient information on vaccine risks from HCWs (33.3%), perceived judgement by HCWs for vaccine refusal (40.3%), and suspected financial interests of HCWs in vaccination (19.5%). CONCLUSIONS: Some HIV+ patients may hesitate to be vaccinated or hold misconceptions about the severity of certain infectious diseases. Additionally, there are concerns about trust in the Italian NHS and communication by HCWs.

Real-life safety of Emtricitabine/Tenofovir Alafenamide/Bictegravir.

INTRODUCTION: Integrase strand transfer inhibitors (INSTI) are one of the most prescribed drug classes for the treatment of HIV infection worldwide. Emtricitabine/Tenofovir Alafenamide/ Bictegravir (FTC/TAF/BIC) has been evaluated in randomized clinical trials; few studies have verified tolerability and safety in clinical practice. Our aim was to investigate the metabolic and hepatic safety in a real-life setting of FTC/TAF/BIC. MATERIALS AND METHODS: Consecutive people living with HIV infection (PLWH) enrolled in the SCOLTA project, switching to or initiating their first antiretroviral treatment with FTC/TAF/BIC were included. PLWH with HBV co-infection were excluded. Metabolic and hepatic variables were collected at T0 and T1, were defined as baseline and 6-month follow-up respectively, and their modifications were analysed using the paired t-test and the analysis of variance. RESULTS: Five hundred and thirty-nine PLWH with at least one follow-up visit were included in the analysis. Mean age was 48 years (±12.1), 74% were male, 16.1% were naïve to antiretrovirals (ART). At T1, ART-experienced PLWH showed a significant reduction of total cholesterol (TC) and triglycerides, and a slight increase in blood glucose (BG) and ALT. On the contrary, in ART-naïve PLWH blood lipids significantly increased, although with an unaffected TC/high density lipoprotein (HDL)-c ratio, while alanine aminotransferase (ALT) decreased significantly, mainly in those with altered baseline level. The treatment interruptions were 45 (8.4%) over the whole observation period, 13 (2.4%) due to AEs. The most frequent AEs were related to the central nervous system (6 events of depression, insomnia, headache, agitation) and 3 PLWH discontinued the regimen because of grade 1-2 weight gain. CONCLUSIONS: In ART-experienced PLWH switching to FTC/TAF/BIC a significant improvement of lipid profile occurred but with significant BG and ALT variation without clinical relevance. In ART-naïve PLWH, blood lipids increased even though lipid profile did not worsen, and a trend towards normalization of liver enzymes was suggested. FTC/TAF/BIC is well tolerated in the real life setting.

Lipids and Transaminase in Antiretroviral-Treatment-Experienced People Living with HIV, Switching to a Doravirine-Based vs. a Rilpivirine-Based Regimen: Data from a Real-Life Setting.

Doravirine (DOR) is a newly approved non-nucleoside reverse transcriptase inhibitor (NNRTI). We aimed to investigate, in a real-life setting, how switching to a DOR-based regimen rather than a rilpivirine (RPV)-based regimen impacted metabolic and hepatic safety. The analysis included 551 antiretroviral treatment (ART)-experienced people living with HIV (PLWH), starting RPV-based or DOR-based regimens with viral load < 200 copies/mL, baseline (T0), and at least one control visit (6-month visit, T1). We enrolled 295 PLWH in the RPV and 256 in the DOR cohort. At T1, total cholesterol (TC), low-density lipoprotein-C (LDL-C), and triglycerides significantly decreased in both DOR and RPV cohorts, while high-density lipoprotein-C (HDL-C) only decreased in RPV-treated people. Consistently, the TC/HDL-C ratio declined more markedly in the DOR (-0.36, p < 0.0001) than in the RPV cohort (-0.08, p = 0.25) (comparison p = 0.39). Similar trends were observed when excluding the PLWH on lipid-lowering treatment from the analysis. People with normal alanine aminotransferase (ALT) levels showed a slight ALT increase in both cohorts, and those with baseline ALT > 40 IU/L experienced a significant decline (-14 IU/L, p = 0.008) only in the DOR cohort. Lipid profile improved in both cohorts, and there was a significant reduction in ALT in PLWH with higher-than-normal baseline levels on DOR-based ART.

Lipids and transaminase elevations in ARV-experienced PLWH switching to a doravirine-based regimen from rilpivirine or other regimens.

BACKGROUND: Doravirine (DOR) is a newly approved antiretroviral belonging to the class of non-nucleoside reverse transcriptase inhibitors (NNRTI), well tolerated and leading to an improved lipid profile in antiretroviral experienced people living with HIV (PLWH). We aimed at evaluating if the lipid-lowering effect is linked to the drug class, using real-life data from the SCOLTA cohort. METHODS: We compared the lipid profile modifications in experienced PLWH switching to a DOR-based regimen from rilpivirine or another NNRTI-based regimen or from an integrase strand transferase (INSTI)-based regimen. T0 and T1 were defined as the baseline and 6-month follow-up respectively. Data were collected at baseline and prospectively every six months and changes from baseline were compared using a multivariable linear model. RESULTS: In 107 PLWH, enrolled in the SCOLTA DOR cohort, with undetectable HIV-RNA at baseline, 32.7% switched from RPV-based regimens (DOR1), 29.9% from other NNRTI-including regimens (DOR2) and 37.4% switched from INSTI-including regimens (DOR3). At T1, TC significantly decreased in DOR2 (-15 mg/dL) and DOR3 (-23 mg/dL), and significantly more in DOR3 than in DOR1 (-6 mg/dL) (p = 0.016). HDL-C declined in DOR2 (-2 mg/dL) whereas it increased in DOR1 (+ 3 mg/dL) (p = 0.042) and remained stable in DOR3. LDL-C significantly decreased from baseline in DOR2 (-12 mg/dL) and DOR3 (-22 mg/dL) and was different between DOR1 (-8 mg/dL) and DOR3 (p = 0.022). TC/HDL ratio showed a significant decline in the DOR3 group (-0.45), although similar to DOR1 (-0.23, p = 0.315) and DOR2 (-0.19, p = 0.254). Triglycerides did not noticeably change. ALT significantly decreased in PLWH with a baseline level > 40 UI/mL. CONCLUSIONS: PLWH on doravirine treatment showed different trends in blood lipids according to their previous regimen. In PLWH switching from RPV, minimal modifications were seen, whereas in those switching from other NNRTIs and from INSTI-including regimens, we observed an overall improvement in lipid profile, seemingly independent of the "statin effect" of TDF.

Causes of HIV Treatment Interruption during the Last 20 Years: A Multi-Cohort Real-Life Study.

In the last years, many antiretroviral drugs (ART) have been developed with increased efficacy. Nowadays, the main reasons for treatment switches are adverse events, proactive strategy or simplification. We conducted a retrospective cohort study to investigate the reason for treatment interruption in the last 20 years. We merged data of eight cohorts of the SCOLTA project: lopinavir/r (LPV), atazanavir/r (ATV), darunavir/r or /c (DRV), rilpivirine (RPV), raltegravir (RAL), elvitegravir/c (EVG), dolutegravir (DTG) and bictegravir (BIC). We included 4405 people with HIV (PWH). Overall, 664 (15.1%), 489 (11.1%), and 271 (6.2%) PWH interrupted the treatment in the first, second, and third years after starting a new ART. Looking at the interruption in the first year, the most frequent causes were adverse events (3.8%), loss to follow-up (3.7%), patients' decisions (2.6%), treatment failure (1.7%), and simplification (1.3%). In the multivariate analysis regarding experienced patients, treatment with LPV, ATV, RPV or EVG/c, having less than 250 CD4 cells/mL, history of intravenous drug use, and HCV positivity were associated with an increased risk of interruption. In naive people, only LPV/r was associated with an increased risk of interruption, while RPV was associated with a lower risk. In conclusion, our data on more than 4400 PWH show that adverse events have represented the most frequent cause of treatment interruptions in the first year of ART (3.84%). Treatment discontinuations were more frequent during the first year of follow-up and decreased thereafter. First-generation PI in both naïve and experienced PWH, and EVG/c, in experienced PWH, were associated with a higher risk of treatment interruptions.

Italian Translation and Validation of the Original ABC Taxonomy for Medication Adherence.

Medication adherence represents a complex and multifaceted process. Standardized terminology is essential to enable a reproducible process in various languages. The study's aim was to translate and adapt the original Ascertaining Barriers for Compliance (ABC) Taxonomy on medication adherence, first proposed in 2012, into Italian language. The study was carried out according to the Preferred Methods for Translation of the ABC Taxonomy for Medication Adherence adopted by the ESPACOMP. Key steps included: (1) a systematic literature review using PubMed and Embase according to the PRISMA Guidelines to identify published Italian terms and definitions, and Italian adherence experts; (2) a forward translation of terms and definitions; (3) panelists' selection; (4) a three-round Delphi survey. From the systematic review, 19 studies allowed detection of 4 terms, 4 definitions and 767 Italian experts. To these, Italian ESPACOMP members and experts though snowball sampling were added. The identified Italian adherence experts received the Delphi questionnaire. The Italian ABC Taxonomy was achieved after three rounds of Delphi survey by reaching at least a moderate consensus on unambiguous naming and definition of medication adherence-related terms. The Taxonomy is intended to be used in research, academic, and professional fields in order to harmonize adherence terminology and avoid confusion in comparing research findings.

Incident diabetes in course of antiretroviral therapy.

OBJECTIVE: Recent reports of excessive weight gain in people with HIV (PWH) have raised increasing concerns on the possible increase of diabetes mellitus (DM) risk in course of integrase inhibitors (INSTIs) treatment. In this study, we aimed at describing DM incidence in course of antiretroviral therapy (ART) and identifying the factors associated with new DM onset. DESIGN: Observational prospective SCOLTA (Surveillance Cohort Long-Term Toxicity Antiretrovirals) cohort. METHODS: All people enrolled in SCOLTA between January 2003 and November 2021 were included. Multivariable Cox regression yielded adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for incident DM. RESULTS: 4366 PWH were included, 72.6% male, with mean age 45.6 years, and median CD4 + 460 [interquartile range (IQR) 256-710] cells/mm 3 cells/mm 3 . During the follow up, 120 incident cases of DM occurred (1.26 cases/100 person year-follow up, 95% CI 1.05-1.50).Baseline weight, but not the amount of weight gain, resulted significantly correlated to diabetes incidence (aHR by 1 kg 1.03; 95% CI 1.01-1.04), as well as older age (aHR 1.03 by 1 year; 95% CI 1.01-1.06), being ART-experienced with detectable HIV RNA at study entry (aHR 2.27, 95% CI 1.48-3.49), having untreated high blood pressure (aHR 2.90; 95% CI 1.30-6.45) and baseline blood glucose >100 mg/dl (aHR 5.47; 95% CI 3.82-7.85). Neither the INSTI class nor individual antiretrovirals were associated with an increased risk of DM. CONCLUSIONS: Baseline weight, but not weight gain or the ART class, was associated with incident DM in this observational cohort.

Prevalence of HDV infection in people living with HIV: Data from a multicenter Italian cohort.

Objectives: The development of novel antiviral agents active against Hepatitis Delta Virus (HDV) might change the natural history of chronic infection, reducing the risk for end-stage liver disease. People living with HIV (PWH) are at risk for bloodborne pathogens infection, but limited data on epidemiology of HDV infection is available in this setting. The aim of this study was to investigate HDV prevalence and attitude toward HDV testing and treatment in infectious diseases centers. Methods: A cross sectional survey was performed among centers participating in the CISAI (Coordinamento Italiano per lo Studio dell'Allergia in Infezione da HIV) Group. The survey addressed anti-HDV prevalence and HDV-RNA detectability rates in PWH as well as perceived obstacles to treatment. Results: Overall, responses from ten sites were collected. Among participating centers, 316 PWH with HBV chronic infection are currently followed. Of them, 15.2% had positive anti-HDV antibodies, while 13.9% were not tested yet. Overall, 17% of anti-HDV positive PWH tested at least once for HDV-RNA had active HDV infection, and 71% of them had advanced liver disease. Most infectious diseases centers intend to treat locally HDV infection with upcoming anti-HDV drugs, but some concerns exist regarding treatment schedule. Discussion: HDV testing needs to be implemented in PWH. At present, few patients followed in the CISAI centers seem to be candidate to receive new direct active anti-HDV agents, but repeated HDV-RNA measures could change this proportion.

Trajectories of CD4+/CD8+ T-Cells Ratio 96 Weeks after Switching to Dolutegravir-Based Two-Drug Regimens: Results from a Multicenter Prospective Cohort Study.

The aim of the present study was to evaluate CD4/CD8 dynamics in patients on dolutegravir (DTG)-based two-drug regimens (2DRs) and compare them with DTG-containing triple-drug regimens (3DRs). A prospective observational study was performed in the context of the SCOLTA cohort. Experienced PWH with HIV-RNA < 50 copies/mL were included if they were on the DTG-2DR, the DTG + tenofovir/emtricitabine (TDF/FTC) regimen, the DTG + tenofovir alafenamide (TAF)/FTC regimen, or the DTG + abacavir/lamivudine (ABC/3TC) regimen; they were followed-up for at least one year. A total of 533 PWH were enrolled, 120 in the DTG + 3TC group, 38 in the DTG + protease inhibitors (PI) group, 67 in the DTG + rilpivirine (RPV) group, 49 in the DTG + TDF/FTC group, 27 in the DTG + TAF/FTC group, and 232 in the DTG + ABC/3TC group. After one year, the CD4/CD8 ratio significantly increased in the PWH treated with DTG + 3TC (+0.08 ± 0.26), DTG + TDF/FTC (+0.1 ± 0.19), and DTG + ABC/3TC (+0.08 ± 0.25). At two years, the CD4/CD8 increase was confirmed for PWH on DTG + TDF/FTC (+0.16 ± 0.28) and DTG + ABC/3TC (+0.1 ± 0.3). In the SCOLTA cohort, PWH on 2DRs experienced a CD4/CD8 increase only in the DTG + 3TC group. Controlled studies with longer follow-up will clarify the long-term immunological and clinical impacts of DTG-2DR.

Growing old with antiretroviral therapy or elderly people in antiretroviral therapy: two different profiles of comorbidity?

BACKGROUND: In persons living with HIV (PLWH), the burden of non-communicable chronic diseases increased over time, because of aging associated with chronic inflammation, systemic immune activation, and long-term exposure to the combination antiretroviral therapy (ART). METHODS: To explore the association of chronological age, age at first ART, and exposure to ART with non-communicable chronic diseases, we performed a cross-sectional analysis to evaluate the prevalence of comorbidities in patients enrolled in the SCOLTA Project, stratified by groups of chronological age (50-59 and 60-69 years) and by years of antiretroviral treatment (ART, ≤ 3 or > 3 years). RESULTS: In 1394 subjects (23.8% women), mean age at enrollment was 57.4 (SD 6.5) years, and at first ART 45.3 (SD 10.7). Men were older than women both at enrollment (57.6 vs 56.8, p = 0.06) and at first ART (45.8 vs 43.6, p = 0.0009). ART duration was longer in women (13.1 vs 11.7 years, p = 0.01). The age- and sex-adjusted rate ratios (aRRs, and 95% confidence interval, CI) showed that longer ART exposure was associated with dyslipidemia (aRR 1.35, 95% CI 1.20-1.52), hypertension (aRR 1.52, 95% CI 1.22-1.89), liver disease (aRR 1.78, 95% CI 1.32-2.41), osteopenia/osteoporosis (aRR 2.88, 95% CI 1.65-5.03) and multimorbidity (aRR 1.36, 95% CI 1.21-1.54). These findings were confirmed in strata of age, adjusting for sex. CONCLUSIONS: Our data suggest that longer ART exposure was associated with increased risk of dyslipidemia, hypertension, and osteopenia/osteoporosis, hence the presence of multimorbidity, possibly due to the exposition to more toxic antiretrovirals. We observed different comorbidities, according to ART exposure and age.

COVID-19 Vaccination among HIV+ Patients: An Italian Cross-Sectional Survey.

BACKGROUND: This study aims to evaluate knowledge, attitudes and practices (KAP) of HIV-patients about COVID-19 vaccination. METHODS: A cross-sectional study was conducted by administering questionnaires to 160 patients followed by Amedeo di Savoia Hospital in Turin. Statistical analyses were performed in order to identify predictors of infection and severity of COVID-19 disease risk perception. RESULTS: The 86.2% of patients were vaccinated for COVID-19, while 7.6% do not intend to be vaccinated; 50.7% thought that there is a minimal risk to get COVID-19; 85.8% thought that COVID-19 is a serious illness. The 56% and the 36.5 thought that seropositivity carries a greater risk to develop respectively COVID-19-related complications or vaccine complications. At the multivariate analysis having a job, proactive research of vaccine information and being HIV+ for several years are related to a lower risk perception of infection. The perception of COVID-19 severity is influenced by age, by being LGB and by believing that HIV+ status correlates with a higher risk of developing complications from COVID-19. CONCLUSIONS: as the pandemic can adversely impact the HIV care with increasing loss to follow-up, vaccination is essential to contrast infection in HIV+ patients. Our findings suggested that some HIV+ patients refuse vaccination against COVID-19.

Reversibility of Central Nervous System Adverse Events in Course of Art.

The purpose of this study is to evaluate the frequency of central nervous system adverse events (CNS-AE) on dolutegravir (DTG) and non-DTG containing ART, and their reversibility, in the observational prospective SCOLTA cohort. Factors associated with CNS-AE were estimated using a Cox proportional-hazards model. 4939 people living with HIV (PLWH) were enrolled in DTG (n = 1179) and non-DTG (n = 3760) cohorts. Sixty-six SNC-AE leading to ART discontinuation were reported, 39/1179 (3.3%) in DTG and 27/3760 (0.7%) in non-DTG cohort. PLWH naïve to ART, with higher CD4 + T count and with psychiatric disorders were more likely to develop a CNS-AE. The risk was lower in non-DTG than DTG-cohort (aHR 0.33, 95% CI 0.19−0.55, p < 0.0001). One-year follow-up was available for 63/66 PLWH with CNS-AE. AE resolution was reported in 35/39 and 23/24 cases in DTG and non-DTG cohorts, respectively. The probability of AE reversibility was not different based on ART class, sex, ethnicity, CDC stage, or baseline psychiatric disorder. At the same time, a lower rate of event resolution was found in PLWH older than 50 years (p = 0.017). In conclusion, CNS-AE leading to ART discontinuation was more frequent in DTG than non-DTG treated PLWH. Most CNS-AE resolved after ART switch, similarly in both DTG and non-DTG cohorts.

Metabolic syndrome and body weight in people living with HIV infection: analysis of differences observed in three different cohort studies over a decade.

OBJECTIVES: The aim of this study was to assess the incidence of being overweight and metabolic syndrome (MS) among people living with HIV (PHIV) in three different cross-sectional studies conducted over three different periods: 2005, 2011 and 2015. METHODS: This was a multi-centre, nationwide study. Data were collected in three studies from the CISAI group - SIMOne, HIV-HY and STOPSHIV - and included a total of 3014 PHIV. Logistic regression [odds ratio (OR), 95% confidence interval (CI)] was used to account for age and gender difference among three groups when comparing MS prevalence and being overweight; potential confounders were accounted for by including them in the regression equation. RESULTS: Overall, the mean age was 46.9 ± 10.2 years, and men comprised 73.3% of participants. Comparing 2005, 2011 and 2015, MS was present in 34.5%, 33.0% and 29.3% of PHIV, respectively. Adjusted OR for MS was 0.64 (95% CI: 0.52-0.78) in 2011 and 0.56 (95% CI: 0.46-0.69) in 2015 compared with 2005, while BMI (kg/m2 ) increased from 23.6 in 2005, 24.5 in 2011 and 24.5 in 2015, with a concomitant increase of being overweight from 29.4% to 39.5% to 39.6% (p < 0.0001). CONCLUSIONS: In recent years, PHIV have had a significantly improved metabolic profile compared with previously, despite increasing weight and BMI.

Dupilumab in HIV-positive patients with atopic dermatitis: a long-term follow-up patient and a literature review.

Dupilumab is an IgG4 human monoclonal antibody licensed for the treatment of moderate-to-severe atopic dermatitis. Despite evidence suggesting that T helper type two cytokines can modulate HIV-1 replication and anti-HIV-specific immune responses, impacting on viral reservoirs, HIV-positive patients under immunomodulating therapy have been excluded from clinical trials. We report a 47-year-old HIV-positive man with late-onset severe atopic dermatitis, treated with dupilumab and followed up for 27 months. Improvements in skin lesions and quality of life were observed after four months. Blood tests showed normalization of IgE levels, with the clinical condition remaining stable at a 27- month follow-up. We gathered 16 other cases reported in the literature of HIV-positive patients treated with dupilumab, with no, or few adverse reactions, for which it is unclear if dupilumab should be held accountable. With our case and literature review, we aim to shed light on dupilumab efficacy, safety, and tolerability among HIV-positive patients suffering from atopic dermatitis. In this regard, future research should focus on the effective role, underlying mechanisms, and efficacy of dupilumab in HIV-positive patients and HIV-positivity could be questioned as a valid exclusion criterion for clinical trials.

Alzheimer Dementia in People Living With HIV.

OBJECTIVE: Given the aging of people living with HIV (PLWH) and the high prevalence of HIV-associated neurocognitive disorders, we aimed at describing the clinical, instrumental, and CSF features of PLWH diagnosed with Alzheimer dementia (AD). METHODS: The databases of 3 large Italian outpatient clinics taking care of more than 9,000 PLWH were searched for the diagnosis of AD. After obtaining patients' or their next of kin's consent for publication, anonymous data were collected in an excel spreadsheet and described. Routinely collected CSF biomarkers and radiologic imaging results were recorded whether available. RESULTS: Four patients were included in this case series who were diagnosed with AD aged between 60 and 74 years. All participants were on highly active antiretroviral therapy and showed nondetectable serum HIV RNA. Memory impairment was the most prominent cognitive feature. The diagnosis was obtained considering the exclusion of other potential causes, MRI and fluorodeoxyglucose-PET features, and, in (in 2/4), CSF AD biomarkers levels. In 1 patient, longitudinal CSF tau/p-tau increased, and beta-amyloid1-42 decreased over time despite antiretroviral therapy containing nucleotide reverse transcriptase inhibitors. CONCLUSIONS: In older PLWH cognitive symptoms may represent the onset of AD: a multidisciplinary team may be needed for reaching a likely in vivo diagnosis.

Durability of Integrase STrand Inhibitor (InSTI)-based regimen in geriatric people living with HIV in the GEPPO cohort.

OBJECTIVE: To investigate the durability of the first integrase inhibitor-based regimen in a HIV geriatric multicentric prospective cohort and to explore the reasons of regimen discontinuation. DESIGN: This is an analysis conducted on the Geriatric Patients Living with HIV/AIDS (GEPPO) cohort, an Italian prospective observational multicentre cohort of people living with HIV with 65 years of age or more. METHODS: The analysis was performed using R (version 4.0.2). The tests performed were two sided assuming a 5% significance level (Kruskal-Wallis test, Chi-squared test, log-rank test and a Cox Proportional Hazard model). The proportion of participants discontinuing the three regimens was displayed using cumulative curves. RESULTS: Among 1531 patients enrolled between 2017 and 2019 in the GEPPO cohort, we included 822 participants in this analysis. At baseline, median age was 69.8, the immunovirological profile good, multimorbidity was present in 42.3% of participants, while 27.4% were on polypharmacy. Overall, 483, 243 and 96 participants received DTG, RAL and EVG/c respectively as first InSTI. At the end of the follow up 6.4%, 21.1% and 22.9% participants discontinued DTG, RAL and EVG/c respectively. Using a log-rank test, EVG showed a significantly lower durability than DTG (p<0.001) or RAL (p 0.05) or both, DTG and RAL (p<0.001). Among participants who discontinued their regimen we found 0 virological failure and 56.7% simplification/deprescription. CONCLUSIONS: The three integrase inhibitors considered showed a good durability and no virological failures in geriatric patients such as those enrolled in the GEPPO cohort when used in a two or three drug regimen.