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BackgroundIn the aging HIV population, comorbidities such as cardiovascular disease, diabetes and dyslipidemia are increasing and with them, the need to take medications to manage them.The need to take antiretroviral drugs lifelong implies on the one hand the importance of adopting effective, safe, well-tolerated and manageable drug combinations with few drug interactions and with a high genetic barrier to limit the risks of virological failure and the consequent development of resistance mutations and, on the other hand, since they themselves can affect metabolism and the risk of developing metabolic disorders, the choice of a regimen with a favorable impact on the metabolic profile.Material and MethodsWe retrospectively analyzed data in 126 people living with HIV (PWLH) on antiretroviral therapy switching from TAF/FTC/RPV to BIC/TAF/FTC between June 2020 and January 2025. We analyzed the efficacy, safety and tolerability of switch to BIC/TAF/FTC from TAF/FTC/RPV. We also studied the cardiovascular and metabolic effect of the switch through the change in FINDRISC score and ASCVD scores after 24 and 48 weeks, as well as changes in lipid profile and body weight. Statistical analyses were mostly descriptive, and association analysis was performed to assess changes in laboratory parameters from baseline to data cut-off.Clinical, sociodemographic data are summarized in table 1.Results126 patients, 82% males, median age 57 years (IQR 52–65) were enrolled. They had experienced a median of 3 therapeutic lines (IQR). At switch all of them presented an HIV-RNA <20 copies/ml and a CD4 mean count of 872 cells/mcL (IQR 646–1093) but 89,7% of them presented at least one co-morbidity mainly involving the cardio-vascular system (36.3%), bone (32.3%), CNS (18.6%), liver (16.2%) or lipids (25.7%) and glucose (10.9%) homeostasis, 20 (16%) had HBV co-infection. During the 48 weeks of follow-up no virological failure occurred. Treatment was discontinued in 4 (%) subjects because of death (1 prostatic cancer), of intolerance (3 cases: 1 insomnia, 1 intestinal disorder, 1 headache).No difference in the FINDRISC score nor in the ASCVD score was observed 24 and 48 weeks from the switch. No significant overtime variation in mean cholesterol, triglycerides and glucose levels was observed at week 24 and 48. A slight increase in body weight and BMI was observed at wk 24 but the values did not change significantly at wk 48. No significant change in creatinine levels was observed (table 2)Abstract P30 Table 1Baseline characteristicsAbstract P30 Table 2Changes from baseline to week 48ConclusionsNo significant differences in metabolic status were observed 48 weeks after the switch from TAF/FTC/RPV to BIC/TAF/FTC; this regimen has shown a positive impact both in terms of efficacy, safety and tolerability and in terms of the metabolic profile.

BackgroundLong-acting injectable (LAI) therapy with cabotegravir and rilpivirine (CAB/RPV) represents a significant and innovative advancement in switch strategies for the treatment of HIV. Such an option, characterized by bimonthly intramuscular administrations received in hospital setting, may offer several advantages over conventional regimens based on daily oral drugs, mainly associated to enhanced adherence and de-stigmatization.However, a subset of people living with HIV (PLWH), who qualify for LAI and after direct proposal, decline this option. We aimed to investigate the reasons for refusal despite qualification.Material and MethodsRetrospective, multicenter, observational cohort study aimed at investigating the reasons why persons eligible for LAI treatment decline this option.From 1 January 2025 to 7 March 2025, all consecutive PLWH attending two HIV centers in northern Italy, were offered LAI therapy (if they qualified for) during routine follow-up visits and the reasons for refusal were collected by proponent physicians.Eligibility criteria were: HBsAg negativity, virological suppression for at least six months, no history of virological failures and adherence to scheduled visits (not necessarily to ART).Clinical, sociodemographic data and comedications were retrieved from medical records.ResultsA total of 432 subjects were enrolled. Reasons for LAI declination (table 1) were: logistical challenges in 272 subjects (63%). Among these reasons (multiple choices were admitted), the distance from the HIV center (34%), the number (62%) and frequency (bimonthly) (4%) of required visits by current LAI were the most frequent complaints.Other reasons werereluctance to change current and well tolerated therapy (95 pts, 22%) and fear of needles (43 pts, 10%), the impossibility of self-administration for 13 patients (3%), the absence of benefit (as they were already taking oral comedications) for 9 subjects (2%) 2 (figure 1).Only 99 subjects (23%) were aware of this LA option before the doctor’s interview.Abstract SC29 Table 1Patients‘ characteristicsAbstract SC29 Figure 1Reasons for LAI declination[Figure omitted. See PDF]ConclusionsLogistical challenges represent the main reasons for declining LAI therapy in eligible and successfully treated PLWH. In this perspective, the possibility of administering LAI therapy at longer intervals and the availability of facilities closer to home might facilitate the acceptance rate.

BackgroundLAI CAB/RPV is a two-drug intramuscular regimen for PLWH with stable virological suppression. Clinical trials have confirmed its efficacy, safety, and non-inferiority to oral regimens. However, up to date real-world data are needed to optimize its use in clinical practice.Materials and MethodsWe conducted a retrospective observational study on patients switched to LAI CAB/RPV at the Infectious Diseases Unit of IRCCS Policlinico San Matteo, Pavia. Data were collected from May 2023 to February 2025. We analyzed eligibility criteria, clinical and epidemiological profiles, HIV-RNA levels, and adverse events after one month (4W), 6 months (24W), and 12 months (48W) of injectable therapy.ResultsWe analyzed 100 patients: 21 who have been on LAI for at least 12 months, 27 who reached 6 months, and 52 who were on LAI for less than 6 months. Characteristics of study population are shown in table 1. All patients met eligibility criteria. At baseline (BL), all had virologic suppression for at least 6 months (VL ≤ 20 cps/ml; median TCD4: 806 cells/mm³, IQR 556.5–966.5), no virological failure, and a median BMI of 24.75 (IQR 21.65–26.95). Oral ART difficulties were reported by 52 patients, mainly due to pills fatigue burden (47%) rather than stigma (5%). Overall, 98% received injections within the scheduled time window.Figure 1 presents adverse effects at 4W, 24W, and 48W in all patients.Despite 3 cases of persistent injection site pain at 48W, adherence remained high. There were eight discontinuations: three due to injection site pain, two patients lost to follow-up, one non-related death, one for work-related reasons, and one due to a viral blip (92 copies/ml). In this case HIV-RNA and DNA genotypic testing were performed documenting no resistance mutations; however, while awaiting the outcome, the patient was switched to triple oral therapy. No cases of virological failure were recorded, and 99% maintained viral suppression. Figure 2 shows Kaplan-Meier analysis of non-discontinuation probability for LAI therapy.We also evaluated the impact of CAB/RPV LAI therapy on BMI, lipid metabolism (total cholesterol and LDL), and CD4+ T lymphocyte levels in 21 patients who completed 48W of treatment, confirming no significant effects.Abstract P105 Table 1Population characteristics of PLWH at baseline (BL)Abstract P105 Figure 1Adverse effects in all patients at 4W, 24W and 48W[Figure omitted. See PDF]Abstract P105 Figure 2The Kaplan-Meier curve illustrates the probability of treatment non-discontinuation in patients who started with LAI CAB/RPV in the period between May 2023 and September 2024 (n = 59). Vertical dashes represent censored data (end of observation while still on therapy)[Figure omitted. See PDF]ConclusionsOur real-life results confirm that CAB/RPV LAI was safe, well-tolerated and effective in PLWH who met the eligibility criteria, with high adherence and minimal discontinuation. In our opinion, pending more solid data and based on our experience, it would seem necessary both a careful selection of eligibility for LAI, to reduce the risk of therapeutic failures (due to adverse events/lost at follow-up) associated with close virological monitoring in the first six months of therapy, to minimize the risk of VF. Furthermore, although sometimes apparently excessive, a return to oral therapy in the case of repeated virological blips could be the most precautionary choice to avoid virological failure.

BackgroundPeople with HIV (PWH) are aging and may have a long history of HIV infection, long exposure to antivirals, increasing comorbidities and polypharmacy. We aim to assess the use of two drug regimens (2DR) in geriatric population of PWH.MaterialsThis is a cross-sectional study in PWH older than 64 years and currently followed up in 3 HIV centers in northern Italy. Data were collected from medical reports or electronic database in February 2025 and subjects with the last visit within 9 months and currently receiving ARVs were included. Polypharmacy (PP) was defined as 5 or more non-HIV drugs. The primary endpoint was the use of 2DR, secondary end-points were prevalence and characterization of comorbidities, polypharmacy and viroimmunological status. Multiple cox regression model was used to assess factors associated to 2DR treatmentsResults655 PWH were included (80%, males, median (IQR) age was 70 (66–75), 54% heterosex, 23% MSM, 13% past-IVUs, 95% were Caucasians. A total of 315 (48%), 243 (37%) and 42 (6.4%) subjects had received <3, 3–6 and more than 6 lines of HIV therapy, respectively. Median (IQR) duration of HIV infection was 25 (19–33) years, median (IQR) nadir and current CD4 count were 146 (3–50) and 689 (504–926) cells/mL, respectively, while 611 (93%) subjects had plasma HIV RNA <50 copies/ml. A total of 18 (3%), 212 (36%), 304 (53%) and 43 (7.5%) individuals had 0, 1–2, 3–5 and ≥6 comorbidities, respectively. A total of 266/525 (50.6%) had polypharmacy, while 21/570 (3.7%) were HBsAg positive. Overall, primary RAMs were documented in 159 subjects in NRTI- (124), NNRTI- (103), PI- (68) and INI- (10) regions, respectively.A total of 329 (50.2%) and 322 (49%) were on 2DR and ≥3DR, respectively; 4 were on DRV-monotherapy. 2DRs were as follows: DTG/3TC (175/329, 53.2%), boosted PI+X (57, 17%), DTG/RPV (53, 16%), CAB/RPV (17, 5%), DTG/DOR (13, 4%) and others (15, 4.5%). The most used 3DRs were BIC/F/TAF (160/322, 49.6%), RPV/F/TAF (65, 20.2%) and DTG/ABC/3TC (22, 6.8%) and DRVc/F/TAF (20, 6.2%). Overall, boosted PIs were used in 100 (15.2%) individuals, in different combinations. At Cox regression analysis, factors associated with a higher probability of being on 2DR were the number of comorbidities (HR of ≥ 6 comorbidities compared to 0–2: 0.52, 95% CI 0.3–0.9, global p <0.001), the presence of major mutations (HR = 0.67, 95%CI 0.48–0.94; p = 0.02) and the value of nadir CD4+ count (increase of 50, HR = 1.08, 95%CI 1.02–1.15; p = 0.015) (table 1).Abstract P106 Table 1Conclusions2DRs, INSTI-based and in different combinations, are used in up to half of geriatric PWH, with DTG/3TC being the most frequent, while CAB/RPV LA underused.

BackgroundMultiple posttranslational modifications (PTM) of HIV-1 integrase such as acetylation, phosphorylation, sumoylation and ubiquitination have been described. Variations in PTM sites might impact viral fitness but nothing is known about variability of PTM sites in vivo and their association with drug-resistance. The aim of this study was to characterize integrase PTM in heavily treatment experienced (HTE) multidrug resistant (MDR) individuals compared to individuals never exposed to antiretrovirals or to those treated but never exposed to integrase inhibitors (INI).Material and methodsHIV-1 Integrase sequences from plasma RNA specimens of viremic HTE MDR individuals from the PRESTIGIO registry were compared to sequences from drug-experienced INI naïve and drug-naïve individuals, all harboring subtype B virus. The MusiteDeep tool (https://www.musite.net/) was used to evaluate known PTM sites for acetylation, phosphorylation, sumoylation and ubiquitination. Associations between CD4 count, viremia and integrase resistance (HIVdb ver 9.5) and the number and type of PTM sites were evaluated.Results38 integrase sequences from distinct individuals were compared with 48 and 76 sequences from INI-naive and drug-naïve individuals, respectively (table 1). PTM frequency for each group is reported in Figure 1. All acetylation sites were fully conserved in 99.4% of individuals. No significant differences in the number of phosphorylation sites were observed among the three groups. By contrast, the number of sumoylation sites was lower in HTE MDR individuals compared to those drug-naïve or INI-naïve. This was driven by a lower frequency of K136 and K244 PTM sites in HTE MDR individuals. The number of ubiquitination sites was higher in HTE MDR individuals than in other groups (P=0.043). CD4 counts and viremia levels were not significantly different according to PTM sites within treatment groups. Concerning INI resistance in HTE MDR, individuals with cross resistance to all INI showed less than three phosphorylation sites as opposed to HTE individuals with lower-level or no resistance (P=0.001, figure 2A). The proportion of individuals with intermediate or high-level resistance to bictegravir/dolutegravir increased with increasing numbers of sumoylation sites (P=0.021, figure 2B).Abstract OC-49 Table 1Individual characteristicsAbstract OC-49 Figure 1Prevalence of integrase known post translational modifications (PTM) in cART naive, cART experienced INI-naive and HTE-MDR individualsAbstract OC-49 Figure 2PTM sites significantly affected by INI resistance in HTE-MDR individualsConclusionsThe number of integrase phosphorylation, sumoylation and ubiquitination sites seems to be affected by a complex and prolonged treatment history associated with multidrug resistance. The presence of high-level resistance to second generation INI seems to impact phosphorylation and sumoylation sites in integrase. Further longitudinal studies are needed to unveil the nature and implications of these correlations.

Nestlings of many avian brood parasites are virtuosos at mimicking host nestling vocalizations, which, like egg mimicry, presumably ensures acceptance by host parents. Having been accepted, parasitic nestlings then often exaggerate the aspects of the host's display to increase parental care. Host nestlings may, in turn, exaggerate their vocalizations to keep up with the parasite, though this possibility has not been evaluated. We experimentally parasitized song sparrow (Melospiza melodia) nests with a brown-headed cowbird (Molothrus ater) chick to evaluate how host nestlings respond. Vocalizations emitted from experimentally parasitized nests were higher in frequency, and louder, than those from unparasitized nests, consistent with the cowbird exaggerating its signalling. In response, host nestlings exaggerated the frequency and amplitude of their vocalizations, such that they resembled the cowbird's while they 'scaled back' on calls per parental provisioning bout. Sparrows in parasitized nests were fed equally often as sparrows in unparasitized nests, suggesting that exaggerating some aspects of vocalization while scaling back on others can help host nestlings confronted with a cowbird. Our results support the recently proposed hypothesis that signalling in parasitized nests involves a dynamic interaction between parasitic and host nestlings, rather than a one-way process of mimicry by the parasite.

Bone marrow (BM) and/or peripheral blood progenitor cells (PBPC) given after high-dose chemo-radiotherapy are commonly cryopreserved. Re-infusion of the thawed product can cause cardiovascular and other complications. We compared two groups of adult patients receiving autologous BM or PBPC transplant to assess the incidence of adverse events occurring during infusion. Fifty-one patients received BM, and 75 PBPC. The two groups were comparable in respect of age, total volume infused, quantity of dimethylsulfoxide (DMSO) and number of polymorphonuclear neutrophils. Patients receiving PBPC had a higher number of nucleated cells per kg of body weight; those in the BM group received a significantly greater quantity of red cells. Non-cardiovascular complications occurred in 19% and 8% of patients rescued by BM and PBPC respectively. The incidence of hypertension was 21% in the BM and 36% in the PBPC group. Asymptomatic hypotension was more frequent in PBPC patients (P<0.001). Bradyarrhythmia was noticed in two of 75 PBPC patients and in 14 of 51 BM patients (P<0.001). In the former group one patient had heart block; he died of renal failure 10 days later. Bradycardia and hemoglobinuria were more common in patients receiving BM where a higher concentration of red cells was present (P<0.001). Since bradyarrhythmias may be a life-threatening complication we advise continuous careful monitoring during infusion of thawed BM. The strong correlation between bradycardia and red blood cell contamination suggests the use of purified products with a very low red cell content.

The purpose of the study was to identify factors that could predict good yields of peripheral blood stem cells (PBSC) in multiple myeloma (MM). Fifty-one MM patients, nine with refractory disease and 42 in plateau phase, were mobilized with high-dose cyclophosphamide (HD-Cy) at 4 g/m2 followed by granulocyte colony-stimulating factor (G-CSF) 5 microg/kg/day. Clinical and laboratory parameters at the time of mobilization were analyzed for correlations with the number of CD34+ cells collected, with the colony-forming unit granulocyte-macrophage (CFU-GM) count, and the mononuclear cell (MNC) count. In univariate analysis, low WBC count, low platelet count, prior exposure to melphalan, and an interval >6 months from the start of treatment correlated with poor yields of CD34+ cells. Low platelet count, prior exposure to melphalan or to radiotherapy, and an interval >6 months from the start of treatment were associated with a low CFU-GM count. On the basis of these data, we defined a scoring system able to predict the yield of the mobilizing procedure. According to this system, the presence of more than one risk factor (low WBC and platelet counts, prior exposure to melphalan, interval from first chemotherapy >6 months) was predictive of insufficient collections when a conventional combination of mobilizing measures are used.

Ten patients with acute leukemia (AL) in early relapse after allo-BMT were treated with a modified MEC (mitoxantrone, etoposide and Ara-C) regimen followed by donor PBPC collected after mobilization with G-CSF. Seven patients achieved CR or had normal hemopoietic reconstitution: two had an early relapse at days +53 and +48, two patients died from acute GVHD at days +31 and +96, one died of interstitial pneumonia at day +55, and two patients experienced long-term survival. One patient with refractory disease and nodal involvement who did not respond to the first BMT had overt expansion of the leukemia at day +36; one patient with Ph+ ALL and one with ANLL evolving from MDS, both with skin involvement, had blast cells in peripheral blood at day +27 and +26, respectively. Transient cytopenia occurred in all patients; a normal granulocyte and platelet count was achieved within 3 weeks in all patients but one; acute GVHD occurred in six patients, and four had chronic GVHD. This approach is feasible in patients in early relapse after allo-BMT. It assists prompt re-establishment of normal donor hematopoiesis avoiding the prolonged cytopenia observed after donor lymphocyte infusion in AL patients relapsed after allo-BMT.

Standard conditioning for allogeneic bone marrow transplantation induces high transplant-related mortality (TRM) in patients with a poor performance status. Less intensive regimens have been tested to reduce the TRM; our purpose was to evaluate the feasibility and tolerability of a new combination: thiotepa and fludarabine (TT-FLUDA). Six patients received 5 mg thiotepa/kg daily from day -8 to -7 and 25 mg fludarabine/m2 daily from day -6 to -2 followed by an allogeneic peripheral blood progenitor cell infusion; three of these patients with signs of overt leukemia received 18 mg idarubicin/m2 i.v. at day -12. Graft-versus-host-disease (GVHD) prophylaxis was performed i.v. with 1 mg cyclosporine A/kg per day from day -5 to the day of marrow engraftment, then 6 mg/kg per day orally up to day +100, and 10 mg methotrexate/m2 at day +1, and 8 mg/m2 at days +3, +6, and +11. Chimerism was studied with fluorescent in situ hybridization for sex chromosomes (XY-FISH) and minisatellite polymerase chain reaction (PCR) at days +30, +100, +180, and +360. Engraftment was achieved in all cases with complete donor chimerism in all but one patient who had refractory acute leukemia. No major toxicity was noticed; only one patient died at day +51 of acute GVHD because of early cyclosporine A discontinuation. One patient with refractory non-Hodgkin's lymphoma (NHL) had a testicular relapse at day +180. Three patients (one with mantle cell lymphoma, two with acute myeloid leukemia) are still in continuous complete remission (CR) with complete donor chimerism at days +180, +210, and +450, respectively. TT-FLUDA seems to be well tolerated, allowing engraftment and stable donor chimerism in patients who are poor candidates for conventional conditioning regimens.