ObjectiveThe objective was to evaluate the safety, pharmacokinetics and efficacy of an alternative deltoid site for CAR-LA.DesignThis is a prospective cohort of people living with HIV (PLWHIV) switching for intramuscular long acting cabotegravir and rilpivirine (CAR-LA).MethodsClinical and biological data were collected at baseline, month 1 (M1), month 3 (M3), and every three months thereafter, when available.ResultsA total of 15 patients were enrolled between August 2022 and October 2024. Of these, 11 were transgender women, 1 cisgender woman, and 3 cisgender males. The median duration of plasma HIV-1-RNA (pVL) <50 copies/mL before switching to CAR-LA was 42 months. The main criterion for selecting PLWHIV was the presence of injected silicone in the gluteal region (12 out of 15 cases). Median duration of CAR-LA was 13 months. All patients maintained a pVL<50 copies/mL at M1 and M3. No virological failure was observed in the 13 patients who were followed up to M12. One PLWHIV discontinued deltoid injections due to low plasma concentrations at M2, while another discontinued due to non-adherence which led to cabotegravir resistance at M13. Three PLWHIV reported moderate pain at the injection site, with one discontinuing treatment at M12. All CAB and RPV plasma concentrations measured after deltoid CAR-LA were comparable with those obtained following gluteal CAR-LA phase 3 studies.ConclusionDeltoïd CAR-LA seems to be a reliable and well-tolerated alternative for PLWHIV with contraindications for gluteal injections.

ObjectiveThis systematic review summarizes factors associated with immunological non-response (INR) among people with HIV on antiretroviral therapy (ART) in Southeast Asia.MethodsWe conducted a systematic search of PubMed, ScienceDirect, DOAJ, and Lens.org for studies published between 2010 and 2025. Observational studies examining immunological outcomes following ART initiation and related factors were included. Study quality was assessed using the Newcastle-Ottawa Scale, and results were synthesized using a harvest plot.ResultTen eligible studies were included in the synthesis, comprising a total of 6,988 participants with substantial heterogeneity observed across studies. Factors associated with INR included age, sex, baseline CD4 cell count, HIV RNA levels, and co-infections. Among these factors, baseline CD4 cell count at the initiation of ART emerged as the most consistently associated determinant; lower baseline CD4 levels were linked to a higher risk of INR even with virological suppression.ConclusionThis review highlights baseline immunological status at ART initiation as a key predictor of immunological non-response in Southeast Asia. These findings underscore the critical importance of early HIV diagnosis and timely initiation of ART to prevent advanced immune damage and optimize immunological recovery.

Data from the REPRIEVE trial have been used to study the association between treatment with abacavir and cardiovascular disease in people with HIV. Past exposure to abacavir before the trial was found to be just as risky as exposure during the trial. This calls into doubt the widely accepted hypothesis that recent exposure to abacavir increases the risk of cardiovascular disease but that risk rapidly attenuates after exposure ends. The evidence for this hypothesis is weak while evidence for an alternative hypothesis has been neglected. An alternative hypothesis is that risk from exposure to abacavir is not immediate but increases as exposure cumulates, plateauing after about three years. Confusion over the likely effect of abacavir has arisen partly because overly simplistic methods have been used to model the exposure outcome relationship in observational cohort data. Better methods are available and should be used in future to avoid misdirected research effort.

BackgroundPosttransplant cytomegalovirus (PT-CMV) infection remains a challenging complication and a major cause of morbidity and mortality in transplant recipients.MethodsThis cross-sectional study surveyed physicians treating solid organ and hematopoietic stem cell transplantation recipients from Central and Eastern European countries. Physician-reported CMV infection prevalence in transplant recipients, treatment regimens, and unmet needs for managing patients with refractory with/without resistance (R+/R-) PT-CMV infection were assessed.ResultsOverall, 164 physicians completed the survey, 23.8% of whom were nephrologists. Physicians estimated that 26.4% of patients who received a transplant in the past 12 months developed PT-CMV infection, of whom 12.9% had refractory R+/R- PT-CMV infection. On average, 66.5%, 16.5%, and 4.0% of physicians' current patients with PT-CMV infection received first-, second-, and third- or later-line treatments, respectively. Physicians considered maintenance of CMV viremia clearance (94.5%), good symptom control (94.5%), and lack of renal toxicity (93.9%) as moderately-to-extremely important treatment attributes for managing PT-CMV infection. Compared with other available treatments, more physicians indicated oral valganciclovir to have a strong-to-complete association with these treatment attributes. Overall, 63.4% of physicians indicated some level of satisfaction with conventional refractory R+/R- PT-CMV treatments. However, 54.9% of physicians reported limited experience with newly approved therapies, such as maribavir. Most physicians considered limited treatment options as a major barrier for improving patient outcomes.ConclusionSurvey findings of physicians treating transplant recipients in Central and Eastern Europe suggest the need for increased awareness of newly approved therapies with better efficacy and less toxicity for refractory R+/R- PT-CMV infection.

BackgroundIntravenous hyper-immune anti-cytomegalovirus immunoglobulins (CMV-IG) therapy are licensed for prophylaxis, yet their therapeutic value in established CMV disease remains poorly defined. We aimed to evaluate the clinical and virological impact of adjunctive CMV-IG in combination with standard antiviral therapy in immunocompromised patients with CMV disease, compared with standard antiviral therapy alone.MethodsWe performed a single-center retrospective case-control study at A.O.U. "Federico II" University Hospital, Naples, Italy, including consecutive immunocompromised patients with CMV disease between March 2021 and November 2024. Cases received standard antiviral therapy plus CMV-IG (100 IU kg-1 day-1 for three consecutive days). Controls received antivirals only.ResultsThirty-four patients were analyzed (15 cases, 19 controls). Thirty-day survival was 93% vs 95% (p=>0.9) and composite outcome (combination of 30-day mortality and clinical response) occurred in 93% vs 90% (p=>0.9) in cases and controls, respectively. Median time-to-virological response in days was achieved 4 vs 7 days (p=<0.001), as was median duration of antiviral therapy in days 12 vs 16 days (p=0.001) and hospitalization 14 vs 19 days (p=0.004) in cases and controls, respectively. Adverse-event rates were low and comparable in the 2 groups.ConclusionsIn this real-world cohort, adjunctive CMV-IG did not affect mortality, but was associated with faster virological clearance and shorter antiviral and hospital courses, without additional toxicity.

BackgroundClass E (empty) capsid assembly modulators (CAM-Es) inhibit HBV capsid assembly, pregenomic RNA encapsidation preventing formation the establishment of covalently closed circular HBV DNA (ccDNA). ALG-000184 (pevifoscorvir sodium), is a prodrug of the Class E CAM ALG-001075.MethodsALG-000184-201 was a Phase 1 randomized, double-blind, placebo-controlled study to evaluate the safety, tolerability and pharmacokinetics of ALG-000184. Healthy participants (n = 8/cohort) received oral single-ascending doses (SAD) of ALG-000184 (40, 100, 250, and 500mg) or placebo, and multiple-ascending daily doses (MAD) (150mg and 250mg) or placebo for 7 days.ResultsALG-000184 was well tolerated by 48 participants who received single doses up to 500mg and multiple daily doses up to 250mg for 7 days. ALG-000184 was rapidly converted to the active moiety, ALG-001075. ALG-001075 had dose-proportional increase in plasma exposure, low-to-moderate variability (18%-34% CV for AUC0-24), rapid absorption (median tmax 1-3.5 h), and biphasic distribution/elimination with terminal t½ 7-8 h and minimal accumulation (∼30%). A major oxidative metabolite, ALG-000302, was identified in plasma (∼17%-24% of ALG-001075). A high-fat/high-calorie meal did not significantly impact the plasma pharmacokinetics. No differences in pharmacokinetics between Asian and non-Asian participants were observed. A concentration QT analysis indicated no statistically significant change in ΔΔQTcF with plasma ALG-001075. Urinary excretion of ALG-001075 was low following single or multiple ALG-000184 doses.ConclusionsALG-000184 demonstrated good tolerability, safety and pharmacokinetic properties in healthy participants. The pharmacokinetic profile suggests that a daily dose of 100mg or higher will provide efficacious exposures in patients with chronic HBV infection.Clinical trial numberNCT04536337 (https://clinicaltrials.gov/study/NCT04536337).

Ebola virus is a member of the Filoviridae family, which causes hemorrhagic fever in primates, exhibiting a mortality rate that can reach up to 90%. The VP35 suppresses the host IFN-β/α production by disrupting the immune responses of the host during viral infection, making it a putative target for therapeutic intervention. Herein, the UMH SuperNatural II database was mined to identify prospective VP35 inhibitors employing advanced in silico approaches. Filtration of the UMH SuperNatural II database was first conducted based on drug-likeness features. These compounds were screened towards VP35, and those exhibiting docking scores lower than 1DK, a reference ligand, further underwent molecular dynamics simulations (MDS), followed by binding energy calculations. Upon the assessed binding energy throughout 200 ns MDS, UMHSN00005544 and UMHSN00005545 disclosed superior binding affinity against VP35 compared to 1DK, with ΔGbinding values of -35.5, -34.9, and -29.3kcal/mol, respectively. Energetic and structural evaluations were conducted for the identified natural compounds in complex with VP35 over 200 ns MDS. Post-MD analyses demonstrated the significant constancy of the investigated complexes. RMSD values averaged 0.14, 0.13, and 0.12nm for UMHSN00005544, UMHSN00005545, and 1DK bound to VP35 over 200 ns MDS, indicating stable protein-ligand conformations. Furthermore, the ADMET characteristics of the identified natural compounds were assessed, revealing favorable pharmacokinetic and non-toxicity profiles. Density functional theory computations unveiled the electronic stability and chemical reactivity of the identified natural compounds. The obtained outcomes affirmed the substantial therapeutic potential of UMHSN00005544 and UMHSN00005545 as prospective candidates for combating EBOV, thereby necessitating further experimental investigations.

Severe influenza infections involve an exacerbation of the pro-inflammatory response, which is influenced by both viral and host factors. Protectins PD1 and PDX previously demonstrated anti-influenza activity as well as anti-inflammatory properties. We recently reported that the combination of AN-137B, a molecular analogue of PDX, with oseltamivir or baloxavir provided synergism/additive effects against influenza, in vitro. Herein, we investigated potential benefits of the AN-137B-oseltamivir combination in mice infected with influenza A/Puerto Rico/8/1934 (H1N1) virus. Untreated animals and those that received single oseltamivir or AN-137B treatment showed mortality rates of 80%, 100% and 100%, respectively, whereas only 40% of mice that received the oseltamivir-AN-137B combination had to be euthanized. Body weight loss was also lower in the group of the combination. In the latter group, the mean lung viral titre (LVT), as determined by plaque assay (2.53 ± 0.63 × 105 PFU/mL) and by qRT-PCR (2.39 ± 1.3 × 108 copies/mL), was significantly lower than that of the untreated group (4.76 ± 0.9 × 105 PFU/mL and 3.75 ± 0.86 × 108 copies/mL (p < .05), contrasting with LVTs of animals that received single therapies. These in vivo results reinforce the potential of AN-137B when combined to a potent anti-influenza agent against severe influenza.

Enteroviruses can cause severe, chronic infections in patients with primary and secondary humoral immunodeficiencies. These patients may benefit from anti-enteroviral therapy. Here, we report a patient with mantle cell lymphoma treated with chemotherapy followed by autologous stem cell transplantation and rituximab maintenance therapy, who presented with echovirus 7-associated deafness and myositis leading to severe disability. She showed marked clinical improvement and enterovirus clearance from faeces and blood after treatment with intravenous immunoglobulins (IVIgs) followed by remdesivir. We demonstrated efficacy of IVIg and remdesivir against echovirus 7 using virus neutralization and cell culture assays, which supports a potential contribution to the treatment success for both therapies.

BackgroundHepatitis D virus (HDV) represents the most severe form of human viral hepatitis, associated with rapid progression to cirrhosis and increased liver-related mortality. Globally, an estimated 9-19 million individuals are anti-HDV positive. To ensure early detetion, current guidelines recommend screening all HBsAg-positive individuals or, at a minimum, those with defined risk factors.MethodsThis expert consensus paper updates the current landscape of HDV management. Recommendations were derived from a structured expert panel discussion, incorporating recent evidence and clinical guideline developments, with a focus on screening, diagnosis, and antiviral therapy.ResultsThe panel emphasized the importance of systematic HDV screening in HBsAg-positive individuals. Therapeutic strategies aim at sustained HDV-RNA suppression and, ideally, HBV surface antigens (HBsAg) loss. Bulevirtide was recommended as a long-term monotherapy. Pegylated interferon alpha (PEG-IFNα), if used, should be limited to 48weeks and tailored based on viral response and tolerability. Combination therapy with bulevirtide and PEG-IFNα may be considered in selected cases.ConclusionThis consensus provides updated recommendations for the screening, diagnosis, and treatment of HDV infection, highlighting the role of bulevirtide and individualized therapeutic approaches. As the treatment landscape continues to evolve, combination regimens and novel agents currently under investigation may offer additional options in the near future.