Antiviral Therapy最新文献

Background: Cohort studies suggest higher discontinuation rates with integrase strand transfer inhibitors (INSTIs) than are seen in clinical trials. We assessed discontinuations and adverse events (AEs) that were considered related to the initial INSTI in the first year following initiation among treatment-naïve people living with HIV (PLWH).

Methods: Newly diagnosed PLWH initiating raltegravir, elvitegravir/cobicistat, dolutegravir or bictegravir in combination with emtricitabine/tenofovir alafenamide or emtricitabine/tenofovir disoproxil fumarate between 10/2007 and 1/2020 at the Orlando Immunology Center were included. Unadjusted incidence rates (IRs) and incidence rate ratios (IRRs) were calculated for treatment-related discontinuations and AEs associated with the initial INSTI in the first year following initiation.

Results: Of 331 enrolled, 26 (8%) initiated raltegravir, 151 (46%) initiated elvitegravir/cobicistat, 74 (22%) initiated dolutegravir and 80 (24%) initiated bictegravir. Within the first year, treatment-related discontinuations occurred in 3 on elvitegravir/cobicistat (IR 0.02 per person-years (PPY)) and 5 on dolutegravir (IR 0.08 PPY); no treatment-related discontinuations occurred among those initiating raltegravir or bictegravir. Eleven treatment-related AEs occurred in 7 on raltegravir (IR 0.46 PPY), 100 treatment-related AEs occurred in 63 on elvitegravir/cobicistat (IR 0.72 PPY), 66 treatment-related AEs occurred in 37 on dolutegravir (IR 0.97 PPY) and 65 treatment-related AEs occurred in 34 on bictegravir (IR 0.88 PPY). Unadjusted IRRs did not reveal any significant difference between INSTIs in terms of early treatment-related discontinuations or AEs.

Conclusions: In our cohort, treatment-related AEs occurred in 43% initiating INSTIs but were responsible for early discontinuation in only 2% with no treatment-related discontinuations observed among those initiating RAL or BIC.

Background: WHO guidelines recommend abacavir in first-line antiretroviral treatment for children and neonates. However, there is no approved dose <3 months of age, and data in neonates are limited.

Methods: We included infants who initiated ART aged <3 months, between 2006 and 2019, in nine South African cohorts. In those who received abacavir or zidovudine, we described antiretroviral discontinuation rates; and 6- and 12-month viral suppression (<400 copies/mL). We compared infants aged <28 and ≥28 days, those weighing <3 and ≥3 kg.

Results: Overall 837/1643 infants (51%) received abacavir and 443 (27%) received zidovudine. Median (interquartile range, IQR) age was 52 days (23-71), CD4 percentage was 27.9 (19.2-38.0), and weight was 4.0 kg (3.0-4.7) at ART initiation. In those with ≥1 month's follow-up, 100/718 (14%) infants discontinued abacavir, at a median of 17.5 months (IQR 6.5-39.5). Abacavir discontinuations did not differ by age or weight category (p = 0.4 and 0.2, respectively); and were less frequent than zidovudine discontinuations (adjusted hazard ratio 0.14, 95% confidence interval 0.10-0.20). Viral suppression at 12 months occurred in 43/79 (54%) and 130/250 (52%) of those who started abacavir aged <28 and ≥28 days, respectively (p = 0.8); 11/19 (58%) and 31/60 (52%) in those who weighed <3 and ≥3 kg, respectively (p = 0.6); and 174/329 (53%) in those on abacavir versus 77/138 (56%) in those on zidovudine (adjusted odds ratio 1.8, 95% confidence interval 1.0-3.2).

Conclusion: Our data suggest that abacavir may be used safely in infants <28 days old or who weigh <3 kg.

Background: Polyamines are involved in several cellular processes and inhibiting their synthesis affects chikungunya virus (CHIKV) replication and translation, and, therefore, reduces the quantity of infectious viral particles produced. In this study, we evaluated the inhibition of CHIKV replication by N-ω-chloroacetyl-L-ornithine (NCAO), a competitive inhibitor of ornithine decarboxylase, an enzyme which is key in the biosynthesis of polyamines (PAs).

Methods: The cytotoxicity of NCAO was evaluated by MTT in cell culture. The inhibitory effect of CHIKV replication by NCAO was evaluated in Vero and C6/36 cells. The intracellular polyamines were quantified by HPLC in CHIKV-infected cells. We evaluated the yield of CHIKV in titres via the addition of PAs in Vero, C6/36 cells and human fibroblast BJ treated with NCAO.

Results: We found that NCAO inhibits the replication of CHIKV in Vero and C6/36 cells in a dose-dependent manner, causing a decrease in the PFU/mL of at least 4 logarithms (p < 0.01) in both cell lines. Viral yields were restored by the addition of exogenous polyamines, mainly putrescine. The HPLC analyses showed that NCAO decreases the content of intracellular PAs, even though it is predominantly spermidines and spermines which are present in infected cells. Inhibition of CHIKV replication was observed in human fibroblast BJ treated with 100 μM NCAO 24 h before and 48 h after the infection at a MOI 1.

Conclusions: NCAO inhibits CHIKV replication by depleting the intracellular polyamines in Vero, C6/36 cells and human fibroblast BJ, suggesting that this compound is a possible antiviral agent for CHIKV.

Brainstem encephalitis is rare and this study aims to report the clinical course, imaging features, and therapeutic response of hiccup patient with gastric ulcer who developed brainstem encephalitis with Epstein-Barr virus (EBV) detected in cerebrospinal fluid and then subsequently followed by development of duodenal perforation. Data of a gastric ulcer patient who suffered from hiccups, with brainstem encephalitis detected and then subsequently suffered from duodenal perforation were collected retrospectively and analyzed. A literature search was conducted on Epstein-Barr virus associated encephalitis using keywords like "Epstein-Barr virus encephalitis" and "brainstem encephalitis," "hiccup." The etiology of EBV-related brainstem encephalitis in this case report is not clear. However, from the initial hiccup to the presentation of both brainstem encephalitis and duodenal perforation during the course of hospitalizations builds up an uncommon case.

Background: Direct-acting antivirals (DAAs) have revolutionized treatment for HCV. Compared to interferon-based therapies, DAAs achieve higher rates of sustained virologic response, with more tolerable side effects. Nonetheless, interferon-based therapies have the potential to cause weight loss, and literature documenting the impact of DAAs on weight is limited. Appetite suppression may occur with chronic HCV. It is plausible that DAAs may indirectly cause weight gain given their ability to cause rapid virologic suppression, leading to improved hepatic function.

Methods: A retrospective chart review identified 220 patients who initiated DAA therapy between 1 February 2019, and 29 February 2020. Patients 18 years and older who completed therapy with a DAA were included in the study if they had a documented initial weight (weight on the day therapy was initiated) and final weight (weight 12 weeks after therapy completion). Change in weight was assessed as the primary outcome. Comorbidities with the potential to impact weight were assessed as confounders.

Results: Multiple variables were analyzed and baseline BMI was the only factor that influenced a change in weight (P = 0.016). Patients with a higher BMI at baseline experienced statistically significant weight gain. Weight was increased by 0.14 kg per unit of BMI (95% CI: 0.026, 0.25). Patient demographics relating to age and gender, progression of cirrhosis and concurrent comorbidities had no statistically significant impact on change in weight.

Conclusion: Weight changes after treatment with a DAA may be related to the individual's weight prior to treatment.

Although favipiravir is a promising drug for coronavirus disease 2019, some adverse effects, including skin lesions, have been reported. A 56-year-old female who was prescribed favipiravir by a filiation team following a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test presented to our hospital. After examination, favipiravir and paracetamol were prescribed. She represented to the hospital with facial swelling and itchy rashes on her forearm. Angioedema and urticaria were diagnosed. Favipiravir was discontinued. Steroid and antihistaminic therapy were administered for angioedema. To our knowledge, this is the first reported case of favipiravir-induced angioedema and urticaria in Turkey.

Epstein-Barr virus-associated smooth muscle tumor (EBV-SMT) is a rare mesenchymal tumor which occurs in immunocompromised patients. The immune status is an important factor in the treatment of EBV-SMTs, but the efficacy of antiretroviral therapy (ART) is not elucidated in acquired immune deficiency syndrome (AIDS) related EBV-SMTs. Here, we report the first successful case of a 29-year-old man with hepatic AIDS related EBV-SMT treated with ART solely. Positron emission tomography scan was useful for the evaluation of disease status. Recent advances in ART that enables to restore patient's immune status rapidly may change the treatment strategy in AIDS related EBV-SMT.

Background: The GSK3732394 multivalent protein was developed as a novel, long-acting, antiretroviral biologic treatment regimen with three independent, non-cross-resistant mechanisms for inhibiting HIV-1 entry.

Methods: A single-centre, Phase 1, double-blind, randomized, placebo-controlled study was conducted in healthy volunteers, using a 2-part adaptive study design: in Part 1, participants were randomized to receive subcutaneous injection of GSK3732394 or placebo (3:1) as single ascending doses (10-mg starting dose); in Part 2, participants were intended to receive multiple ascending doses. Primary and secondary objectives included safety, pharmacokinetics (PK) and pharmacodynamics (PD; cluster of differentiation four receptor occupancy [CD4 RO]) of GSK3732394 in healthy adults; PK/PD results in healthy volunteers were used to project HIV-1 treatment success.

Results: The most frequently reported adverse event was injection site reactions (ISRs; 8/18 [44%]). Most ISRs were mild (Grade 1-2; n = 7); one participant experienced a Grade 3 ISR (erythema ≥10 cm). All ISRs were delayed in onset (after Day 10). GSK3732394 demonstrated linear PK across all cohorts. Clearance was faster than expected, and PK/PD results were lower than expected, with the maximum dose investigated (80 mg) achieving mean trough CD4 RO of ∼25% on Day 7. The study was terminated as the PK/PD model linking PK and CD4 RO indicated that the maximum planned doses would not achieve the desired therapeutic profile.

Conclusions: This study demonstrated successful deployment of PK/PD dose relationships in the design and conduct of clinical trials by leveraging the findings toward predicting probability of success, resulting in appropriate early termination (ClinicalTrials.gov, NCT03984812).