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1.
Hepatology International ; 17(Supplement 1):S123, 2023.
Artigo em Inglês | EMBASE | ID: covidwho-2327134

RESUMO

Background/Aims: The clinical course of hepatitis B virus (HBV) infection in individuals with HIV-1 coinfection is marked by accelerated disease progression. A tenofovir-containing antiretroviral regimen is recommended in most people with HIV-1/HBV-coinfection, but there have not been randomized studies of tenofovir disoproxil fumarate (TDF) vs tenofovir alafenamide (TAF) in treatment- naive HIV-1/HBV-coinfected individuals. We report primary endpoint results from a Phase 3 study comparing bictegravir/emtricitabine/ TAF (B/F/TAF) vs dolutegravir + emtricitabine/TDF (DTG + F/TDF) at Week (W)48 in participants initiating treatment for both viruses. Method(s): Adults with HIV-1/HBV coinfection were randomized 1:1 to initiate blinded treatment with B/F/TAF or DTG + F/TDF (with placebo). Primary endpoints were the proportion of participants with HIV-1 RNA<50 copies/mL (FDA Snapshot) and plasma HBV DNA<29 IU/mL (missing = failure) at W48. Noninferiority was assessed with 95% CI (12% margin). Secondary and other endpoints included change from baseline cluster of differentiation 4 (CD4) count, proportion with hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) loss/seroconversion, and alanine transaminase (ALT) normalization (AASLD criteria). Result(s): Participants (N = 243) were randomized and treated (B/F/ TAF [n = 121], DTG + F/TDF [n = 122]) from 11 countries in Asia, Europe, North, and Latin America. Baseline characteristics were median age of 32 years, 4.5% female, 88% Asian, 30% HIV-1 RNA>100,000 c/mL, 40% CD4<200 cells/lL, median HBV DNA 8.1 log10 IU/mL, 78% HBeAg+. At W48, B/F/TAF was noninferior to DTG + F/TDF at achieving HIV-1 RNA<50 copies/mL (95% vs 91%, difference 4.1%;95% CI -2.5%-10.8%;P = 0.21), with mean CD4 gains of + 200 and + 175 cells/lL, respectively. B/F/TAF was superior to DTG + F/TDF at achieving HBV DNA<29 IU/mL (63% vs 43%, difference 16.6%;95% CI 5.9%-27.3%;P = 0.0023). Participants treated with B/F/TAF vs DTG + F/TDF had numerically higher HBsAg loss (13% vs 6%;P = 0.059), HBeAg loss (26% vs 14%;P = 0.055), HBeAg seroconversion (23% vs 11%;P = 0.031), and ALT normalization (73% vs 55%;P = 0.066). The most frequent adverse events among participants treated with B/F/TAF vs DTG + F/TDF were upper respiratory tract infection (17% vs 11%), COVID- 19 (13% vs 11%), pyrexia (9% vs 12%), ALT increase (7% vs 11%), and nasopharyngitis (11% vs 4%). ALT flares (elevations at >= 2 consecutive postbaseline visits) occurred in 11 participants (7 B/F/ TAF, 4 DTG + F/TDF), and all resolved. Conclusion(s): Among adults with HIV-1/HBV-coinfection starting antiviral therapy, both B/F/TAF and DTG + F/TDF had high HIV-1 suppression at year 1, with B/F/TAF resulting in superior HBV DNA suppression and significantly more HBeAg seroconversion. Safety findings were similar between groups.

2.
American Journal of Transplantation ; 22(Supplement 3):876, 2022.
Artigo em Inglês | EMBASE | ID: covidwho-2063427

RESUMO

Purpose: An additional dose of the COVID-19 vaccine following a primary series is recommended for solid organ transplant recipients. However, a comparison of the immunogenicity and safety of an additional dose of COVID-19 vaccine among different platforms has not been investigated. Method(s): Eligible adult KT recipients were randomized using a stratified (by a previous vaccine regimen) block randomization approach to receive either ChAdOx1 nCoV-19 vaccine (AstraZeneca);V group, or mRNA vaccine (Pfizer-BioNTech or mRNA-1273);M group. Two weeks later, humoral immunity (HMI) was evaluated by anti-RBD IgG level, and percentages of neutralizing antibody inhibition using surrogate viral neutralization test (%SVNT), and cell-mediated immunity (CMI) was investigated by the ELISpot assays. Result(s): A total of 85 KT recipients were included. Of those, 62% were male with the median (IQR) age of 50 (43-59) years. The median (IQR) duration after transplantation was 46 (26-82) months. Twenty-six (34%) and 51 (66%) of those received two-dose of CoronaVac followed by one dose of ChAdOx1 nCoV-19 vaccine and two-dose of ChAdOx1 nCoV-19 vaccine, respectively. Of all, 42 and 43 patients were assigned to V and M groups, respectively. At two weeks after an additional dose, KT recipients in the M group elicited a greater trend of the median (IQR) anti-RBD antibody levels compared to those in the V group (51.8 [5.1-591] vs. 28.5 [2.9-119.3] BAU/mL,p=0.18), which resulted in significantly higher seroconversion rate (anti-RBD antibody > 7.1 BAU/mL) in M group than those in V group (83%vs.51%, p<0.01). Additionally, sVNT positivity rate (%SVNT > 35%) were also significantly greater in M group (58%vs32%, p=0.03). However, there was no difference in S1-specific T cell and RBD-specific B cell responses between M and V groups (230 [41-420] vs. 268 [118-510] SFUs/106 PMBCs, p=0.65 and 2 [0-10] vs. 2 [0-13] SFUs/106 PMBCs, p=0.60). Adverse events were mild and similar between groups (p=NS). Conclusion(s): KT recipients who received an additional dose of mRNA COVID-19 vaccine could elicit HMI greater than a viral vector COVID-19 vaccine along with comparable CMI and safety profile.

3.
Nephrology Dialysis Transplantation ; 37(SUPPL 3):i127-i128, 2022.
Artigo em Inglês | EMBASE | ID: covidwho-1915677

RESUMO

BACKGROUND AND AIMS: Patients with end-stage kidney disease (ESKD) are at risk of coronavirus disease 2019 infection and its associated complications. A previous study demonstrated that patients with ESKD on dialysis generated suboptimal humoral immune response (HIR) and lower seroconversion rate after two-dose inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination as compared to healthy individuals. In this study, we examined HIR of the additional dose of ChAdOx1 nCoV-19 vaccine following a standard two-dose inactivated wholevirus SARS-CoV-2 vaccination in patients on dialysis, and compared to those of healthy controls. METHOD: We recruited 59 patients with ESKD [31 patients on haemodialysis (HD) and 28 on peritoneal dialysis (PD)) and 16 healthy controls who received two doses of inactivated SARS-CoV-2 vaccine (V2) from Ramathibodi hospital and Banphaeo General Hospital, Bangkok, Thailand, from July 2021 to September 2021. All participants were administered a third dose of the ChAdOx1nCoV-19 vaccine (V3) with a 6-week interval between the V2 to V3. HIR was measured 2 weeks after V2 and V3 using SARS-CoV-2 immunoglobulin G (IgG) assay, which detects antibodies against the S1 receptor-binding domain (RBD) of the SARSCoV- 2 spike protein. Median anti-RBD IgG titer and seroconversion rate, defined as anti-RBD IgG titre ≥ 7.1 BAU/mL, were compared among ESKD patients and to those of healthy controls using the Kruskal-Wallis H test and the chi-squared test, respectively. RESULTS: Baseline characteristics of patients on HD, PD and healthy controls are shown in Table 1. Demographic characteristics and baseline laboratory parameters were comparable between the HD and PD groups, except for a lower mean serum albumin level in the PD group (P<.001). None of the healthy controls were immunocompromised or receiving immunosuppressive therapies. At 2 weeks after V3, the median anti-RBD IgG titres were significantly increased in all groups compared to those levels after V2 (85[33-412] versus 1566 [861-3083] BAU/mL for patients on HD, 81 [15-144] versus 913 [293-1359] BAU/mL for patients on PD and 250 [92-603] versus 2210 [1531-2782] BAU/mL for healthy controls;P < .001 for all groups). Comparing antibody levels between groups after V3, patients on PD generated significantly lower anti-RBD IgG titer than patients on HD (P = .02) and healthy controls (P < .01) (Figure 1A). The seroconversion rate of the HD and PD groups improved from 94% and 82% after V2 to 100% after V3 in both groups (P = .16 and P = .03, respectively) (Figure 1B). All patients on dialysis who had anti- RBD IgG < 7.1 BAU/mL after V2 (7/59 patients) seroconverted after the additional dose of ChAdOx1 nCoV-19 vaccine. CONCLUSION: We suggest that an additional ChAdOx1 nCoV-19 vaccine after a primary two doses inactivated SARS-CoV-2 vaccination could improve seroconversion rate and magnitude of humoral immune response in patients on dialysis. The durability of the immune response to this vaccination regimen requires further study. (Table Presented).

4.
Pharmaceutical Sciences Asia ; 48(5):425-431, 2021.
Artigo em Inglês | Scopus | ID: covidwho-1529086

RESUMO

Optimized dosage regimens of hydroxychloroquine (HCQ) in coronavirus disease 2019 (COVID-19) are currently unknown. We aimed to determine regimens that rapidly achieved the pharmacokinetic-pharmacodynamic (PKPD) target for virological clearance in COVID-19 patients. Plasma HCQ concentration was simulated using a non-steady state, 2-compartment linear model. The plasma trough concentration (Ctrough) > 0.7 mg/L was used as the PKPD target. The loading dose of 800 mg three times daily and 1,200 mg twice daily achieved the target on the first day with the probability of target attainment (PTA) 97.53% and 82.63%, respectively. Maintenance dose of 200 mg three times daily and 400 mg twice daily provided PTA > 80% from day 3 through day 10 after the initiation of HCQ therapy. All proposed regimens had the PTA < 1% to achieve toxic level of 4 mg/L. The optimal dose regimens for early viral clearance in COVID-19 patients were HCQ 800 mg three times daily on the first day followed by 200 mg three times daily for 9 days, and HCQ 1,200 mg twice daily on the first day followed by 400 mg twice daily for 9 days. Further clinical study is needed to ensure clinical efficacy and safety of these regimens. © 2021 Pharmaceutical Sciences Asia by Faculty of Pharmacy, Mahidol University, Thailand is licensed under CC BY-NC-ND 4.0. To view a copy of this license, visit https:// www.creativecommons.org/licenses/by-nc-nd/4.0/. All Rights Reserved.

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