Patients with HBeAg-negative chronic hepatitis B may experience an immune response after stopping nucleos(t)ide analogue (NA)therapy, which may potentially trigger HBsAg loss or off-therapy sustained ...viral control. The immunological mechanisms determining clinical response remain poorly understood. To identify inflammatory signatures associated with defined outcomes, we analysed plasma cytokines and chemokines from 57 HBeAg-negative patients enrolled in the Nuc-Stop Study at baseline and 12 weeks after NA cessation. Clinical response at 12 weeks was classified into four groups: immune control, viral relapse, evolving clinical relapse, and resolving clinical relapse. Twelve weeks after treatment cessation 17 patients (30%) experienced immune control, 19 (33%) viral relapse, 6 (11%) evolving clinical relapse, and 15 (26%) resolving clinical relapse. There was a significant increase in interferon-γ-induced protein 10 (IP-10; p = 0.012) and tumor necrosis factor (TNF; p = 0.032) in patients with evolving clinical relapse. Sparse partial least-squares multivariate analyses (sPLS-DA) showed higher first component values for the clinical relapse group compared to the other groups, separation was driven mainly by IP-10, TNF, IL-9, IFN-γ, MIP-1β, and IL-12. Our results demonstrate that evolving clinical relapse after NA cessation is associated with a systemic increase in the proinflammatory cytokines IP-10 and TNF.Clinical trial registration: ClinicalTrials.gov, Identifier: NCT03681132.
Objectives
Our objective was to determine whether antiretroviral drugs (ARVs) were used according to the European AIDS Clinical Society (EACS) guidelines for people with HIV/hepatitis C virus (HCV) ...coinfection treated with direct‐acting antivirals (DAAs) between 30 November 2014 and 31 December 2019 in the pan‐European EuroSIDA study.
Methods
At each publication date of the EACS guidelines, plus 3 and 6 months, we calculated the number of people receiving DAAs with potential and actual ARV contraindications (‘red shading’ in the EACS guidelines). We used logistic regression to investigate factors associated with using contraindicated ARVs.
Results
Among 1406 people starting DAAs, the median age was 51 years, 75% were male, 57% reported injected drug use as an HIV risk, and 76% were from western Europe. Of 1624 treatment episodes, 609 (37.5%) occurred while the patient was receiving ARVs with potential contraindications; among them, 38 (6.2%; 95% confidence interval CI 4.3–8.2) involved a contraindicated ARV (18 non‐nucleoside reverse transcriptase inhibitors), 16 involved protease inhibitors, and four involved integrase strand transfer inhibitors. The adjusted odds of receiving a contraindicated ARV were higher (3.25; 95% CI 1.40–7.57) among participants from east/central east Europe (vs. south) and lower (0.22; 95% CI 0.08–0.65) for 2015–2018 guidelines (vs. 2014). In total, 29 of the 32 (90.6%) patients receiving a contraindicated ARV and 441 of the 461 (95.7%) with potential ARV contraindications experienced a sustained virological response ≥12 weeks after stopping treatment (SVR12; p = 0.55).
Conclusion
In this large heterogenous European cohort, more than one‐third of people with HIV/HCV coinfection received DAAs with potential ARV contraindications, but few received a contraindicated ARV. Use of contraindicated ARVs declined over time, corresponding to the increased availability of ARV therapy regimens without interactions with DAA across Europe. Participants who received a contraindicated DAA and ARV combination still had a high rate of SVR12.
