Changes in mental and sexual health among MSM using HIV pre-exposure prophylaxis during the SARS-CoV-2 pandemic: longitudinal analysis of the SwissPrEPared cohort study.

BACKGROUND: Changes in mental and sexual health among men having sex with men (MSM) due to the SARS-CoV-2 pandemic remain unclear. METHODS: Design: Longitudinal analysis of an ongoing, multicentre, pre-exposure prophylaxis (PrEP) cohort (NCT03893188) in Switzerland. Participants: HIV-negative MSM aged ≥18 who completed at least one questionnaire before and one after the start of the SARS-CoV-2 pandemic. Outcomes: Primary: mental health, defined as anxiety and depression scores assessed by the Patient Health Questionnaire-4. Secondary: sexual behaviour, well-being, PrEP use and disruption of care. Outcomes were assessed over seven periods corresponding to different SARS-CoV-2 prevention measures in Switzerland. We performed pairwise comparisons between periods (Wilcoxon signed rank test). RESULTS: Data from 1,043 participants were included. Whilst anxiety scores remained stable over time, depression scores worsened in the second wave and the second lockdown period compared to pre-pandemic scores. This was confirmed by pairwise comparisons (pre-SARS-CoV-2/second wave and pre-SARS-CoV-2/second lockdown: p <0.001). Downward trends in sexual activity,sexualized substance use, and a switch from daily to "event-driven" PrEP were found. Disruption of care affected 42.6% (790/1856) of daily PrEP users' follow-up visits. CONCLUSION: In this longitudinal analysis of a PrEP cohort enrolling MSM, depression scores worsened in the second wave and the second lockdown compared to the pre-pandemic period.

Medication Adherence Evaluated Through Electronic Monitors During the 2020 COVID-19 Pandemic Lockdown in Switzerland: A Longitudinal Analysis.

Background: During the 2020 COVID-19 lockdown, patients included in the Interprofessional Medication Adherence Program (IMAP) in Switzerland continued to use electronic monitors (EMs) that registered daily drug-dose intake. We aimed to understand to what extent patients' medication implementation (ie, the extent to which the patient took the prescribed medicine), measured with EMs, was impacted by the lockdown. Methods: Patients participating in the IMAP were diagnosed with diabetic kidney disease (DKD), solid cancer, human immunodeficiency virus (HIV) and miscellaneous long-term diseases (MLTD). Patient implementation was defined through a proxy: if all patient EMs were opened at least once daily, implementation was considered active (=1), and no implementation was considered (=0) otherwise. Implementation before (from December 2019 to March 2020), during (March to June 2020) and after (June to September 2020) the lockdown was compared. Subanalyses were performed according to the patients' diseases. Subanalyses were performed in patients who used at least one EM in 2018-2019 during the same periods (defined as winter, spring and summer). The logistic regression models used to estimate medication implementation according to the period were fitted using generalized estimating equations. Results: In 2020, patient implementation (n = 118) did not differ significantly before versus during (OR = 0.98, 95% CI: 0.84-1.15, p = 0.789) and before versus after (OR = 0.91, 95% CI: 0.79-1.06, p = 0.217) the lockdown. These findings remained stable when separately analyzing the implementation of patients with HIV (n = 61), DKD (n = 25) or MLTD (n = 22). Too few patients with cancer were included (n = 10) to interpret the results. In 2019, the implementation of 61/118 (51.7%) patients was significantly lower during summertime versus wintertime (OR = 0.73, 95% CI: 0.60-0.89, p = 0.002). Conclusion: Medication implementation remained steady before, during and after the lockdown in 2020. The IMAP before, during and after the lockdown may have supported the adherence of most patients, by ensuring continuity of care during periods of routine disturbances.

High-dimensional immune phenotyping of blood cells by mass cytometry in patients infected with hepatitis C virus.

OBJECTIVES: Chronic hepatitis C virus (HCV) infection affects the immune system. Whether elimination of HCV with direct-acting antivirals (DAA) restores immunity is unclear. We used mass cytometry to get a broad and in-depth assessment of blood cell populations of patients with chronic HCV before and after DAA therapy. METHODS: Before and 12 weeks after sustained virological response (SVR12) to DAA therapy, 22 cell populations were analysed by mass cytometry in blood collected from ten healthy control individuals and 20 HCV-infected patients with (ten patients) or without (ten patients) human immunodeficiency virus (HIV) infection. RESULTS: HCV infection altered the frequency of 14/22 (64%) blood cell populations. At baseline, the frequencies (median, interquartile range (IQR); control, HCV, HCV/HIV) of intermediate monocytes (1.2, IQR 0.47-1.46; 1.76, IQR 0.83-2.66; 0.78, IQR 0.28-1.77), non-classical monocytes (1.11, IQR 0.49-1.26; 0.9, IQR 0.18-0.99; 0.54, IQR 0.28-1.77), conventional dendritic cells type 2 (0.55, IQR 0.35-0.59; 0.31, IQR 0.16-0.38; 0.19, IQR 0.11-0.36) and CD56dim natural killer cells (8.08, IQR 5.34-9.79; 4.72, IQR 2.59-6.05) 3.61, IQR 2.98-5.07) were reduced by 35% to 65%, particularly in HCV/HIV co-infected patients. In contrast, activated double-negative T cells (0.07, IQR 0.06-0.10; 0.10, IQR 0.09-0.19; 0.19, IQR 0.12-0.25), activated CD4 T cells (0.28, IQR 0.21-0.36; 0.56, IQR 0.33-0.77; 0.40, IQR 0.22-0.53) and activated CD8 T cells (0.23, IQR 0.14-0.42; 0.74, IQR 0.30-1.65; 0.80, IQR 0.58-1.16) were increased 1.4 to 3.5 times. Upon stimulation with Toll-like receptor ligands, the expression of cytokines was up-regulated in 7/9 (78%) and 17/19 (89%) of the conditions in HCV- and HCV/HIV-infected patients, respectively. Most alterations persisted at SVR12. CONCLUSIONS: Chronic HCV and HCV/HIV infections induce profound and durable perturbations of innate and adaptive immune homeostasis.

A trial platform to assess approved SARS-CoV-2 vaccines in immunocompromised patients: first sub-protocol for a pilot trial comparing the mRNA vaccines Comirnaty® and COVID-19 mRNA Vaccine Moderna®.

BACKGROUND: Late 2019, a new highly contagious coronavirus SARS-CoV-2 has emerged in Wuhan, China, causing within 2 months a pandemic with the highest disease burden in elderly and people with pre-existing medical conditions. The pandemic has highlighted that new and more flexible clinical trial approaches, such as trial platforms, are needed to assess the efficacy and safety of interventions in a timely manner. The two existing Swiss cohorts of immunocompromised patients (i.e., Swiss HIV Cohort Study (SHCS) and Swiss Transplant Cohort Study (STCS)) are an ideal foundation to set-up a trial platform in Switzerland leveraging routinely collected data. Within a newly founded trial platform, we plan to assess the efficacy of the first two mRNA SARS-CoV-2 vaccines that reached market authorization in Switzerland in the frame of a pilot randomized controlled trial (RCT) while at the same time assessing the functionality of the trial platform. METHODS: We will conduct a multicenter randomized controlled, open-label, 2-arm sub-study pilot trial of a platform trial nested into two Swiss cohorts. Patients included in the SHCS or the STCS will be eligible for randomization to either receiving the mRNA vaccine Comirnaty® (Pfizer/BioNTech) or the COVID-19 mRNA Vaccine Moderna®. The primary clinical outcome will be change in pan-lg antibody response (pan-Ig anti-S1-RBD; baseline vs. 3 months after first vaccination; binary outcome, considering ≥ 0.8 units/ml as a positive antibody response). The pilot study will also enable us to assess endpoints related to trial conduct feasibility (i.e., duration of RCT set-up; time of patient recruitment; patient consent rate; proportion of missing data). Assuming vaccine reactivity of 90% in both vaccine groups, we power our trial, using a non-inferiority margin such that a 95% two-sided confidence interval excludes a difference in favor of the reference group of more than 10%. A sample size of 380 (190 in each treatment arm) is required for a statistical power of 90% and a type I error of 0.025. The study is funded by the Swiss National Science Foundation (National Research Program NRP 78, "COVID-19"). DISCUSSION: This study will provide crucial information about the efficacy and safety of the mRNA SARS-CoV-2 vaccines in HIV patients and organ transplant recipients. Furthermore, this project has the potential to pave the way for further platform trials in Switzerland. TRIAL REGISTRATION: ClinicalTrials.gov NCT04805125 . Registered on March 18, 2021.