Katharina Kusejko

Background: Immediate antiretroviral therapy (ART) initiation after HIV diagnosis is a clinical and public health priority. The “treat all” strategy—ART initiation irrespective of CD4+ cell count—improves health outcomes and curtails further transmissions. Using data from the Swiss HIV Cohort Study, we assessed time from HIV diagnosis to ART initiation and associated sociodemographic and clinical characteristics to evaluate how rapidly and equitably it was adopted at a national level. Methods: We analyzed participants diagnosed in 1996–2025. Time from HIV diagnosis to ART initiation was assessed by Kaplan-Meier estimates, and associated characteristics were evaluated by fitting time-updated Cox proportional hazards models. Results: Among 7525 participants diagnosed between 1996 and 2025, 93.1% initiated ART. Median time to ART initiation declined steeply from 983 days (2005) to 63 days (2010), reaching 12 days by 2025; 42.2% initiated ART within 1 week in 2025. CD4+-based differences disappeared, with median ART initiation times falling below 3 weeks across all strata by 2025. Higher viral load remained associated with faster ART initiation, although absolute differences in ART timing among viral load strata were small. Participants from Africa and the Americas showed significantly lower initiation hazards than Europeans in 2017–2025, with absolute differences of at most 1 week by 2025. By transmission mode, people who inject drugs consistently showed the lowest ART initiation hazard. Conclusions: Universal treatment was rapidly implemented in Switzerland, with a shift toward rapid and equitable ART initiation. Residual differences for viral load, region of origin, and people who inject drugs warrant continued monitoring.

Background: Prior to the COVID‐19 pandemic, antiretroviral therapy (ART) coverage and viral suppression were improving across Europe; however, the impact of the pandemic on HIV care remains uncertain. Methods: In‐person visits, ART coverage and viral suppression among those on ART were described in the EuroSIDA cohort for each calendar year from 2016 to 2022 and compared across five European regions. Multivariable logistic regression was used to assess factors associated with having an in‐person visit and with viral suppression. Results: Among 6740 participants, 71.9% were men, 34.9% were MSM, and the median age was 50 years (IQR: 42–56) at baseline (2016). The proportion of in‐person visits dropped from 75.0% in 2019 to 67.8% in 2020, increased to 74.5% in 2021 and was 72.3% in 2022. We observed a consistent increase in ART uptake over the years and a slight increase in missing HIV‐RNA data in 2020. The odds of attending clinic in person were lower in 2020 compared with 2016 (aOR: 0.81, 95% CI 0.75–0.87) but not in 2021 or 2022, while viral suppression increased over calendar time ( p < 0.0001). Compared to Central‐Western Europe, the other regions had lower odds of in‐person visits ( p < 0.0001, most prominently for Southern Europe, aOR: 0.18) and viral suppression ( p < 0.0001, most prominently for Eastern Europe, aOR: 0.07). Conclusions: Our study confirmed the resilience of HIV care across Europe during the COVID‐19 pandemic, whereas the regional and country differences in clinic attendance and viral suppression highlighted the need to address persisting gaps in HIV care on a national level.

Introduction: Global awareness to chemsex, a specific form of sexualized psychoactive substance (“chems”) use among gay, bisexual and other men who have sex with men (gbMSM), is increasing. We aimed to assess prevalence, patterns and implications of “chems” use on chemsex‐related outcomes. Methods: We conducted a Swiss‐wide longitudinal study using individual‐level data from April 2019 to December 2024 of adult gbMSM with HIV, enrolled in the Swiss HIV Cohort Study (SHCS), or taking HIV pre‐exposure prophylaxis (PrEP), enrolled in SwissPrEPared. Determinants of “chems” (methamphetamine, new psychoactive stimulants, GHB/GBL) use and clinical implications were analysed using logistic regression. Longitudinal “chems” use patterns were distinguished by rule‐based classification. Point‐prevalences of “chems” use, including COVID‐19 and mpox periods, were analysed using interrupted time series analysis. Results: We analysed 107,855 follow‐up visits from 13,304 gbMSM. “Chems” were used by 17.2% of gbMSM (21.4% in SwissPrEPared vs. 11.2% in the SHCS). Age below 26 (compared to 26−37, adjusted odds ratio [aOR]: 0.82, 95%‐confidence interval: 0.68−0.96), over 37 (aOR for 38−48: 0.84, 0.75−0.94; aOR for over 48: 0.54, 0.47−0.62) and bisexual orientation showed lower odds (aOR: 0.78, 0.66−0.90), while participation in French‐speaking SwissPrEPared centres (aOR compared to SHCS Eastern Switzerland: 1.41, 1.22−1.64) and sex with non‐steady partners showed higher odds for “chems” use (aOR: 12.44, 8.85−18.17). “Chems” use was associated with depression, inconsistent condom use, high non‐steady partner count and sexually transmitted infections (STIs). Comparing longitudinal use patterns, temporally restricted use, that is, recovering from stable use, reported “chems” use only once, or for a single episode shorter than 1 year, showed the lowest risk for STIs and high partner count, whereas intermittent use showed lower risk only for syphilis. “Chems” use decreased marginally during COVID‐19 and mpox, with a quick return and no difference to levels before COVID‐19. Conclusions: A large proportion of gbMSM use “chems,” with congruent determinants across both cohorts but heterogeneous impact on sexual and mental health that varies by specific substance and longitudinal use patterns. Further understanding of underlying mechanisms driving this heterogeneity is needed before delivering mechanism‐informed interventions tailored to “chems” use patterns, like STI and depression screening, harm‐reduction counselling and linkage to addiction care.

Despite suppressive antiretroviral therapy, many people with HIV (PWH) retain chronic interferon-associated immune dysregulation. Observational data from the Swiss HIV Cohort Study linked asymptomatic mycobacterial exposure to lower viral set points, reduced interferon-associated activity, and attenuated HIV-specific antibody responses, a pattern sharing features with HIV elite controllers and natural hosts of primate lentiviruses. We therefore examined whether Bacillus Calmette-Guérin (BCG) vaccination could induce a related immune configuration in ART-treated PWH. Using longitudinal systems-level profiling within the BELIEVE trial, we found that BCG reduced constitutive NK cell IFN-γ production and PBMC-mediated direct cytotoxicity without impairing inducible cytokine responses or antibody-dependent cellular cytotoxicity. Multiomic and proteomic analyses showed reduced interferon- and activation-associated programs, while adaptive immune parameters remained largely stable and follow-up revealed no obvious adverse clinical pattern. This configuration, reduced baseline interferon activity coexisting with preserved Fc-dependent effector function, shares selected features with immune states described in natural lentiviral control and provides a rationale for testing BCG in combination with antibody-based HIV interventions.

Background: Vaccination of people with HIV (PWH) on suppressive antiretroviral therapy (ART) represents a novel approach for evaluating candidate broadly neutralizing antibody (bnAb) immunogens for preventive and therapeutic HIV vaccines. Given pre-existing immunity in PWH, the safety of this approach requires careful assessment prior to broader application. Here, we report on the design and safety of the RENEW-SHCS study which evaluates the immunization of PWH with BG505 SOSIP.v4.1-GT1.1, an immunogen engineered to induce precursors of CD4 binding site (CD4bs)- and V2-apex targeting bnAbs. Methods: RENEW-SHCS is a phase I, open-label, non-randomized vaccination trial evaluating a single dose of the recombinant germline-targeting envelope trimer BG505 SOSIP.v4.1-GT1.1 (GT1.1), adjuvanted with 3M052-AF and Aluminum hydroxide (alum), in PWH on suppressive ART enrolled from the Swiss HIV Cohort Study. Participants were previously classified as bnAb or non-neutralizing antibody (nnAb) inducers, with a target enrollment of 15 per group, and were monitored for safety and immunogenicity for 24 weeks while continuing standard ART. Due to an out-of-specification stability measurement of adjuvant 3M052-AF the trial was paused after 23 immunizations and subjected to an unscheduled interim safety and reactogenicity assessment comprising protocol defined outcome measures (adverse events, clinical laboratory measurements and HIV-1 viral load). Results: Twenty-three participants (10 bnAb and 13 nnAb inducers, median age 59 years, 17 male / 6 female) were vaccinated between March and August 2025 before interruption of the trial. All participants completed follow-up with full protocol adherence. The interim-safety analysis confirmed that no vaccine-related serious adverse events occurred. Solicited local (96%) and systemic (83%) reactions were common, predominantly grade 1–2, transient, and self-limited. Transient laboratory changes occurred but mostly remained within the normal range, with no vaccine-related grade 3 abnormalities. We observed predominantly transient local and systemic reactions, which were similar or milder to the reactogenicity profile reported for immunization of adult people without HIV (PWOH) with GT1.1 adjuvanted with AS01b reported in the IAVI C101 trial. No viral rebound under ART occurred. One participant experienced two viral blips (>50 HIV-1 RNA copies/ml), one before and one 16 weeks after vaccination with subsequent re-suppression. All others maintained viral suppression (<50 copies/ml) throughout follow-up. Conclusion: RENEW-SHCS demonstrated a favorable safety and reactogenicity profile of single dose immunization with GT1.1 in PWH, comparable to that observed in PWOH. The findings of this phase I study support the feasibility of vaccinating ART-treated PWH in trials of preventive and therapeutic HIV vaccine strategies. Trial registration: SNCTP000006192 | BASEC2024-01623. ClinicalTrials.gov NCT07769983

Introduction: Tobacco smoking is an insufficiently addressed health burden among people living with HIV. The Reduce tobacco use in people living with HIV in Switzerland (RETUNE) trial tests the effectiveness of offering a menu of nicotine substitute products, including e-cigarettes, nicotine...

Background: Among people living with HIV, there has been a shift of focus from HIV-related health issues to cardiovascular diseases and cancer. For both, tobacco smoking is a major but insufficiently addressed etiological factor. Evidence from randomized trials suggests that nicotine substitute products such as e-cigarettes and nicotine patches can reduce tobacco smoking and its associated health burden. However, most previous smoking cessation trials primarily included people who are motivated to quit smoking and focused on testing a single nicotine substitute product. The effectiveness of offering a menu of nicotine substitute products to tobacco smokers regardless of their willingness to quit smoking (“opt-out” approach) is unknown. Methods: Reduce tobacco use in people living with HIV in Switzerland (RETUNE, NCT06789692) is a pragmatic, 1:1 randomized, multicenter, superiority clinical trial using the Trials within Cohorts (TwiCs) design within the Swiss HIV Cohort Study. RETUNE assesses the effectiveness of offering a menu of different nicotine substitute products, namely electronic cigarettes, nicotine pouches, and nicotine patches, versus usual care. Cohort participants are eligible if they smoke more than one tobacco cigarette per day, do not use any of the substitute products, and have signed the randomization consent following the TwiCs design. Participants randomized to the intervention may choose any of the offered substitutes to be used free of charge for 6 months or decline the offer. Overall, we plan to recruit 972 participants. The primary outcome is tobacco abstinence at 6 months measured as participant-reported past 7-day prevalence abstinence. The primary outcome will be assessed in the intention-to-treat set using a logistic regression model adjusted for region, men having sex with men, current drug users, and number of cigarettes per day at baseline. Secondary outcomes are long-term smoking cessation rates and tobacco-associated health outcomes. Discussion: RETUNE started recruitment in February 2025 and is currently ongoing. RETUNE using the TwiCs design will clarify the effectiveness of a preference-based opt-out smoking cessation intervention among people living with HIV. Trial registration: Clinicaltrials.gov NCT06789692. Registered on January 17th, 2025. The manuscript is aligned with the registry. https://clinicaltrials.gov/study/NCT06789692?cond=NCT06789692&rank=1

Improved biomarkers for predicting progression to active tuberculosis (TB) are urgently needed, especially in people with HIV, who are at elevated risk. We used high-throughput plasma proteomics and machine learning to identify signatures associated with TB progression in this population. From the Swiss HIV Cohort Study, we analyzed plasma samples collected at least 6 months before TB diagnosis from 91 participants who later developed TB. We selected 293 controls matched for demographic and clinical parameters who remained TB-free to achieve a risk score specific to active TB. In total, 583 samples were analyzed, with 613–1,283 proteins quantified per sample. A random forest classifier predicted a significantly higher median probability of TB progression for cases (33%) than for controls (16%; P < 0.001). In this matched population, the score achieved an area under the receiver-operating characteristic curve of 0.77, an area under the precision-recall curve (AUPRC) of 0.60 (as compared to an expected AUPRC of 0.29), as well as a specificity of 87.3% and a sensitivity of 58.6% using the optimal threshold of 0.311. The plasma proteome of individuals who progressed to active TB showed a distinct shift toward systemic inflammation, B cell activation, and immunoglobulin production. Independent of progression to active TB, the proteome score correlated with broader indicators of immune suppression, including lower CD4 counts and unsuppressed HIV RNA. This suggests that integrating proteomic and clinical data could enhance the overall predictive power of the score. IMPORTANCE: We still lack reliable tools to predict who will develop tuberculosis (TB) among people with HIV. Moreover, the underlying biological events driving progression remain poorly understood. Our study reveals early immune changes that include unexpected alterations in B cell activation and antibody responses. These findings suggest that humoral immunity may play a more important role in TB pathogenesis than previously recognized and offer promising new directions for biomarker discovery and targeted prevention.