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Abstract Background Since the implementation of universal antiretroviral therapy, kidney transplantation (K-Tx) has become a valuable option for treatment of end-stage kidney disease for people with HIV (PWH) with similar patient and graft survival as compared to HIV-uninfected patients. Little is known about the hazards and manifestations of infectious disease (ID) events occurring in kidney transplant recipients with HIV. Methods Using linked information collected in the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS), we described in-depth demographical and clinical characteristics of PWH who received a K-Tx since 2008. Further, we performed recurrent time to event analyses to understand whether HIV was an independent risk factor for ID events. Results Overall, 24 PWH with 57 ID events were included in this study (100% match of SHCS to STCS). Of these, 17 (70.8%) patients had at least one ID event: 22 (38.6%) viral (HIV not counted), 18 (31.6%) bacterial, one (1.8%) fungal and 16 (28.1%) probable infections. Most ID events affected the respiratory tract (25, 37.3%) or the urinary tract (13, 19.4%). Pathogen types and infection sites were similar in PWH and a matched control group of HIV-uninfected patients. HIV was not an independent risk factor for ID events (adjusted hazard ratio 0.94, p = 0.9). Conclusion By linking data from two large national Swiss cohorts, we provided in-depth information on ID events in PWH receiving a K-Tx in Switzerland. HIV infection was not associated with an increased hazard for ID events after K-Tx.

Summary: In people with HIV-1 (PWH), Mycobacterium tuberculosis (MTB) infection poses a significant threat. While active tuberculosis (TB) accelerates immunodeficiency, the interaction between MTB and HIV-1 during asymptomatic phases remains unclear. Analysis of peripheral blood mononuclear cells (PBMC) transcriptomic profiles in PWH, with and without controlled viral loads, revealed distinct clustering in MTB-infected individuals. Functional annotation identified alterations in IL-6, TNF, and KRAS pathways. Notably, MTB-related genes displayed an inverse correlation with HIV-1 viremia, at both individual and signature score levels. These findings suggest that MTB infection in PWH induces a shift in immune system activation, inversely related to HIV-1 viral load. These results may explain the observed enhanced antiretroviral control in MTB-infected PWH. This study highlights the complex interplay between MTB and HIV-1, emphasizing the importance of understanding their interaction for managing co-infections in this population.

Abstract Background The burden of herpes zoster (shingles) virus and associated complications, such as post-herpetic neuralgia, is higher in older adults and has a significant impact on quality of life. The incidence of herpes zoster and post-herpetic neuralgia is increased in people living with HIV (PLWH) compared to an age-matched general population, including PLWH on long-term antiretroviral therapy (ART) with no detectable viremia and normal CD4 counts. PLWH – even on effective ART may- exhibit sustained immune dysfunction, as well as defects in cells involved in the response to vaccines. In the context of herpes zoster, it is therefore important to assess the immune response to varicella zoster virus vaccination in older PLWH and to determine whether it significantly differs to that of HIV-uninfected healthy adults or younger PLWH. We aim at bridging these knowledge gaps by conducting a multicentric, international, non-randomised clinical study (SHINGR’HIV) with prospective data collection after vaccination with an adjuvant recombinant zoster vaccine (RZV) in two distinct populations: in PLWH on long-term ART (> 10 years) over 50 years of and age/gender matched controls. Methods We will recruit participants from two large established HIV cohorts in Switzerland and in France in addition to age-/gender-matched HIV-uninfected controls. Participants will receive two doses of RZV two months apart. In depth-evaluation of the humoral, cellular, and innate immune responses and safety profile of the RZV will be performed to address the combined effect of aging and potential immune deficiencies due to chronic HIV infection. The primary study outcome will compare the geometric mean titer (GMT) of gE-specific total IgG measured 1 month after the second dose of RZV between different age groups of PLWH and between PLWH and age-/gender-matched HIV-uninfected controls. Discussion The SHINGR’HIV trial will provide robust data on the immunogenicity and safety profile of RZV in older PLWH to support vaccination guidelines in this population. Trial registration ClinicalTrials.gov NCT05575830. Registered on 12 October 2022. Eu Clinical Trial Register (EUCT number 2023-504482-23-00).

The pathogenesis of HIV-1 infection is governed by a highly dynamic, time-dependent interaction between the host and the viral genome. In this study, we developed a novel systematic approach to assess the host-virus interaction, using average pairwise viral diversity as a proxy for time since infection, and applied this method to nearly whole viral genome sequences (n = 4,464), human leukocyte antigen (HLA) genotyping data (n = 1,044), and viral RNA load (VL) measurements during the untreated chronic phase (n = 829) of Swiss HIV Cohort Study participants. Our systematic genome-wide screen revealed for 98 HLA/viral-variant pairs a signature of immune-driven selection in the form of an HLA-dependent effect of infection time on the presence of HIV amino acid variants. Of these pairs, 12 were found to have an effect on VL. Furthermore, 28/58 pairs were validated by time-to-event analyses and 48/92 by computational HLA-epitope predictions. Our diversity-based approach allows a powerful and systematic investigation of the interaction between the virus and cellular immunity, revealing a notable subset of such interaction effects. From an evolutionary perspective, these observations underscore the complexity of HLA-mediated selection pressures on the virus that shape viral evolution and pathogenesis.

BACKGROUND: Clinical and laboratory monitoring of patients on antiretroviral therapy is an integral part of HIV care and determines whether treatment needs enhanced adherence or modification of the drug regimen. However, different monitoring and treatment strategies carry different costs and health consequences. MATERIALS AND METHODS: The SIMPL’HIV study was a randomised trial that assessed the non-inferiority of dual maintenance therapy. The co-primary outcome was a comparison of costs over 48 weeks of dual therapy with standard antiretroviral therapy and the costs associated with a simplified HIV care approach (patient-centred monitoring [PCM]) versus standard, tri-monthly routine monitoring. Costs included outpatient medical consultations (HIV/non-HIV consultations), non-medical consultations, antiretroviral therapy, laboratory tests and hospitalisation costs. PCM participants had restricted immunological and blood safety monitoring at weeks 0 and 48, and they were offered the choice to complete their remaining study visits via a telephone call, have medications delivered to a specified address, and to have blood tests performed at a location of their choice. We analysed the costs of both strategies using invoices for medical consultations issued by the hospital where the patient was followed, as well as those obtained from health insurance companies. Secondary outcomes included differences between monitoring arms for renal function, lipids and glucose values, and weight over 48 weeks. Patient satisfaction with treatment and monitoring was also assessed using visual analogue scales. RESULTS: Of 93 participants randomised to dolutegravir plus emtricitabine and 94 individuals to combination antiretroviral therapy (median nadir CD4 count, 246 cells/mm3; median age, 48 years; female, 17%),patient-centred monitoring generated no substantial reductions or increases in total costs (US$ –421 per year [95% CI –2292 to 1451]; p = 0.658). However, dual therapy was significantly less expensive (US$ –2620.4 [95% CI –2864.3 to –2331.4]) compared to standard triple-drug antiretroviral therapy costs. Approximately 50% of participants selected one monitoring option, one-third chose two, and a few opted for three. The preferred option was telephone calls, followed by drug delivery. The number of additional visits outside the study schedule did not differ by type of monitoring. Patient satisfaction related to treatment and monitoring was high at baseline, with no significant increase at week 48. CONCLUSIONS: Patient-centred monitoring did not reduce costs compared to standard monitoring in individuals switching to dual therapy or those continuing combined antiretroviral therapy. In this representative sample of patients with suppressed HIV, antiretroviral therapy was the primary factor driving costs, which may be reduced by using generic drugs to mitigate the high cost of lifelong HIV treatment. Trial registration: ClinicalTrials.gov NCT03160105.

Summary: Background: The efficacy and tolerability of long-acting cabotegravir and rilpivirine were demonstrated in Phase III trials. However, low concentrations combined with other risk factors have been associated with an increased risk of virologic failure. This study aims to verify whether drug concentrations measured in a real-world setting are consistent with those previously reported. Methods: SHCS-879 is a nationwide observational study within the Swiss HIV Cohort Study for the monitoring of people with HIV (PWH) on long-acting cabotegravir plus rilpivirine. Samples were collected from March 2022 to March 2023. Findings: Overall, 725 samples were obtained from 186 PWH. Our data show a large inter-individual variability in cabotegravir and rilpivirine concentrations, with some individuals exhibiting repeatedly low concentrations. Rilpivirine trough concentrations were consistent with those from Phase III trials, while cabotegravir concentrations were lower. The first concentrations quartile was only slightly above the target of 664 ng/mL. Exploratory statistical analyses found 35% (p

Listeria monocytogenes is a Gram-positive pathogenic bacterium which can be found in soil or water. Infection with the microorganism can occur after ingestion of contaminated food products. Small and large outbreaks of listeriosis have been described in the past. L. monocytogenes can cause a number of different clinical syndromes, most frequently sepsis, meningitis, and rhombencephalitis, particularly in immunocompromised hosts. L. monocytogenes systemic infections can develop following tissue penetration across the gastrointestinal tract or to hematogenous spread to sterile sites, possibly evolving towards bacteremia. L. monocytogenes only rarely causes bone or joint infections, usually in the context of prosthetic material that can provide a site for bacterial seeding. We describe here the clinical findings of invasive listeriosis, mainly focusing on the diagnosis, clinical management, and treatment of bone and vertebral infections occurring in the context of invasive listeriosis.