Trends in mortality in people with HIV from 1999 to 2020: a multi-cohort collaboration.

BACKGROUND: Mortality among people with HIV declined with the introduction of combination antiretroviral therapy. We investigated trends over time in all-cause and cause-specific mortality in people with HIV from 1999-2020. METHODS: Data were collected from the D:A:D cohort from 1999 through January 2015 and RESPOND from October 2017 through 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV (CoDe), were calculated. Poisson regression models were used to assess mortality trends over time. RESULTS: Among 55716 participants followed for a median of 6 years (IQR 3-11), 5263 participants died (crude mortality rate [MR] 13.7/1000 PYFU; 95%CI 13.4-14.1). Changing patterns of mortality were observed with AIDS as the most common cause of death between 1999- 2009 (n = 952, MR 4.2/1000 PYFU; 95%CI 4.0-4.5) and non-AIDS defining malignancy (NADM) from 2010 -2020 (n = 444, MR 2.8/1000 PYFU; 95%CI 2.5-3.1). In multivariable analysis, all-cause mortality declined over time (adjusted mortality rate ratio [aMRR] 0.97 per year; 95%CI 0.96, 0.98), mostly from 1999 through 2010 (aMRR 0.96 per year; 95%CI 0.95-0.97), and with no decline shown from 2011 through 2020 (aMRR 1·00 per year; 95%CI 0·96-1·05). Mortality due all known causes except NADM also declined over the entire follow-up period. CONCLUSION: Mortality among people with HIV in the D:A:D and/or RESPOND cohorts decreased between 1999 and 2009 and was stable over the period from 2010 through 2020. The decline in mortality rates was not fully explained by improvements in immunologic-virologic status or other risk factors.

Immune response to the recombinant herpes zoster vaccine in people living with HIV over 50 years of age compared to non-HIV age-/gender-matched controls (SHINGR'HIV): a multicenter, international, non-randomized clinical trial study protocol.

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).

[HealthyTravel.ch - The reference website for traveler's health advice]. / HealthyTravel.ch ­ Le site internet de référence pour les conseils de santé aux voyageurs.

The Swiss Expert Committee on Travel Medicine (ECTM) - a body of the Swiss Society of Tropical Medicine and Travel Medicine (FMH) - publishes recommendations and information on travel medicine on the website www.healthytravel.ch in four languages (German, French, Italian, English). HealthyTravel.ch, which has replaced Safetravel.ch, is the reference website for travelers' health advice in Switzerland supported by the Federal Office of Public Health (FOPH). It consists of a free version with basic travel medicine recommendations for the public, and a fee-based PRO version for professionals, containing more detailed information and recommendations. This article provides an overview of the available content and tips on how to make the best use of www.healthytravel.ch.

Le Comité suisse d'experts en médecine des voyages (CFMV), un organe de la Société suisse de médecine tropicale et de médecine des voyages (FMH), publie sur le site internet www.healthytravel.ch des recommandations et des informations sur la médecine des voyages en quatre langues (allemand, français, italien et anglais). HealthyTravel.ch, qui a remplacé le site Safetravel.ch, est le site internet de référence pour les conseils de santé aux voyageurs soutenu par l'Office fédéral de la santé publique (OFSP). Il est composé d'une version gratuite, avec des recommandations de base en matière de médecine des voyages pour le public, et d'une version PRO, payante, pour les professionnels, contenant des informations et des recommandations plus détaillées. Cet article donne un aperçu des contenus disponibles et des conseils d'utilisation optimale du site www.healthytravel.ch.

Ongoing toxin-positive diphtheria outbreaks in a federal asylum centre in Switzerland, analysis July to September 2022.

Two diphtheria outbreaks occurred in a Swiss asylum center from July to October 2022, one is still ongoing. Outbreaks mainly involved minors and included six symptomatic respiratory diphtheria cases requiring antitoxin. Phylogenomic analyses showed evidence of imported and local transmissions of toxigenic strains in respiratory and skin lesion samples. Given the number of cases (n = 20) and the large genetic diversity accumulating in one centre, increased awareness and changes in public health measures are required to prevent and control diphtheria outbreaks.

Cost Estimates for Human Immunodeficiency Virus (HIV) Care and Patient Characteristics for Health Resource Use From Linkage of Claims Data With the Swiss HIV Cohort Study.

BACKGROUND: Comprehensive and representative data on resource use are critical for health policy decision making but often lacking for human immunodeficiency virus (HIV) infection. Privacy-preserving probabilistic record linkage of claim and cohort study data may overcome these limitations. METHODS: Encrypted dates of birth, sex, study center, and antiretroviral therapy (ART) from the Swiss HIV Cohort Study (SHCS) records for 2012 and 2013 were linked by privacy-preserving probabilistic record linkage with claim data from the largest health insurer covering 15% of the Swiss residential population. We modeled predictors for mean annual costs adjusting for censoring and grouped patients by cluster analysis into 3 risk groups for resource use. RESULTS: The matched subsample of 1196 patients from 9326 SHCS and 2355 claim records was representative for all SHCS patients receiving ART. The corrected mean (standard error) total costs in 2012 and 2013 were $30462 ($582) and $30965 ($629) and mainly accrued in ambulatory care for ART (70% of mean costs). The low-risk group for resource use had mean (standard error) annual costs of $26772 ($536) and $26132 ($589) in 2012 and 2013. In the moderate- and high-risk groups, annual costs for 2012 and 2013 were higher by $3526 (95% confidence interval, $1907-$5144) (13%) and $4327 ($2662-$5992) (17%) and $14026 ($8763-$19289) (52%) and $13567 ($8844-$18288) (52%), respectively. CONCLUSIONS: In a representative subsample of patients from linkage of SHCS and claim data, ART was the major cost factor, but patient profiling enabled identification of factors related to higher resource use.

Hantavirus Cardiopulmonary Syndrome Due to Imported Andes Hantavirus Infection in Switzerland: A Multidisciplinary Challenge, Two Cases and a Literature Review.

Two travellers returning from South America were diagnosed with Andes hantavirus infection, the only member of the Hantaviridae family known to be transmitted from person to person. We describe the clinical course and therapeutic and infection control measures. While both patients showed high viral load (VL) and shedding over several months, 1 patient recovered within 1 week from severe respiratory illness that required noninvasive ventilation, whereas the second patient developed severe hantavirus cardiopulmonary syndrome that required extracorporeal membrane oxygenation for 27 days. The clinical course in the latter patient was complicated by severe disseminated intravascular coagulopathy with diffuse hemorrhage that necessitated mass transfusions, as well as by multiple organ failure, including the need for renal replacement therapy. Results of VL in blood, respiratory secretions, and semen for the first 9 months of follow-up are reported. To our knowledge, these are the first cases of Andes hantavirus infection detected in Europe.

Long-term Immune Response to Yellow Fever Vaccination in Human Immunodeficiency Virus (HIV)-Infected Individuals Depends on HIV RNA Suppression Status: Implications for Vaccination Schedule.

Background: In human immunodeficiency virus (HIV)-infected individuals, the immune response over time to yellow fever vaccination (YFV) and the necessity for booster vaccination are not well understood. Methods: We studied 247 participants of the Swiss HIV Cohort Study (SHCS) with a first YFV after HIV diagnosis and determined their immune responses at 1 year, 5 years, and 10 years postvaccination by yellow fever plaque reduction neutralization titers (PRNTs) in stored blood samples. A PRNT of 1:≥10 was regarded as reactive and protective. Predictors of vaccination response were analyzed with Poisson regression. Results: At vaccination, 82% of the vaccinees were taking combination antiretroviral therapy (cART), 83% had suppressed HIV RNA levels (<400 copies/mL), and their median CD4 T-cell count was 536 cells/µL. PRNT was reactive in 46% (95% confidence interval [CI], 38%-53%) before, 95% (95% CI, 91%-98%) within 1 year, 86% (95% CI, 79%-92%) at 5 years, and 75% (95% CI, 62%-85%) at 10 years postvaccination. In those with suppressed plasma HIV RNA at YFV, the proportion with reactive PRNTs remained high: 99% (95% CI, 95%-99.8%) within 1 year, 99% (95% CI, 92%-100%) at 5 years, and 100% (95% CI, 86%-100%) at 10 years. Conclusions: HIV-infected patients' long-term immune response up to 10 years to YFV is primarily dependent on the control of HIV replication at the time of vaccination. For those on successful cART, immune response up to 10 years is comparable to that of non-HIV-infected adults. We recommend a single YFV booster after 10 years for patients vaccinated on successful cART, whereas those vaccinated with uncontrolled HIV RNA may need an early booster.

Population-based outcome analysis of diffuse large B-cell lymphoma in people living with HIV infection and competent individuals.

The prognostic factors and outcome of 58 acquired immunodeficiency syndrome-related diffuse large B-cell lymphoma (AR-DLBCL) patients from the Swiss HIV Cohort Study, diagnosed from 2004 to 2011, were compared with those of 326 immunocompetent (IC)-DLBCL from the Hematology Division of the Amedeo Avogadro University (Italy) and the Oncology Institute of Southern Switzerland. Median follow-up was 6 years; 5-year overall survival (OS) was 68% (95% CI: 63%-73%) in IC-DLBCL and 63% (95% CI: 49%-75%) in AR-DLBCL (P = .220). The acquired immunodeficiency syndrome-related lymphoma international prognostic index predicted OS in AR-DLBCL. Among 148 patients younger than 61 years (40 AR-DLBCL and 108 IC-DLBCL) treated with RCHOP/RCHOP-like regimens, 20 IC-DLBCL and 9 AR-DLBCL patients died and OS was not significantly different. A higher proportion of early deaths occurred in the AR-DLBCL: indeed, 1-year OS was 94% (95% CI: 87%-97%) in IC-DLBCL and 82% (95% CI: 66%-91%) in AR-DLBCL patients. After rituximab and active antiretroviral therapy introduction, AR-DLBCL and IC-DLBCL patients treated with curative intent have similar long-term survival.

A severe case of visceral leishmaniasis and liposomal amphotericin B treatment failure in an immunosuppressed patient 15 years after exposure.

BACKGROUND: Visceral leishmaniasis (VL) is a protozoan disease, which is responsible for 200.000-400.000 yearly infections worldwide. If left untreated, the fatality rate can be as high as 100% within 2 years. 90% of cases occur in just six countries: India, Bangladesh, Sudan, South Sudan, Ethiopia and Brazil. It is thus a disease rarely seen by physicians in Europe or North America. We report on the fatal case of VL in an 80-year-old immunosuppressed patient who presented with a latency of over 15 years after having visited an endemic region. This is the first report showing such extreme latency of VL in a European traveller. This case is furthermore unusual because it suggests primary treatment failure to liposomal amphotericin B. CASE PRESENTATION: An 80-year-old man who was on immunosuppressive treatment due to a non-specific inflammatory disease of the liver and kidney presented to our hospital with recurrent fever, fatigue and bloody diarrhoea. Histopathological analysis from a colon biopsy showed intracellular amastigotes. The diagnosis of VL was confirmed by polymerase-chain-reaction (PCR) of the colon biopsy. PCR was also performed in plasma, a bronchopulmonary lavage, a lymph node, liver and bone marrow biopsy and proved L. donovani as causative species. The disseminated infection was unresponsive to treatment with liposomal amphotericin B as recommended in immunosuppressed individuals despite stopping immunosuppressive treatment. CONCLUSION: Imported cases of VL to non-endemic regions are increasing due to extensive international travel and migration. Furthermore, the increase of elderly patients and immunosuppressed individuals, secondary to HIV, post-transplant and chemotherapeutic agents, has resulted in an increase of VL also in endemic regions of Europe. It is thus important for physicians to be able to recognize the infection. This case also demonstrates treatment failure to amphotericin B, which was only a known problem in patients with HIV until now. The knowledge of this as a possible complication is important for specialists treating the disease.

Immunodeficiency and the risk of cervical intraepithelial neoplasia 2/3 and cervical cancer: A nested case-control study in the Swiss HIV cohort study.

HIV-infected women are at increased risk of cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir [odds ratio (OR) per 100-cell/µL decrease = 1.15, 95% CI: 1.08, 1.22], or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/µL (OR = 1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use = 0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 vs. >350 cells/µL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts, is a significant risk factor for CIN2/3 and cervical cancer.

[Vaccinations for immunocompromised hosts ­ focussing on patients after a hematological stem cell or organ transplantation, with HIV or with functional or anatomical asplenia]. / Impfungen bei Immunsupprimierten.

Patients with an acquired immune deficiency, for example due to HIV-infection, after a solid organ or haematological stem cell transplantation or due to functional or anatomical asplenia, have a greater risk to experience severe complications or a chronic course of infection compared to healthy individuals. Vaccinations would pose an ideal primary preventive method. However, their efficacy is reduced if applied during the immunosuppressed period. Therefore, whenever possible, vaccinations should be administered before the period of immunosuppression starts ­ or caught up later during the period of minimal possible immunosuppression. Nevertheless, the benefit conveyed through vaccines is undisputed, particularly if indications regarding dosing of vaccines (amount and frequency of doses) are optimized according to the given state of immunosuppression. Live attenuated vaccines are contraindicated during severe immunosuppression. Serologies should still be analysed and documented however, since these vulnerable patients require passive immunization through specific or standard intravenous immunoglobulins in case of relevant exposure to the respective antigens. For all patients therefore, careful documentation and communication of previous vaccinations and serologies (protective or not) among the various medical specialties is required to optimize patient management. For all immunosuppressed patients the efficacy of polysaccharide vaccines (such as the pneumococcal and meningococcal vaccines PSV-23 and MPV-ACWY) is strongly reduced compared to the conjugated ones (PCV13 and MCV-ACWY). Therefore, contrary to most other national guidelines, the Swiss guidelines recommend to use only the conjugated versions in primary vaccination series as well as in boosters ­ this applies strongly for immunosuppressed patients, but is recommended also for the general population in Switzerland. Another common management recommendation specific for transplant patients is the indication to control vaccine efficacy by measuring titers. This is also indicated for hepatitis B in HIV-positive patients, but not required for any vaccine in asplenic patients. In summary, vaccines pose an important opportunity for primary and secondary prevention for vulnerable patients at highest risk of experiencing the worst forms of the diseases to be prevented.

Transient detectable viremia and the risk of viral rebound in patients from the Swiss HIV Cohort Study.

BACKGROUND: Temporary increases in plasma HIV RNA ('blips') are common in HIV patients on combination antiretroviral therapy (cART). Blips above 500 copies/mL have been associated with subsequent viral rebound. It is not clear if this relationship still holds when measurements are made using newer more sensitive assays. METHODS: We selected antiretroviral-naive patients that then recorded one or more episodes of viral suppression on cART with HIV RNA measurements made using more sensitive assays (lower limit of detection below 50 copies/ml). We estimated the association in these episodes between blip magnitude and the time to viral rebound. RESULTS: Four thousand ninety-four patients recorded a first episode of viral suppression on cART using more sensitive assays; 1672 patients recorded at least one subsequent suppression episode. Most suppression episodes (87 %) were recorded with TaqMan version 1 or 2 assays. Of the 2035 blips recorded, 84 %, 12 % and 4 % were of low (50-199 copies/mL), medium (200-499 copies/mL) and high (500-999 copies/mL) magnitude respectively. The risk of viral rebound increased as blip magnitude increased with hazard ratios of 1.20 (95 % CI 0.89-1.61), 1.42 (95 % CI 0.96-2.19) and 1.93 (95 % CI 1.24-3.01) for low, medium and high magnitude blips respectively; an increase of hazard ratio 1.09 (95 % CI 1.03 to 1.15) per 100 copies/mL of HIV RNA. CONCLUSIONS: With the more sensitive assays now commonly used for monitoring patients, blips above 200 copies/mL are increasingly likely to lead to viral rebound and should prompt a discussion about adherence.

[Treatment and prevention of opportunistic infections]. / Therapie und Prävention von opportunistischen Infektionen.

Incidence as well as morbidity and mortality of opportunistic infections (OI) have declined remarkably since the availability of antiretroviral treatment (ART). Nearly half of all persons infected with HIV however do not know their HIV-status, and the diagnosis of an OI may be the first manifestation of their HIV infection. Therefore, knowledge of the presentation of OIs as well as their management should remain an essential part of clinicians' expertise. After starting ART the immune system will improve; in this context OI may be unmasked or the clinical presentation of known OI may worsen. Before starting ART therefore, it is essential to rule out any asymptomatic or latent OI. For the same reason, in the case of a known OI, the start of ART must often be deferred for some weeks after the start of OI treatment. Treatment of OIs is complex and often results in a large pill-burden for the patient with the potential for multiple drug-drug-interactions, particularly once ART has to be started. Many of the OI treatments are also associated with frequent drug side-effects and allergies. OIs can be prevented with specific antimicrobial agents once the CD4 have decreased below a defined threshold. However, the main prevention of OI is the timely recognition of HIV infection and an early start of ART before complications of OI appear.

[Psychosocial aspects on the treatment of HIV-infection]. / Psychosoziale Aspekte bei der Behandlung der HIV-Infektion.

Psychological and social factors have a deep impact on the treatment of HIV-infection, from the readiness to start antiretroviral therapy to treatment adherence over time. Among psychological factors, anxiety may affect HIV-infected persons in all stages of disease, from the disclosure of HIV diagnosis to the decision to start and maintain treatment. This is a lifelong challenge for both patients and doctors. Psychiatric comorbidities (depression, addiction) may enhance negative psychological effects of HIV. Among social factors, stigma and discrimination may occur in families and at work, leading to a loss of social support resulting in isolation and poverty. This may prevent HIV-positive individuals from seeking medical care. These aspects are particularly important in some groups of patients as injecting drug users and migrants. Acknowledgment and consideration of psychosocial factors are therefore essential for the long term success of antiretroviral therapy.

Presence and Persistence of Andes Virus RNA in Human Semen.

When infecting humans, Andes orthohantavirus (ANDV) may cause a severe disease called hantavirus cardiopulmonary syndrome (HCPS). Following non-specific symptoms, the infection may progress to a syndrome of hemorrhagic fever combined with hyper-acute cardiopulmonary failure. The case fatality rate ranges between 25-40%, depending on the outbreak. In this study, we present the follow-up of a male patient who recovered from HCPS six years ago. We demonstrate that the ANDV genome persists within the reproductive tract for at least 71 months. Genome sequence analysis early and late after infection reveals a low number of mutations (two single nucleotide variants and one deletion), suggesting limited replication activity. We can exclude the integration of the viral genome into the host genome, since the treatment of the specimen with RNAse led to a loss of signal. We demonstrate a long-lasting, strong neutralizing antibody response using pseudovirions expressing the ANDV glycoprotein. Taken together, our results show that ANDV has the potential for sexual transmission.

The role of migration and domestic transmission in the spread of HIV-1 non-B subtypes in Switzerland.

BACKGROUND: By analyzing human immunodeficiency virus type 1 (HIV-1) pol sequences from the Swiss HIV Cohort Study (SHCS), we explored whether the prevalence of non-B subtypes reflects domestic transmission or migration patterns. METHODS: Swiss non-B sequences and sequences collected abroad were pooled to construct maximum likelihood trees, which were analyzed for Swiss-specific subepidemics, (subtrees including ≥80% Swiss sequences, bootstrap >70%; macroscale analysis) or evidence for domestic transmission (sequence pairs with genetic distance <1.5%, bootstrap ≥98%; microscale analysis). RESULTS: Of 8287 SHCS participants, 1732 (21%) were infected with non-B subtypes, of which A (n = 328), C (n = 272), CRF01_AE (n = 258), and CRF02_AG (n = 285) were studied further. The macroscale analysis revealed that 21% (A), 16% (C), 24% (CRF01_AE), and 28% (CRF02_AG) belonged to Swiss-specific subepidemics. The microscale analysis identified 26 possible transmission pairs: 3 (12%) including only homosexual Swiss men of white ethnicity; 3 (12%) including homosexual white men from Switzerland and partners from foreign countries; and 10 (38%) involving heterosexual white Swiss men and females of different nationality and predominantly nonwhite ethnicity. CONCLUSIONS: Of all non-B infections diagnosed in Switzerland, <25% could be prevented by domestic interventions. Awareness should be raised among immigrants and Swiss individuals with partners from high prevalence countries to contain the spread of non-B subtypes.

Humoral Responses to Repetitive Doses of COVID-19 mRNA Vaccines in Patients with CAR-T-Cell Therapy.

Background: Due to B-cell aplasia following CAR-T-cell therapy, patients are at risk of severe SARS-CoV-2 course. Methods: COVID-19 vaccines were assessed by IgG antibody tests against SARS-CoV-2 spike protein (anti-S1/S2). Vaccination procedures: group (1): CAR-T-cells followed by two to four vaccine doses; group (2): Two vaccine doses prior to CAR-T-cells, followed by doses 3 or 4. Results: In group 1 (n = 32), 7/30 patients (23.2%) had positive antibody tests after a second dose, 9/23 (39.1%) after a third dose, and 3/3 patients after a fourth dose. A third dose led to seroconversion in 5 of 21 patients (23.8%) with available data, while a fourth dose did so in 2/3 patients. Higher B-cells (AUC: 96.2%, CI: 89-100, p = 0.0006) and lower CAR-T-cell copies (AUC: 77.3%, CI: 57-97, p = 0.0438) were predictive of positive humoral vaccine response. In group 2 (n = 14), 6/14 patients (42.9%) had a positive antibody test after a second dose, 3/8 patients (37.5%) after a third dose, and 3/4 patients after a fourth dose. A third dose led to seroconversion in 1/8 patients (12.5%), while a fourth dose did so in 3/4 patients. Conclusion: Additional vaccine doses increased seroconversion rates whilst high B-cell counts and low CAR-T-cell copy numbers were associated with positive antibody response.

Humoral response to mRNA vaccines against SARS-CoV-2 in patients with humoral immunodeficiency disease.

OBJECTIVES: Although mRNA-based vaccines against SARS-CoV-2 induce a robust immune response and prevent infections and hospitalizations, there are limited data on the antibody response in individuals with humoral immunodeficiency. The aim of this study was to evaluate the humoral immune response after two vaccine doses with BNT162b2 or mRNA-1273 in patients with humoral immunodeficiency disease. METHODS: This cross-sectional study assessed 39 individuals with hypogammaglobulinemia under immunoglobulin replacement therapy. IgG anti-SARS-CoV-2 spike protein antibodies (anti-S) were measured 4 weeks to 4 months after two doses of an mRNA vaccine against SARS-CoV-2. The proportion of patients, who developed a humoral immune response to the spike protein were evaluated and compared to 19 healthy controls. RESULTS: After vaccination with two vaccine doses, 26/39 patients (66.7%) with humoral immunodeficiency disease and all healthy controls developed anti-S. In subjects with baseline IgG <3 g/l, only 1/5 (20%) showed a humoral immune response. 10 out of 26 with CVID (38.5%) and 7/9 under immunosuppressive drugs (77.8%) developed no immune response (13 subjects with no response) compared to 0/19 in healthy controls. Subgroup analysis in patients without immunosuppressive drugs revealed lower anti-S in patients with moderate to severe humoral immunodeficiency disease: baseline IgG <3 g/l: 12.0 AU/ml (95%CI 12.0-125.0), baseline IgG 3-5 g/l: 99.9 AU/ml (95%CI 14.4-400.0), baseline IgG >5 g/l: 151.5 AU/ml (95%CI 109.0-400.0), healthy controls 250.0 AU/ml (95%CI 209.0-358.0), p = 0.007. CONCLUSION: In most patients with mild to moderate humoral immunodeficiency we found only slightly lower anti-S antibodies compared with healthy controls after two vaccine doses with BNT162b2 and mRNA-1273. However, in patients with a decreased baseline IgG below 3 g/l and/or under immunosuppressive drugs, we found severely impaired humoral immune responses.

Trajectories of humoral and cellular immunity and responses to a third dose of mRNA vaccines against SARS-CoV-2 in patients with a history of anti-CD20 therapy.

BACKGROUND: The majority of patients with B-cell-depleting therapies show compromised vaccination-induced immune responses. Herein, we report on the trajectories of anti-SARS-CoV-2 immune responses in patients of the RituxiVac study compared with healthy volunteers and investigate the immunogenicity of a third vaccination in previously humoral non-responding patients. METHODS: We investigated the humoral and cell-mediated immune response after SARS-CoV-2 messanger RNA vaccination in patients with a history with anti-CD20 therapies. Coprimary outcomes were antispike and SARS-CoV-2-stimulated interferon-γ concentrations in vaccine responders 4.3 months (median; IQR: 3.6-4.8 months) after first evaluation, and humoral and cell-mediated immunity (CMI) after a third vaccine dose in previous humoral non-responders. Immunity decay rates were compared using analysis of covariance in linear regression. RESULTS: 5.6 months (IQR: 5.1-6.7) after the second vaccination, we detected antispike IgG in 88% (29/33) and CMI in 44% (14/32) of patients with a humoral response after two-dose vaccination compared with 92% (24/26) healthy volunteers with antispike IgG and 69% (11/16) with CMI 6.8 months after the second vaccination (IQR: 6.0-7.1). Decay rates of antibody concentrations were comparable between patients and controls (p=0.70). In two-dose non-responders, a third SARS-CoV-2 vaccine elicited humoral responses in 19% (6/32) and CMI in 32% (10/31) participants. CONCLUSION: This study reveals comparable immunity decay rates between patients with anti-CD20 treatments and healthy volunteers, but inefficient humoral or CMI after a third SARS-CoV-2 vaccine in most two-dose humoral non-responders calling for individually tailored vaccination strategies in this population.Trial registration numberNCT04877496; ClinicalTrials.gov number.

Impact of rosuvastatin on atherosclerosis in people with HIV at moderate cardiovascular risk: a randomised, controlled trial.

BACKGROUND: People living with HIV-1 (PLHIV) are at increased risk for cardiovascular disease. OBJECTIVE: This study aimed to determine if PLHIV would benefit from starting statins at a lower threshold than currently recommended in the general population. DESIGN: A double-blind multicentre, randomised, placebo-controlled trial was performed. METHODS: Participants (n = 88) with well controlled HIV, at moderate cardiovascular risk (Framingham score of 10-15%), and not recommended for statins were recruited from Australia and Switzerland. They were randomized 1 : 1 to rosuvastatin (n = 44) 20 mg daily, 10 mg if co-administered with ritonavir/cobicistat-boosted antiretroviral therapy, or placebo (n = 40) for 96 weeks. Assessments including fasting blood collection and carotid--intima media thickness (CIMT) were performed at baseline, and weeks 48 and 96. The primary outcome was the change from baseline to week 96 in CIMT (clinicaltrials.gov: NCT01813357). RESULTS: Participants were predominantly men [82 (97.6%); mean age 54 years (SD 6.0)]. At 96 weeks, there was no difference in the progression of CIMT between the rosuvastatin (mean 0.004 mm, SE 0.0036) and placebo (0.0062 mm, SE 0.0039) arms (P = 0.684), leading to no difference in CIMT levels between groups at week 96 [rosuvastatin arm, 0.7232 mm (SE 0.030); placebo arm 0.7785 mm (SE 0.032), P = 0.075].Adverse events were common (n = 146) and predominantly in the rosuvastatin arm [108 (73.9%)]. Participants on rosuvastatin were more likely to cease study medication because of an adverse event [7 (15.9%) vs. 2 (5.0%), P = 0.011]. CONCLUSION: In PLHIV, statins prescribed at a lower threshold than guidelines did not lead to improvements in CIMT but was associated with significant adverse events.