BACKGROUND AND OBJECTIVES:Self-administration of outpatient parenteral antimicrobial therapy (S-OPAT) aligns with the growing emphasis on patient and caregiver engagement in healthcare. Despite its potential benefits, S-OPAT use varies widely, suggesting that many eligible patients are not offered this option. Insight into S-OPAT decision-making is needed to improve its broader implementation and quality. The objectives of this study were to identify determinants that (i) influence healthcare professionals' (HCPs) decisions to offer S-OPAT and (ii) affect patients' and caregivers' acceptance or refusal of S-OPAT. METHODS:Semi-structured interviews were performed with HCPs involved in S-OPAT and with patients and caregivers who either self-administered OPAT or declined S-OPAT. Participants were recruited from four hospitals and six home care organizations. Transcripts were analysed using thematic analysis. RESULTS:Fifty-one interviews were conducted with HCPs, patients and caregivers. The determinants reported were related to cognitions or affect (e.g. emotions or personality traits, such as patients' reluctance to accept help), skills and capabilities (e.g. patients' perceived skills for S-OPAT, or the ability of HCPs to explain what S-OPAT entails) and collaboration and communication (e.g. between healthcare organizations and between patients and caregivers). CONCLUSIONS:Decisions regarding S-OPAT are influenced by cognitive, skill-related, and collaborative determinants shaping inter-stakeholder cooperation. Addressing these determinants may help create a more person-centred approach and support further expansion of S-OPAT. We recommend increasing HCP awareness of S-OPAT, discussing S-OPAT with all patients or their caregivers, emphasizing the freedom to try S-OPAT, and tailoring the content, timing, and location of the S-OPAT offer to individual needs.

BACKGROUND:Although self-administered outpatient parenteral antimicrobial therapy (S-OPAT) has several advantages over nurse-administered therapy, it remains underused. A comprehensive understanding of the determinants of S-OPAT-the factors that hinder or promote its use-is essential to improve the quality of care and increase uptake. OBJECTIVE:This systematic review aimed to identify and synthesize determinants influencing the entire S-OPAT patient care pathway, from the offer of S-OPAT to its acceptance, training and performance, considering the perspectives of healthcare professionals, patients and their caregivers. METHODS:We systematically searched PubMed, Embase, PsycINFO and CINAHL for original articles published between January 2000 and July 2024 on determinants influencing decision-making and experiences regarding S-OPAT and other self-administered intravenous therapies. Determinants were thematically analysed to construct overarching themes. This review was registered in PROSPERO (CRD42022311294). RESULTS:In 23 studies reporting behavioural determinants (11 on S-OPAT), a total of 238 determinants were identified to influence the offer, acceptance, training and performance of self-administration. A limited number of studies explored determinants influencing the offer of S-OPAT and the caregiver's perspective. The overarching themes included stakeholders' cognitions or affect, collaboration and communication, context, resources and skills and capabilities, which influenced all steps in the patient care pathway. Many determinants were identified regarding cognitions or affect and collaboration and communication, stressing the importance of considering stakeholders' opinions on self-administration and improving transmural collaboration. CONCLUSIONS:This review revealed key behavioural determinants shaping the success of S-OPAT. Targeting these factors can overcome implementation barriers and improve access, caregiver engagement and quality of care.

BACKGROUND:Starting antiretroviral treatment (ART) at higher CD4 cell counts is associated with reduced non-AIDS-defining malignancy (NADM) risk. We studied whether starting ART within 1 year after acquiring human immunodeficiency virus type 1 (HIV-1) reduces this risk while also adjusting for socioeconomic status. METHODS:We included individuals (≥18 years) from the Dutch national ATHENA cohort diagnosed with human immunodeficiency virus (HIV) and having started ART between 2000 and 2022 without prior NADM with ≥6 months of follow-up. "Early ART" initiators were defined as starting ART <365 days following a negative HIV test or primary HIV infection, all others as "late-ART" starters. Hazard ratios (HR) for NADM were estimated using Cox regression, adjusted for a priori selected confounders (age, sex at birth, smoking, alcohol use, calendar time, HIV transmission route, region of origin, nadir CD4 cell count, HIV-1 viral copy-years), and socioeconomic status (SES) using data from Statistics Netherlands. RESULTS:Compared to "late-ART" (n = 17 965) participants, "early-ART" participants (n = 1858) were younger (median 34.8 vs 39.0 years), with a higher nadir CD4 count (median 478 vs 260 cells/µL). NADM were diagnosed in 25 "early-ART" and 869 "late-ART" starters resulting in an incidence rate of 2.22/1000 person-years (PY) (95% confidence interval [CI] = 1.50-3.28) and 4.87/1000 PY (95% CI = 4.56-5.21), respectively. "Early-ART" initiation was associated with a reduced risk of any NADM (HR = 0.60 [95% CI = .40-.91]) and infection-unrelated NADM (HR = 0.60 [95% CI = .37-.98]), but not of infection-related NADM (HR = 0.58 [95% CI = .27-1.28]). Additional adjustment for SES only minimally changed the hazard ratios. CONCLUSIONS:Starting ART within 1 year of HIV acquisition is associated with a reduced NADM risk compared to starting ART later.

BACKGROUND:People with HIV (PWH) using antiretroviral therapy are at increased risk to develop cardiovascular diseases (CVD). We hypothesized that residual viremia (RV; unquantifiable low, but detectable viral load) increases CVD risk. METHODS:We enrolled 1895 virally suppressed PWH and compared CVD incidence in participants with and without RV. Extensive multi-omics characterization was performed. Incident CVD was registered after 2-year follow-up and adjusted odds ratios (aOR) calculated accounting for classical CVD risk factors. The numbers of expected and actual CVD events were compared using CVD risk scores. FINDINGS:RV, detected in one-third of participants, strongly increased the risk of developing a first cardiovascular event (3.1% vs 1.2%, aOR 2.8, p=0.004). Participants with RV experienced twice the number of events predicted by the SCORE2 risk model. The association between RV and CVD was not driven by inflammation, immune activation, gut barrier dysfunction, or lipometabolic perturbations. INTERPRETATION:Residual viremia independently associated with CVD development, highlighting the need for tailored prevention and examination of novel intervention strategies.

Supplementary Figure S1: Trial Flowchart.

Supplementary material 2: HPV-Typing of AIN lesions.

Supplementary material 1: Rationale for intradermal administration of the vaccine, the use of pegylated interferon-alpha-2b (PegIntron) as adjuvant, immune assays.

Supplementary Table S3: Representativeness of Study Participants.

Supplementary Figure S2: HPV16-specific T cell responses at different dose levels and time points.

Supplementary Table S2: T-cell responses determined by 4-day IFNγ-ELISPOT assay.

Supplementary Figure S3: Type of T cells responding to HPV16 oncoproteins.

Supplementary Table S1: Proliferative T-cell responses determined by Lymphocyte Stimulation Test (LST).

Purpose Obesity is rising among people with HIV (PLWH), sparking interest in bariatric surgery (BS) for this group. Yet, large-scale comparative research on BS outcomes in PLWH is lacking. Methods We performed a retrospective, matched cohort analysis in PLWH and HIV uninfected controls. Subjects were retrieved from the Dutch Audit for Treatment of Obesity (DATO) registry. Matching (1:7 ratio) included age (± 5-years), sex, body-mass index (BMI) of ± 3 kg/m 2 , surgery type, and associated health problems (AHPs) at baseline. The primary endpoint was total weight loss percentage (%TWL) ≥ 20% achieved at 1-year post-BS. Secondary endpoints were cumulative %TWL achieved at 2-years post-BS, a reported remission or improvement in AHPs post-BS, and surgical complications, both at 1-year post-BS. Comparisons were performed using conditional logistic regression. Results Twenty-seven PLWH and 168 controls were included. At 1-year post-BS, 89% PLWH achieved ≥ 20%TWL, compared to 94% of controls ( p = 0.4). Cumulative %TWL at 2-years post-BS were 82% and 92% in PLWH and controls, respectively ( p = 0.2). Improvement rates in hypertension and type 2 diabetes mellitus were 50% and 86% in PLWH, versus 87% and 87% in controls. Full remission occurred in 20% and 71% of PLHIV, versus 49% and 44% of controls, respectively. No improvement or remission was observed for dyslipidaemia in PLHIV compared to 54% improvement and 29% remission in controls. Surgical complications were 0% in PLHIV and 13% ( n = 21) in controls. Conclusion Efficacy and safety outcomes of BS were similar between PLWH and controls except for the lack of improvement in dyslipidaemia in PLWH. Graphical abstract

Background:Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use.Methods:Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA-suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4+ T-cell nadir, and HIV RNA zenith. The primary endpoint was the treatment failure rate in cases versus controls at 1 year by intention-to-treat and on-treatment analyses with 5% noninferiority margin.Results:The 2040 participants were 680 cases and 1380 controls. Treatment failure in the 390 dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference: -3.78% [95% confidence interval {CI}, -7.49% to .08%]) by intention-to-treat and 1.39% and 0.80% (difference: 0.59% [95% CI, -.80% to 1.98%]) by on-treatment analyses. The treatment failure risk in 290 non-dolutegravir-based cases was also noninferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure, defined as 2 consecutive HIV RNA >50 copies/mL, occurred in 4 cases and 5 controls but without genotypic resistance detected. Viral blips occured comparable in cases and controls but cases gained more weight, especially when tenofovir-based regimens were discontinued.Conclusions:In routine care, dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral regimens after 1 year, supporting the use of dolutegravir/lamivudine in clinical practice.Clinical Trials Registration:NCT04707326.

Objectives: Evidence on the optimal frequency of laboratory testing during outpatient parenteral antimicrobial therapy (OPAT) is lacking. Therefore, we investigated how often and when laboratory abnormalities occur during OPAT and which factors are associated with these abnormalities. Methods: We performed a multicenter cohort study in four Dutch hospitals among adult patients receiving OPAT and collected routinely obtained laboratory test results. Incidence and incidence rates were calculated for various laboratory abnormalities. Survival analysis was performed to visualize the time to the first occurrence of laboratory abnormalities and Poisson regression analysis to compare the number of abnormalities in the first and second 30 OPAT days among patients receiving OPAT for >= 60 days. Predictors were identified using a multivariable Cox proportional hazard regression model. Results: 45.1% of 1152 included patients developed laboratory abnormalities, but only 2% led to OPAT discontinuation. Hepatotoxicity was most common (33.9 events/1000 OPAT days), with a time-dependent decrease in the occurrence of the first hepatotoxic event, while hypokalemia was rare (1.7 events/ 1000 OPAT days). In the subgroup of patients receiving >= 60 days of OPAT, nephrotoxicity was more common in days 31-60. We observed partly toxicity-specific associations between antibiotic type, concomitant medication, baseline laboratory values, patient characteristics, and the occurrence of laboratory abnormalities. Conclusions: While laboratory abnormalities are frequently observed during OPAT, they rarely lead to discontinuation of OPAT. Specific patient, treatment and laboratory characteristics were associated with the occurrence of laboratory abnormalities. Based on our results, we recommend a more personalized laboratory monitoring policy with less blood sampling. (c) 2024 The Author(s). Published by Elsevier Ltd on behalf of The British Infection Association. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Abstract Purpose: Anal cancer is increasing in HIV-positive men who have sex with men (MSM). Treatment options for its precursor, high-grade anal intraepithelial neoplasia (HGAIN), are suboptimal. In this phase I-II dose-finding study we assessed the safety and efficacy of the human papillomavirus type 16 (HPV16) synthetic long peptide vaccine (SLP-HPV-01®) in HIV-positive MSM with HPV16-positive HGAIN. Patients and Methods: Four dosage schedules (1-5-10; 5-10-20; 10-20-40 and 40-40-40-40 mg) of SLP-HPV-01® were administered intradermally with a three-week interval in 10 patients per dose level. In each dose group, five patients also received 1 µg/kg pegylated interferon-alpha-2b subcutaneously. Primary endpoints were safety and regression of HGAIN at 3,6 and 12 months. Results: Eighty-one of 134 screened patients (60%) had HPV16-negative HGAIN lesions, leaving 53 eligible patients. Thirteen patients were excluded, leaving 40 men. The vaccine was well tolerated. One patient developed a generalized rash. The highest dosage level induced the strongest immune responses. There was no indication for stronger reactivity in the IFN-α groups. Up to 18 months of follow-up, 8/38 intention-to-treat patients had a complete clinical and histological response (CR) and one had a partial response (PR) (in total 9/38, 23.7%). At the highest dosage level the clinical response was 4/10 (40%). Stronger immune responses were detected among clinical responders. Conclusions: The highest dose level is safe, immunogenic and associated with clinical responses to HPV16-induced lesions. However, as the majority of HGAIN is caused by the other HPV types, further studies should aim at pan-HPV vaccination to prevent or treat HGAIN.

IntroductionDuring the COVID-19 pandemic, major events with immune-modulating effects at population-level included COVID-19 infection, lockdowns, and mass vaccinations campaigns. As immune responses influence many immune-mediated diseases, population scale immunological changes may have broad consequences.MethodsWe investigated the impact of lockdowns, COVID-19 infection and vaccinations on immune responses in the 2000HIV study including 1895 asymptomatic virally-suppressed people living with HIV recruited between October 2019 and October 2021. Their inflammatory profile was assessed by targeted plasma proteomics, immune responsiveness by cytokine production capacity of circulating immune cells, and epigenetic profile by genome-wide DNA methylation of immune cells.ResultsPast mild COVID-19 infection had limited long-term immune effects. In contrast, COVID-19 vaccines and especially lockdowns significantly altered both the epigenetic profile in immune cells at DNA methylation level and immune responses. Lockdowns resulted in a strong overall exaggerated immune responsiveness, while COVID-19 vaccines moderately dampened immune responses. Lockdown-associated immune responsiveness alterations were confirmed in 30 healthy volunteers from the 200FG cohort that, like the 2000HIV study, is part of the Human Functional Genomics Project.DiscussionOur data suggest that lockdowns have unforeseen immunological effects. Furthermore, COVID-19 vaccines have immunological effects beyond anti-SARS-CoV-2 activity, and studies of their impact on non-COVID-19 immune-mediated pathology are warranted.

BACKGROUND:Incidence of anal cancer is high in people living with HIV, particularly in men who have sex with men (MSM). Screening for and treatment of precursor lesions might prevent progression to anal cancer in people living with HIV. We examined trends in incidence of and mortality after anal cancer diagnosis in people living with HIV, including the effect of screening from 2007 onwards, in the Netherlands. METHODS:In this observational cohort study, we analysed data from the ongoing open nationwide Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort. We included all consenting adults living with HIV and identified all primary anal squamous cell carcinoma. We reported temporal trends in incident anal cancer cases from Jan 1, 1996, to Dec 31, 2020, and all-cause and anal cancer-related mortality in individuals diagnosed with anal cancer. Multivariable Poisson regression was used to explore risk factors for incident anal cancer and multivariable Cox regression was used to explore risk factors for anal cancer-related mortality. FINDINGS:Among 28 175 individuals in HIV care (59·7% MSM), 227 primary anal cancer cases were diagnosed. Despite the increasing average age of the cohort, crude incidence rates of anal cancer in MSM declined slowly over time, from 107·0 (95% CI 75·7-147·0) per 100 000 person-years in 1996-2005 to 93·7 (75·3-115·0) per 100 000 person-years in 2013-20 (p=0·49). Crude incidence rates in men who do not have sex with men (non-MSM) and women were generally lower than in MSM, but increased slightly over time, from 51·08 (95% CI 20·54-105·25) to 67·82 (40·83-105·91; p=0·52) per 100 000 person-years in non-MSM and from 8·09 (0·20-45·06) to 24·95 (10·03-51·40; p=0·29) per 100 000 person-years in women. The age-adjusted incidence rate in MSM in 2013-20 was significantly lower (rate ratio 0·62 [95% CI 0·41-0·92]) compared with in 1996-2005. Changes in risk factors (less smoking, cumulative exposure to CD4 count of <200 cells per μL, and plasma HIV-1 RNA of >1000 copies per mL) mostly explained the decrease in anal cancer risk over time in MSM. 3866 (23·0%) of 16 819 MSM participated in anal cancer screening at least once. TNM tumour staging was more favourable (Cochrane-Armitage test for trend p=0·033) in individuals diagnosed during screening. Crude anal cancer-associated 5-year mortality in people living with HIV decreased from 30·4% (1996-2005) to 18·3% (2013-20; odds ratio 0·48; p=0·070). Anal cancer-related mortality was 3·7% (95% CI 0·5-23·5) in all men who had been screened and 24·0% (95% CI 18·1-31·3) in men who had not been screened (p=0·023). In men, screening participation (hazard ratio [HR] 0·31, p=0·051) and cumulative exposure to CD4 counts of less than 200 cells per μL (HR 1·11 per year; p=0·0022) were independently associated with anal cancer-related mortality. INTERPRETATION:As anal cancer incidence is slowly declining in MSM but not in non-MSM and women, health-care professionals should not focus only on MSM for anal cancer prevention. Men diagnosed with anal cancer during screening had improved survival, probably because they were diagnosed at an earlier disease stage. Next to preventing anal cancer, these data are an important justification to screen those most at risk of anal cancer. FUNDING:None.

Background and objectives: Obesity trends and metabolic dysregulation are rising in people living with HIV using antiretrovirals (ARVs). Underlying causes and preventive strategies are being investigated. Two glucagon like-peptide 1 (GLP-1) agonists, liraglutide and semaglutide, were formerly approved as glucose-lowering drugs and have been recently approved for long-term weight loss in people with obesity. Due to the lack of therapeutic guidelines or clinical trials in people with HIV, we discuss the potential benefits, safety aspects and pharmacological considerations of prescribing liraglutide and semaglutide in people with HIV. Results: Clinical experience is limited to two clinical cases of diabetic people with HIV using liraglutide after which a successful weight loss and glycaemic control were observed. None of the adverse events associated with liraglutide and semaglutide usage indicate an additional risk for people with HIV. Extra caution showed be warranted when initiating GLP-1 agonist therapy in people with HIV taking protease inhibitors who have pre-existing risk factors for heart rate variability to reduce the incidence of RP interval prolongation. GLP-1 agonists are metabolized by endopeptidases, and thus do not generate major drug-drug interactions with most drugs, including ARVs. GLP-s agonists are known to inhibit gastric acid secretion, which warrants caution and close monitoring when combined with atazanavir and oral rilpivirine, two ARVs that require low gastric pH for an optimal absorption. Conclusion: Theoretical considerations and a few available clinical observations support semaglutide and liraglutide prescription in people with HIV, with, thus far, no indications of concern regarding efficacy, safety or pharmacological interactions with ARVs.

Abstract Background The implications of bariatric surgery (BS) on virologic and metabolic outcomes in people with human immunodeficiency virus (HIV; PWH) on antiretroviral therapy (ART) are unknown. Methods Here, we report a retrospective analysis up to 18 months post-BS in PWH from the AIDS Therapy evaluation in The Netherlands (ATHENA) cohort with data from all dutch HIV treating Centers. Primary end points were a confirmed virologic failure (2 consecutive HIV-RNA measurements >200 copies/mL) and the percentage of patients who achieved >20% total body weight loss up to 18 months post-BS. Switches from baseline ART and trough plasma concentrations of antiretrovirals were also reported post-BS. Metabolic parameters and medication usage were compared pre- and post-BS. Results Fifty-one patients were included. One case of confirmed virologic failure and 3 cases with viral blips were detected in this cohort up to 18 months post-BS. Eighty-five percent of patients achieved >20% total body weight loss at 18 months post-BS, with a mean difference from baseline (95% confidence interval) of −33.5% (−37.7% to −29.3%). Trough plasma concentrations of measured antiretroviral agents were all above minimum effective concentrations, except for 1 sample of darunavir. Lipid profiles, but not serum creatinine and blood pressure, improved significantly (P < .01) post-BS. Total medications and obesity-related comedications declined from 203 to 103 and from 62 to 25, respectively, at 18 months post-BS. Conclusions BS was an effective intervention for weight loss and lipid control in PWH using ART in this cohort with no clear link to poor virologic outcomes.