Cardiovascular risks associated with protease inhibitors for the treatment of HIV

Introduction: Cumulative use of some first-generation protease inhibitors has been associated with higher rates of dyslipidemia and increased risk of cardiovascular disease. The protease inhibitors most commonly in use are atazanavir and darunavir, which have fewer detrimental lipid effects and greater tolerability. This paper aims to review the evidence of a potential association of these contemporary protease inhibitors with the risk of ischemic CVD and atherosclerotic markers.Areas covered: We searched for publications of randomized trials and observational studies on PubMed from 1st January 2000 onwards, using search terms including: protease inhibitors; darunavir; atazanavir; cardiovascular disease; cardiovascular events; dyslipidemia; mortality; carotid intima media thickness; arterial elasticity; arterial stiffness and drug discontinuation. Ongoing studies registered on clinicaltrials.gov as well as conference abstracts from major HIV conferences from 2015-2020 were also searched.Expert opinion: Atazanavir and darunavir are no longer part of first-line HIV treatment, but continue to be recommended as alternative first line, second- and third-line regimens, as part of two drug regimens, and darunavir is used as salvage therapy. Although these drugs will likely remain in use globally for several years to come, baseline CVD risk should be considered when considering their use, especially as the population with HIV ages

Trends in Mortality in People With HIV From 1999 through 2020:A Multicohort Collaboration

Background: Mortality among people with human immunodeficiency virus (HIV) declined with the introduction of combination antiretroviral therapy. We investigated trends in mortality in people with HIV from 1999 through 2020. Methods: Data were collected from the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) cohort between January 1999 through January 2015 and the International Cohort Consortium of Infectious Disease (RESPOND) from October 2017 through December 2020. Age-standardized all-cause and cause-specific mortality rates, classified using Coding Causes of Death in HIV, were calculated. Poisson models were used to assess mortality over time. Results: Among 55 716 participants followed for median 6 years (interquartile range, 3-11), 5263 died (mortality rate [MR], 13.7/1000 person-years of follow-up [PYFU]; 95% confidence interval [CI], 13.4-14.1). Changing mortality was observed: AIDS mortality was most common between 1999-2009 (n = 952; MR, 4.2/1000 PYFU; 95% CI, 4.0-4.5) and non-AIDS-defining malignancy (NADM) between 2010-2020 (n = 444; MR, 2.8/1000 PYFU; 95% CI, 2.5-3.1). In multivariable analysis, all-cause mortality declined (adjusted mortality rate ratio [aMRR], 0.97 per year; 95% CI,. 96-.98), mostly 1999-2010 (aMRR, 0.96 per year; 95% CI,. 95-.97) but was stable 2011-2020 (aMRR, 1.00 per year; 95% CI,. 96-1.05). Mortality due to all known causes except NADM also declined. Conclusions: Mortality among people with HIV in the D:A:D and/or RESPOND cohorts declined between 1999-2009 and was stable over the period 2010-2020. This decline in mortality was not fully explained by improvements in immunologic-virologic status or other risk factors.</p

Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study

Background No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011. Methods Two definitions were evaluated; RP definition A: An average eGFR decline (slope) ≥5 ml/min/1.73 m2/year over four years of follow-up with ≥3 eGFR measurements/year, last eGFR <90 ml/min/1.73 m2 and an absolute decline ≥5 ml/min/1.73 m2/year in two consecutive years. RP definition B: An absolute annual decline ≥5 ml/min/1.73 m2/year in each year and last eGFR <90 ml/min/1.73 m2. Sensitivity analyses were performed considering two and three years' follow-up. The percentage with and without RP who went on to subsequently develop incident chronic kidney disease (CKD; 2 consecutive eGFRs <60 ml/min/1.73 m2 and 3 months apart) was calculated. Results 22,603 individuals had baseline eGFR ≥90 ml/min/1.73 m2. 108/3655 (3.0%) individuals with ≥4 years' follow-up and ≥3 measurements/year experienced RP under definition A; similar proportions were observed when considering follow-up periods of three (n=195/6375; 3.1%) and two years (n=355/10756; 3.3%). In contrast under RP definition B, greater proportions experienced RP when considering two years (n=476/10756; 4.4%) instead of three (n=48/6375; 0.8%) or four (n=15/3655; 0.4%) years' follow-up. For RP definition A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD. Conclusions Our results suggest using three years' follow-up and at least two eGFR measurements per year is most appropriate for a RP definition, as it allows inclusion of a reasonable number of individuals and is associated with the known risk factors. The definition does not necessarily identify all those that progress to incident CKD, however, it can be used alongside other renal measurements to early identify and assess those at risk of developing CKD. Future analyses will use this definition to identify other risk factors for RP, including the role of antiretrovirals

Antiretroviral Drug-Related Liver Mortality Among HIV-Positive Persons in the Absence of Hepatitis B or C Virus Coinfection: The Data Collection on Adverse Events of Anti-HIV Drugs Study

In a large prospective multicohort study 22 910 human immunodeficiency virus-positive participants without hepatitis B or C virus coinfection were followed for 114 478 patient-years. The incidence of liver-related death was low at 0.10 per 1000 patient-years. Liverrelated mortality due to antiretroviral drug-related toxicity was rar

Integrase Strand Transfer Inhibitor Use and Cancer Incidence in a Large Cohort Setting

BACKGROUND Limited data exist examining the association between incident cancer and cumulative integrase inhibitor (INSTI) exposure. METHODS Participants were followed from baseline (latest of local cohort enrollment or January 1, 2012) until the earliest of first cancer, final follow-up, or December 31, 2019. Negative binomial regression was used to assess associations between cancer incidence and time-updated cumulative INSTI exposure, lagged by 6 months. RESULTS Of 29 340 individuals, 74% were male, 24% were antiretroviral treatment (ART)-naive, and median baseline age was 44 years (interquartile range [IQR], 36-51). Overall, 13 950 (48%) individuals started an INSTI during follow-up. During 160 657 person-years of follow-up ([PYFU] median 6.2; IQR, 3.9-7.5), there were 1078 cancers (incidence rate [IR] 6.7/1000 PYFU; 95% confidence interval [CI], 6.3-7.1). The commonest cancers were non-Hodgkin lymphoma (n = 113), lung cancer (112), Kaposi's sarcoma (106), and anal cancer (103). After adjusting for potential confounders, there was no association between cancer risk and INSTI exposure (≤6 months vs no exposure IR ratio: 1.15 [95% CI, 0.89-1.49], >6-12 months; 0.97 [95% CI, 0.71-1.32], >12-24 months; 0.84 [95% CI, 0.64-1.11], >24-36 months; 1.10 [95% CI, 0.82-1.47], >36 months; 0.90 [95% CI, 0.65-1.26] [P = .60]). In ART-naive participants, cancer incidence decreased with increasing INSTI exposure, mainly driven by a decreasing incidence of acquired immune deficiency syndrome cancers; however, there was no association between INSTI exposure and cancer for those ART-experienced (interaction P < .0001). CONCLUSIONS Cancer incidence in each INSTI exposure group was similar, despite relatively wide CIs, providing reassuring early findings that increasing INSTI exposure is unlikely to be associated with an increased cancer risk, although longer follow-up is needed to confirm this finding

Social prescribing initiatives connecting general practice patients with community-based physical activity: A scoping review with expert interviews

Aims: The World Health Organization states that physical inactivity is one of the leading behavioural risk factors for disability and mortality in Europe. Social prescribing holds promise as a possible solution by connecting patients from general practice to community-based physical activity. Although research within social prescribing exists, the process of connecting general practice patients to community-based physical activity is not well investigated. This scoping review aimed to summarise and synthesise knowledge on social prescribing provided by health professionals in general practice towards community-based physical activity. Methods: A systematic search for literature in PubMed, Embase, Scopus, SportsDiscus and other sources was conducted to identify initiatives connecting general practice to community-based physical activity. Semi-structured interviews were then conducted with subject-specific national experts. Finally, preliminary findings from the literature and the interviews were used in a co-creation process with experts to synthesise and finalise the results of a thematic analysis across data sources. Results: Based on 19 records, five expert interviews and subsequent co-creation, we identified three themes: (a) barriers and facilitators, (b) organisational perspectives and (c) value-based considerations. Conclusions: This review illuminates the complex nature of social prescribing programmes that connect general practice patients to community-based physical activity in Denmark. It also presents practical and fundamental considerations when applying social prescribing across different settings

Graviditet og infektion

Infections in pregnancy are common, and although often not harmful to the woman or her unborn child, some infections may be associated with severe adverse outcomes. Pregnancy causes physiological and immunological adaptations which may make pregnant women more susceptible to infections and at increased risk of more severe illness. Infections in pregnancy represent a challenging area of concern for many specialists and general practitioners. Center for Pregnancy and Infection was developed to enhance knowledge, diagnosis, treatment, and care for pregnant women with infection in Denmark, as pointed out in this review.</p

Defining Social Prescribing within a physical activity context

PurposeSocial prescribing involves linking citizens with non-medical services and support within their community to enhance their health and well-being. In social prescribing, referring citizens to physical activities are often emphasized, probably due to their already existing availability within most communities. Various definitions of social prescribing exist in the scientific literature. Since then, a call for constructive criticism and incorporation of unique perspectives from different contexts was made as it was acknowledged that the definition of social prescribing will evolve over time, including within the domain of physical activity. On this basis, the purpose of the present study was to develop a definition of social prescribing within a physical activity context.MethodsBased on previous consensus-based and non-consensus-based definitions of social prescribing published in scientific journals (n = 3), the authors (n = 12) of the present abstract co-produced a new definition of social prescribing within the context of physical activity based on face-to-face meetings and correspondence.ResultsThe new definition of social prescribing reads: “Social prescribing in a physical activity context has the overall goal of contributing to health and well-being through a process of trusted entities (e.g. GPs) referring individuals directly or through a link worker to groups that are physically active and that support social belongingness”. In this definition, the individual has medial or non-medical needs and is therefore in need of help from trusted entities. Trusted entities can be, but are not limited to: family, friends, health professionals, authorities, job-center personel and patient associations. Link workers are knowledgeable about the possibilities of physical activity in the local area and they support the individual in a co-creating manner to find the best fitting activity. Social belongingness is essential, meaning that the physical activity is not carried out on one’s own, but together with others, thereby supporting physical, mental and social well-being, including the need to belong.ConclusionGiven the rapid scaling and rollout of social prescribing globally, we hope this definition serves as a complementary contribution to the field of social prescribing by helping to build a common understanding of social prescribing within the field of physical activity