There is evidence that the life expectancy (LE) of individuals infected with the human immunodeficiency virus (HIV) has increased since the introduction of combination antiretroviral therapy (cART). ...However, mortality rates in recent years in HIV-positive individuals appear to have remained higher than would be expected based on rates seen in the general population. A low CD4 count, whether due to late HIV diagnosis, late initiation of cART, or incomplete adherence to cART, remains the dominant predictor of LE, and thus the individual's disease stage at initiation of cART (or thereafter) certainly contributes to these higher mortality rates. However, individuals with HIV also tend to exhibit lifestyles and behaviors that place them at increased risk of mortality, particularly from non-AIDS causes. Thus, although mortality rates among the HIV population may indeed remain slightly higher than those seen in the general population, they may be no higher than those seen in a more appropriately matched control group. Thus, further improvements in LE may now only be possible if some of the other underlying issues (for example, modification of lifestyle or behavioral factors) are tackled.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The last decade has seen a dramatic change in the demographic structure of the population of people living with HIV (PLWH). The majority of PLWH who start treatment with combination antiretroviral ...therapy now have good virological and immunological responses and this has resulted in improvements in life expectancy. In addition, there have also been continued new HIV diagnoses (and new HIV infections) in those aged more than 50 years. The average age of those attending HIV clinics has therefore increased, with this trend expected to continue into the future. As the cohort of PLWH has aged, so the spectrum and burden of age-associated noncommunicable comorbidities (AANCCs) in the cohort has increased. PLWH are likely, therefore, to have increased healthcare needs for the foreseeable future. Although it appears that the average age at diagnosis of several AANCC is lower in PLWH, current evidence remains insufficient to demonstrate that HIV infection leads to either accelerated or accentuated aging. The results from several well designed longitudinal cohorts, with appropriately matched control groups, will provide more robust evidence to confirm a potential impact of HIV on the incidence of these AANCC. However, regardless of the impact of HIV itself, the role of other, non-HIV, factors is becoming increasingly important, with coinfection with other viral infections and lifestyle factors playing an increasing role in the development of many AANCC. It is likely that attempts to reduce smoking prevalence and obesity may be associated with important reductions in the incidence of some of these events in the future.
Summary Background With the advent of effective antiretroviral treatment, the life expectancy for people with HIV is now approaching that seen in the general population. Consequently, the relative ...importance of other traditionally non-AIDS-related morbidities has increased. We investigated trends over time in all-cause mortality and for specific causes of death in people with HIV from 1999 to 2011. Methods Individuals from the Data collection on Adverse events of anti-HIV Drugs (D:A:D) study were followed up from March, 1999, until death, loss to follow-up, or Feb 1, 2011, whichever occurred first. The D:A:D study is a collaboration of 11 cohort studies following HIV-1-positive individuals receiving care at 212 clinics in Europe, USA, and Australia. All fatal events were centrally validated at the D:A:D coordinating centre using coding causes of death in HIV (CoDe) methodology. We calculated relative rates using Poisson regression. Findings 3909 of the 49 731 D:A:D study participants died during the 308 719 person-years of follow-up (crude incidence mortality rate, 12·7 per 1000 person-years 95% CI 12·3–13·1). Leading underlying causes were: AIDS-related (1123 29% deaths), non-AIDS-defining cancers (590 15% deaths), liver disease (515 13% deaths), and cardiovascular disease (436 11% deaths). Rates of all-cause death per 1000 person-years decreased from 17·5 in 1999–2000 to 9·1 in 2009–11; we saw similar decreases in death rates per 1000 person-years over the same period for AIDS-related deaths (5·9 to 2·0), deaths from liver disease (2·7 to 0·9), and cardiovascular disease deaths (1·8 to 0·9). However, non-AIDS cancers increased slightly from 1·6 per 1000 person-years in 1999–2000 to 2·1 in 2009–11 (p=0·58). After adjustment for factors that changed over time, including CD4 cell count, we detected no decreases in AIDS-related death rates (relative rate for 2009–11 vs 1999–2000: 0·92 0·70–1·22). However, all-cause (0·72 0·61–0·83), liver disease (0·48 0·32–0·74), and cardiovascular disease (0·33 0·20–0·53) death rates still decreased over time. The percentage of all deaths that were AIDS-related (87/256 34% in 1999–2000 and 141/627 22% in 2009–11) and liver-related (40/256 16% in 1999–2000 and 64/627 10% in 2009–11) decreased over time, whereas non-AIDS cancers increased (24/256 9% in 1999–2000 to 142/627 23% in 2009–11). Interpretation Recent reductions in rates of AIDS-related deaths are linked with continued improvement in CD4 cell count. We hypothesise that the substantially reduced rates of liver disease and cardiovascular disease deaths over time could be explained by improved use of non-HIV-specific preventive interventions. Non-AIDS cancer is now the leading non-AIDS cause and without any evidence of improvement. Funding Oversight Committee for the Evaluation of Metabolic Complications of HAART, with representatives from academia, patient community, US Food and Drug Administration, European Medicines Agency and consortium of AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, ViiV Healthcare, Merck, Pfizer, F Hoffmann-La Roche, and Janssen Pharmaceuticals.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
England has committed to the World Health Organization target to eliminate hepatitis C virus (HCV) as a public threat by the year 2030. Given successful treatments for HCV in recent years, it is ...unclear whether HCV reinfection will impact England's ability to achieve HCV elimination. We aimed to estimate the HCV reinfection rate among a cohort of patients receiving antiviral treatment using available surveillance data. Linkage between a treatment dataset from 2015 to 2019 and an HCV RNA testing dataset were used to identify people who experienced reinfection using three criteria. A Cox proportional hazards model was used to determine risk factors associated with HCV reinfection among a cohort who received treatment and had follow‐up HCV RNA testing. The reinfection rate among those receiving HCV treatment was 7.91 per 100 person‐years (PYs, 95% confidence interval (CI) 7.37–8.49) and highest among current injecting drug users (22.55 per 100 PYs, 95% CI 19.98–25.46) and people who had been in prison (20.42 per 100 PYs, 95% CI 17.21–24.24). In the adjusted model, women had a significantly reduced risk of reinfection. Being of younger age, current injecting drug users, and receipt of first treatment in prison were each significantly associated with increased risk of reinfection. Two‐fifths of those with reinfection (43%, n = 329/767) were linked to treatment after reinfection, and of those starting treatment, three quarters (75%, n = 222/296) achieved a sustained virologic response. Guidance for testing groups at risk of reinfection and harm reduction strategies to minimize transmission should be implemented if England is to achieve HCV elimination targets.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Despite the growing utilization of data-driven methods to investigate multimorbidity patterns, there is currently no consensus or guidance on the conditions to include when ...identifying patterns. This scoping review aims to systematically examine the nature of conditions included in existing studies using data-driven techniques.
Methods
A comprehensive search of three electronic databases (MEDLINE, Web of Science and Scopus) was conducted to identify relevant publications from inception to 28 February 2022 using predefined search terms and inclusion/exclusion criteria. The reference lists and citations of relevant papers were also searched.
Results
Among 7326 search results, 5444 relevant articles were identified. After screening against the eligibility criteria, 60 articles were included in the review. Half of the reviewed studies reported selection criteria for conditions, with prevalence in the population of interest being the most common criterion (40%). Most studies included at least one neurological 59 (98.3%), musculoskeletal 58 (96.7%), respiratory 57 (95.0%) or mental health 56 (93.3%) condition. In contrast, only a small proportion of studies included skin 17 (28.3%), infections 14 (23.3%) or autoimmune conditions 10 (16.7%). Nine conditions (hypertension, diabetes, cancer, arthritis, COPD, asthma, depression, stroke and osteoporosis) were included by more than half of the studies.
Conclusions
This review highlights the considerable heterogeneity among the conditions included in analyses of multimorbidity patterns. Researchers should provide a clear rationale for the selection of conditions to facilitate comparisons across studies and ensure reproducibility, as well as consider selecting a diverse range of conditions to capture the complexity of multimorbidity.
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NUK, OILJ, UL, UM, UPUK, VSZLJ
Evidence is conflicting about how human immunodeficiency virus (HIV) modulates coronavirus disease 2019 (COVID-19). We compared the presentation characteristics and outcomes of adults with and ...without HIV who were hospitalized with COVID-19 at 207 centers across the United Kingdom and whose data were prospectively captured by the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) World Health Organization (WHO) Clinical Characterization Protocol (CCP) study.
We used Kaplan-Meier methods and Cox regression to describe the association between HIV status and day-28 mortality, after separate adjustment for sex, ethnicity, age, hospital acquisition of COVID-19 (definite hospital acquisition excluded), presentation date, 10 individual comorbidities, and disease severity at presentation (as defined by hypoxia or oxygen therapy).
Among 47 592 patients, 122 (0.26%) had confirmed HIV infection, and 112/122 (91.8%) had a record of antiretroviral therapy. At presentation, HIV-positive people were younger (median 56 vs 74 years; P < .001) and had fewer comorbidities, more systemic symptoms and higher lymphocyte counts and C-reactive protein levels. The cumulative day-28 mortality was similar in the HIV-positive versus HIV-negative groups (26.7% vs. 32.1%; P = .16), but in those under 60 years of age HIV-positive status was associated with increased mortality (21.3% vs. 9.6%; P < .001 log-rank test). Mortality was higher among people with HIV after adjusting for age (adjusted hazard ratio aHR 1.47, 95% confidence interval CI 1.01-2.14; P = .05), and the association persisted after adjusting for the other variables (aHR 1.69; 95% CI 1.15-2.48; P = .008) and when restricting the analysis to people aged <60 years (aHR 2.87; 95% CI 1.70-4.84; P < .001).
HIV-positive status was associated with an increased risk of day-28 mortality among patients hospitalized for COVID-19.
Although multimorbidity (defined as the coexistence of multiple conditions) presents significant health challenges to people with HIV, there is currently no consensus on how it should be defined ...among this population. This review aimed to examine the definition of multimorbidity in existing studies among people with HIV ( n = 22).
Variation in the definition of multimorbidity (in terms of the number and nature of conditions included) across studies among people with HIV was observed, with less than half (45%) reporting a selection criteria for conditions. The number of conditions considered ranged from 4 to 65. Certain conditions (e.g. stroke, myocardial infarction and chronic kidney disease) and risk factors (e.g. hypertension) were more frequently included, while other symptoms (e.g. joint pain, peripheral neuropathy and sleeping problems) and mental health conditions (e.g. anxiety and panic attacks) were rarely included in the definition of multimorbidity.
The definition of multimorbidity among people with HIV is highly variable, with certain conditions overlooked. We propose recommendations that researchers should consider when defining multimorbidity among this population to not only enable comparisons between studies/settings but also to ensure studies consider a person-centred approach that can accurately capture multimorbidity among people with HIV.
While life expectancies of people with HIV (PWH) have increased through the successes of antiretroviral treatment, cognitive impairment remains a pressing concern. Prevalence estimates vary worldwide ...as different definitions for cognitive impairment are used and resource availability differs across geographical settings. We aim to explore this heterogeneity and estimate the global cognitive impairment burden in PWH.
Systematic literature review and meta-analysis.
We searched PubMed, Embase, SCOPUS, and Web of Science for studies reporting on cognitive impairment prevalence in PWH. Nine factors were investigated for their potential association with the prevalence using a univariate meta-analysis and a meta-regression: assessment method, geographical region, country income, exclusion criteria, study quality, age, sex, publication year, and sample size.
The literature search identified 8539 records, of which 225 were included. The adjusted prevalence was significantly lower in males than females. Across 44 countries, 12 assessment methods were used; the HIV-associated neurocognitive disorder/Frascati criteria, known for high false-positive rates, was employed in 44.4% of studies. The pooled cognitive impairment prevalence estimate in PWH, including asymptomatic cases, was 39.6% (95% confidence interval: 37.2-42.1%; range: 7-87%). The meta-regression explained 13.3% of between-study variation, with substantial residual heterogeneity ( I2 = 97.7%).
Lack of data from more than 70% of the world's countries, cohorts being unselected for symptoms in most research studies, and limitations of the HIV-associated neurocognitive disorder/Frascati criteria restrict the ability to accurately determine the global burden of cognitive impairment in PWH. More studies in low-resource settings and a standardized approach to assessing cognitive impairment, bridging research and clinical realms, are needed.
The reported prevalence of cognitive impairment remains similar to that reported in the pre-antiretroviral therapy era. This may be partially artefactual due to the methods used to diagnose ...impairment. In this study, we evaluated the diagnostic performance of the HIV-associated neurocognitive disorder (Frascati criteria) and global deficit score (GDS) methods in comparison to a new, multivariate method of diagnosis.
Using a simulated 'normative' dataset informed by real-world cognitive data from the observational Pharmacokinetic and Clinical Observations in PeoPle Over fiftY (POPPY) cohort study, we evaluated the apparent prevalence of cognitive impairment using the Frascati and GDS definitions, as well as a novel multivariate method based on the Mahalanobis distance. We then quantified the diagnostic properties (including positive and negative predictive values and accuracy) of each method, using bootstrapping with 10,000 replicates, with a separate 'test' dataset to which a pre-defined proportion of 'impaired' individuals had been added.
The simulated normative dataset demonstrated that up to ~26% of a normative control population would be diagnosed with cognitive impairment with the Frascati criteria and ~20% with the GDS. In contrast, the multivariate Mahalanobis distance method identified impairment in ~5%. Using the test dataset, diagnostic accuracy 95% confidence intervals and positive predictive value (PPV) was best for the multivariate method vs. Frascati and GDS (accuracy: 92.8% 90.3-95.2% vs. 76.1% 72.1-80.0% and 80.6% 76.6-84.5% respectively; PPV: 61.2% 48.3-72.2% vs. 29.4% 22.2-36.8% and 33.9% 25.6-42.3% respectively). Increasing the a priori false positive rate for the multivariate Mahalanobis distance method from 5% to 15% resulted in an increase in sensitivity from 77.4% (64.5-89.4%) to 92.2% (83.3-100%) at a cost of specificity from 94.5% (92.8-95.2%) to 85.0% (81.2-88.5%).
Our simulations suggest that the commonly used diagnostic criteria of HIV-associated cognitive impairment label a significant proportion of a normative reference population as cognitively impaired, which will likely lead to a substantial over-estimate of the true proportion in a study population, due to their lower than expected specificity. These findings have important implications for clinical research regarding cognitive health in people living with HIV. More accurate methods of diagnosis should be implemented, with multivariate techniques offering a promising solution.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVE:We studied the association of plasma albumin with cardiovascular disease (CVD) and explored potential mechanisms behind the association in the CGPS (Copenhagen General Population Study). We ...also performed a meta-analysis to summarize the association between plasma albumin and CVD in individuals without preexisting CVD.
APPROACH AND RESULTS:We included 100 520 individuals without prior CVD with 8247 incident CVD events developed during a median follow-up of 8.5 years. Rates of CVD outcomes were calculated using Cox regression and Fine and Gray competing-risks regression. The association of plasma albumin and CVD was approximately linear and confounder adjustment had little influence on the effect estimates, except for some attenuation after CRP (C-reactive protein) adjustment. In analyses according to subtypes of CVD events, the hazard ratios for each 10 g/L lower plasma albumin were 1.17 (95% CI, 1.08–1.28) for ischemic heart disease, 1.25 (95% CI, 1.09–1.43) for myocardial infarction, 1.37 (95% CI, 1.21–1.54) for any stroke, and 1.46 (95% CI, 1.28–1.68) for ischemic stroke. In the meta-analysis, we combined estimates from prospective and nested case-control studies investigating the association of plasma albumin with CVD. The meta-analysis included 14 studies with 150 652 individuals (12 studies reported events totaling 11 872). The risk ratio for a CVD event per 10 g/L lower plasma albumin was 1.96 (95% CI, 1.43–2.68) in previous studies and 1.85 (95% CI, 1.39–2.47) including our study with 57% weight in the meta-analysis. Exploratory analyses of the mechanism of the association indicated that it was probably not due to fatty acid binding but may be due to the regulation of plasma albumin by inflammation.
CONCLUSIONS:There is a robust, independent association of low plasma albumin with CVD, partly explained by plasma albumin as a negative acute-phase reactant.
CLINICAL TRIAL REGISTRATION:URLhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=95796. Unique identifierCRD42018095796
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