Objectives
The aim of the study was to assess the impact of the gain in body mass index (BMI) observed immediately after antiretroviral therapy (ART) initiation on the subsequent risk of ...cardiovascular disease (CVD) and diabetes.
Methods
We analysed data from the Data Collection on Adverse Events of Anti‐HIV Drugs (D:A:D) cohort study. Outcomes were development of (i) CVD (composite of myocardial infarction/stroke/coronary procedure) and (ii) diabetes. The main exposure variable was change in BMI from ART initiation (pre‐ART) to 1 year after initiation (continuous variable) in treatment‐naïve individuals initiating ART with no history of CVD or diabetes (for respective outcomes). BMI weight (kg)/(height (m))2 was categorized as underweight (< 18.5), normal (18.5–25), overweight (25–30) and obese (> 30). Poisson regression models were fitted stratified for each pre‐ART BMI category to allow for category‐specific estimates of incidence rate ratio (IRR). Models were adjusted for pre‐ART BMI and CD4 count, key known risk factors (time‐updated where possible) and calendar year.
Results
A total of 97 CVD events occurred in 43 982 person‐years (n = 9321) and 125 diabetes events in 43 278 person‐years (n = 9193). In fully adjusted analyses for CVD, the IRR/unit gain in BMI (95% confidence interval) in the first year of ART, by pre‐ART BMI category, was: underweight, 0.90 (0.60–1.37); normal, 1.18 (1.05–1.33); overweight, 0.87 (0.70–1.10), and obese, 0.95 (0.71–1.28) (P for interaction = 0.04). For diabetes, the IRR/unit gain in BMI was 1.11 (95% confidence interval 1.03 to 1.21), regardless of pre‐ART BMI (P for interaction > 0.05).
Conclusions
Short‐term gain in BMI following ART initiation appeared to increase the longer term risk of CVD, but only in those with pre‐ART BMI in the normal range. It was also associated with increased risk of diabetes regardless of pre‐ART BMI.
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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
Since the introduction of highly active antiretroviral therapy (HAART), little is known about whether changes in HIV-1 mortality and morbidity rates have been sustained. We aimed to assess possible ...changes in these rates across Europe.
We analysed data for 9803 patients in 70 European HIV centres including ones in Israel and Argentina. Incidence rates of AIDS or death were calculated for overall and most recent CD4 count in 6–monthly periods and in three treatment eras (pre-HAART, 1994–1995; early-HAART, 1996–1997; and late-HAART, 1998–2002).
The incidence of AIDS or death fell after September, 1998, by 8% per 6–month period (rate ratio 0·92, 95% CI 0·88–0·95, p<0·0001). When AIDS and death were analysed separately, the incidence of all deaths during the late-HAART era was significantly lower than that during the early-HAART era in patients whose latest CD4 count was 20 cells/μL or less (0·43, 0·35–0·53, p<0·0001), but at higher CD4 counts, did not differ between early-HAART and late-HAART. Incidence of AIDS was about 50% lower in late-HAART than in early-HAART, irrespective of latest CD4 count (p<0·0001). In multivariate Cox's models, with early-HAART as the reference, there was an increased risk of AIDS (relative hazard 1–39; 95% CI 1–16–1–67, p=0·0004) and all deaths (1–29; 1–08–1–56, p=0·0065) in the pre-HAART era, and a reduced risk of AIDS (0·62; 0·50–0–77, p<0·0001) and all deaths (0·66; 0·53–0·82, p=0·0002) in the late-HAART era.
The initial drop in mortality and morbidity after the introduction of HAART has been sustained. Potential long-term adverse effects associated with HAART have not altered its effectiveness in treating AIDS.
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DOBA, GEOZS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SIK, UILJ, UKNU, UL, UM, UPCLJ, UPUK, VSZLJ
Objectives
Across Europe, almost a third of individuals infected with HIV do not enter health care until late in the course of their infection. Surveillance to identify the extent to which late ...presentation occurs remains inadequate across Europe and is further complicated by the lack of a common clinical definition of late presentation. The objective of this article is to present a consensus definition of late presentation of HIV infection.
Methods
Over the past year, two initiatives have moved towards a harmonized definition. In spring 2009, they joined efforts to identify a common definition of what is meant by a ‘late‐presenting’ patient.
Results
Two definitions were agreed upon, as follows. Late presentation: persons presenting for care with a CD4 count below 350 cells/μL or presenting with an AIDS‐defining event, regardless of the CD4 cell count. Presentation with advanced HIV disease: persons presenting for care with a CD4 count below 200 cells/μL or presenting with an AIDS‐defining event, regardless of the CD4 cell count.
Conclusion
The European Late Presenter Consensus working group believe it would be beneficial if all national health agencies, institutions, and researchers were able to implement this definition (either on its own or alongside their own preferred definition) when reporting surveillance or research data relating to late presentation of HIV infection.
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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
European guidelines recommend the routine offer of an HIV test in patients with a number of AIDS-defining and non-AIDS conditions believed to share an association with HIV; so called indicator ...conditions (IC). Adherence with this guidance across Europe is not known. We audited HIV testing behaviour in patients accessing care for a number of ICs. Participating centres reviewed the case notes of either 100 patients or of all consecutive patients in one year, presenting for each of the following ICs: tuberculosis, non-Hodgkins lymphoma, anal and cervical cancer, hepatitis B and C and oesophageal candidiasis. Observed HIV-positive rates were applied by region and IC to estimate the number of HIV diagnoses potentially missed. Outcomes examined were: HIV test rate (% of total patients with IC), HIV test accepted (% of tests performed/% of tests offered) and new HIV diagnosis rate (%). There were 49 audits from 23 centres, representing 7037 patients. The median test rate across audits was 72% (IQR 32-97), lowest in Northern Europe (median 44%, IQR 22-68%) and highest in Eastern Europe (median 99%, IQR 86-100). Uptake of testing was close to 100% in all regions. The median HIV+ rate was 0.9% (IQR 0.0-4.9), with 29 audits (60.4%) having an HIV+ rate >0.1%. After adjustment, there were no differences between regions of Europe in the proportion with >0.1% testing positive (global p = 0.14). A total of 113 patients tested HIV+. Applying the observed rates of testing HIV+ within individual ICs and regions to all persons presenting with an IC suggested that 105 diagnoses were potentially missed. Testing rates in well-established HIV ICs remained low across Europe, despite high prevalence rates, reflecting missed opportunities for earlier HIV diagnosis and care. Significant numbers may have had an opportunity for HIV diagnosis if all persons included in IC audits had been tested.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives
Switching from tenofovir (TDF) to tenofovir alafenamide (TAF) affects lipid profile. The aim of this study was to evaluate whether this results in an increased frequency of patients with ...low‐density lipoprotein (LDL) above their cardiovascular‐related target.
Methods
All HIV patients switching from TDF to TAF, with no changes of the anchor drug, and with plasma lipids available within 6 months before and after the switch, were included. Demographic, HIV‐related parameters, cardiovascular (CV) risk factors and lipid profile on both TDF and TAF were collected. The CV risk score and the relative target of LDL for each patient were calculated according to 2016 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for the management of dyslipidaemias. Modifications in lipid profiles and in the prevalence of patients with LDL above their CV‐related target were evaluated after switch to TAF.
Results
Overall, 221 HIV patients were included, according to CV risk: 55% at low risk, 34% at moderate risk, and 11% at high/very high risk. By analysing lipid profiles according to CV risk, 38% of patients on TDF had LDL above their CV target; this prevalence increases to 60% after switching to TAF (P < 0.0001). The presence of cobicistat in the combination antiretroviral therapy (cART) regimen was associated with an increased risk of LDL above the CV‐related target after switch to TAF adjusted odds ratio (aOR) = 2.4, 95% confidence interval (CI): 1–5.1, P = 0.03) and with an increased prescription of lifestyle/therapeutic intervention (OR = 3.0, 95% CI: 1.7–5.3, P < 0.0001).
Discussion
Switching from TDF to TAF affects lipid parameters, and data from real life suggest a clinical relevance of this worsening that often leads clinicians to implement lifestyle/therapeutic interventions.
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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
Undoubtedly, comorbidities complicate long‐term HIV management and have significant cost implications for healthcare systems. A better understanding of these comorbidities and underlying causes would ...allow for a more considered and proactive approach to the long‐term management of HIV. This review examines cross‐sectional analyses of six European cohort studies (Athens Multicenter AIDS Cohort Study, Aquitaine Cohort, EuroSIDA Cohort study, French claims EGB, German InGef Cohort and the Italian Cohort of Individuals, Naïve for Antiretrovirals), which included individuals with HIV followed over a certain period of time. Based on these cohorts, we examined how comorbidities have changed over time; how they compromise HIV management; and how much of a financial burden they impart. These data also provided a framework to explore the major issues of ageing and HIV and the practical implications of managing such issues in real‐life practice.
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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
The EuroSIDA study was initiated in 1994 and follows adult people living with HIV (PLHIV) in 100 collaborating clinics across 35 countries covering all European regions, Israel and Argentina. The ...study aims to study the long‐term virological, immunological and clinical outcomes of PLHIV and to monitor temporal changes and regional differences in outcomes across Europe. Annually collected data include basic demographic characteristics, information on AIDS‐ and non‐AIDS‐related clinical events, and details about antiretroviral therapy (ART), hepatitis C treatment and other medications, in addition to a range of laboratory values. The summer 2016 data set held data from a total of 23 071 individuals contributing 174 481 person‐years of follow‐up, while EuroSIDA’s unique plasma repository held over 160 000 samples. Over the past 25 years, close to 300 articles have been published in peer‐reviewed journals (h‐index 52), covering a range of scientific focus areas, including monitoring of clinical and virological outcomes, ART uptake, efficacy and adverse events, the influence of hepatitis virus coinfection, variation in the quality of HIV care and management across settings and regions, and biomarker research. Recognizing that there remain unresolved issues in the clinical care and management of PLHIV in Europe, EuroSIDA was one of the cohorts to found The International Cohort Consortium of Infectious Disease (RESPOND) cohort consortium on infectious diseases in 2017. In celebration of the EuroSIDA study’s 25th anniversary, this article aims to summarize key scientific findings and outline current and future scientific focus areas.
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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
Levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c), as well as the TC:HDL-c ratio, were compared in ...patients receiving different antiretroviral therapy regimens. Patients receiving first-line regimens including protease inhibitors (PIs) had higher TC and TG levels and TC:HDL-c ratios than did antiretroviral-naive patients; patients receiving 2 PIs had higher levels of each lipid. Ritonavir-containing regimens were associated with higher TC and TG levels and TC:HDL-c ratios than were indinavir-containing regimens; however, receipt of nelfinavir was associated with reduced risk of lower HDL-c levels, and receipt of saquinavir was associated with lower TC:HDL-c ratios. Patients receiving nonnucleoside reverse-transcriptase inhibitors had higher levels of TC and LDL-c than did antiretroviral-naive patients, although the risk of having lower HDL-c levels was lower than that in patients receiving a single PI. Efavirenz was associated with higher levels of TC and TG than was nevirapine.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Objectives
Previous studies have suggested that hypertension in HIV‐positive individuals is associated primarily with traditional risk factors such as older age, diabetes and dyslipidaemia. However, ...controversy remains as to whether exposure to antiretroviral (ARV) drugs poses additional risk, and we investigated this question in the Data Collection on Adverse Events of Anti‐HIV Drugs (D:A:D) cohort.
Methods
The incidence of hypertension systolic blood pressure (BP) > 140 and/or diastolic BP > 90 mmHg and/or initiation of antihypertensive treatment was determined overall and in strata defined by demographic, metabolic and HIV‐related factors, including cumulative exposure to each individual ARV drug. Predictors of hypertension were identified using uni‐ and multivariable Poisson regression models.
Results
Of 33 278 included persons, 7636 (22.9%) developed hypertension over 223 149 person‐years (PY) incidence rate: 3.42 (95% confidence interval (CI) 3.35–3.50) per 100 PY. In univariable analyses, cumulative exposure to most ARV drugs was associated with an increased risk of hypertension. After adjustment for demographic, metabolic and HIV‐related factors, only associations for nevirapine rate ratio 1.07 (95% CI: 1.04–1.13) per 5 years and indinavir/ritonavir rate ratio 1.12 (95% CI: 1.04–1.20) per 5 years remained statistically significant, although effects were small. The strongest independent predictors of hypertension were male gender, older age, black African ethnicity, diabetes, dyslipidaemia, use of lipid‐lowering drugs, high body mass index (BMI), renal impairment and a low CD4 count.
Conclusions
We did not find evidence for any strong independent association between exposure to any of the individual ARV drugs and the risk of hypertension. Findings provide reassurance that screening policies and preventative measures for hypertension in HIV‐positive persons should follow algorithms used for the general population.
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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
Objectives
The aim of the study was to estimate the rates of cardiovascular disease (CVD) events after stopping smoking in patients with HIV infection.
Methods
Patients who reported smoking status ...and no previous CVD prior to enrolment in the Data Collection on Adverse Events of Anti‐HIV Drugs (D:A:D) study were included in this study. Smoking status is collected at each visit as current smoker (yes/no) and ever smoker (yes/no). Time since stopping smoking was calculated for persons who had reported current smoking during follow‐up and no current smoking subsequently. Endpoints were: myocardial infarction (MI); coronary heart disease (CHD: MI plus invasive coronary artery procedure or death from other CHD); CVD (CHD plus carotid artery endarterectomy or stroke); and all‐cause mortality. Event rates were calculated for never, previous and current smokers, and smokers who stopped during follow‐up. Incidence rate ratios (IRRs) were determined using Poisson regression adjusted for age, sex, cohort, calendar year, family history of CVD, diabetes, lipids, blood pressure and antiretroviral treatment.
Results
A total of 27 136 patients had smoking status reported, with totals of 432, 600, 746 and 1902 MI, CHD, CVD and mortality events, respectively. The adjusted IRR of CVD in patients who stopped smoking during follow‐up decreased from 2.32 within the first year of stopping to 1.49 after >3 years compared with those who never smoked. Similar trends were observed for the MI and CHD endpoints. Reductions in risk were less pronounced for all‐cause mortality.
Conclusion
The risk of CVD events in HIV‐positive patients decreased with increasing time since stopping smoking. Smoking cessation efforts should be a priority in the management of HIV‐positive patients.
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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
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