Cohort profile:Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord

Many questions about the long-term effects of combination antiretroviral therapy (cART) on clinical 3 outcomes in people living with HIV (PLWH) and their impact on health systems remain unanswered. The 4 Collaboration of Observational HIV Epidemiological Research Europe (COHERE) was formed in 2005 to 5 pool and harmonize existing longitudinal data on people living with HIV in Europe, to answer key 6 research questions that could not be addressed adequately by individual cohorts. Key research 7 questions include long-term prognosis, rare outcomes, and variations across patient groups, settings 8 and health systems. COHERE uses the HIV Cohorts Data Exchange Protocol, a standardized and validated 9 method of data structure and transfer, to compile data from over 40 cohorts of PLWH residing in 10 Europe, representing 331 481 individuals, including 2808 children (<13), representing 2 135 896 person- 11 years of follow-up. COHERE compiles data on clinical characteristics, antiretroviral therapy and other 12 medications, HIV seroconversion, opportunistic infections, laboratory results and socio demographic 13 data. External collaborators interested in conducting a project in COHERE should submit a project 14 proposal to the Regional Coordinating Centres in Bordeaux and Copenhagen for review by COHERE’s 15 governing bodies (see www.cohere.org for further information)

Inflammation predicts changes in high-density lipoprotein particles and apolipoprotein A1 following initiation of antiretroviral therapy

BACKGROUND:: The effects of HIV infection and antiretroviral therapy (ART) on usual lipid levels have been reported. The effects of initiating versus deferring ART on high-density and low-density lipoprotein particle (HDL-P and LDL-P, respectively) concentrations and apolipoprotein (Apo) levels are not well described. METHODS:: In a subgroup of participants not taking ART at study entry who were randomized in the Strategies for Management of Antiretroviral Therapy (SMART) trial to immediately initiate ART (\u27viral suppression group\u27) or to defer it (\u27drug conservation group\u27), lipoprotein particle concentrations and ApoA1 and ApoB levels were measured at baseline and at 2 and 6 months following randomization. RESULTS:: Compared with drug conservation group (n = 126), HDL-P and ApoA1 levels increased among viral suppression participants (n = 128) after starting ART. At 6 months, viral suppression participants had 13% higher total HDL-P (P \u3c 0.001) and 9% higher ApoA1 (P \u3c 0.001). LDL-P, very low density lipoprotein particle, and ApoB did not differ significantly between the viral suppression and drug conservation groups. Among viral suppression participants, predictors of HDL-P and ApoA1 increases included baseline levels of high-sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6), but not HIV RNA level, CD4 cell count, or traditional cardiovascular disease risk factors. The effect of starting ART on changes in HDL-P and ApoA1 was greater for those with higher versus lower baseline levels of IL-6 (P = 0.001 and 0.08, respectively, for interaction) or hsCRP (P = 0.01 and 0.04, respectively, for interaction). CONCLUSION:: HDL-P and ApoA1 increase following ART initiation, to a degree that depends on the degree of inflammation present at entry. These findings suggest that activation of inflammatory pathways contribute to HIV-associated changes in HDL. © 2011 Wolters Kluwer Health Lippincott Williams & Wilkins

Changes in lipids and lipoprotein particle concentrations after interruption of antiretroviral therapy

The effect of interruption of antiretroviral therapy (ART) on lipoprotein particle subclasses has not been studied. We examined short-term changes in lipids and lipoprotein particles among 332 HIV-infected individuals randomized to interrupt or continue ART in the "Strategies for Management of Antiretroviral Therapy" trial. Lipids and lipoprotein particles measured by nuclear magnetic resonance spectroscopy were compared between randomized groups at month 1; associations with inflammatory and coagulation markers (high sensitivity C-reactive protein; interleukin 6; amyloid A; amyloid P; D-dimer; prothrombin fragment 1 + 2) were assessed. Compared with continuation of ART, treatment interruption resulted in substantial declines in total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and triglyceride, at month 1 but had little net effect on total/HDL cholesterol ratio [baseline-adjusted mean difference [95% confidence interval (CI)] interruption versus continuation arms: -0.10 (-0.59 to 0.38); P = 0.67]. ART interruption resulted in declines in total, large, and medium very low density lipoprotein (VLDL) particle concentrations (VLDL-p) and total and medium HDL-p. However, there was no change in small HDL-p [baseline-adjusted percentage difference between arms: -4.6% (-13.1%, +5.1% ); P = 0.35], small LDL-p [-5.0% (-16.9%, +8.6%); P = 0.45], or other LDL-p subclasses. Changes in lipid parameters on ART interruption did not differ according to baseline ART class (protease inhibitor versus non-nucleoside reverse transcriptase inhibitor) but were negatively associated both with changes in HIV viral load and with changes in inflammatory and coagulation markers, particularly D-dimer. These results suggest that ART interruption does not favorably influence overall lipid profile: there was little net effect on total/HDL cholesterol ratio, and no change in small LDL-p or small HDL-p, the lipoprotein particle subclasses most consistently linked to coronary risk. Short-term declines in lipid parameters after ART interruption were not associated with class of ART and may be linked to increases in viral replication, inflammation and coagulatio

Cohort Profile: Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord

International audienceMany questions about the long-term effects of combination antiretroviral therapy (cART) on clinical outcomes in people living with HIV (PLWH) and their impact on health systems remain unanswered. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) was formed in 2005 to pool and harmonize existing longitudinal data on people living with HIV in Europe, to answer key research questions that could not be addressed adequately by individual cohorts. Key research questions include long-term prognosis, rare outcomes, and variations across patient groups, settings and health systems. COHERE uses the HIV Cohorts Data Exchange Protocol, a standardized and validated method of data structure and transfer, to compile data from over 40 cohorts of PLWH residing in Europe, representing 331 481 individuals, including 2808 children (<13), representing 2 135 896 person-years of follow-up. COHERE compiles data on clinical characteristics, antiretroviral therapy and other medications, HIV seroconversion, opportunistic infections, laboratory results and socio demographic data. External collaborators interested in conducting a project in COHERE should submit a project proposal to the Regional Coordinating Centres in Bordeaux and Copenhagen for review by COHERE’s governing bodies (see www.cohere.org for further information)

Lipoprotein particle subclasses, cardiovascular disease and HIV infection

Objective: To study the association of lipoprotein particles with CVD in a subgroup of HIV-infected patients who were enrolled in the Strategies for Management of Anti-Retroviral Therapy (SMART) study. SMART was a trial of intermittent use of ART (drug conservation [DC]) versus continuous of ART (viral suppression [VS]). Methods: In a nested case-control study, lipoprotein particles (p) by nuclear magnetic resonance were measured at baseline and at the visit prior to the CVD event (latest levels) for 248 patients who had a CVD event and for 480 matched controls. Odds ratios (ORs) were estimated using conditional logistic models. Results: Total, large and small HDL-p, but not VLDL-p nor LDL-p, were significantly and inversely associated with CVD and its major component, non-fatal coronary heart disease. The HDL-p associations with CVD were reduced after adjustment for high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6) and D-dimer. Latest levels of total HDL-p were also significantly inversely associated with CVD; treatment interruption led to decrease of total HDL-p; adjusting for latest HDL-p did not explain the greater risk of CVD that was observed in the DC versus VS group. Conclusions: Lipoprotein particles, especially lower levels of small and large HDL-p identify HIV-infected patients at increased risk of CVD independent of other CVD risk factors. © 2009 Elsevier Ireland Ltd

Predicting the risk of cardiovascular disease in HIV-infected patients: The Data collection on Adverse Effects of Anti-HIV Drugs Study

Aims: HIV-infected patients receiving combination antiretroviral therapy may experience metabolic complications, potentially increasing their risk of cardiovascular diseases (CVDs). Furthermore, exposures to some antiretroviral drugs seem to be independently associated with increased CVD risk. We aimed to develop cardiovascular risk-assessment models tailored to HIV-infected patients. Methods and results: Prospective multinational cohort study. The data set included 22 625 HIV-infected patients from 20 countries in Europe and Australia who were free of CVD at entry into the Data collection on Adverse Effects of Anti-HIV Drugs Study. Using cross-validation methods, separate models were developed to predict the risk of myocardial infarction, coronary heart disease, and a composite CVD endpoint. Model performance was compared with the Framingham score. The models included age, sex, systolic blood pressure, smoking status, family history of CVD, diabetes, total cholesterol, HDL cholesterol and indinavir, lopinavir/r and abacavir exposure. The models performed well with area under the receiver operator curve statistics of 0.783 (range 0.642–0.820) for myocardial infarction, 0.776 (0.670–0.818) for coronary heart disease and 0.769 (0.695–0.824) for CVD. The models estimated more accurately the outcomes in the subgroups than the Framingham score. Conclusion: Risk equations developed from a population of HIV-infected patients, incorporating routinely collected cardiovascular risk parameters and exposure to individual antiretroviral therapy drugs, might be more useful in estimating CVD risks in HIV-infected persons than conventional risk prediction models

Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration

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.SCOPUS: ar.jinfo:eu-repo/semantics/publishe