Major Clinical Outcomes in Antiretroviral Therapy (ART)–Naive Participants and in Those Not Receiving ART at Baseline in the SMART Study

Emery, Sean; Neuhaus, Jacqueline; Phillips, Andrew; Babiker, Abdel; Cohen, Calvin; Gatell, José M.; Girard, Pierre Marie; Grund, Birgit; Law, Matthew; Losso, Marcelo; Palfreeman, Adrian; Wood, Robin

doi:10.1086/586713

Cited by 347 publications

(138 citation statements)

References 19 publications

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“…The study design was a nested case‐control study, sampling patients from the control arms (continuous use of ART) of two large, international HIV clinical outcome trials, Strategies for Management of Antiretroviral Therapy (SMART)42, 43 and Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT) 44. In SMART, 5472 HIV‐positive adults with CD4+ cell count >350 cells/mm 3 in 33 countries were randomized to receive continuous ART with the goal of viral suppression (control group) or episodic ART guided by the CD4+ count.…”

Section: Methodsmentioning

confidence: 99%

In silico thrombin generation: Plasma composition imbalance and mortality in human immunodeficiency virus

Brummel‐Ziedins

Gissel

Neuhaus

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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BackgroundEffective HIV treatment with antiretroviral therapy has prolonged survival and shifted causes of death to non‐AIDS illnesses such as cardiovascular disease. We have shown that inflammation and HIV viral load associate with pro‐ and anticoagulant factor imbalances resulting in increased thrombin generation when mathematically modeled. We explore the hypothesis that factor compositional imbalance, corresponding to increased in silico thrombin generation, predicts mortality among HIV+ persons.MethodsIn a nested case‐control study of HIV+ individuals on continuous antiretroviral therapy in two large trials, we evaluated cases (any non‐violent mortality, n = 114) and matched controls (n = 318). Thrombin generation in response to a tissue‐factor initiator for each individual was calculated by a mathematical model incorporating levels of factors (F)II, V, VII, VIII, IX, X, antithrombin, tissue factor pathway inhibitor, and protein C (PC) measured at study entry to the trials. In silico thrombin generation metrics included clot time, maximum rate (MaxR), maximum level (MaxL), and area under the curve (AUC).ResultsLevels of antithrombin and PC decreased, while FV and FVIII were higher in cases vs controls. This resulted in a more procoagulant phenotype with increased MaxR, MaxL, and AUC in cases compared to controls (P < 0.05 for all).ConclusionsAntithrombin, FV, FVIII, and PC were the major contributors to the increased thrombin generation associated with mortality risk. Our results suggest that mortality in HIV is associated with an increase in in silico thrombin generation via altered balance of pro‐ and anticoagulant factors, likely due to an inflammatory response signal, and resulting coagulopathy.

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Section: Methodsmentioning

confidence: 99%

In silico thrombin generation: Plasma composition imbalance and mortality in human immunodeficiency virus

Brummel‐Ziedins

Gissel

Neuhaus

et al. 2018

Research and Practice in Thrombosis and Haemostasis

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“…There was a significantly reduced risk of clinical disease in the intervention group, mainly driven by a reduction in extrapulmonary tuberculosis, although the study power was low for serious clinically manifest disease endpoints. In a subset of participants in the Strategies for Management of Antiretroviral Therapy (SMART) trial with CD4 count >350 cells/mm 3 who were ART naive at baseline, there was a reduced risk of clinical disease in those initiating ART upon entry into the study compared with those who deferred it (CD4 count <250 cells/mm 3 ), but the size of this subsample was small [56]. Both these trials were based on a comparison involving deferral until the CD4 count falls below 250 cells/mm 3 , which is now no longer the standard of care.…”

Section: Implications For Hiv-positive Individualsmentioning

confidence: 99%

Antiretroviral therapy for prevention of HIV transmission: implications for Europe

et al. 2013

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The aim of this review is to summarise the evidence on the population-level effect of antiretroviral therapy (ART) in preventing HIV infections, and to discuss potential implications in the European context of recommending starting ART when the CD4 count is above 350 cells/mm 3 . The ability of ART to reduce the risk of HIV transmission has been reported in observational studies and in a randomised controlled trial (HPTN 052), in which ART initiation reduced HIV transmission by 96% within serodiscordant couples. As yet, there is no direct evidence for such an effect among men having sex with men or people who inject drugs. HPTN 052 led international organisations to develop recommendations with a higher CD4 threshold for ART initiation. However, there remains a lack of strong evidence of clinical benefit for HIV-positive individuals starting ART with CD4 count above 350 cells/mm 3 . The main goal of ART provision should be to increase ART coverage for all those in need, based on the current guidelines, and the offer of ART to those who wish to reduce infectivity; increased HIV testing is therefore a key requirement. Other proven prevention means such as condom use and harm reduction for people who inject drugs remain critical.

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“…Theoretical Framework Rogers' (2003) diffusion of innovations theory for new knowledge dissemination and adoption was the primary framework for this project. Rogers defined diffusion as communication specifically focused on dissemination of new knowledge or innovations.…”

Section: Evidence-based Practice Implementationmentioning

confidence: 99%

“…The innovator uses the innovation-decision process to implement new knowledge or behavior and uses information to ameliorate uncertainty among adopters. Rogers (2003) theorized that ''the main elements in the diffusion of new ideas are: (1) an innovation (2) that is communicated through certain channels (3) over time (4) among the members of a social system'' (p. 36).…”

Section: Evidence-based Practice Implementationmentioning

confidence: 99%

Integrating HIV-Related Evidence-Based Renal Care Guidelines Into Adult HIV Clinics

Goodroad¹,

Wright²,

Rhame³

2010

Journal of the Association of Nurses in AIDS Care

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The purpose of this evidence-based practice (EBP) project was to implement research-based, clinic-specific renal care guidelines into two adult HIV clinics. The two main components of the project included (a) implementation of clinic-specific renal care guidelines and (b) initiation of renal and general health patient education by clinic support staff. Overall, statistically significant improvement was shown postguideline implementation in proportion of urinalyses (UA) (p 5 .01) and estimated glomerular filtration rates (eGFR) (p 5 .002) completion for patients during initial clinic visits and for those requiring yearly (UA p , .001, eGFR p , .001) or twice-yearly (UA p , .001, eGFR p , .001) renal testing. The rate of renal health education provided to patients by nurses was 60.7%. Results suggest that advanced practice nurse-led EBP change implementation can result in better renal care in outpatient HIV care settings. The process described could be used to implement EBP in other clinic sites.

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Major Clinical Outcomes in Antiretroviral Therapy (ART)–Naive Participants and in Those Not Receiving ART at Baseline in the SMART Study

Abstract: Initiation of ART at CD4+ cell counts >350 cells/microL compared with <250 cells/microL may reduce both OD and serious non-AIDS events. These findings require validation in a large, randomized clinical trial.

Cited by 347 publications

References 19 publications

In silico thrombin generation: Plasma composition imbalance and mortality in human immunodeficiency virus

In silico thrombin generation: Plasma composition imbalance and mortality in human immunodeficiency virus

Antiretroviral therapy for prevention of HIV transmission: implications for Europe

Integrating HIV-Related Evidence-Based Renal Care Guidelines Into Adult HIV Clinics

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