Essentials From the 2015 European AIDS Clinical Society (EACS) Guidelines for the Treatment of Adult HIV-positive Persons

L Ryom; C Boesecke; V Gisler; C Manzardo; JK Rockstroh; M Puoti; H Furrer; JM Miro; JM Gatell; A Pozniak; G Behrens; M Battegay; JD Lundgren

Disclosures

HIV Medicine. 2016;17(2):83-88. 

In This Article

Abstract and Introduction

Abstract

Background The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android.

Guideline highlights The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug—drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes.

Conclusions The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview.

Introduction

The European AIDS Clinical Society (EACS) philosophy and methodology

The EACS is a nonprofit organization that aims to promote excellence in standards of care, research and education in HIV infection and related coinfections, and to actively engage in the formulation of public health policy, with the aim of reducing HIV disease burden across Europe.[1]

The overall scope of the EACS guidelines is hence to provide easily accessible recommendations to clinicians centrally involved in the care of HIV-positive individuals. Importantly, the guidelines are not to be considered as a full overview of all aspects of HIV infection, for which we refer to more elaborate work, but rather as a continuously updated overview of the most relevant clinical issues in HIV infection.

The EACS guidelines were first published in 2005 and are currently available in print, online on the EACS website (http://www.eacsociety.org/guidelines/eacs-guidelines/eacs-guidelines.html) and, since 2015, as a free App for download for iPhone and Android. The guidelines are revised annually for the electronic versions, and biennally for the printed version, and released during the EACS Conference. While the guidelines are developed by European HIV experts and were initially targeted primarily at European clinicians, the use of the guidelines has in recent years been more widely spread, and the guidelines are therefore now translated into more than 10 different languages.[2]

The EACS guidelines consist of five main sections, including a general table overview of all major issues in HIV infection as well as more detailed recommendations on antiretroviral treatment (ART), diagnosis, monitoring and treatment of comorbidities, coinfections and opportunistic diseases. Only drugs currently licensed by the European Medicines Agency (EMA) are taken into consideration in the guidelines.

Each respective section (I—V) of the guidelines is managed by a panel of experienced European HIV experts, and additional experts, where needed, (e.g. the Comorbidity section), and governed by a three-person leadership group consisting of a Panel Chair, Co-chair and Young scientist. Furthermore, the guidelines are managed by a guidelines Coordination Chair and Coordinator Assistant from the Center for Health and Infectious Disease Research (CHIP) in Copenhagen, Denmark, who work closely with the EACS secretariat in Brussels, Belgium. Each panel leadership group is responsible for the annual content revision of their section and will convene with other panels where there are potential overlaps between panels. Once all panels have finalized their revisions, these are extensively cross-reviewed by the remaining panels and by the Guidelines Coordinating Chair and Assistant for consistency. A team of linguistics, translators and layout designers/typesetters then take over to produce the final version of the guidelines to be released into the public domain.

All recommendations provided in the EACS guidelines are evidence-based whenever possible, and, based on expert opinions in the rare instance where adequate evidence is unavailable. A list of the main references used is provided as a separate section of the guidelines. All panel members have declared their interests, which are available upon request.

EACS Guidelines Version 8.0

In the 2015 revision of the EACS guidelines,[3] major revisions have been made in almost all sections. Most notably in the ART section the recommendations of when to start ART were changed based on the new results of the Strategic Timing of Antiretroviral Treatment (START) study[4] (Table 1), and the coinfection section was revised to reflect the major advances in anti-hepatitis C virus (HCV) treatment with the use of direct-acting antivirals (DAAs) phasing out use of interferon (IFN)-containing treatment. The following paragraphs describe, in more detail, the most important changes made in each section of the guidelines.

ART Section. When to Start: ART is now recommended for all HIV-positive persons, irrespectively of the CD4 count. The main reasons for this change in recommendation are the results of the START trial showing more favourable clinical outcomes among HIV-positive persons initiating ART at high CD4 counts as compared with persons initiating ART at lower CD4 counts.[2] Along with this change, the recommendations of what to start have also been changed in the new version of the guidelines.

What to Start: Preferred regimens have been reduced from 13 to six options: four integrase inhibitor (INSTI)-based, one non-nucleoside reverse transcriptase inhibitor (NNRTI)-based, and one ritonavir-boosted protease inhibitor (PI/r)-based (Table 2). Changes are mainly based on the results of trials with regimens containing INSTIs. The Panel also considered that at least one regimen containing a PI/r and one containing an NNRTI should be listed as 'preferred' treatment options.

Post-exposure Prophylaxis (PEP): Based on the results of the PARTNER study, the recommendations on PEP for sexual exposure to HIV were revised to reflect the fact that, if an HIV-positive source person has documented undetectable plasma HIV-RNA, PEP is no longer recommended. Use of tenofovir (TDF)/emtricitabine (FTC) + raltegravir or boosted darunavir is now also recommended as an ART regimen for PEP.

Pre-exposure Prophylaxis (PrEP): A brand new section on PrEP has been added to the guidelines. PrEP (TDF/FTC) should be recommended for high-risk men who have sex with men (MSM) and transgender individuals and considered for high-risk heterosexual men and women. Both continuous and 'on demand' options are discussed as possible approaches.

Comorbidity Section. Ageing and Comorbidities: A closer attention was brought to the growing proportion of HIV-positive individuals with advanced age and multiple simultaneous comorbidities, who may benefit most from a multidisciplinary assessment. As such intensified monitoring of renal function is now recommended in individuals with an estimated glomerular filtration rate (eGFR) < 90 mL/min and with progressively declining eGFR. The use of a chronic kidney disease risk equation is also recommended. Furthermore, screening for depression is now encouraged more widely because of its high prevalence, recommendations for smoking cessation have been further elaborated and recommendations for regular assessment of liver disease in individuals with viral hepatitis coinfection with ultrasound and fibrosis staging have been added.

New Drugs/Drug Combinations: A number of new antiretroviral drugs/drug combinations have been included in the revised tables on drug—drug interactions, adverse effects, and dose adjustment for renal/liver insufficiency and in the table on administration of ART in individuals with swallowing difficulties. Several of these tables have, in previous version of the EACS guidelines, been available exclusively in the electronic version; however, as a result of requests from the guideline users, the tables on dose adjustment for renal/liver insufficiency and administration of ART in individuals with swallowing difficulties are now also available in the print version.

Drug—Drug Interactions: Two new drug—drug interaction tables on interactions with corticosteroids and contraceptive drugs with the use of ART have been included in the 2015 version of the guidelines.

Cardiovascular Disease (CVD) Risk Factors: In the general population, several guidelines on risk factors (e.g. dyslipidaemia) for CVD have ceased to use threshold values. However, the Comorbidity panel have in the revised version kept threshold values for all CVD risk factors to aid everyday clinical practice.

Vaccination: A general recommendation to avoid polysaccharide vaccination has been added, as has a recommendation for influenza and Streptococcus pneumonia vaccination in all HIV-positive persons.

Coinfection Section. Treatment of Hepatitis B Virus (HBV) Infection: The guideline text and tables now reflect the general recommendation to start ART in the presence of HBV coinfection regardless of the CD4 count. ART should contain TDF as a dually active agent against HIV and HBV infection.

Treatment of Chronic HCV Infection: Analogous to the situation for HBV, the guideline text and tables now also reflect the general recommendation to start ART in the presence of HCV coinfection regardless of the CD4 count. A stronger emphasis is placed on IFN-free treatment regimens (Table 3) as well as earlier start of DAA treatment in cases where there is a risk of liver disease progression. All detailed recommendations on IFN-containing regimens have therefore been removed from the main HCV treatment section. Acknowledging that IFN-containing treatment is still being used in certain countries, recommendations on IFN-containing treatment have been collected in an addendum available online. Text and tables have furthermore been updated following the licensing of sofosbuvir/ledipasvir and AbbVie 3D combo. The drug—drug interaction table on DAAs and antiretrovirals has subsequently also been updated.

Treatment of Acute HCV Infection: In the absence of randomized, controlled data on the use of DAAs in the setting of acute HCV coinfection, treatment with pegylated IFN and ribavirin should be based on an individual decision, weighing the known toxicities and long treatment duration against a potentially strong patient wish for early HCV cure, particularly in HIV-positive MSM with a higher risk of HCV transmission and in countries where the cost of DAAs will only be reimbursed in chronic HCV infection with advanced fibrosis.

Opportunistic Diseases Section. While the overall content of this section has not undergone major changes, the structure has changed considerably. In previous versions of the guidelines, the recommendations for opportunistic diseases were subdivided into three overview tables on primary prophylaxis, treatment and secondary prophylaxis/maintenance treatment. In the 2015 version, the recommendations are now structured according to the individual pathogens/diseases to ease the overview. Now, each section contains a short abstract on diagnostics for each opportunistic disease. Additionally, a new overview table on CD4 count thresholds as indication for different primary prophylaxes has been added. The section on Cryptococcosis has been complemented with a recommendation for pre-emptive treatment.

New Tables: Entirely new tables with recommendations on treatment of progressive multifocal leukoencephalopathy (PML), histoplasmosis, cryptosporidiosis and cystoisosporiasis have been added.

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