2019 Update of the European AIDS Clinical Society Guidelines for Treatment of People Living With HIV Version 10.0

Additional guidance: (I) ABC contraindicated if HLA-B*57:01 positive. Even if HLA-B*57:01 negative, counselling on hypersensitivity reaction risk still mandatory. ABC should be used with caution in persons with a high CVD risk (> 10%). (II) In certain countries, TDF is labelled as 245 mg rather than 300 mg to reflect the amount of the prodrug (tenofovir disoproxil) rather than the fumarate salt (tenofovir disoproxil fumarate). There are available generic forms of TDF, which instead of fumarate use phosphate, maleate, and succinate salts. They can be used interchangeably. When available, combinations containing TDF can be replaced by the same combinations containing TAF. TAF is used at 10 mg when coadministered with drugs that inhibit p-glycoprotein (P-gp), and at 25 mg when co-administered with drugs that do not inhibit P-gp. The decision whether to use TDF or TAF depends on individual characteristics as well as availability. So far, there are only limited long-term data on TAF. If the antiretroviral (ART) regimen does not include a booster, TAF and TDF have similar short-term risks of renal adverse events leading to discontinuation and bone fractures.
TAF*** should be considered as a first choice**** over TDF in individuals with:
(1) established or high risk of chronic kidney disease (see Guideliness page 64); (2) co-administration of medicines with nephrotoxic drugs or prior TDF toxicity (see Guidelines page 65); (3) osteoporosis/progressive osteopenia, high fracture risk asessement tool score or risk factors (see Guidelines page 61); (4) history of fragility fracture (see Guidelines pages 61 and 63).
***There are limited data on use of TAF with estimated glomerular filtration rate (eGFR) < 30 mL/min;
****Expert opinion pending clinical data.
(III) Two randomized controlled trials (performed in South Africa and Cameroon) showed that, in comparison with EFV, treatment with DTG in naïve persons was associated with increased weight gain when combined with TAF/FTC, TDF/FTC or TDF/3TC. The effect on increased weight was more important for women under treatment containing both DTG and TAF (reference [12], [13] in the Guidelines). (IV) RAL can be given as RAL 400 mg bid or RAL 1200 mg (two 600 mg tablets) qd. Note: RAL qd should not be given in the presence of an inducer (i.e. TB drugs or antiepileptics) or divalent cations (i.e. calcium, magnesium or iron), in which case RAL should be used bid. (V) DOR is not active against HIV-2. (VI) RPV is not active against HIV-2. (VII) A single study has shown an increase in CVD risk with cumulative use of DRV/r (reference [14] in the Guidelines). (VIII) TDF/FTC/EVG/c to be used only if eGFR ≥ 70 mL/min. It is recommended that TDF/FTC/EVG/c is not initiated in persons with eGFR < 90 mL/min unless this is the preferred treatment. (IX) EFV: not to be given if history of suicide attempts or mental illness; not active against HIV-2 and HIV-1 group O strains. (X) Potential renal toxicity with ATV/b.
NRTI, nucleoside reverse transcriptase inhibitor; INSTI, integrase strand transfer inhibitor; HLA, human leucocyte antigen; ABC, abacavir; HBsAg, hepatitis B virus surface antigen; 3TC, lamivudine; DTG, dolutegravir; TAF, tenofovir alafenamide; FTC, emtricitabine; TDF, tenofovir disoproxil fumarate), BIC, bictegravir; DOR, doravirine; RAL, raltegravir; qd, once daily; bid, twice a day; VL, viral load; RPV, rilpivirine; PI/r, ritonavir-boosted protease inhibitor; PI/c, cobicistat-boosted protease inhibitor; EVG, elvitegravir; NNRTI, nonnucleoside reverse transcriptase inhibitor; ATV, atazanavir; CVD, cardiovascular disease.

CTP, child-Turcotte-Pugh; DAA, direct-acting antiviral; DCV, daclatasvir; DSV, dasabuvir; EBR, elbasvir; GLE, glecaprevir; GT, genotype; GZR, grazoprevir; LDV, ledipasvir; NS5A, Nonstructural protein 5A; OBV, ombitasvir; PIB, pibrentasvir; PTV/r, paritaprevir/RTV; RAS, resistance-associated substitution; RBV, ribavirin; SOF, sofosbuvir; VEL, velpatasvir; VOX, voxilaprevir.
^aExtension of treatment to 16 weeks and addition of RBV in PLWH with GT1a with baseline HCV RNA > 800 000 IU/mL and/or NS5A RASs causing at least 5-fold reduction in activity of EBR to minimize the risk of treatment failure and in HCV GT4-experienced PLWH with HCV RNA > 800 000 IU/mL at 8 weeks can be considered in GT1b treatment-naïve patients with F0–F2.
^b8 weeks of treatment without RBV only in treatment-naïve PLWH with F < 3 and baseline HCV RNA < 6 million IU/mL.
^cIn persons intolerant to RBV, treatment may be prolonged to 24 weeks. RBV can be omitted in treatment-naïve or -experienced PLWH with compensated cirrhosis without baseline NS5A RAS.
^dTreatment duration in HCV GT3 who failed previous treatment with interferon (IFN) and RBV ± SOF or SOF and RBV should be 16 weeks.
^eAddition of RBV in treatment-experienced PLWH with baseline NS5A RASs, if RAS testing available; if these persons are intolerant to RBV, treatment may be prolonged to 24 weeks without RBV.
^fIf RAS testing is available and demonstrates absence of NS5A RAS Y93H, RBV can be omitted in treatment-naïve PLWH with compensated cirrhosis.
^gIn treatment-experienced (exposure to IFN/RBV/SOF) PLWH, treat with RBV for 12 weeks or prolong treatment to 24 weeks without RBV.

CTP, child-Turcotte-Pugh; DAA, direct-acting antiviral; DCV, daclatasvir; DSV, dasabuvir; EBR, elbasvir; GLE, glecaprevir; GT, genotype; GZR, grazoprevir; LDV, ledipasvir; NS5A, Nonstructural protein 5A; OBV, ombitasvir; PIB, pibrentasvir; PTV/r, paritaprevir/RTV; RAS, resistance-associated substitution; RBV, ribavirin; SOF, sofosbuvir; VEL, velpatasvir; VOX, voxilaprevir.
^a8 weeks of treatment without RBV only in PLWH without cirrhosis.
^bAddition of RBV in GT1a treatment-experienced PLWH, but not in PLWH without NS5A RASs, if RAS testing is available.
^cIn PLWH intolerant to RBV, treatment may be prolonged to 24 weeks. RBV can be omitted in treatment-naïve or -experienced PLWH with compensated cirrhosis without baseline NS5A RAS.
^dExtension of treatment to 12 weeks in DAA treatment-experienced PLWH.
^eAddition of RBV only in treatment-experienced persons with baseline NS5A RASs, if RAS testing available; if these PLWH are intolerant to RBV, treatment may be prolonged to 24 weeks without RBV.
^fIn treatment-experienced (exposure to IFN/RBV/SOF) PLWH, treat with RBV for 12 weeks or prolong treatment to 24 weeks without RBV.

Authors and Disclosures

L Ryom¹, A Cotter², R De Miguel³, C Béguelin⁴, D Podlekareva¹, JR Arribas³, C Marzolini^5,6, PGM Mallon², A Rauch⁴, O Kirk¹, JM Molina⁷, G Guaraldi⁸, A Winston⁹, S Bhagani¹⁰, P Cinque¹¹, JD Kowalska¹², S Collins¹³ and M Battegay¹⁴ on behalf of the EACS Governing Board*

¹CHIP, Center of Excellence for Health, Immunity and Infections, Department of Infectious Diseases, Section 2100, Center for Cardiac, Vascular, Pulmonary and Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark, ²University College Dublin Centre for Experimental Pathogen Host Research, Dublin, Ireland, ³Infectious Diseases Unit, La Paz Hospital, Madrid, Spain, ⁴Department of Infectious Diseases, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland, ⁵Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital of Basel and University of Basel, Basel, Switzerland, ⁶Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool, UK, ⁷Department of Infectious Diseases, St Louis and Lariboisière Hospitals, APHP and University of Paris, Paris, France, ⁸Department of Surgical, Medical, Dental and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy, ⁹Imperial College London, London, UK, ¹⁰Department of Infectious Diseases/HIV Medicine, Royal Free London NHS Trust, Institute of Global Health, University College London, London, UK, ¹¹Division of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy, ¹²Faculty of Medicine, Medical University of Warsaw, Warsaw, Poland, ¹³HIV i-Base and EATG, London, UK and ¹⁴Division of Infectious Diseases et Hospital Epidemiology, University Hospital Basel and University of Basel, Basel, Switzerland

Correspondence
Dr Lene Ryom, CHIP, Center of Excellence for Health, Immunity and Infections, Rigshospitalet, University of Copenhagen, Department of Infectious Diseases, Section 2100, Center for Cardiac, Vascular, Pulmonary and Infectious Diseases, Blegdamsvej 9, DK-2100 Copenhagen O, Denmark. Tel: + 45 35 45 57 65; fax: +45 35 45 57 57; e-mail: lene.ryom.nielsen@regionh.dk

*Members of the EACS Panels and Governing Board are listed in the Acknowledgements.

Appendix 1

Guidelines Panel Members 2019

Medical secretariat: the EACS Medical Secretariat is responsible for the coordination and update of the EACS guidelines based on the recommendations from the five EACS panels.

Guidelines Chair: Manuel Battegay (Basel, Switzerland);

Guidelines Coordinator: Lene Ryom (Copenhagen, Denmark).

Panel members:

HIV treatment:

Chair: José Arribas (Madrid, Spain); Vice-Chair: Jean-Michel Molina (Paris, France); Young Scientist: Rosa De Miguel Buckley (Madrid, Spain); Antonella d'Arminio Monforte (Milan, Italy), Manuel Battegay (Basel, Switzerland), Margherita Bracchi (London, UK), Nikos Dedes (Athens, Greece), Andrzej Horban (Warsaw, Poland), Christine Katlama (Paris, France), Inga Latysheva (Saint Petersburg, Russia), Jens D. Lundgren (Copenhagen, Denmark), Sheena McCormack (London, UK), Cristina Mussini (Modena, Italy), Anton Pozniak (London, UK), Federico Pulido (Madrid, Spain), François Raffi (Nantes, France), Peter Reiss (Amsterdam, The Netherlands), Hans-Jürgen Stellbrink (Hamburg, Germany), Marta Vasylyev (Lviv, Ukraine).

Drug–drug interactions:

Chair: Catia Marzolini (Basel, Switzerland); Vice-Chair: Giovanni Guaraldi (Modena, Italy); Sara Gibbons (Liverpool, UK), Françoise Livio (Lausanne, Switzerland).

Comorbidities:

Chair: Patrick Mallon (Dublin, Ireland); Vice-Chair: Alan Winston (London, UK); Young Scientist: Aoife Cotter (Dublin, Ireland); Manuel Battegay (Basel, Switzerland), Georg Behrens (Hannover, Germany), Mark Bower (London, UK), Paola Cinque (Milan, Italy), Simon Collins (London, UK), Juliet Compston (Cambridge, UK), Stéphane De Wit (Brussels, Belgium), Leonardo M. Fabbri (Modena, Italy), Christoph A. Fux (Aarau, Switzerland), Magnus Gisslen (Gothenburg, Sweden), Giovanni Guaraldi (Modena, Italy), Justyna D. Kowalska (Warsaw, Poland), Jens D. Lundgren (Copenhagen, Denmark), Esteban Martínez (Barcelona, Spain), Catia Marzolini (Basel, Switzerland), José M. Miro (Barcelona, Spain), Eugenia Negredo (Barcelona, Spain), Neil Poulter (London, UK), Peter Reiss (Amsterdam, The Netherlands), Lene Ryom (Copenhagen, Denmark), Giada Sebastiani (Montreal, Canada).

Viral hepatitis co-infections:

Chair: Andri Rauch (Bern, Switzerland); Vice-Chair: Sanjay Bhagani (London, UK); Young Scientist: Charles Béguelin (Bern, Switzerland); Juan Berenguer (Madrid, Spain), Christoph Boesecke (Bonn, Germany), Raffaele Bruno (Pavia, Italy), Svilen Konov (London, UK), Karine Lacombe (Paris, France), Stefan Mauss (Düsseldorf, Germany), Luís Mendão (Lisbon, Portugal), Lars Peters (Copenhagen, Denmark), Massimo Puoti (Milan, Italy), Jürgen K. Rockstroh (Bonn, Germany).

Opportunistic infections:

Chair: Ole Kirk (Copenhagen, Denmark); Vice-Chair: Paola Cinque (Milan, Italy); Young Scientist: Daria Podlekareva (Copenhagen, Denmark); Juan Ambrosioni (Barcelona, Spain), Nathalie De Castro (Paris, France), Gerd Fätkenheuer (Cologne, Germany), Hansjakob Furrer (Bern, Switzerland), José M. Miro (Barcelona, Spain), Cristiana Oprea (Bucharest, Romania), Anton Pozniak (London, UK), Alain Volny-Anne (Paris, France). WAVE representative: Justyna D. Kowalska (Warsaw, Poland).

Governing board members:

Jürgen K. Rockstroh (President) (Bonn, Germany), Sanjay Bhagani (Vice-President) (London, UK), Ann Sullivan (Secretary) (London, UK), Esteban Martínez (Treasurer) (Barcelona, Spain), Fiona Mulcahy (Immediate, Past President) (Dublin, Ireland), Antonella d'Arminio Monforte (Milan, Italy), Manuel Battegay (Basel, Switzerland), Georg Behrens (Hannover, Germany), Christine Katlama (Paris, France), Jens D. Lundgren (Copenhagen, Denmark), Cristina Mussini (Modena, Italy), Cristiana Oprea (Bucharest, Romania), Anton Pozniak (London, UK), Peter Reiss (Amsterdam, The Netherlands), Annemarie Wensing (Utrecht, The Netherlands).