GUIDELINES

1 GUIDELINESV ersion 2019 EnglishGUIDELINESV ersion 2021 EnglishEACS EuropeanAIDS Clinical Society1 EACS GUIDELINES of Contents Introduction to EACS GUIDELINES 20213 Summary of Changes from to Members5 Governing Board Members5 Abbreviations6 Part IAssessment of PLWH at Initial & Subsequent Visits7 Part IIART of PLWH10 Assessing PLWH's Readiness to Start and Maintain ART 10 Recommendations for Initiation of ART in PLWH with Chronic Infection without prior ART exposure 12 Initial Combination Regimen for ART-na ve Adult PLWH 13 Primary HIV Infection (PHI)15 Switch Strategies for Virologically Suppressed Persons16 Virological Failure17 Treatment of Pregnant Women Living with HIV or Women Considering Pregnancy18 ART in TB/HIV Co-infection20 post - exposure prophylaxis (PEP) 22 Pre- exposure prophylaxis (PrEP)23 Adverse Effects of ARVs and Drug Classes 24 Part IIIDrug-drug Interactions and Other Prescribing Issues in PLWH26 Drug-drug Interactions between ARVs and Non-ARVs27 Drug-drug Interactions between Analgesics and ARVs29 Drug-drug Interactions between Anticoagulants/Antiplatelet Agents and ARVs30 Drug-drug Interactions between Antidepressants and ARVs31 Drug-drug Interactions between Antihypertensives and ARVs32 Drug-drug Interactions between Anti-malarial Drugs and ARVs34 Drug-drug Interactions between Anti-tuberculosis Drugs and ARVs35 Drug-drug Interactions between Anxiolytics and ARVs36 Drug-drug Interactions between Bronchodilators (for COPD)

2 And ARVs37 Drug-drug Interactions between Contraceptives and ARVs38 Drug-drug Interactions between Corticosteroids and ARVs40 Drug-drug Interactions between COVID-19 Therapies and ARVs41 Drug-drug Interactions between Hormone Replacement Therapy (HRT) and ARVs42 Drug-drug Interactions between Immunosuppressants (for SOT) and ARVs43 Drug-drug Interactions between Pulmonary Antihypertensives and ARVs44 Drug-drug interactions between Viral Hepatitis Drugs and ARVs45 Administration of ARVs in PLWH with Swallowing Difficulties46 Dose Adjustment of ARVs for Impaired Hepatic Function49 Dose Adjustment of ARVs for Impaired Renal Function50 Selected Non-ARV Drugs Requiring Dosage Adjustment in Renal Insufficiency52 Prescribing in Older PLWH54 Selected Top 10 Drug Classes to Avoid in Older PLWH55 Dosage Recommendations for Hormone Therapy when Used at High Doses for Gender Transitioning56 Part IVPrevention and Management of Co-morbidities in PLWH57 Opioid Addiction58 Cancer: Screening Methods59 Cancer: Treatment Monitoring60 Lifestyle Interventions61 Prevention of Cardiovascular Disease (CVD)62 Hypertension.

3 Diagnosis, Grading and Management63 Hypertension: Drug Sequencing Management64 Drug-drug Interactions between Antihypertensives and ARVs65 Type 2 Diabetes: Diagnosis67 Type 2 Diabetes: Management68 Dyslipidaemia 69 Treatment Goal for LDL-c for Very High and High CVD Risk Persons70 Bone Disease: Screening and Diagnosis71 Vitamin D Deficiency: Diagnosis and Management72 Approach to Fracture Reduction in PLWH73 Kidney Disease: Definition, Diagnosis and Management74 ARV-associated Nephrotoxicity75 Indications and Tests for Proximal Renal Tubulopathy (PRT)76 Dose Adjustment of ARVs for Impaired Renal Function77 Work-up and Management of PLWH with Increased ALT/AST79 Liver Cirrhosis: Classification and Surveillance80 Liver Cirrhosis: Management81 Non-Alcoholic Fatty Liver Disease (NAFLD)82 Diagnosis and Management of Hepatorenal Syndrome / Acute Kidney Injury (HRS-AKI)83 Dose Adjustment of ARVs for Impaired Hepatic Function84 Lipodystrophy and Obesity: Prevention and Management85 Hyperlactataemia and Lactic Acidosis: Diagnosis, Prevention and Management87 Travel88 Drug-drug Interactions between Anti-malarial Drugs and ARVs89 Vaccination90 Sexual and Reproductive Health of PLWH91 Sexual Dysfunction 94 Treatment of Sexual Dysfunction in PLWH95 Mental Health in PLWH: Depression and Anxiety Disorders96 Depression: Screening and Diagnosis96 Depression: Management 97 Classification, Doses, Safety and Adverse Effects of Antidepressants98 Drug-drug Interactions between Antidepressants and ARVs99 Anxiety Disorders: Screening and Diagnosis100 Anxiety Disorders.

4 Management101 Classification, Doses and Adverse Effects of Anxiolytics102 Drug-drug Interactions between Anxiolytics and ARVs103 Algorithm for Diagnosis & Management of Cognitive Impairment in PLWH without Obvious Confounding Conditions 104 Chronic Lung Disease in PLWH105 Drug-drug Interactions between Bronchodilators (for COPD) and ARVs106 Drug-drug Interactions between Pulmonary Antihypertensives and ARVs107 Managing Older PLWH108 Solid Organ Transplantation (SOT) in PLWH113 Drug-drug Interactions between Immunosuppressants (for SOT) and ARVs114 Part VClinical Management and Treatment of Viral Hepatitis Co-infections in PLWH115 General Recommendations for Persons with Viral Hepatitis/HIV Co-infection115 Treatment and Monitoring of Persons with HBV/HIV Co-infection116 Treatment and Monitoring of Persons with HCV/HIV Co-infection117 HCV Treatment Options in HCV/HIV Co-infected Persons118 Drug-drug Interactions between Viral Hepatitis Drugs and ARVs119 Management of Recently Acquired HCV Infection in PLWH120 EACS EuropeanAIDS Clinical Society2 EACS GUIDELINES Values of Non-invasive Tests for the Detection of Advanced Fibrosis and Cirrhosis121 Hepatitis D and E in PLWH122 Part VIOpportunistic Infections and COVID-19123 When to start ART in PLWH with Opportunistic Infections (OIs)123 Immune Reconstitution Inflammatory Syndrome (IRIS)

5 124 Primary prophylaxis of OIs According to Stage of Immunodeficiency125 Primary prophylaxis , Treatment and Secondary prophylaxis /Maintenance Treatment of Individual OIs126 Diagnosis and Treatment of TB in PLWH135TB Drug Doses138 Management of COVID-19 in PLWH139 Part VIIP aediatric HIV Treatment140 Initiation of ART in Children and Adolescents Living with HIV140 Initial Combination Regimen for ART-na ve Children and AdolescentsLiving with HIV140 Additional Specific Paediatric Considerations140 Adherence, Virological Failure and Second Line ART143 Virological Failure on Second Line Combination143 ReferencesVideo links144 References to All Sections145 EACS EuropeanAIDS Clinical Society3 EACS GUIDELINES to the EACS GUIDELINES 2021 Welcome to the EACS GUIDELINES !These GUIDELINES were developed by the European AIDS Clinical Society (EACS), a not-for-profit organisation, whose mission is to promote excel-lence in standards of care, research and education in HIV infection and re-lated co-infections, and to actively engage in the formulation of public health policy, with the aim of reducing the HIV disease burden across EACS GUIDELINES were first published in 2005, and are currently avail- able, online as a pdf and web-based version, and as a free App for iOS and Android devices.

6 The GUIDELINES are as of 2021 no longer produced as a printed booklet, but continue to be translated into several different languages. The GUIDELINES undergo formal minor revisions annually and major revisions every second year. Interim updates may however also be provide at any time the panels consider it aim of the EACS GUIDELINES is to provide easily accessible and compre- hensive recommendations to clinicians involved in all aspects of care of people living with HIV (PLWH).The EACS GUIDELINES cover a relatively large and diverse area geograph-ically, with different national levels of access to care. As a natural conse-quence, the GUIDELINES aim to cover a relatively wide range of recommenda-tions as opposed to the often more uniform national 2021 version of the GUIDELINES includes updates of all existing sections but have also included an entirely new section on COVID-19 in PLWH and recommendations on paediatric ART developed in collaboration with Penta.

7 The most essential changes are listed in the Summary of changes from to Each respective section of the GUIDELINES is managed by a panel of expe-rienced European HIV experts, with additional experts in other fields of ex-pertise included where necessary. All recommendations are evidence-based whenever possible and based on expert opinions in the rare instances where adequate evidence is unavailable. The GUIDELINES do not provide formal grades of evidence, panels make decisions by consensus or by vote when necessary and we do not publish results of the votes or discrepancies if any EACS GUIDELINES panels are overseen by a GUIDELINES Chair who serves a three-year term and is elected from the Governing Board. Each panel is led by a Panel Chair, supported by a Vice-Chair and a Young Scientist. The Co-Chair will take over the role of Chair after the Chair s term expires.

8 Panel membership is reviewed annually and rotation is overseen by the Panel Leads and GUIDELINES Chair according to a standard operating procedure. Operational matters of the EACS GUIDELINES are led by a Coordi-nator in the Medical Secretariat, supported by the EACS Secretariat. Only the latest and key references used to produce the GUIDELINES are pro-vided in a separate section, see References. New in 2021 is the inclusion of a short summary of the key findings of highligted references. Please reference the EACS GUIDELINES as follows: EACS GUIDELINES version , October 2021. Video links to the EACS online course on Management of HIV and Co-infections are provided throughout the GUIDELINES , see Video diagnosis and management of HIV infection and related co-infections, opportunistic diseases and co-morbidities across all ages continue to require a multidisciplinary effort for which we hope the 2021 version of the EACS GUIDELINES will provide you with an easily accessible comments to the GUIDELINES are welcome and can be directed to wish to warmly thank all panellists, external experts, linguists, transla-tors, the EACS Secretariat, the Sanford team and everyone else who helped to build up and to publish the EACS GUIDELINES for their dedicated !

9 Georg Behrens and Lene RyomOctober 2021 EACS EuropeanAIDS Clinical Society4 EACS GUIDELINES COVID-19 situation is rapidly changing, and evidence is constantly accu-mulating. Therefore, we refer to the regularly updated BHIVA, DAIG, EACS, GESIDA & Polish Scientific AIDS Society Statement on risk of COVID-19 for PLWH section What to start with, pages 13-14 New organization of treatment categories which are now divided into recommended regimens and alternative regimens DOR has been included as a recommended drug in a triple drug tenofovir-based regimen EVG and ATV-based regimens, DRV/b + RAL and ABC combinations with either EFV, DRV/b or RAL have been removed New guidance for PrEP failure is included Switch strategies for virologically suppressed persons, page 16 Long-acting CAB + RPV has been included as dual therapy option 3TC + ATV/b has been removed from recommended dual therapies Virological failure.

10 Page 17 Section has been updated including new wording for treatment recommendations in the presence of resistance mutations Treatment of pregnant women living with HIV or women considering pregnancy, page 18 Section has been re-organized ART choice should be discussed with women wishing to conceive or pregnant. DTG to be discussed with women considering to become pregnant or if to be used in first 6 weeks of pregnancy TAF has been included among recommended/alternative regimens as a drug option after 14 weeks of pregnancy ATV, ZDV and LPV/r are removed from alternative regimens ART and TB co-infection, page 20 ART should be started as soon as possible (within two weeks of initiating TB treatment) regardless of CD4 count, with the exception of TB meningitis Pre- exposure prophylaxis page 23 Whole section has been updated including on demand PrEP for men, and indication to continue PrEP during pregnancy and breast-feeding if the risk of acquiring HIV persists DDI section CAB oral, CAB/RPV LA and FTR have been added to all DDI tables.