Patient evaluation and antiretroviral treatment for adults ...

1 IClinical Protocol for the WHO European Region(2012 revision)1 Patient evaluation and antiretroviral treatment for adults and adolescentsiiKEYWORDSANTIRETROVIRAL THERAPY, HIGHLY ACTIVEHIV INFECTIONS PREVENTION AND CONTROL DRUG THERAPYADOLESCENTPATIENT COMPLIANCEPROGRAM EVALUATIONGUIDELINESEUROPEA ddress requests about publications of the WHO Regional Office for Europe to: Publications WHO Regional Office for Europe Scherfigsvej 8 DK-2100 Copenhagen , DenmarkAlternatively, complete an online request form for documentation, health information, or for permission to quote or translate, on the Regional Office web site ( ). World Health Organization 2012 All rights reserved. The Regional Office for Europe of the World Health Organization welcomes requests for permission to reproduce or translate its publications, in part or in designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries.

2 Dotted lines on maps represent approximate border lines for which there may not yet be full mention of specific companies or of certain manufacturers products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader.

3 In no event shall the World Health Organization be liable for damages arising from its use. The views expressed by authors, editors, or expert groups do not necessarily represent the decisions or the stated policy of the World Health and acronyms .. vDefinitions for strength and quality of recommendations .. viiAcknowledgement .. viiiI. Introduction .. 1II. Medical management of PLHIV .. 21. Initial Patient evaluation .. Personal, family and medical history .. Physical examination .. Laboratory and other examinations ..52. Counselling on issues related to living with HIV ..63. Prevention of opportunistic and other infections .. 84. antiretroviral treatment .. Initiation of ART .. Clinical and immunological considerations .. HIV-RNA load (VL) considerations.

4 Drug resistance testing considerations .. Age considerations .. HIV transmission considerations .. Considerations for initiation of ART in PLHIV with an OI .. First-line ART regimen .. NRTI combination considerations .. Third-drug considerations .. Choice of first-line ART regimens in special situations .. ART adherence .. Barriers to high adherence and counteracting strategies .. ART success and failure .. Virological response and failure .. Immunological response .. Clinical response .. Dissociation between virological and immunological response criteria .. Second-line ART regimen .. NRTI component considerations .. PI component considerations .. Salvage regimens .. Structured treatment interruption ..225.

5 Clinical monitoring of PLHIV .. Monitoring of laboratory indicators before ART .. Monitoring of laboratory indicators of ART Immune reconstitution inflammatory syndrome (IRIS) .. Monitoring adherence .. Management of ARV adverse drug reactions .. Drug-drug interactions ..29 III. Suggested minimum data to be collected at the clinical level .. 30ivAnnex 1. Essential information on personal history of HIV/AIDS treatment and care .. 31 annex 2. Revised WHO clinical staging of HIV/AIDS for adults and adolescents .. 32 annex 3. Resistance 34 annex 4. HIV-1 protease and reverse transcriptase mutations for drug resistance surveillance .. 35 annex 5. Essential information about ARVs .. 36 annex 6. Drug 40 annex 7. Tools for adherence monitoring.

6 57 annex 8. List of antiretroviral drugs .. 58 annex 9. Glossary .. 62 annex 10. Beyond the 63 References .. 64 Patient evaluation and antiREtROvi Ral treatment fOR adults and adOlEsCEntsvAbbreviations and acronyms3TC lamivudineABC abacavirALT alanine aminotransferaseARDS acquired respiratory distress syndromeART antiretroviral treatmentARV antiretroviralAST aspartate aminotransferaseATV atazanavirBID twice dailyBUN blood urea nitrogenCK creatine kinaseCMV cytomegalovirusCNS central nervous systemCRP C-reactive proteinCVD cardiovascular diseased4T stavudineddI didanosineDOT directly observed treatmentDRV darunavirEAP expanded access programmeEFV efavirenzeGFR estimated glomerular filtration rate (=creatinine clearance)ELISA enzyme-linked immunosorbent assayENF enfurvitideETR etravirineFDC fixed-dose combinationFPV fosamprenavirFTC emtricitabineGI gastrointestinalHBsAg hepatitis B surface antigenHBV hepatitis B virusHCV hepatitis C virusHDL-c high-density lipoprotein cholesterolHPV human papillomavirusHSR hypersensitivity reactionHSV herpes simplex virusIC50 50% inhibitory concentrationIDU injecting drug userIDV indinavirIgG immunoglobulin GIHR ischaemic heart diseaseINR international normalized ratioIRIS immune reconstitution inflammatory syndromeLDH lactate dehydrogenaseLDL-c low-density lipoprotein cholesterolLFT liver function testLPV lopinavirNTM non-tuberculosis Mycobacterium infectionMTCT mother-to-child transmissionMRV maravirocNFV

7 NelfinavirviNNRTI non-nucleoside reverse transcriptase inhibitorNRTI nucleoside/nucleotide reverse transcriptase inhibitorNVP nevirapineOI opportunistic infectionOST opioid substitution therapyPCP Pneumocystis jirovecii pneumonia (formerly P. carinii pneumonia)PCR polymerase chain reactionPEP post-exposure chemoprophylaxis (medicine given after exposure)PGL persistent generalized lymphadenopathyPI protease inhibitorPI/r PI with low dose ritonavir to increase plasma concentration (booster)PLHIV people living with HIV (=HIV positive people)PML progressive multifocal leukoencephalopathyPREP pre-exposure chemoprophylaxis (medicine given before exposure)QD once daily/r ritonavir given as pharmacological boosterRAL raltegravir SQV saquinavirSTI sexually transmitted infection TAM thymidine analogue mutationTC total cholesterolTDF tenofovirTDM therapeutic drug monitoringTG triglycerideTID three times dailyTPV tipranavirTSH thyroid-stimulating hormoneVDRL venereal disease research laboratoryVL viral load (number of viral copies in plasma)ZDV zidovudine (also known as azidothymidine (AZT))

8 Patient evaluation and antiREtROvi Ral treatment fOR adults and adOlEsCEntsviiDefinitions for strength and quality of recommendationsConcepts relating to strength of recommendations for use of a given interventionStrongstrong recommendation for the statementModeratemoderate recommendation for the statementOptionaloptional recommendation for the statementNo recommendationno evidence to inform use of interventionConcepts relating to quality of evidence guiding recommendations for use of interventionsAdata from reasonable powered randomized controlled trials using relevant endpointsBdata only from well-designed prospective observational studies assessing clinical endpoints onlyCdata from case stories and/or expert opinion onlyWhen recommendations on choices between regimens are expressed, the following concepts are usedPreferredregimens shown to have optimal and durable virological efficacy, and favourable tolerabilityAlternativeregimens that are virologically effective but have potential disadvantages when compared to preferred regimensAcceptableregimens that are less well studied or are associated with impaired tolerability or efficacy compared to the preferred or alternative regimensviiiAcknowledgementThis document in an update of the version of this clinical protocol released in 2007.

9 It is one of 13 clinical protocols released by the WHO Regional Office for Europe in 2006 as a part of the HIV/AIDS treatment and Care Clinical Protocols of the WHO European Region. This update was edited by Jens Lundgren, Jesper Grarup and Irina updated version of the protocol is built on new evidence in the area of HIV/AIDS treatment and the global WHO 2010 recommendations for a public health approach antiretroviral therapy for HIV Infection in adults and Adolescents . The process included consultation with Regional clinical experts through a 2010 meeting in Kyiv (Ukraine) and electronic communication with them to ensure that the updated version of the protocol corresponds to the countries needs and reflects diverse capacity to implement it.

10 The protocol is in line with the WHO/UNAIDS treatment policy document ( ).This update was performed by the University of Copenhagen in collaboration with the WHO Regional Office for Europe, and a panel of experts that provided valuable comments on draft versions. The panel consisted of: Esmira Almamedova (Republican HIV/AIDS Centre, Baku, Azerbaijan), Svetlana Antonyak (Academy of Medical Sciences, Kyiv, Ukraine), David Back (University of Liverpool, United Kingdom of Great Britain and Northern Ireland), Anna Bobrova (WHO, Kyiv, Ukraine), Mette Brandt-Madsen (Copenhagen HIV Programme, University of Copenhagen, Denmark), David Burger (Radboud University Nijmegen, The Netherlands), Bonaventura Clotet (University Hospital Germans Trias i Pujol, Barcelona, Spain), Marsudzhon Dodarbekov (National AIDS Centre, Dushanbe, Tajikistan), Saule Doskozhaeva (State Institute of Advanced Medical Education, Almaty, Kazakhstan), Gert F tkenheuer (University of Cologne, Germany)