# paper.pdf ## Metadata - PDFFormatVersion=1.7 - Language=EN-US - IsLinearized=true - IsAcroFormPresent=false - IsXFAPresent=false - IsCollectionPresent=false - IsSignaturesPresent=false - Author=DAIDS RSC - Custom.NCCL_App=PDF - Custom.NCCL_Standard=Section 508;PDF/UA;HHS;WCAG 2.0 AA; - Custom.NCCL_Status=Passed - Custom.SourceModified=D:20170703161851 - CreationDate=D:20170703121911-04'00' - Creator=Acrobat PDFMaker 15 for Word - Keywords=Grading Table - ModDate=D:20250221160712-05'00' - Producer=Adobe PDF Library 15.0 - Subject=DAIDS Grading table for severity of adult and pediatric adverse events - Title=Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events - xmp:modifydate=2025-02-21T16:07:12-05:00 - xmp:createdate=2017-07-03T12:19:11-04:00 - xmp:metadatadate=2025-02-21T16:07:12-05:00 - xmp:creatortool=Acrobat PDFMaker 15 for Word - xmpmm:documentid=uuid:e70b8af5-40f7-4f39-a5b0-50bd28fe39a9 - xmpmm:instanceid=uuid:e7f5c46d-915f-465b-b782-c5a932dc1414 - xmpmm:subject=8 - dc:format=application/pdf - dc:title=Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events - dc:description=DAIDS Grading table for severity of adult and pediatric adverse events - dc:creator=DAIDS RSC - dc:subject=Adverse Events,DAIDS Safety Information,Corrected Version - pdf:producer=Adobe PDF Library 15.0 - pdf:keywords=Grading Table - pdfx:sourcemodified=D:20170703161851 - pdfx:nccl_standard=Section 508;PDF/UA;HHS;WCAG 2.0 AA; - pdfx:nccl_app=PDF - pdfx:nccl_status=Passed - pdfuaid:part=1 ## Contents ### Page 1 # Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events Corrected Version 2.1 July 2017 Division of AIDS National Institute of Allergy and Infectious Diseases National Institutes of Health US Department of Health and Human Services ### Page 2 ### Page 3 ## Table of Contents ### Page 4 ## Glossary and Acronyms AE Adverse event; Any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medical treatment or procedure regardless of whether it is considered related to the medical treatment or procedure. ALT (SGPT) Alanine aminotransferase (serum glutamic pyruvic transaminase) ANC Absolute neutrophil count AST (SGOT) Aspartate aminotransferase (serum glutamic-oxaloacetic transaminase) AV Atrioventricular Basic Self-care Functions Adult Activities such as bathing, dressing, toileting, transfer or movement, continence, and feeding. Young Children Activities that are age and culturally appropriate, such as feeding one’s self with culturally appropriate eating implements. BMI z-score Body mass index z- score; A body reference norm. Specifically, thenumber of standard deviations a participant's BMI differs from theaverage BMI for their age, sex, and ethnicity. BMD t-score Bone mineral density t-score; The number of standard deviations aboveor below the mean bone mineral density of a healthy 30 year old adultof the same sex and ethnicity as the participant. BMD z-score Bone mineral density z-score; The number of standard deviations aparticipant's BMD differs from the average BMD for their age, sex, andethnicity. BPAP Bilevel positive airway pressure; A mode used during noninvasive positive pressure ventilation. Chemical Pregnancy A pregnancy in which a positive pregnancy test is followed by anegative pregnancy test without evidence of a clinical pregnancy loss. CNS Central nervous system CPAP Continuous positive airway pressure DAERS DAIDS Adverse Experience Reporting System; An internet-basedsystem developed for clinical research sites to report ExpeditedAdverse Events (EAEs) to DAIDS. It facilitates timely EAE reportsubmission and serves as a centralized location for accessing andprocessing EAE information for reporting purposes. Disability A substantial disruption of a person’s ability to conduct normal lifefunctions. ECG Electrocardiogram eGFR Estimated glomerular filtration rate Hospitalization Does not include the following hospital admissions: under 24 hours, unrelated to an adverse event (e.g., for labor and delivery, cosmetic surgery, social or administrative for temporary placement [for lack of a place to sleep]), protocol-specified, and for diagnosis or therapy of a condition that existed before the receipt of a study agent and which has not increased in severity or frequency. INR International normalized ratio ### Page 5 Intervention Medical, surgical, or other procedures recommended or provided by a healthcare professional for the treatment of an adverse event. IV Intravenous IVIG Intravenous immune globulin LDL Low density lipoprotein LLN Lower limit of normal Life-threatening AE Any adverse event that places the participant, in the view of theinvestigator, at immediate risk of death from the reaction when itoccurred (i.e., it does not include a reaction that would have causeddeath if it had occurred in a more severe form). NA Not applicable Participant ID The identification number assigned to a study participant which is usedto track study-related documentation, including any reported AEs. PR Interval The interval between the beginning of the P wave and the beginning ofthe QRS complex of an electrocardiogram that represents the timebetween the beginning of the contraction of the atria and the beginningof the contraction of the ventricles. PT Prothrombin time PTT Partial thromboplastin time QTc Interval The measure of time between the onset of ventricular depolarizationand completion of ventricular repolarization corrected for ventricularrate. RBC Red blood cell SI Standard international unit ULN Upper limit of normal Usual Social & Functional Activities Activities which adults and children perform on a routine basis andthose which are part of regular activities of daily living, for example:AdultsAdaptive tasks and desirable activities, such as going to work,shopping, cooking, use of transportation, or pursuing a hobby.Young ChildrenActivities that are age and culturally appropriate, such as socialinteractions, play activities, or learning tasks. WBC White blood cell WHO World Health Organization WNL Within normal limits ### Page 6 ## Introduction The Division of AIDS (DAIDS) oversees more than 300 clinical trials domestically and internationally, which evaluate the safety and efficacy of therapeutic products, vaccines, and other preventive modalities. Adverse event (AE) data collected during these clinical trials form the basis for subsequent safety and efficacy analyses of pharmaceutical products and medical devices. Incorrect and inconsistent AE severity grading can lead to inaccurate data analyses and interpretation, which in turn can impact the safety and well-being of clinical trial participants and future patients using pharmaceutical products. Over the years, DAIDS scientific knowledge and experience have expanded, necessitating revisions of the DAIDS grading table which serves as a guide for assessing the severity of AEs (including clinical and laboratory abnormalities) in participants enrolled in DAIDS-sponsored and -supported clinical trials. The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 (July 2017) updates and replaces version 2.1 (March 2017). DAIDS is grateful to the DAIDS Grading Table Working Group, numerous government and non-government affiliated medical subject matter experts and reviewers who were instrumental in the revision of the DAIDS grading table. ### Page 7 ## Instructions for Use ### General Considerations The Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 consists of parameters, or AEs, with severity grading guidance that are to be used in DAIDS clinical trials for safety data reporting to maintain accuracy and consistency in the evaluation of AEs. The term “severe” is not the same as the term “serious” in classifying AEs. The severity of a specific event describes its intensity, and it is the intensity which is graded. Seriousness, which is not graded, relates to an outcome of an AE and is a regulatory definition. Clinical sites are encouraged to report parameters in the DAIDS grading table as they are written to maintain data consistency across clinical trials. However, since some parameters can be reported with more specificity, clinical sites are encouraged to report parameters that convey additional clinical information. For example, diarrhea could be reported as neonatal diarrhea; seizures, as febrile seizures; and pain, as jaw pain. The DAIDS grading table provides an AE severity grading scale ranging from grades 1 to 5 with descriptions for each AE based on the following general guidelines: - • Grade 1 indicates a mild event - • Grade 2 indicates a moderate event - • Grade 3 indicates a severe event - • Grade 4 indicates a potentially life-threatening event - • Grade 5 indicates death (Note: This grade is not specifically listed on each page of the grading table). Other points to consider include: - • Use age and sex values as applicable. - • Unless noted, laboratory values are for term neonates. Preterm neonates should be assessed using local laboratory normal ranges. - • Where applicable, Standard International (SI) units are included in italics. ### Selecting and Reporting a Primary AE Term When selecting a primary AE term to report, sites should select the term that best describes what occurred to the participant. For example, a participant may present with itching, urticaria, flushing, angioedema of the face, and dyspnea. If the underlying diagnosis is determined to be an acute allergic reaction, sites should report “Acute Allergic Reaction” as the primary AE term. Primary AE terms should be reported using the DAIDS Adverse Experience Reporting System (DAERS) only if they meet expedited reporting criteria. However, all primary AE terms should be reported using protocol-specific case report forms (CRFs). Because the reported information is stored in different databases (i.e., safety and clinical), sites should report primary AE terms using the same terminology for data consistency. ### Page 8 When reporting using DAERS, other clinically significant events associated with a primary AE term that more fully describe the nature, severity, or complications of the primary AE term should be entered in the “Other Events” section. However, the severity grade for these events must be lower than or equal to the severity grade of the primary AE term.In the example above, dyspnea and angioedema of the face may be entered in the “Other Events” section, because they are more descriptive and provide additional information on the severity of the acute allergic reaction. However, their severity grades must be lower than or equal to the severity grade of the primary AE term of “Acute Allergic Reaction”. Differences exist in the reporting and recording of information (e.g., signs and symptoms, clinically significant events) in DAERS and CRFs. Therefore, sites should refer to their protocols and CRF requirements for further instructions. ### Grading Adult and Pediatric AEs When a single parameter is not appropriate for grading an AE in both adult and pediatric populations, separate parameters with specified age ranges are provided. If no distinction between adult and pediatric populations has been made, the listed parameter should be used for grading an AE in both populations. ### Reporting Pregnancy Outcomes In the Pregnancy, Puerperium, and Perinatal section, all parameters are pregnancy outcomes and should be reported using the mother's participant ID. If an infant is not enrolled in the s ame study as the mother, any identified birth defects should be reported using the mother's participant ID. However, if an infant is enrolled in the same study as the mother or in another study, any identified birth defects should be reported using the infant's participant ID. Sites should refer to the applicable network standards for reporting abnormal pregnancy outcomes on the CRFs. ### Determining Severity Grade for Parameters between Grades If the severity of an AE could fall in either one of two grades (i.e., the severity of an AE could be either grade 2 or grade 3), sites should select the higher of the two grades. ### Laboratory Values General. An asymptomatic, abnormal laboratory finding without an accompanying AE should not be reported to DAIDS in an expedited timeframe unless it meets protocol-specific reporting requirements. Sites should refer to the applicable network standards for reporting abnormal laboratory findings on the clinical case report forms. Values below Grade 1. Any laboratory value that is between the ULN and grade 1 (for high values) or the LLN and grade 1 (for low values) should not be graded or reported as an AE. Sites should consult the Manual for Expedited Reporting of Adverse Events to DAIDS, Version 2.0 and their protocol when making an assessment of the need to report an AE. Overlap of Local Laboratory Normal Values with Grading Table Ranges . When local laboratory normal values fall within grading table laboratory ranges, the severity grading is based on the ranges in the grading table unless there is a protocol-specific grading criterion for the laboratory ### Page 9 value. For example, “Magnesium, Low" has a grade 1 range of 1.2 to < 1.4 mEq/L, while a particular laboratory’s normal range for magnesium may be 1.3 to 2.8 mEq/L. If a study participant’s magnesium laboratory value is 1.3 mEq/L, the laboratory value should be graded as grade 1. ### Appendix Usage Appendix A takes priority over the main grading table in all assessments of total bilirubin for term and preterm neonates. ### Using Addenda 1-3: Grading Tables Used in Microbicide Studies In protocols involving topical application of products to the female and male genital tracts or rectum, strong consideration should be given to using Addenda 1-3 (see below) as the primary grading tables for these areas. Although these grading tables are used specifically in microbicide studies, they may be used in other protocols as adjuncts to the main grading table (i.e., theDivision of AIDS (AIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0). It should be clearly stated in a protocol which addendum is being used as the primary grading table (and thus takes precedence over the main grading table) and which addendum is being used in a complementary fashion. - • Addendum 1 – Female Genital Grading Table for Use in Microbicide Studies-http://rsc.tech-res.com/clinical-research-sites/safety-reporting/daids-grading-tables - • Addendum 2 – Male Genital Grading Table for Use in Microbicide Studies –http://rsc.tech-res.com/clinical-research-sites/safety-reporting/daids-grading-tables - • Addendum 3 – Rectal Grading Table for Use in Microbicide Studies–http://rsc.tech-res.com/clinical-research-sites/safety-reporting/daids-grading-tables ### Estimating Severity Grade for Parameters Not Identified in the Grading Table The functional table below should be used to grade the severity of an AE that is not specifically identified in the grading table. In addition, all deaths related to an AE are to be classified as grade 5. | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Clinical adverse event NOTidentified elsewhere in the grading table | Mild symptoms causing no or minimal interference with usual social & functional activities with intervention not indicated | Moderate symptoms causing greater than minimal interference with usual social & functional activities with intervention indicated | Severe symptoms causing inability to perform usual social & functional activities with intervention or hospitalization indicated | Potentially life-threatening symptoms causing inability to perform basic self-care functions with intervention indicated to prevent permanent impairment, persistent disability, or death | ### Page 10 ## Major Clinical Conditions ### Cardiovascular | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Arrhythmia(by ECG or physical examination)Specify type, if applicable | No symptoms ANDNo intervention indicated | No symptoms ANDNon-urgent intervention indicated | Non-life-threatening symptoms AND Non-urgent intervention indicated | Life-threatening arrhythmia OR Urgentintervention indicated | | Blood Pressure Abnormalities1 Blood pressure norms for children < 18 years of age can be found in: Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents. Pediatrics 2011;128;S213; originally published online November 14, 2011; DOI: 10.1542/peds.2009-2107C.Hypertension (with the lowest reading taken after repeat testing during a visit)≥ 18 years of age | 140 to < 160 mmHg systolic OR90 to < 100 mmHg diastolic | ≥ 160 to < 180 mmHg systolic OR≥ 100 to < 110 mmHg diastolic | ≥ 180 mmHg systolic OR≥ 110 mmHg diastolic | Life-threatening consequences in a participant not previously diagnosed with hypertension (e.g., malignant hypertension) OR Hospitalizationindicated | | < 18 years of age | > 120/80 mmHg | ≥ 95th to < 99th percentile + 5 mmHg adjusted for age, height, and gender (systolic and/or diastolic) | ≥ 99th percentile + 5 mmHg adjusted for age, height, and gender (systolic and/or diastolic) | Life-threatening consequences in a participant not previously diagnosed with hypertension (e.g., malignant hypertension) OR Hospitalizationindicated | | Hypotension | No symptoms | Symptoms corrected with oral fluid replacement | Symptoms AND IVfluids indicated | Shock requiring use of vasopressors or mechanical assistance to maintain blood pressure | | Cardiac Ischemia or InfarctionReport only one | NA | NA | New symptoms with ischemia (stable angina) OR Newtesting consistent with ischemia | Unstable angina ORAcute myocardial infarction | | Heart Failure | No symptoms ANDLaboratory or cardiac imaging abnormalities | Symptoms with mild to moderate activity or exertion | Symptoms at rest or with minimal activity or exertion (e.g., hypoxemia) ORIntervention indicated (e.g., oxygen) | Life-threatening consequences ORUrgent intervention indicated (e.g., vasoactive medications, ventricular assist device, heart transplant) | ### Page 11 | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Hemorrhage(with significant acute blood loss) | NA | Symptoms AND Notransfusion indicated | Symptoms ANDTransfusion of ≤ 2 units packed RBCs indicated | Life-threatening hypotension ORTransfusion of > 2 units packed RBCs (for children, packed RBCs > 10 cc/kg) indicated | | Prolonged PR Interval or AV BlockReport only one> 16 years of age | PR interval 0.21 to < 0.25 seconds | PR interval ≥ 0.25 seconds OR Type I2nd degree AV block | Type II 2 nd degree AV block ORVentricular pause ≥ 3.0 seconds | Complete AV block | | ≤ 16 years of age | 1st degree AV block (PR interval > normal for age and rate) | Type I 2 nd degree AV block | Type II 2 nd degree AV block ORVentricular pause ≥ 3.0 seconds | Complete AV block | | Prolonged QTc Interval2 As per Bazett’s formula. | 0.45 to 0.47 seconds | > 0.47 to 0.50 seconds | > 0.50 seconds OR≥ 0.06 seconds above baseline | Life-threatening consequences (e.g., Torsade de pointes, other associated serious ventricular dysrhythmia) | | Thrombosis or EmbolismReport only one | NA | Symptoms AND Nointervention indicated | Symptoms ANDIntervention indicated | Life-threatening embolic event (e.g., pulmonary embolism, thrombus) | ### Page 12 ### Dermatologic | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Alopecia (scalp only) | Detectable by study participant, caregiver, or physician ANDCausing no or minimal interference with usual social & functional activities | Obvious on visual inspection ANDCausing greater than minimal interference with usual social & functional activities | NA | NA | | Bruising | Localized to one area | Localized to more than one area | Generalized | NA | | Cellulitis | NA | Non-parenteral treatment indicated (e.g., oral antibiotics, antifungals, antivirals) | IV treatment indicated (e.g., IV antibiotics, antifungals, antivirals) | Life-threatening consequences (e.g., sepsis, tissue necrosis) | | Hyperpigmentation | Slight or localized causing no or minimal interference with usual social & functional activities | Marked or generalized causing greater than minimal interference with usual social & functional activities | NA | NA | | Hypopigmentation | Slight or localized causing no or minimal interference with usual social & functional activities | Marked or generalized causing greater than minimal interference with usual social & functional activities | NA | NA | | Petechiae | Localized to one area | Localized to more than one area | Generalized | NA | | Pruritus3 For pruritus associated with injections or infusions, see the Site Reactions to Injections and Infusions section (page 23).(without skin lesions) | Itching causing no or minimal interference with usual social & functional activities | Itching causing greater than minimal interference with usual social & functional activities | Itching causing inability to perform usual social & functional activities | NA | | RashSpecify type, if applicable | Localized rash | Diffuse rash ORTarget lesions | Diffuse rash ANDVesicles or limited number of bullae or superficial ulcerations of mucous membrane limited to one site | Extensive or generalized bullous lesions ORUlceration of mucous membrane involving two or more distinct mucosal sites ORStevens-Johnson syndrome OR Toxicepidermal necrolysis | ### Page 13 ### Endocrine and Metabolic | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Diabetes Mellitus | Controlled without medication | Controlled with medication ORModification of current medication regimen | Uncontrolled despite treatment modification ORHospitalization for immediate glucose control indicated | Life-threatening consequences (e.g., ketoacidosis, hyperosmolar non- ketotic coma, end organ failure) | | Gynecomastia | Detectable by study participant, caregiver, or physician ANDCausing no or minimal interference with usual social & functional activities | Obvious on visual inspection ANDCausing pain with greater than minimal interference with usual social & functional activities | Disfiguring changes AND Symptomsrequiring intervention or causing inability to perform usual social & functional activities | NA | | Hyperthyroidism | No symptoms ANDAbnormal laboratory value | Symptoms causing greater than minimal interference with usual social & functional activities OR Thyroidsuppression therapy indicated | Symptoms causing inability to perform usual social & functional activities OR Uncontrolleddespite treatment modification | Life-threatening consequences (e.g., thyroid storm) | | Hypothyroidism | No symptoms ANDAbnormal laboratory value | Symptoms causing greater than minimal interference with usual social & functional activities OR Thyroidreplacement therapy indicated | Symptoms causing inability to perform usual social & functional activities OR Uncontrolleddespite treatment modification | Life-threatening consequences (e.g., myxedema coma) | | Lipoatrophy4 Definition: A disorder characterized by fat loss in the face, extremities, and buttocks. | Detectable by study participant, caregiver, or physician ANDCausing no or minimal interference with usual social & functional activities | Obvious on visual inspection ANDCausing greater than minimal interference with usual social & functional activities | Disfiguring changes | NA | ### Page 14 | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Lipohypertrophy5 Definition: A disorder characterized by abnormal fat accumulation on the back of the neck, breasts, and abdomen. | Detectable by study participant, caregiver, or physician ANDCausing no or minimal interference with usual social & functional activities | Obvious on visual inspection ANDCausing greater than minimal interference with usual social & functional activities | Disfiguring changes | NA | ### Page 15 ### Gastrointestinal | PARAMETER | GRADE 1 MILD | GRADE 2 MODERATE | GRADE 3 SEVERE | GRADE 4 POTENTIALLY LIFE- THREATENING | | - | - | - | - | - | | Anorexia | Loss of appetite without decreased oral intake | Loss of appetite associated with decreased oral intake without significant weight loss | Loss of appetite associated with significant weight loss | Life-threatening consequences ORAggressive intervention indicated (e.g., tube feeding, total parenteral nutrition) | | Ascites | No symptoms | Symptoms ANDIntervention indicated (e.g., diuretics, therapeutic paracentesis) | Symptoms recur or persist despite intervention | Life-threatening consequences | | Bloating or DistensionReport only one | Symptoms causing no or minimal interference with usual social & functional activities | Symptoms causing greater than minimal interference with usual social & functional activities | Symptoms causing inability to perform usual social & functional activities | NA | | Cholecystitis | NA | Symptoms ANDMedical intervention indicated | Radiologic, endoscopic, or operative intervention indicated | Life-threatening consequences (e.g., sepsis, perforation) | | Constipation | NA | Persistent constipation requiring regular use of dietary modifications, laxatives, or enemas | Obstipation with manual evacuation indicated | Life-threatening consequences (e.g., obstruction) | | Diarrhea≥ 1 year of age | Transient or intermittent episodes of unformed stools ORIncrease of ≤ 3 stools over baseline per 24-hour period | Persistent episodes of unformed to watery stools ORIncrease of 4 to 6 stools over baseline per 24-hour period | Increase of ≥ 7 stools per 24-hour period OR IV fluidreplacement indicated | Life-threatening consequences (e.g., hypotensive shock) | | < 1 year of age | Liquid stools (more unformed than usual) but usual number of stools | Liquid stools with increased number of stools OR Milddehydration | Liquid stools with moderate dehydration | Life-threatening consequences (e.g., liquid stools resulting in severe dehydration, hypotensive shock) | | Dysphagia or OdynophagiaReport only one and specify location | Symptoms but able to eat usual diet | Symptoms causing altered dietary intake with no intervention indicated | Symptoms causing severely altered dietary intake with intervention indicated | Life-threatening reduction in oral intake | | Gastrointestinal Bleeding | Not requiring intervention other than iron supplement | Endoscopic intervention indicated | Transfusion indicated | Life-threatening consequences (e.g., hypotensive shock) | ### Page 16 | PARAMETER | GRADE 1 MILD | GRADE 2 MODERATE | GRADE 3 SEVERE | GRADE 4 POTENTIALLY LIFE- THREATENING | | - | - | - | - | - | | Mucositis or StomatitisReport only one and specify location | Mucosal erythema | Patchy pseudomembranes or ulcerations | Confluent pseudomembranes or ulcerations ORMucosal bleeding with minor trauma | Life-threatening consequences (e.g., aspiration, choking) ORTissue necrosis ORDiffuse spontaneous mucosal bleeding | | Nausea | Transient (< 24 hours) or intermittent ANDNo or minimal interference with oral intake | Persistent nausea resulting in decreased oral intake for 24 to 48 hours | Persistent nausea resulting in minimal oral intake for > 48 hours ORRehydration indicated (e.g., IV fluids) | Life-threatening consequences (e.g., hypotensive shock) | | Pancreatitis | NA | Symptoms with hospitalization not indicated | Symptoms with hospitalization indicated | Life-threatening consequences (e.g., circulatory failure, hemorrhage, sepsis) | | Perforation(colon or rectum) | NA | NA | Intervention indicated | Life-threatening consequences | | Proctitis | Rectal discomfort with no intervention indicated | Symptoms causing greater than minimal interference with usual social & functional activities OR Medicalintervention indicated | Symptoms causing inability to perform usual social & functional activities OR Operativeintervention indicated | Life-threatening consequences (e.g., perforation) | | Rectal Discharge | Visible discharge | Discharge requiring the use of pads | NA | NA | | Vomiting | Transient or intermittent ANDNo or minimal interference with oral intake | Frequent episodes with no or mild dehydration | Persistent vomiting resulting in orthostatic hypotension ORAggressive rehydration indicated (e.g., IV fluids) | Life-threatening consequences (e.g., hypotensive shock) | ### Page 17 ### Musculoskeletal | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Arthralgia | Joint pain causing no or minimal interference with usual social & functional activities | Joint pain causing greater than minimal interference with usual social & functional activities | Joint pain causing inability to perform usual social & functional activities | Disabling joint pain causing inability to perform basic self-care functions | | Arthritis | Stiffness or joint swelling causing no or minimal interference with usual social & functional activities | Stiffness or joint swelling causing greater than minimal interference with usual social & functional activities | Stiffness or joint swelling causing inability to perform usual social & functional activities | Disabling joint stiffness or swelling causing inability to perform basic self-care functions | | Myalgia (generalized) | Muscle pain causing no or minimal interference with usual social & functional activities | Muscle pain causing greater than minimal interference with usual social & functional activities | Muscle pain causing inability to perform usual social & functional activities | Disabling muscle pain causing inability to perform basic self-care functions | | Osteonecrosis | NA | No symptoms but with radiographic findings AND Nooperative intervention indicated | Bone pain with radiographic findings OR Operativeintervention indicated | Disabling bone pain with radiographic findings causing inability to perform basic self-care functions | | Osteopenia6 BMD t and z scores can be found in: Kanis JA on behalf of the World Health Organization Scientific Group (2007). Assessment of osteoporosis at the primary health- care level. Technical Report. World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK. 2007: Printed by the University of Sheffield.≥ 30 years of age | BMD t-score -2.5 to -1 | NA | NA | NA | | < 30 years of age | BMD z-score -2 to -1 | NA | NA | NA | | Osteoporosis 6≥ 30 years of age | NA | BMD t-score < -2.5 | Pathologic fracture (e.g., compression fracture causing loss of vertebral height) | Pathologic fracture causing life-threatening consequences | | < 30 years of age | NA | BMD z-score < -2 | Pathologic fracture (e.g., compression fracture causing loss of vertebral height) | Pathologic fracture causing life-threatening consequences | ### Page 18 ### Neurologic | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Acute CNS Ischemia | NA | NA | Transient ischemic attack | Cerebral vascular accident (e.g., stroke with neurological deficit) | | Altered Mental Status(for Dementia, seeCognitive, Behavioral, or Attentional Disturbancebelow) | Changes causing no or minimal interference with usual social & functional activities | Mild lethargy or somnolence causing greater than minimal interference with usual social & functional activities | Confusion, memory impairment, lethargy, or somnolence causing inability to perform usual social & functional activities | Delirium ORObtundation ORComa | | Ataxia | Symptoms causing no or minimal interference with usual social & functional activities OR No symptomswith ataxia detected on examination | Symptoms causing greater than minimal interference with usual social & functional activities | Symptoms causing inability to perform usual social & functional activities | Disabling symptoms causing inability to perform basic self-care functions | | Cognitive, Behavioral, or Attentional Disturbance (includes dementia and attention deficit disorder)Specify type, if applicable | Disability causing no or minimal interference with usual social & functional activities OR Specializedresources not indicated | Disability causing greater than minimal interference with usual social & functional activities OR Specializedresources on part - time basis indicated | Disability causing inability to perform usual social & functional activities OR Specializedresources on a full- time basis indicated | Disability causing inability to perform basic self-care functions OR Institutionalizationindicated | | Developmental Delay< 18 years of ageSpecify type, if applicable | Mild developmental delay, either motor or cognitive, as determined by comparison with a developmental screening tool appropriate for the setting | Moderate developmental delay, either motor or cognitive, as determined by comparison with a developmental screening tool appropriate for the setting | Severe developmental delay, either motor or cognitive, as determined by comparison with a developmental screening tool appropriate for the setting | Developmental regression, either motor or cognitive, as determined by comparison with a developmental screening tool appropriate for the setting | | Headache | Symptoms causing no or minimal interference with usual social & functional activities | Symptoms causing greater than minimal interference with usual social & functional activities | Symptoms causing inability to perform usual social & functional activities | Symptoms causing inability to perform basic self-care functions OR Hospitalizationindicated OR Headachewith significant impairment of alertness or other neurologic function | ### Page 19 | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Neuromuscular Weakness (includes myopathy and neuropathy)Specify type, if applicable | Minimal muscle weakness causing no or minimal interference with usual social & functional activities OR No symptomswith decreased strength on examination | Muscle weakness causing greater than minimal interference with usual social & functional activities | Muscle weakness causing inability to perform usual social & functional activities | Disabling muscle weakness causing inability to perform basic self-care functions OR Respiratory muscleweakness impairing ventilation | | Neurosensory Alteration (includes paresthesia and painful neuropathy)Specify type, if applicable | Minimal paresthesia causing no or minimal interference with usual social & functional activities OR No symptomswith sensory alteration on examination | Sensory alteration or paresthesia causing greater than minimal interference with usual social & functional activities | Sensory alteration or paresthesia causing inability to perform usual social & functional activities | Disabling sensory alteration or paresthesia causing inability to perform basic self-care functions | | SeizuresNew Onset Seizure≥ 18 years of age | NA | NA | 1 to3 seizures | Prolonged and repetitive seizures (e.g., status epilepticus) ORDifficult to control (e.g., refractory epilepsy) | | < 18 years of age(includes new or pre- existing febrile seizures) | Seizure lasting < 5 minutes with < 24 hours postictal state | Seizure lasting 5 to < 20 minutes with < 24 hours postictal state | Seizure lasting ≥ 20 minutes OR > 24hours postictal state | Prolonged and repetitive seizures (e.g., status epilepticus) ORDifficult to control (e.g., refractory epilepsy) | | Pre-existing Seizure | NA | Increased frequency from previous level of control without change in seizure character | Change in seizure character either in duration or quality (e.g., severity or focality) | Prolonged and repetitive seizures (e.g., status epilepticus) ORDifficult to control (e.g., refractory epilepsy) | | Syncope | Near syncope without loss of consciousness (e.g., pre-syncope) | Loss of consciousness with no intervention indicated | Loss of consciousness ANDHospitalization or intervention required | NA | ### Page 20 ### Pregnancy, Puerperium, and Perinatal | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Stillbirth (report using mother’s participant ID)Report only one | NA | NA | Fetal death occurring at ≥ 20 weeks gestation | NA | | Preterm Birth (report using mother’s participant ID) | Live birth at 34 to < 37 weeks gestational age | Live birth at 28 to < 34 weeks gestational age | Live birth at 24 to < 28 weeks gestational age | Live birth at < 24 weeks gestational age | | Spontaneous Abortion or Miscarriage7 Definition: A pregnancy loss occurring at < 20 weeks gestational age. (report using mother’s participant ID)Report only one | Chemical pregnancy | Uncomplicated spontaneous abortion or miscarriage | Complicated spontaneous abortion or miscarriage | NA | ### Page 21 ### Psychiatric | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Insomnia | Mild difficulty falling asleep, staying asleep, or waking up early causing no or minimal interference with usual social & functional activities | Moderate difficulty falling asleep, staying asleep, or waking up earlycausing more than minimal interference with usual social & functional activities | Severe difficulty falling asleep, staying asleep, or waking up early causing inability to perform usual social & functional activities requiring intervention or hospitalization | NA | | Psychiatric Disorders(includes anxiety,depression, mania, andpsychosis)Specify disorder | Symptoms with intervention not indicated ORBehavior causing no or minimal interference with usual social & functional activities | Symptoms with intervention indicated ORBehavior causing greater than minimal interference with usual social & functional activities | Symptoms with hospitalization indicated ORBehavior causing inability to perform usual social & functional activities | Threatens harm to self or others OR Acutepsychosis OR Behaviorcausing inability to perform basic self-care functions | | Suicidal Ideation or AttemptReport only one | Preoccupied with thoughts of death AND No wish tokill oneself | Preoccupied with thoughts of death AND Wish to killoneself with no specific plan or intent | Thoughts of killing oneself with partial or complete plans but no attempt to do so OR Hospitalizationindicated | Suicide attempted | ### Page 22 ### Respiratory | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Acute Bronchospasm | Forced expiratory volume in 1 second or peak flow reduced to ≥ 70to < 80% ORMild symptoms with intervention not indicated | Forced expiratory volume in 1 second or peak flow 50to < 70% OR Symptomswith intervention indicated ORSymptoms causing greater than minimal interference with usual social & functional activities | Forced expiratory volume in 1 second or peak flow 25to < 50% ORSymptoms causing inability to perform usual social & functional activities | Forced expiratory volume in 1 second or peak flow < 25% ORLife-threatening respiratory or hemodynamic compromise ORIntubation | | Dyspnea or Respiratory DistressReport only one | Dyspnea on exertion with no or minimal interference with usual social & functional activities OR Wheezing ORMinimal increase in respiratory rate for age | Dyspnea on exertion causing greater than minimal interference with usual social & functional activities OR Nasal flaring ORIntercostal retractions OR Pulse oximetry90 to < 95% | Dyspnea at rest causing inability to perform usual social & functional activities OR Pulseoximetry < 90% | Respiratory failure with ventilator support indicated (e.g., CPAP, BPAP, intubation) | ### Page 23 ### Sensory | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Hearing Loss≥ 12 years of age | NA | Hearing aid or intervention not indicated | Hearing aid or intervention indicated | Profound bilateral hearing loss (> 80 dB at 2 kHz and above) ORNon-serviceable hearing (i.e., >50 dB audiogram and <50% speech discrimination) | | < 12 years of age (based on a 1, 2, 3, 4, 6 and 8 kHz audiogram) | > 20 dB hearing loss at ≤ 4 kHz | > 20 dB hearing loss at > 4 kHz | > 20 dB hearing loss at ≥ 3 kHz in one ear with additional speech language related services indicated (where available) ORHearing loss sufficient to indicate therapeutic intervention, including hearing aids | Audiologic indication for cochlear implant and additional speech- language related services indicated (where available) | | Tinnitus | Symptoms causing no or minimal interference with usual social & functional activities with intervention not indicated | Symptoms causing greater than minimal interference with usual social & functional activities with intervention indicated | Symptoms causing inability to perform usual social & functional activities | NA | | Uveitis | No symptoms ANDDetectable on examination | Anterior uveitis with symptoms ORMedical intervention indicated | Posterior or pan- uveitis OR Operativeintervention indicated | Disabling visual loss in affected eye(s) | | Vertigo | Vertigo causing no or minimal interference with usual social & functional activities | Vertigo causing greater than minimal interference with usual social & functional activities | Vertigo causing inability to perform usual social & functional activities | Disabling vertigo causing inability to perform basic self-care functions | | Visual Changes(assessed from baseline) | Visual changes causing no or minimal interference with usual social & functional activities | Visual changes causing greater than minimal interference with usual social & functional activities | Visual changes causing inability to perform usual social & functional activities | Disabling visual loss in affected eye(s) | ### Page 24 ### Systemic | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Acute Allergic Reaction | Localized urticaria (wheals) with no medical intervention indicated | Localized urticaria with intervention indicated OR Mildangioedema with no intervention indicated | Generalized urticaria OR Angioedema withintervention indicated OR Symptoms ofmild bronchospasm | Acute anaphylaxis ORLife-threatening bronchospasm ORLaryngeal edema | | Chills | Symptoms causing no or minimal interference with usual social & functional activities | Symptoms causing greater than minimal interference with usual social & functional activities | Symptoms causing inability to perform usual social & functional activities | NA | | Cytokine Release Syndrome8 Definition: A disorder characterized by nausea, headache, tachycardia, hypotension, rash, and/or shortness of breath. | Mild signs and symptoms ANDTherapy (i.e., antibody infusion) interruption not indicated | Therapy (i.e., antibody infusion) interruption indicated ANDResponds promptly to symptomatic treatment ORProphylactic medications indicated for ≤ 24 hours | Prolonged severe signs and symptoms OR Recurrence ofsymptoms following initial improvement | Life-threatening consequences (e.g., requiring pressor or ventilator support) | | Fatigue or MalaiseReport only one | Symptoms causing no or minimal interference with usual social & functional activities | Symptoms causing greater than minimal interference with usual social & functional activities | Symptoms causing inability to perform usual social & functional activities | Incapacitating symptoms of fatigue or malaise causing inability to perform basic self-care functions | | Fever (non-axillary temperatures only) | 38.0 to < 38.6°C or 100.4 to < 101.5°F | ≥ 38.6 to < 39.3°C or ≥ 101.5 to < 102.7°F | ≥ 39.3 to < 40.0°C or ≥ 102.7 to < 104.0°F | ≥ 40.0°C or ≥ 104.0°F | | Pain9 For pain associated with injections or infusions, see the Site Reactions to Injections and Infusions section (page 23). (not associated with study agent injections and not specified elsewhere)Specify location | Pain causing no or minimal interference with usual social & functional activities | Pain causing greater than minimal interference with usual social & functional activities | Pain causing inability to perform usual social & functional activities | Disabling pain causing inability to perform basic self-care functions ORHospitalization indicated | ### Page 25 | Serum Sickness10 Definition: A disorder characterized by fever, arthralgia, myalgia, skin eruptions, lymphadenopathy, marked discomfort, and/or dyspnea. | Mild signs and symptoms | Moderate signs and symptoms ANDIntervention indicated (e.g., antihistamines) | Severe signs and symptoms ANDHigher level intervention indicated (e.g., steroids or IV fluids) | Life-threatening consequences (e.g., requiring pressor or ventilator support) | | - | - | - | - | - | | Underweight11 WHO reference tables may be accessed by clicking the desired age range or by accessing the following URLs: http://www.who.int/growthref/who2007_bmi_for_age/en/ for participants > 5 to 19 years of age and http://www.who.int/childgrowth/standards/chart_catalogue/en/ for those ≤ 5 years of age.> 5 to 19 years of age | WHO BMI z-score< -1 to -2 | WHO BMI z-score < -2 to -3 | WHO BMI z-score < -3 | WHO BMI z-score < -3 with life-threatening consequences | | 2 to 5 years of age | WHO Weight-for- height z-score< -1 to -2 | WHO Weight-for- height z-score< -2 to -3 | WHO Weight-for- height z-score < -3 | WHO Weight-for-height z-score < -3 with life- threatening consequences | | < 2 years of age | WHO Weight-for- length z-score< -1 to -2 | WHO Weight-for- length z-score< -2 to -3 | WHO Weight-for- length z-score < -3 | WHO Weight-for-length z-score < -3 with life- threatening consequences | | Unintentional Weight Loss(excludes postpartum weight loss) | NA | 5 to < 9% loss in body weight from baseline | ≥ 9 to < 20% loss in body weight from baseline | ≥ 20% loss in body weight from baseline ORAggressive intervention indicated (e.g., tube feeding, total parenteral nutrition) | ### Page 26 ### Urinary | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Urinary Tract Obstruction | NA | Signs or symptoms of urinary tract obstruction without hydronephrosis or renal dysfunction | Signs or symptoms of urinary tract obstruction with hydronephrosis or renal dysfunction | Obstruction causing life-threatening consequences | ### Page 27 ## Site Reactions to Injections and Infusions | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Injection Site Pain or TendernessReport only one | Pain or tenderness causing no or minimal limitation of use of limb | Pain or tenderness causing greater than minimal limitation of use of limb | Pain or tenderness causing inability to perform usual social & functional activities | Pain or tenderness causing inability to perform basic self-care function ORHospitalization indicated | | Injection Site Erythema or Redness12 Injection Site Erythema or Redness should be evaluated and graded using the greatest single diameter or measured surface area.Report only one> 15 years of age | 2.5 to < 5 cm in diameter OR 6.25 to< 25 cm 2 surface area ANDSymptoms causing no or minimal interference with usual social & functional activities | ≥ 5 to < 10 cm in diameter OR ≥ 25 to< 100 cm 2 surface area OR Symptomscausing greater than minimal interference with usual social & functional activities | ≥ 10 cm in diameter OR ≥ 100 cm2surface area ORUlceration ORSecondary infection OR Phlebitis ORSterile abscess ORDrainage ORSymptoms causing inability to perform usual social & functional activities | Potentially life- threatening consequences (e.g., abscess, exfoliative dermatitis, necrosis involving dermis or deeper tissue) | | ≤ 15 years of age | ≤ 2.5 cm in diameter | > 2.5 cm in diameter with < 50% surface area of the extremity segment involved (e.g., upper arm or thigh) | ≥ 50% surface area of the extremity segment involved (e.g., upper arm or thigh) OR UlcerationOR Secondaryinfection ORPhlebitis OR Sterileabscess OR Drainage | Potentially life- threatening consequences (e.g., abscess, exfoliative dermatitis, necrosis involving dermis or deeper tissue) | | Injection Site Induration or SwellingReport only one> 15 years of age | Same as forInjection SiteErythema or Redness, > 15 years of age | Same as forInjection SiteErythema or Redness, > 15 years of age | Same as forInjection SiteErythema or Redness, > 15 years of age | Same as for Injection Site Erythema or Redness, > 15 years of age | | ≤ 15 years of age | Same as forInjection SiteErythema or Redness, ≤ 15 years of age | Same as forInjection SiteErythema or Redness, ≤ 15 years of age | Same as forInjection SiteErythema or Redness, ≤ 15 years of age | Same as for Injection Site Erythema or Redness, ≤ 15 years of age | | Injection Site Pruritus | Itching localized to the injection site that is relieved spontaneously or in < 48 hours of treatment | Itching beyond the injection site that is not generalized ORItching localized to the injection site requiring ≥ 48 hours treatment | Generalized itching causing inability to perform usual social & functional activities | NA | ### Page 28 ## Laboratory Values* *Reminder: An asymptomatic abnormal laboratory finding without an accompanying AE should not be reported to DAIDS in an expedited time frame unless it meets protocol-specific reporting requirements. ### Chemistries | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Acidosis | NA | pH ≥ 7.3 to < LLN | pH < 7.3 without life - threatening consequences | pH < 7.3 with life- threatening consequences | | Albumin, Low(g/dL; g/L) | 3.0to < LLN30to < LLN | ≥ 2.0 to < 3.0≥ 20 to < 30 | < 2.0< 20 | NA | | Alkaline Phosphatase, High | 1.25 to < 2.5 x ULN | 2.5 to < 5.0 x ULN | 5.0 to < 10.0 x ULN | ≥ 10.0 x ULN | | Alkalosis | NA | pH > ULN to ≤ 7.5 | pH > 7.5 without life - threatening consequences | pH > 7.5 with life- threatening consequences | | ALT or SGPT, HighReport only one | 1.25 to < 2.5 x ULN | 2.5 to < 5.0 x ULN | 5.0 to < 10.0 x ULN | ≥ 10.0 x ULN | | Amylase (Pancreatic) or Amylase (Total), HighReport only one | 1.1 to < 1.5 x ULN | 1.5 to < 3.0 x ULN | 3.0 to < 5.0 x ULN | ≥ 5.0 x ULN | | AST or SGOT, HighReport only one | 1.25 to < 2.5 x ULN | 2.5 to < 5.0 x ULN | 5.0 to < 10.0 x ULN | ≥ 10.0 x ULN | | Bicarbonate, Low(mEq/L;mmol/L) | 16.0to < LLN16.0to < LLN | 11.0to < 16.011.0to < 16.0 | 8.0to < 11.08.0to < 11.0 | < 8.0< 8.0 | | BilirubinDirect Bilirubin13 Direct bilirubin > 1.5 mg/dL in a participant < 28 days of age should be graded as grade 2, if < 10% of the total bilirubin., High> 28 days of age | NA | NA | > ULN with other signs and symptoms of hepatotoxicity. | > ULN with life- threatening consequences (e.g., signs and symptoms of liver failure) | | ≤ 28 days of age | ULN to ≤ 1 mg/dL | > 1 to ≤ 1.5 mg/dL | > 1.5 to ≤ 2 mg/dL | > 2 mg/dL | | Total Bilirubin, High> 28 days of age | 1.1 to < 1.6 x ULN | 1.6 to < 2.6 x ULN | 2.6 to < 5.0 x ULN | ≥5.0 x ULN | | ≤ 28 days of age | See Appendix A. Total Bilirubin for Term and Preterm Neonates | See Appendix A. Total Bilirubin for Term and Preterm Neonates | See Appendix A. Total Bilirubin for Term and Preterm Neonates | See Appendix A. Total Bilirubin for Term and Preterm Neonates | ### Page 29 | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Calcium, High(mg/dL; mmol/L)≥ 7 days of age | 10.6 to < 11.52.65 to < 2.88 | 11.5 to < 12.52.88 to < 3.13 | 12.5 to < 13.53.13 to < 3.38 | ≥ 13.5 ≥ 3.38 | | < 7 days of age | 11.5 to < 12.42.88 to < 3.10 | 12.4 to < 12.93.10 to < 3.23 | 12.9 to < 13.53.23 to < 3.38 | ≥ 13.5 ≥ 3.38 | | Calcium (Ionized), High(mg/dL; mmol/L) | > ULN to < 6.0> ULN to < 1.5 | 6.0 to < 6.41.5 to < 1.6 | 6.4 to < 7.21.6 to < 1.8 | ≥ 7.2≥ 1.8 | | Calcium, Low(mg/dL; mmol/L)≥ 7 days of age | 7.8 to < 8.41.95 to < 2.10 | 7.0 to < 7.81.75 to < 1.95 | 6.1 to < 7.01.53 to < 1.75 | < 6.1< 1.53 | | < 7 days of age | 6.5 to < 7.51.63 to < 1.88 | 6.0 to < 6.51.50 to < 1.63 | 5.50 to < 6.01.38 to < 1.50 | < 5.50< 1.38 | | Calcium (Ionized), Low(mg/dL; mmol/L) | < LLN to 4.0< LLN to 1.0 | 3.6 to < 4.00.9 to < 1.0 | 3.2 to < 3.60.8 to < 0.9 | < 3.2< 0.8 | | Cardiac Troponin I, High | NA | NA | NA | Levels consistent with myocardial infarction or unstable angina as defined by the local laboratory | | Creatine Kinase, High | 3 to < 6 x ULN | 6 to < 10x ULN | 10 to < 20 x ULN | ≥ 20 x ULN | | Creatinine, High*Report only one | 1.1 to 1.3 x ULN | > 1.3 to 1.8 x ULN OR Increase to 1.3 to< 1.5 x participant’s baseline | > 1.8 to < 3.5 x ULN OR Increaseto 1.5 to < 2.0 x participant’s baseline | ≥ 3.5 x ULN ORIncrease of ≥ 2.0 x participant’s baseline | | Creatinine Clearance14 Use the applicable formula (i.e., Cockcroft-Gault in mL/min or Schwartz, MDRD, CKD-Epi in mL/min/1.73m2). Sites should choose the method defined in their study and when not specified, use the method most relevant to the study population.or eGFR, Low*Report only one*Reminder: Choose the method that selects for the higher grade. | NA | < 90 to 60 ml/min or ml/min/1.73 m2 OR10 to < 30% decrease from participant’s baseline | < 60 to 30 ml/min or ml/min/1.73 m2 OR30 to < 50% decrease from participant’s baseline | < 30 ml/min or ml/min/1.73 m2 OR≥ 50% decrease from participant’s baseline or dialysis needed | | Glucose(mg/dL; mmol/L)Fasting, High | 110 to 1256.11 to < 6.95 | > 125 to 2506.95 to < 13.89 | > 250 to 50013.89 to < 27.75 | ≥ 500 ≥ 27.75 | | Nonfasting, High | 116 to 1606.44 to < 8.89 | > 160 to 2508.89 to < 13.89 | > 250 to 50013.89 to < 27.75 | ≥ 500 ≥ 27.75 | ### Page 30 | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Glucose, Low(mg/dL; mmol/L)≥ 1 month of age | 55 to 643.05 to <3.55 | 40 to < 552.22 to < 3.05 | 30 to < 401.67 to < 2.22 | < 30< 1.67 | | < 1 month of age | 50 to 542.78 to < 3.00 | 40 to < 502.22 to < 2.78 | 30 to < 401.67 to < 2.22 | < 30< 1.67 | | Lactate, High | ULN to < 2.0 x ULN without acidosis | ≥ 2.0 x ULN without acidosis | Increased lactate with pH < 7.3 without life - threatening consequences | Increased lactate with pH < 7.3 with life- threatening consequences | | Lipase, High | 1.1 to < 1.5 x ULN | 1.5 to < 3.0 x ULN | 3.0 to < 5.0 x ULN | ≥ 5.0 x ULN | | Lipid Disorders(mg/dL; mmol/L)Cholesterol, Fasting, High≥ 18 years of age | 200 to < 2405.18 to < 6.19 | 240 to < 3006.19 to < 7.77 | ≥ 300 ≥ 7.77 | NA | | < 18 years of age | 170 to < 2004.40 to < 5.15 | 200 to < 3005.15 to < 7.77 | ≥ 300 ≥ 7.77 | NA | | LDL, Fasting, High≥ 18 years of age | 130 to < 1603.37 to < 4.12 | 160 to < 1904.12 to < 4.90 | ≥ 190≥ 4.90 | NA | | > 2 to < 18 years of age | 110 to < 1302.85 to < 3.34 | 130 to < 1903.34 to < 4.90 | ≥ 190≥ 4.90 | NA | | Triglycerides, Fasting, High | 150 to 3001.71 to 3.42 | >300 to 500>3.42 to 5.7 | >500 to < 1,000>5.7 to 11.4 | > 1,000> 11.4 | | Magnesium15 To convert a magnesium value from mg/dL to mmol/L, laboratories should multiply by 0.4114 ., Low(mEq/L; mmol/L) | 1.2 to < 1.40.60 to < 0.70 | 0.9to < 1.20.45to < 0.60 | 0.6to < 0.90.30to < 0.45 | < 0.6< 0.30 | | Phosphate, Low(mg/dL; mmol/L)> 14 years of age | 2.0 to < LLN0.65 to < LLN | 1.4 to < 2.00.45 to < 0.65 | 1.0 to < 1.40.32 to < 0.45 | < 1.0< 0.32 | | 1 to 14 years of age | 3.0 to < 3.50.97 to < 1.13 | 2.5 to < 3.00.81 to < 0.97 | 1.5 to < 2.50.48 to < 0.81 | < 1.5< 0.48 | | < 1 year of age | 3.5 to < 4.51.13 to < 1.45 | 2.5 to < 3.50.81 to < 1.13 | 1.5 to < 2.50.48 to < 0.81 | < 1.5< 0.48 | | Potassium, High(mEq/L; mmol/L) | 5.6 to < 6.05.6 to < 6.0 | 6.0 to < 6.56.0 to < 6.5 | 6.5 to < 7.06.5 to < 7.0 | ≥ 7.0 ≥ 7.0 | | Potassium, Low(mEq/L; mmol/L) | 3.0 to < 3.43.0 to < 3.4 | 2.5 to < 3.02.5 to < 3.0 | 2.0 to < 2.52.0 to < 2.5 | < 2.0< 2.0 | ### Page 31 | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Sodium, High(mEq/L; mmol/L) | 146 to < 150146 to < 150 | 150 to < 154150 to < 154 | 154 to < 160154 to < 160 | ≥ 160≥ 160 | | Sodium, Low(mEq/L; mmol/L) | 130 to < 135130 to < 135 | 125 to < 130125 to < 130 | 121 to < 125121 to < 125 | ≤ 120≤ 120 | | Uric Acid, High(mg/dL; mmol/L) | 7.5 to < 10.00.45 to < 0.59 | 10.0 to < 12.00.59 to < 0.71 | 12.0 to < 15.00.71 to < 0.89 | ≥ 15.0 ≥ 0.89 | ### Page 32 ### Hematology | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Absolute CD4+ Count, Low(cell/mm 3 ; cells/L)> 5 years of age (not HIV infected) | 300 to < 400300 to < 400 | 200 to < 300200 to < 300 | 100 to < 200100 to < 200 | < 100< 100 | | Absolute Lymphocyte Count, Low(cell/mm 3 ; cells/L)> 5 years of age(not HIV infected) | 600 to < 6500.600 x 109 to < 0.650 x 10 9 | 500 to < 6000.500 x 109 to < 0.600 x 10 9 | 350 to < 5000.350 x 109 to < 0.500 x 10 9 | < 350< 0.350 x 10 9 | | Absolute Neutrophil Count (ANC), Low(cells/mm 3 ; cells/L)> 7 days of age | 800 to 1,0000.800 x 10 9 to 1.000 x 10 9 | 600 to 7990.600 x 10 9 to 0.799 x 10 9 | 400 to 5990.400 x 10 9 to 0.599 x 10 9 | < 400< 0.400 x 10 9 | | 2 to 7 days of age | 1,250 to 1,5001.250 x 10 9 to 1.500 x 10 9 | 1,000 to 1,2491.000 x 109 to 1.249 x 10 9 | 750 to 9990.750 x 10 9 to 0.999 x 10 9 | < 750< 0.750 x 10 9 | | ≤ 1 day of age | 4,000 to 5,0004.000 x 109 to 5.000 x 109 | 3,000 to 3,9993.000 x 10 9 to 3.999 x 10 9 | 1,500 to 2,9991.500 x 10 9 to 2.999 x 10 9 | < 1,500< 1.500 x 10 9 | | Fibrinogen, Decreased(mg/dL; g/L) | 100 to < 2001.00 to < 2.00OR0.75 to < 1.00 x LLN | 75 to < 1000.75 to < 1.00OR≥ 0.50 to < 0.75 x LLN | 50 to < 750.50 to < 0.75OR0.25 to < 0.50 x LLN | < 50 < 0.50OR< 0.25 x LLN OR Associated withgross bleeding | | Hemoglobin, Low(g/dL; mmol/L)16 For participants ≥ 13 years of age, hemoglobin is graded based on the predominant sex hormone present in the body, whether endogenous or exogenous, for at least 6 consecutive months.17 The most commonly used conversion factor to convert g/dL to mmol/L is 0.6206. For grading hemoglobin results obtained by an analytic method with a conversion factor other than 0.6206, the result must be converted to g/dL using appropriate conversion factor for the particular laboratory.DAIDS AE Grading Table Corrected Version 2.1-July 2017 Page 29≥ 13 years of age (male only) | 10.0 to 10.96.19 to 6.76 | 9.0 to < 10.05.57 to < 6.19 | 7.0 to < 9.04.34 to < 5.57 | < 7.0< 4.34 | | ≥ 13 years of age (female only) | 9.5 to 10.45.88 to 6.48 | 8.5 to < 9.55.25 to < 5.88 | 6.5 to < 8.54.03 to < 5.25 | < 6.5< 4.03 | ### Page 33 | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | 57 days of age to < 13 years of age (male and female) | 9.5 to 10.45.88 to 6.48 | 8.5 to < 9.55.25 to < 5.88 | 6.5 to < 8.54.03 to < 5.25 | < 6.5< 4.03 | | 36 to 56 days of age (male and female) | 8.5 to 9.65.26 to 5.99 | 7.0 to < 8.54.32 to < 5.26 | 6.0 to < 7.03.72 to < 4.32 | < 6.0< 3.72 | | 22 to 35 days of age (male and female) | 9.5 to 11.05.88 to 6.86 | 8.0 to < 9.54.94 to < 5.88 | 6.7 to < 8.04.15 to < 4.94 | < 6.7< 4.15 | | 8 to ≤ 21 days of age (male and female) | 11.0 to 13.06.81 to 8.10 | 9.0 to < 11.05.57 to < 6.81 | 8.0 to < 9.04.96 to < 5.57 | < 8.0< 4.96 | | ≤ 7 days of age (male and female) | 13.0 to 14.08.05 to 8.72 | 10.0 to < 13.06.19 to < 8.05 | 9.0 to < 10.05.59 to < 6.19 | < 9.0< 5.59 | | INR, High(not on anticoagulation therapy) | 1.1 to < 1.5 x ULN | 1.5 to < 2.0 x ULN | 2.0 to < 3.0 x ULN | ≥ 3.0 x ULN | | Methemoglobin(% hemoglobin) | 5.0 to < 10.0% | 10.0 to < 15.0% | 15.0 to < 20.0% | ≥ 20.0% | | PTT, High(not on anticoagulation therapy) | 1.1 to < 1.66 x ULN | 1.66 to < 2.33 x ULN | 2.33 to < 3.00 x ULN | ≥ 3.00 x ULN | | Platelets, Decreased(cells/mm 3 ; cells/L) | 100,000 to < 125,000100.000 x 10 9 to < 125.000 x 109 | 50,000 to < 100,00050.000 x 10 9 to < 100.000 x 10 9 | 25,000 to < 50,00025.000 x 10 9 to < 50.000 x 10 9 | < 25,000< 25.000 x 10 9 | | PT, High(not on anticoagulation therapy | 1.1 to < 1.25 x ULN | 1.25 to < 1.50 x ULN | 1.50 to < 3.00 x ULN | ≥ 3.00 x ULN | | WBC, Decreased(cells/mm 3 ; cells/L)> 7 days of age | 2,000 to 2,4992.000 x 10 9 to 2.499 x 10 9 | 1,500 to 1,9991.500 x 10 9 to 1.999 x 10 9 | 1,000 to 1,4991.000 x 10 9 to 1.499 x 10 9 | < 1,000< 1.000 x 10 9 | | ≤ 7 days of age | 5,500 to 6,9995.500 x 10 9 to 6.999 x 10 9 | 4,000 to 5,4994.000 x 10 9 to 5.499 x 10 9 | 2,500 to 3,9992.500 x 10 9 to 3.999 x 10 9 | < 2,500< 2.500 x 10 9 | ### Page 34 ### Urinalysis | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Glycosuria (random collection tested by dipstick) | Trace to 1+ or≤ 250 mg | 2+ or ˃ 250 to≤ 500 mg | > 2+ or > 500 mg | NA | | Hematuria (not to be reported based on dipstick findings or on blood believed to be of menstrual origin) | 6 to < 10 RBCs per high power field | ≥ 10 RBCs per high power field | Gross, with or without clots ORWith RBC casts ORIntervention indicated | Life-threatening consequences | | Proteinuria (random collection tested by dipstick) | 1+ | 2+ | 3+ or higher | NA | ### Page 35 ## Appendix A. Total Bilirubin Table for Term and Preterm Neonates | PARAMETER | GRADE 1MILD | GRADE 2MODERATE | GRADE 3SEVERE | GRADE 4POTENTIALLYLIFE-THREATENING | | - | - | - | - | - | | Total Bilirubin18 Severity grading for total bilirubin in neonates is complex because of rapidly changing total bilirubin normal ranges in the first week of life followed by the benign phenomenon of breast milk jaundice after the first week of life. Severity grading in thi s appendix corresponds approximately to cut -offs for indications for phototherapy at grade 3 and for exchange transfusion at grade 4., High(mg/dL; μmol/L)19 A laboratory value of 1 mg/dL is equivalent to 17.1 μmol/L.Term Neonate20 Definitions: Term is defined as ≥ 37 weeks gestational age; near-term, as ≥ 35 weeks gestational age; preterm, as < 35 weeks gestational age; and neonate, as 0 to 28 days of age.< 24 hours of age | 4 to < 768.4 to < 119.7 | 7 to < 10119.7 to < 171 | 10 to < 17171 to < 290.7 | ≥ 17 ≥ 290.7 | | 24 to < 48 hours of age | 5 to < 885.5 to < 136.8 | 8 to < 12136.8 to < 205.2 | 12 to < 19205.2 to < 324.9 | ≥ 19 ≥ 324.9 | | 48 to < 72 hours of age | 8.5 to < 13145.35 to < 222.3 | 13 to < 15222.3 to < 256.5 | 15 to < 22256.5 to < 376.2 | ≥ 22 ≥ 376.2 | | 72 hours to < 7 days of age | 11 to < 16188.1 to < 273.6 | 16 to < 18273.6 to < 307.8 | 18 to < 24307.8 to < 410.4 | ≥ 24 ≥ 410.4 | | 7 to 28 days of age (breast feeding) | 5 to < 1085.5 to < 171 | 10 to < 20171 to < 342 | 20 to < 25342 to < 427.5 | ≥ 25 ≥ 427.5 | | 7 to 28 days of age (not breast feeding) | 1.1 to < 1.6 x ULN | 1.6 to < 2.6 x ULN | 2.6 to < 5.0 x ULN | ≥5.0 x ULN | | Preterm Neonate2035 to < 37 weeks gestational age | Same as for Total Bilirubin, High, Term Neonate (based on days of age). | Same as for Total Bilirubin, High, Term Neonate (based on days of age). | Same as for Total Bilirubin, High, Term Neonate (based on days of age). | Same as for Total Bilirubin, High, Term Neonate (based on days of age). | | 32 to < 35 weeks gestational age and < 7 days of age | NA | NA | 10 to < 14171 to < 239.4 | ≥ 14≥ 239.4 | | 28 to < 32 weeks gestational age and < 7 days of age | NA | NA | 6 to < 10102.6 to < 171 | ≥ 10≥ 171 | | < 28 weeks gestational age and < 7 days of age | NA | NA | 5 to < 885.5 to < 136.8 | ≥ 8≥ 136.8 | | 7 to 28 days of age (breast feeding) | 5 to < 1085.5 to < 171 | 10 to < 20171 to < 342 | 20 to < 25342 to < 427.5 | ≥ 25 ≥ 427.5 | | 7 to 28 days of age (not breast feeding) | 1.1 to < 1.6 x ULN | 1.6 to < 2.6 x ULN | 2.6 to < 5.0 x ULN | ≥5.0 x ULN |