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Antiretroviral Therapy for HIV Infection in Infants and Children: Towards Universal Access: Recommendations for a Public Health Approach: 2010 Revision. Geneva: World Health Organization; 2010.

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Antiretroviral Therapy for HIV Infection in Infants and Children: Towards Universal Access: Recommendations for a Public Health Approach: 2010 Revision.

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ANNEX GSEVERITY GRADING OF SELECTED CLINICAL AND LABORATORY TOXICITIES MOST COMMONLY SEEN WITH RECOMMENDED ANTIRETROVIRAL DRUGS FOR CHILDREN

PARAMETERMILD (grade 1)MODERATE (grade 2)SEVERE (grade 3)SEVERE AND POTENTIALLY LIFE-THREATENING (grade 4)
GENERAL GUIDANCE ON ESTIMATING SEVERITY GRADE
Characterization of symptoms and general guidance on managementSymptoms causing no or minimal interference with usual social and functional activities:a
no therapy needed, monitor
Symptoms causing greater than minimal interference with usual social and functional activities: may require minimal intervention and monitoringSymptoms causing inability to perform usual social and functional activities: requires medical care and possible hospitalizationSymptoms causing inability to perform basic self-care functions:c requires medical or operative intervention to prevent permanent impairment, persistent disability or death
HAEMATOLOGY (Standard international units are listed in italics)
Absolute neutrophil count750 − <1000/mm3
0.75 × 109− < 1 × 109/L
500 – 749/mm3
½ × 1090.749 × 109/L
250 − 500/mm3
0.25 × 109½ × 109/L
<250/mm3
<0.250 × 109/L
Haemoglobin
(child >60 days of age)
8.5–10.0 g/dl
1.321.55 mmol/L
7.5−<8.5 g/dl
1.16<1.32 mmol/L
6.5 − <7.5 g/dl
1.01<1.16 mmol/L
<6.5 g/dl
<1.01 mmol/L
Or severe clinical symptoms attributable to anaemia (e.g. cardiac failure), refractory to supportive therapy
Platelets100000−<125000/mm3
100 × 109125 × 109/L
50000−<100000/mm3
50 × 109<100 × 109/L
25000–<50000/mm3
25 × 109<50 × 109/L
<25000/mm3
<25 × 109/L
Or bleeding
GASTROINTESTINAL
Laboratory
ALT (SGPT)1.25–2.5 × ULN2.6–5.0 × ULN5.1–10.0 × ULN>10.0 × ULN
AST (SGOT)1.25–2.5 × ULN2.6–5.0 × ULN5.1–10.0 × ULN>10.0 × ULN
Bilirubin (>2 weeks of age)1.1–1.5 × ULN1.6–2.5 × ULN2.6–5.0 × ULN>5.0 × ULN
Lipase1.1–1.5 × ULN1.6–3.0 × ULN3.1–5.0 × ULN>5.0 × ULN
Pancreatic amylase1.1–1.5 × ULN1.6–2.0 × ULN2.1–5.0 × ULN>5.0 × ULN
Clinical
Diarrhoea
≥1 year of age

<1 year of age
Transient or intermittent episodes of unformed stools OR increase of ≤3 stools over baseline per day
Liquid stools (more unformed than usual) but usual number of stools
Persistent episodes of unformed to watery stools OR increase of 4 – 6 stools over baseline per day
Liquid stools with increased number of stools OR mild dehydration
Grossly bloody diarrhoea OR increase of ≥7 stools per day OR intravenous fluid replacement indicated
Liquid stools with moderate dehydration
Life-threatening consequences (e.g. hypotensive shock)

Liquid stools resulting in severe dehydration with aggressive rehydration indicated OR hypotensive shock
NauseaTransient (<24 hours) or intermittent nausea with no or minimal interference with oral intakePersistent nausea resulting in decreased oral intake for 24 – 48 hoursPersistent nausea resulting in minimal oral intake for >48 hours OR aggressive rehydration indicated (e.g. intravenous fluids)Persistent nausea with no or minimal oral intake resulting in dehydration with aggressive rehydration indicated
PancreatitisNot applicableSymptomatic AND hospitalization not indicated (other than emergency treatment)Symptomatic AND hospitalization not indicated (other than emergency treatment)Life-threatening consequences (e.g. circulatory failure, haemorrhage, sepsis)
VomitingTransient or intermittent vomiting with no or minimal interference with oral intakeFrequent episodes of vomiting with no or mild dehydrationPersistent vomiting resulting in orthostatic hypotension OR aggressive rehydration indicated (e.g. intravenous fluids)Life-threatening consequences (e.g. hypotensive shock)
ALLERGIC/DERMATOLOGICAL
Acute systemic allergic reactionLocalized urticaria (weals) lasting a few hoursLocalized urticaria with medical intervention indicated OR mild angioedemaGeneralized urticaria OR angioedema with medical intervention indicated OR symptomatic mild bronchospasmAcute anaphylaxis OR life-threatening bronchospasm or laryngeal oedema
Cutaneous reaction – rashLocalized macular rashDiffuse macular, maculopapular, or morbilliform rash OR target lesionsDiffuse macular, maculopapular, or morbilliform rash with vesicles or limited number of bullae OR superficial ulcerations of mucous membrane limited to one siteExtensive or generalized bullous lesions OR Stevens –Johnson syndrome OR ulceration of mucous membrane involving two or more distinct mucosal sites OR toxic epidermal necrolysis (TEN)
NEUROLOGICAL
Alteration in personality, behaviour or moodbAlteration causing no or minimal interference with usual social and functional activitiesbAlteration causing greater than minimal interference with usual social and functional activitiesbAlteration causing inability to perform usual social and functional activitiesb AND intervention indicatedBehaviour potentially harmful to self or others OR life-threatening consequences
Altered mental statusChanges causing no or minimal interference with usual social and functional activitiesbMild lethargy or somnolence causing greater than minimal interference with usual social and functional activitiesbOnset of confusion, memory impairment, lethargy, or somnolence causing inability to perform usual social and functional activitiesbOnset of delirium, obtundation or coma
Neuromuscular weakness (including myopathy and neuropathy)Asymptomatic with decreased strength on examination OR minimal muscle weakness causing no or minimal interference with usual social and functional activitiesbMuscle weakness causing greater than minimal interference with usual social and functional activitiesbMuscle weakness causing inability to perform usual social and functional activitiesbDisabling muscle weakness causing inability to perform basic self-care functions OR respiratory muscle weakness impairing ventilation
Neurosensory alteration (including painful neuropathy)Asymptomatic with sensory alteration on examination OR minimal paraesthesia causing no or minimal interference with usual social and functional activitiesSensory alteration or paraesthesia causing greater than minimal interference with usual social and functional activitiesSensory alteration or paraesthesia causing inability to perform usual social and functional activitiesDisabling sensory alteration or paraesthesia causing inability to perform basic self-care functionsc
OTHER LABORATORY PARAMETERS (Standard international units are listed in italics)
Cholesterol (fasting, paediatric <18 years old)170–<200 mg/dl
4.40 – 5.15 mmol/L
200–300 mg/dl
5.16–7.77 mmol/L
>300 mg/dl
>7.77 mmol/L
Not applicable
Glucose, serum, high: non-fasting116 – <161 mg/dl
6.44–<8.89 mmol/L
161 – <251 mg/dl
8.89–<13.89 mmol/L
251–500 mg/dl
13.89–27.75 mmol/L
>500 mg/dl
>27.75 mmol/L
Glucose, serum, high: fasting110–<126 mg/dl
6.11–<6.95 mmol/L
126–<251 mg/dl
6.95 –<13.89 mmol/L
251–500 mg/dl
13.89–27.75 mmol/L
>500 mg/dl
>27.75 mmol/L
Lactate<2.0 × ULN without acidosis>2.0 × ULN without acidosisIncreased lactate with pH <7.3 without life-threatening consequences or related condition presentIncreased lactate with pH <7.3 with life-threatening consequences (e.g. neurological findings, coma) or related condition present
Triglycerides (fasting)Not applicable500 – <751 mg/dl
5.65–<8.49 mmol/L
751 – 1 200 mg/dl
8.49–13.56 mmol/L
>1 200 mg/dl
>13.56 mmol/L
a

Values are provided for children in general except where age groups are specificied.

b

Usual social and functional activities in young children include those that are appropriate for their age and culture (e.g. social interactions, play activities, learning tasks).

c

Activities that are appropriate for age and culture (e.g. feeding self with culturally appropriate eating implement, walking or using hands).

Source: Adapted from Division of AIDS, National Institute of Allergy and Infectious Diseases, Table for grading the severity of adult and paediatric adverse events, Bethesda, Maryland, USA; December 2004.

Copyright © 2010, World Health Organization.

All rights reserved. Publications of the World Health Organization can be obtained from WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland (tel.: +41 22 791 3264; fax: +41 22 791 4857; e-mail: tni.ohw@sredrokoob). Requests for permission to reproduce or translate WHO publications – whether for sale or for noncommercial distribution – should be addressed to WHO Press, at the above address (fax: +41 22 791 4806; e-mail: tni.ohw@snoissimrep).

Bookshelf ID: NBK138596

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