Diagnostic Criteria for HIV-Related Clinical Events: Adults and Adolescents

WHO/HIV/2013.67 © World Health Organization 2013

Diagnostic criteria for HIV-related clinical events: adults and adolescents

Source: WHO case definitions of HIV for surveillance and revised clinical staging and immunological classification of HIV-related disease in adults and children . Geneva, World Health Organization, 2007 (http://www.who.int/hiv/pub/guidelines/HIVstaging150307.pdf , accessed 15 May 2013).

Clinical event Clinical diagnosis Definitive diagnosis Stage 1 No HIV-related symptoms reported Asymptomatic Not applicable and no clinical signs on examination Painless enlarged lymph nodes >1 cm, in two or more noncontiguous Persistent generalized sites (excluding inguinal), in the Histology lymphadenopathy absence of any known cause and persisting for 3 months or longer Stage 2 Moderate unexplained Reported unexplained weight loss. In Documented weight loss (<10% of weight loss (<10% of body pregnancy, failure to gain weight body weight) weight) Symptoms complex, such as unilateral face pain with nasal Recurrent bacterial upper discharge (sinusitis), painful inflamed respiratory tract infections Laboratory studies if available, such as eardrum (otitis media), or (current event plus one or culture of suitable body fluid tonsillopharyngitis without features more in last 6 months) of viral infection (such as coryza, cough) Painful vesicular rash in dermatomal Herpes zoster distribution of a nerve supply does Clinical diagnosis not cross the midline Splits or cracks at the angle of the mouth not attributable to iron or Angular cheilitis Clinical diagnosis vitamin deficiency and usually responding to antifungal treatment Recurrent oral ulcerations Aphthous ulceration, typically (two or more episodes in past painful with a halo of inflammation Clinical diagnosis 6 months) and a yellow-grey pseudomembrane Papular pruritic lesions, often with Papular pruritic eruption marked postinflammatory Clinical diagnosis pigmentation Itchy scaly skin condition, Seborrhoeic dermatitis particularly affecting hairy areas Clinical diagnosis (scalp, axillae, upper trunk and groin) Paronychia (painful red and swollen nail bed) or onycholysis (separation of the nail from the nail bed) of the fingernails (white discoloration, Fungal culture of the nail or nail plate Fungal nail infections especially involving proximal part of material nail plate, with thickening and separation of the nail from the nail bed)

WHO/HIV/2013.67 © World Health Organization 2013

Clinical event Clinical diagnosis Definitive diagnosis Stage 3 Reported unexplained weight loss (>10% of body weight) and visible thinning of face, waist and Severe unexplained weight Documented loss of >10% of body extremities with obvious wasting or loss (>10% of body weight) weight body mass index below 18.5. In pregnancy, weight loss may be masked Not required but confirmed if three or Unexplained chronic Chronic diarrhoea (loose or watery more stools observed and documented diarrhoea for longer than 1 stools three or more times daily) as unformed and two or more stool tests month reported for longer than 1 month reveal no pathogens Reports of fever or night sweats for more than 1 month, either Documented fever exceeding 37.6°C Unexplained persistent fever intermittent or constant with reported with negative blood culture, negative (intermittent or constant and lack of response to antibiotics or Ziehl-Neelsen stain, negative malaria lasting for longer than 1 antimalarials, without other obvious slide, normal or unchanged chest X-ray month) foci of disease reported or found on and no other obvious focus of infection examination. Malaria must be excluded in malarious areas Persistent or recurring creamy white curd-like plaques that can be scraped off (pseudomembranous), or red Oral candidiasis Clinical diagnosis patches on the tongue, palate or lining of the mouth, usually painful or tender (erythematous form) Fine white small linear or corrugated Oral hairy leukoplakia lesions on the lateral borders of the Clinical diagnosis tongue, which do not scrape off Chronic symptoms (lasting at least 2– 3 weeks): cough, haemoptysis, shortness of breath, chest pain, weight loss, fever, night sweats, plus either positive sputum smear Isolation of Mycobacterium or tuberculosis on sputum culture or Pulmonary TB histology of lung biopsy (together with negative sputum smear compatible symptoms) and compatible chest radiograph (including but not restricted to upper lobe infiltrates, cavitation, pulmonary fibrosis and shrinkage). No evidence of extrapulmonary disease Severe bacterial infection (such as pneumonia, Fever accompanied by specific meningitis, empyema, symptoms or signs that localize Isolation of bacteria from appropriate pyomyositis, bone or joint infection and response to appropriate clinical specimens (usually sterile sites) infection, bacteraemia, antibiotic severe pelvic inflammatory disease) Severe pain, ulcerated gingival Acute necrotizing ulcerative papillae, loosening of teeth, stomatitis, gingivitis or Clinical diagnosis spontaneous bleeding, bad odour, periodontitis rapid loss of bone and/or soft tissue

WHO/HIV/2013.67 © World Health Organization 2013

Clinical event Clinical diagnosis Definitive diagnosis Diagnosed on laboratory testing and not explained by Unexplained anaemia (<8 other non-HIV conditions. g/dl), neutropaenia Not responding to standard therapy with haematinics, (<0.5 10 9/l) and/or No presumptive clinical diagnosis antimalarials or chronic (>1 month) anthelmintics as outlined in thrombocytopaenia 9 relevant national treatment (<50 10 /l) guidelines, WHO IMCI guidelines or other relevant guidelines Stage 4

Reported unexplained weight loss (>10% of body weight) with obvious wasting or body mass index below Documented weight loss 18.5, plus (>10% of body weight) plus two or more unformed either stools negative for pathogens unexplained chronic diarrhoea (loose or watery stools three or more times or HIV wasting syndrome daily) reported for longer than 1 month documented temperature exceeding 37.6°C with no or other cause of disease, negative blood culture, reports of fever or night sweats for negative malaria slide and more than 1 month without other normal or unchanged chest cause and lack of response to X-ray antibiotics or antimalarials. Malaria must be excluded in malarious areas

Dyspnoea on exertion or nonproductive cough of recent onset (within the past 3 months), tachypnoea and fever Cytology or and immunofluorescent microscopy of induced Pneumocystis pneumonia chest X-ray evidence of diffuse sputum or bronchoalveolar bilateral interstitial infiltrates lavage or histology of lung and tissue no evidence of bacterial pneumonia. Bilateral crepitations on auscultation with or without reduced air entry Current episode plus one or more episodes in past 6 months. Acute onset (<2 weeks) of symptoms (such Recurrent bacterial as fever, cough, dyspnoea, and chest Positive culture or antigen pneumonia (this episode pain) test of a compatible plus one or more episodes in plus organism the past 6 months) new consolidation on clinical examination or chest X-ray. Response to antibiotics Painful, progressive anogenital or Chronic herpes simplex virus orolabial ulceration; lesions caused (HSV) infection (orolabial, by recurrent HSV infection and Positive culture or DNA (by genital or anorectal) of more reported for more than 1 month. PCR) of HSV or compatible than 1 month or visceral at History of previous episodes. cytology or histology any site or any duration Visceral HSV requires definitive diagnosis

Clinical event Clinical diagnosis Definitive diagnosis Macroscopic appearance at Recent onset of retrosternal pain or endoscopy or bronchoscopy, Oesophageal candidiasis difficulty in swallowing (food and or by microscopy or fluids) together with oral candidiasis histology Systemic illness (such as fever, night sweats, weakness and weight loss). Other evidence for extrapulmonary or M. tuberculosis isolation or disseminated TB varies by site: compatible histology from pleural, pericardial, peritoneal appropriate site, together involvement, meningitis, mediastinal with compatible symptoms or abdominal lymphadenopathy, Extrapulmonary TB or signs (if the culture or osteitis. Miliary TB: diffuse histology is from a uniformly distributed small miliary respiratory specimen, there shadows or micronodules on chest X- must be other evidence of ray. Discrete cervical lymph node M. extrapulmonary disease) tuberculosis infection is usually considered a less severe form of extrapulmonary TB Typical appearance in skin or oropharynx of persistent, initially flat Macroscopic appearance at patches with a pink or blood-bruise Kaposi sarcoma endoscopy or bronchoscopy colour, skin lesions that usually or by histology develop into violaceous plaques or nodules Retinitis only: may be diagnosed by experienced clinicians. Typical eye Cytomegalovirus disease lesions on fundoscopic examination: Compatible histology or (retinitis or infection of other discrete patches of retinal whitening cytomegalovirus organs, excluding liver, with distinct borders, spreading demonstrated in CSF by spleen and lymph nodes) centrifugally, often following blood culture or DNA (by PCR) vessels, associated with retinal vasculitis, haemorrhage and necrosis Positive serum Toxoplasma Recent onset of a focal neurological antibody abnormality or reduced level of consciousness and CNS toxoplasmosis and (if available) single or multiple intracranial mass response within 10 days to specific lesion on neuroimaging (CT therapy or MRI) Clinical finding of disabling cognitive and/or motor dysfunction interfering with the activities of daily Diagnosis of exclusion, and, living, progressing over weeks or HIV encephalopathy if available, neuroimaging months in the absence of a concurrent (CT or MRI) illness or condition, other than HIV infection, that might explain the findings Isolation of Cryptococcus Meningitis: usually subacute, fever neoformans from Extrapulmonary with increasingly severe headache, extrapulmonary site or cryptococcosis (including meningism, confusion, behavioural positive cryptococcal meningitis) changes that respond to cryptococcal antigen test (CRAG) on therapy CSF or blood Diagnosed by finding atypical mycobacterial Disseminated nontuberculous No presumptive clinical diagnosis species from stool, blood, mycobacterial infection body fluid or other body tissue, excluding lung

Clinical event Clinical diagnosis Definitive diagnosis Progressive neurological disorder (cognitive dysfunction, gait or speech disorder, visual loss, limb Progressive multifocal weakness and cranial nerve No presumptive clinical diagnosis leukoencephalopathy palsies) together with hypodense white matter lesions on neuroimaging or positive polyomavirus (JC virus) PCR on CSF Cysts identified on modified Cryptosporidiosis (with Ziehl-Neelsen microscopic diarrhoea lasting more than 1 No presumptive clinical diagnosis examination of unformed month) stool Chronic isosporiasis No presumptive clinical diagnosis Identification of Isospora Disseminated mycosis Histology, antigen detection (coccidioidomycosis, No presumptive clinical diagnosis or culture from clinical histoplasmosis) specimen or blood culture Recurrent septicaemia (including non-typhoid No presumptive clinical diagnosis Blood culture Salmonella ) Lymphoma (cerebral or B- Histology of relevant cell non-Hodgkin) or other specimen or, for CNS No presumptive clinical diagnosis solid HIV-associated tumours, neuroimaging tumours techniques Invasive cervical carcinoma No presumptive clinical diagnosis Histology or cytology Histology (amastigotes Atypical disseminated visualized) or culture from No presumptive clinical diagnosis leishmaniasis any appropriate clinical specimen HIV-associated nephropathy No presumptive clinical diagnosis Renal biopsy Cardiomegaly and evidence HIV-associated of poor left ventricular No presumptive clinical diagnosis cardiomyopathy function confirmed by echocardiography