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Clinical Staging, AIDS surveillance and Mortality in resource-poor settings a clinician’s view of strategic information needs. Charlie Gilks Surveillance, Research Monitoring and Evaluation Department of HIV/AIDS. HIV slowly destroys part of the immune system
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Clinical Staging, AIDS surveillance and Mortality in resource-poor settingsa clinician’s view of strategic information needs Charlie Gilks Surveillance, Research Monitoring and Evaluation Department of HIV/AIDS
HIV slowly destroys part of the immune system Infected individuals pass through different stages Advanced infection characterised by a few diseases Death is the ultimate outcome for most ARVs successfully modify the course of disease We are in the “three by five” era Some core concepts
Mortality: resource-rich countries • Universal registration of deaths • Cause of death and predispositions included AIDS-defining diseases (ADDs) HIV often listed as predisposition • electronic linkages with HIV databases • comprehensive data with clear time trends • counting deaths is a HUGE advocacy tool
Annual number of reported HIV-related deaths, USA, 1991-2001
Mortality: resource-poor countries • Very little vital registration of deaths • HIV or AIDS rarely included • only data come form population-based studies • much extrapolation from demographic data • huge advocacy value of these estimates BUT how can we capture changes with ART? An information gap - better sentinel surveillance ...
AIDS Surveillance • The first Public Health response to the epidemic • The aim is to capture extent of HIV-related disease: - successful in high and some middle income counties - powerful advocacy tool - clear trends with time emerge - enables impact of ART to be seen quickly and clearly • AIDS (Acquired Immune Deficiency Syndrome) is not a single disease entity but a surveillance definition • The CDC case definition has changed 3 times
CDC case definition, 1993 • Laboratory evidence of HIV infection; and • CD4 cell count less than 200 cells/ mm³ orCD4 cells account for fewer than 14 percent of all lymphocytes or • Presence of one or more indicator diseases: • Candidiasis of bronchi, trachea, or lungs;Candidiasis, esophagea;Cervical cancer, invasive;Coccidioidomycosis, disseminated or extrapulmonary; Cryptococcosis, extrapulmonary; Cryptosporidiosis, chronic intestinal (greater than 1 month's duration); Cytomegalovirus disease (other than liver, spleen, or nodes); Cytomegalovirus retinitis (with loss of vision); Encephalopathy, HIV-related;Herpes simplex: chronic ulcer(s) (greater than 1 month's duration); or bronchitis, pneumonitis, or esophagitis; Histoplasmosis, disseminated or extrapulmonary; Isosporiasis, chronic intestinal (greater than 1 month's duration); Kaposi's sarcoma; Lymphoma, Burkitt's (or equivalent term); Lymphoma, immunoblastic (or equivalent term); Lymphoma, primary, of brain; Mycobacterium avium complex or M. kansasii, disseminated or extrapulmonary; Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary); Mycobacterium, other species or unidentified species, disseminated or extrapulmonary; Pneumocystis carinii pneumonia; Pneumonia, recurrent; Progressive multifocal leukoencephalopathy; Salmonella septicemia, recurrent; Toxoplasmosis of brain; Wasting syndrome due to HIV
European case definition, 1993 • Same as CDC 1993 minus CD4 cell count
WHO case definition for AIDS surveillance (Bangui) At least 2 major signs in combination with at least 1 minor sign • Major signs: • Weight loss of at least 10% of body weight • Chronic diarrhoea for > 1 month • Prolonged fever for > 1 month • Minor signs: • Persistent cough for > 1 month • Generalized pruritic dermatitis • History of herpes zoster • Oropharyngeal candidiasis • Chronic progressive or disseminated herpes virus infection • Generalized lymphadenopathy Or generalized KS or cryptococcal meningitis
Expanded WHO case definition for AIDS surveillance (Abidjan) • Laboratory evidence of HIV infection and • One or more of following: • 10% body weight loss or cachexia, with diarrhoea or fever, or both, intermittent or constant, for > 1 month; Cryptoccocal meningitis; pulmonary or extra-pulmonary TB; KS; Neurological impairment sufficient to prevent independent daily activities not known to be due to a condition unrelated to HIV infection; Candidiasis of the oesophagus; Clinically diagnosed life-threatening or recurrent episodes of pneumonia; invasive cervical cancer
Revised Caracas/PAHO AIDS definition • Laboratory evidence of HIV infection and • Cumulative points assigned to following conditions exceed 10 points: • KS (10); Disseminated/extrapulmonary/non-cavity pulmonary TB (10);Oral candidiasis/hairy leukoplasia (5); Pulmonary TB with cavitation or unspecified (5); Herpes zoster in person of 60 years or less (5); central nervous system dysfunction (5); diarrhoea > 1 month (2); fever at least 38 for at least a month (2); cachexia or weight loss of more than 10% (2); asthenia of at least a month (2); persistent dermatitis (2); anaemia, lymphopenia, and/or thrombocytopenia (2); persistent cough or any pneumonia, and/or thrombocytopenia (2); lymphadenopathy of at least 1 cm at at least two non-inguinal sites (2) (number of points in parenthesis)
Brazil, 1998 • Laboratory evidence of HIV infection and • CD4 cell count categories less than 350 cells/ mm³ or • Oral cadidiasis and/or negative delayed hypersensitivity test (DHT) or • At least 3 of the following for > 1 month:generalized lymphadenopathy; diarrhoea; fever;asthenia; night sweats;weight loss of more than 10% of body weight; invasive cervical cancer
Limitations with current AIDS surveillance in low and middle income counties • Several different definitions of AIDS • Not all are biologically consistent (e.g. pTB, bacteria) • Haphazard self reporting systems with (very) incomplete data collection • Assumes a western natural history of disease - most morbidity is with an ADD - all transit through AIDS to death • Provide an incomplete picture of burden of disease • None are congruent with WHO clinical staging
Do we need AIDS surveillance? Clearly YES • to have any handle on the epidemic of disease • to capture changes in the burden of disease • if we want to be able to show impact of ART BUT it needs to be a better tool, more relevant to HIV disease process in resource-poor settings It MUST BE consistent so trends can be compared
Disease Staging • Hierarchical description of disease progression • Has prognostic significance for the patient • In clinical guidelines, help specify when to use antiretroviral therapy • Allows comparability in clinical trials • entry criteria • outcome • especially where immunological markers not available
Survival by clinical staging at enrolment in a cohort of 1371 HIV-infected adults from TASO, Entebbe in a trial of pneumococcal vaccine Time in years
Limitations with current clinical staging • Staging needs revising - interim proposal from 1990 (several inconsistencies and inaccuracies) • Stage 4 does not correspond with “AIDS” (no correspondence between staging & surveillance) • No clinical criteria proposed for how to establish presumptive or definitive staging diagnosis • Different trial centres using different approaches so results may not be easily comparable
Conclusions • HIV/AIDS disease and death has been largely ignored by epidemiologists • AIDS surveillance inconsistent and incomplete • AIDS relates badly to clinical staging (confusing) • Impact of HIV/AIDS on death rarely measured • Approaches used have been non-standardised • Projections and data cannot easily be compared All this untenable as we enter the 3x5 ART era
Strategic Information Needs • Revised and standardised AIDS case definitions • Updated clinical staging with definitions - must ensure staging and AIDS more compatible - do this for both adults and children • Agree practical approach to count HIV-related deaths in sentinel sites • Move fast to establish baselines and standards as interventions rapidly scaled up