aDepartment of Global Health, University of Washington, Seattle, Washington, USA bThematic Unit of Pharmacology, Department of Clinical Medicine and Therapeutics, University of Nairobi, Nairobi, Kenya cDepartment of Biostatistics, University of Washington, Seattle, Washington, USA dDepartment of Pediatrics and Child Health, University of Nairobi, Nairobi, Kenya eDivision of Allergy and Infectious Diseases, Department of Medicine, University of Washington fDivision of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA. *Lara C. Diener and Jennifer A. Slyker contributed equally to the writing of this article.
Early infant HIV-1 diagnosis and treatment substantially improve survival. Where virologic HIV-1 testing is unavailable, integrated management of childhood illness (IMCI) clinical algorithms may be used for infant HIV-1 screening. We evaluated the performance of the 2008 WHO IMCI HIV algorithm in a cohort of HIV-exposed Kenyan infants.
From 1999 to 2003, 444 infants had monthly clinical assessments and quarterly virologic HIV-1 testing. Using archived clinical data, IMCI sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using virologic testing as a gold standard. Linear regression and survival analyses were used to determine the effect of age on IMCI performance and timing of diagnosis.
Overall IMCI sensitivity, specificity, PPV, and NPV value were 58, 87, 52, and 90%, respectively. Sensitivity (1.4%) and PPV (14%) were lowest at 1 month of age, when 81% of HIV infections already had occurred. Sensitivity increased with age (P < 0.0001), but remained low throughout infancy (range 1.4-35%). Specificity (range 97-100%) was high at each time point and was not associated with age. Fifty-eight percent of HIV-1-infected infants (50 of 86) were eventually diagnosed by IMCI, and use of IMCI was estimated to delay diagnosis in HIV-infected infants by a median of 5.9 months (P < 0.0001).
IMCI had low sensitivity during the first month of life, when the majority of HIV-1 infections had already occurred and initiation of treatment is most critical. Although sensitivity increased with age, the substantial delay in HIV-1 diagnosis using IMCI limits its utility in early infant HIV-1 diagnosis.
[Show abstract][Hide abstract] ABSTRACT: Although antiretroviral treatment (ART) has reduced the incidence of HIV-related opportunistic infections among children living with HIV, access to ART remains limited for children, especially in resource-limited settings. This paper reviews current knowledge on the contribution of opportunistic infections and common childhood illnesses to morbidity and mortality in children living with HIV, highlights interventions known to improve the health of children, and identifies research gaps for further exploration.
Literature review of peer-reviewed articles and abstracts combined with expert opinion and operational experience.
Morbidity and mortality due to opportunistic infections has decreased in both developed and resource-limited countries. However, the burden of HIV-related infections remains high, especially in sub-Saharan Africa, where the majority of HIV-infected children live. Limitations in diagnostic capacity in resource-limited settings have resulted in a relative paucity of data on opportunistic infections in children. Additionally, the reliance on clinical diagnosis means that opportunistic infections are often confused with common childhood illnesseswhich also contribute to excess morbidity and mortality in these children. Although several preventive interventions have been shown to decrease opportunistic infection-related mortality, implementation of many of these interventions remains inconsistent.
In order to reduce opportunistic infection-related mortality, early ART must be expanded, training for front-line clinicians must be improved, and additional research is needed to improve screening and diagnostic algorithms.
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