Presumptive diagnosis of severe HIV infection to determine the need for antiretroviral therapy in children less than 18 months of age

Grundmann, Nicolas K.; Iliff, Peter; Stringer, Jeff; Wilfert, Catherine M.

doi:10.2471/blt.11.085977

Cited by 7 publications

(7 citation statements)

References 20 publications

(28 reference statements)

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“…The accessibility, accuracy and false positive rates of HIV-1 proviral DNA PCR in some resource-limited countries are far from ideal, especially with older assays[24], and children are started on ART without confirmation of HIV status [25]. There are anecdotal reports that caregivers not infrequently doubt the initial diagnosis and request confirmation from healthcare practitioners, or purchase over-the-counter rapid antibody tests, which are increasingly available.…”

Section: Discussionmentioning

confidence: 99%

Reactivity of routine HIV antibody tests in children who initiated antiretroviral therapy in early infancy as part of the Children with HIV Early Antiretroviral Therapy (CHER) trial: a retrospective analysis

Payne

Mkhize

Otwombe

et al. 2015

The Lancet Infectious Diseases

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Background Early ART and virological suppression may impact on evolving antibody responses to HIV-infection. We evaluated frequency and predictors of seronegativity in infants starting early ART. Methods HIV-antibody results were compared between two of three arms of the Children with HIV Early Antiretroviral Therapy (CHER) trial: HIV-infected infants aged <12 weeks with CD4 ≥25% randomised to early-limited ART for 96 weeks (ART-96W) or deferred ART until clinical/immunological progression (ART-Def). HIV-infection was diagnosed by DNA PCR and RNA >1000 copies/ml. ART started at median age 7 and 23 weeks respectively. Antibody was measured from all available stored samples, ART-96W (n=109) and ART-Def (n=75), at trial week 84 (median age 92 (IQR 90.6–93.4) weeks) using 3 assays: 4th generation EIA HIV-antigen/antibody combination; HIV-1/2 rapid-antibody test and quantitative anti-gp120 IgG ELISA. Findings More ART-96W were seronegative than ART-Def by EIA (46% versus 11%, p<0.0001) and rapid-antibody test (53% versus 14%, p<0.0001). Anti-gp120 IgG was lower in ART-96W versus ART-Def (median 230 (133–13,129) versus 6,870 (IQR 1,706–53,645)μg/μl). Starting ART between 12-24 versus 0-12 weeks increased odds of seropositivity 13.7-fold (95%CI 3.1-60.2). All children starting ART aged >24 weeks were seropositive. Cumulative viral load to week 84 correlated with anti-gp120 IgG levels (coefficient=0.54, p<0.0001) and increased odds of seropositivity OR 1.58 (95%CI 1.1-2.3) adjusted for ART-initiation age. Interpretation Almost half children starting ART before aged 12 weeks were HIV-seronegative by at aged ∼2 years. HIV-antibody tests cannot be used to re-confirm HIV-diagnosis in children starting early-ART. Long-term consequences of seronegativity need further study. Funding Wellcome Trust, Medical Research Council, National Institutes of Health.

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Section: Discussionmentioning

confidence: 99%

Reactivity of routine HIV antibody tests in children who initiated antiretroviral therapy in early infancy as part of the Children with HIV Early Antiretroviral Therapy (CHER) trial: a retrospective analysis

Payne

Mkhize

Otwombe

et al. 2015

The Lancet Infectious Diseases

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“…At the least, presumptive diagnosis strategies should be individualized and discussed with caregivers, because although the risk of ART-associated toxicity is low, it is not insignificant. Sensitivity of this approach may be improved to 70–80% by combining antibody testing with clinical criteria and CD4 + cell measurements [48,50]. However, in settings in which virologic testing is absent, CD4 + cell measurement is often also unavailable.…”

Section: Promising Strategies For Pediatric Case Findingmentioning

confidence: 99%

Beyond early infant diagnosis

Ahmed¹,

Kim²,

Sugandhi

et al. 2013

Aids

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There are 3.4 million children infected with HIV worldwide, with up to 2.6 million eligible for treatment under current guidelines. However, roughly 70% of infected children are not receiving live-saving HIV care and treatment. Strengthening case finding through improved diagnosis strategies, and actively linking identified HIV-infected children to care and treatment is essential to ensuring that these children benefit from the care and treatment available to them. Without attention or advocacy, the majority of these children will remain undiagnosed and die from complications of HIV. In this article, we summarize the challenges of identifying HIV-infected infants and children, review currently available evidence and guidance, describe promising new strategies for case finding, and make recommendations for future research and interventions to improve identification of HIV-infected infants and children.

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“…Las recomendaciones de la OMS sobre diagnóstico de la infección por VIH en niños establecen que en caso de que no se disponga de pruebas virológi-cas, se podrá realizar un diagnóstico presuntivo de infección basado en síntomas y signos y test rápido serológico positivo, con confirmación posterior de la infección basada en técnicas serológicas a partir de los 18 meses de edad. Sin embargo, la sensibilidad y la especificidad de esta aproximación diagnóstica son muy variables 21,22 . Además, los niños con infección por VIH que inician TAR precoz pueden no tener respuesta serológica y presentar anticuerpos frente al VIH negativos, a pesar de estar realmente infectados 23 .…”

Section: Discussionunclassified

Evaluación inicial del programa de prevención de la transmisión materno-infantil de la infección por el virus de la inmunodeficiencia humana en Guinea Ecuatorial

Badillo-Navarro

Prieto-Tato

Obiang-Esomoyo³

et al. 2014

Enfermedades Infecciosas y Microbiología Clínica

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Presumptive diagnosis of severe HIV infection to determine the need for antiretroviral therapy in children less than 18 months of age

Cited by 7 publications

References 20 publications

Reactivity of routine HIV antibody tests in children who initiated antiretroviral therapy in early infancy as part of the Children with HIV Early Antiretroviral Therapy (CHER) trial: a retrospective analysis

Reactivity of routine HIV antibody tests in children who initiated antiretroviral therapy in early infancy as part of the Children with HIV Early Antiretroviral Therapy (CHER) trial: a retrospective analysis

Beyond early infant diagnosis

Evaluación inicial del programa de prevención de la transmisión materno-infantil de la infección por el virus de la inmunodeficiencia humana en Guinea Ecuatorial

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