Validation of 2006 WHO Prediction Scores for True HIV Infection in Children Less than 18 Months with a Positive Serological HIV Test

All infants born to HIV-positive mothers have maternal HIV antibodies, sometimes persistent for 18 months. When Polymerase Chain Reaction (PCR) is not available, August 2006 World Health Organization (WHO) recommendations suggest that clinical criteria may be used for starting antiretroviral treatment (ART) in HIV seropositive children <18 months. Predictors are at least two out of sepsis, severe pneumonia and thrush, or any stage 4 defining clinical finding according to the WHO staging system.From January 2005 to October 2006, we conducted a prospective study on 236 hospitalized children <18 months old with a positive HIV serological test at the national reference hospital in Kigali. The following data were collected: PCR, clinical signs and CD4 cell count. Current proposed clinical criteria were present in 148 of 236 children (62.7%) and in 95 of 124 infected children, resulting in 76.6% sensitivity and 52.7% specificity. For 87 children (59.0%), clinical diagnosis was made based on severe unexplained malnutrition (stage 4 clinical WHO classification), of whom only 44 (50.5%) were PCR positive. Low CD4 count had a sensitivity of 55.6% and a specificity of 78.5%.As PCR is not yet widely available, clinical diagnosis is often necessary, but these criteria have poor specificity and therefore have limited use for HIV diagnosis. Unexplained malnutrition is not clearly enough defined in WHO recommendations. Extra pulmonary tuberculosis (TB), almost impossible to prove in young children, may often be the cause of malnutrition, especially in HIV-affected families more often exposed to TB. Food supplementation and TB treatment should be initiated before starting ART in children who are staged based only on severe malnutrition

Validation of 2006 WHO Prediction Scores for True HIV Infection in Children Less than 18 Months with a Positive Serological HIV Test

All infants born to HIV-positive mothers have maternal HIV antibodies, sometimes persistent for 18 months. When Polymerase Chain Reaction (PCR) is not available, August 2006 World Health Organization (WHO) recommendations suggest that clinical criteria may be used for starting antiretroviral treatment (ART) in HIV seropositive children <18 months. Predictors are at least two out of sepsis, severe pneumonia and thrush, or any stage 4 defining clinical finding according to the WHO staging system.From January 2005 to October 2006, we conducted a prospective study on 236 hospitalized children <18 months old with a positive HIV serological test at the national reference hospital in Kigali. The following data were collected: PCR, clinical signs and CD4 cell count. Current proposed clinical criteria were present in 148 of 236 children (62.7%) and in 95 of 124 infected children, resulting in 76.6% sensitivity and 52.7% specificity. For 87 children (59.0%), clinical diagnosis was made based on severe unexplained malnutrition (stage 4 clinical WHO classification), of whom only 44 (50.5%) were PCR positive. Low CD4 count had a sensitivity of 55.6% and a specificity of 78.5%.As PCR is not yet widely available, clinical diagnosis is often necessary, but these criteria have poor specificity and therefore have limited use for HIV diagnosis. Unexplained malnutrition is not clearly enough defined in WHO recommendations. Extra pulmonary tuberculosis (TB), almost impossible to prove in young children, may often be the cause of malnutrition, especially in HIV-affected families more often exposed to TB. Food supplementation and TB treatment should be initiated before starting ART in children who are staged based only on severe malnutrition

Clinical and laboratory side effects.

<p>*other included fatigue, anxiety and nightmares.</p><p>Clinical and laboratory side effects.</p

Number of children with virological failure^* over time.

<p>*Virological failure defined as VL≥1000 copies/mL for one measurement;</p><p>**between group comparisons.</p><p><b>P values bold:</b> significant difference at p<0.05.</p><p>Number of children with virological failure^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111948#nt105" target="_blank">*</a>} over time.</p

Mid-Dosing Interval Efavirenz Plasma Concentrations in HIV-1-Infected Children in Rwanda: Treatment Efficacy, Tolerability, Adherence, and the Influence of CYP2B6 Polymorphisms

This study evaluated mid-dosing interval efavirenz plasma concentrations and the influence of CYP2B6 polymorphisms in relation to efficacy, tolerability, and adherence in 97 Rwandan HIV-infected children (3-16 years). Plasma drug concentrations and CYP2B6 polymorphisms were determined. Ten children were excluded for nonadherence. Large intersubject variability in efavirenz plasma concentrations was found. Of the 87 remaining, efavirenz concentrations were therapeutic, supratherapeutic, and subtherapeutic in 67%, 20%, and 14%, respectively. No associations were found between efavirenz concentrations and central nervous system disturbances or virologic failure. Minor allele frequencies were 0.32 (516G>T), 0.33 (785A>G), and 0.09 (983T>C). Polymorphisms in CYP2B6 were strongly associated with high efavirenz level