ABSTRACT
INTRODUCTION: Early diagnosis and treatment is necessary to prevent HIV-infected infants progressing to AIDS. Antibody testing is not confirmatory before the age of 18 months and PCR not widely available in resource-poor settings. We studied the accuracy of CD4(+) T-lymphocyte count, CD4% and CD4/CD8 ratio as surrogate markers of infant HIV infection. METHODS: Two hundred and fifty-eight HIV-exposed Indian infants at a median age of 5 months (range 1-18) had DNA PCR and CD4, CD8 counts performed. RESULTS: Fifty five infants tested positive by HIV-1 DNA PCR whereas 203 were negative. Median CD4 count, CD4% and CD4/CD8 ratio were significantly lower in DNA PCR+ infants. Overall sensitivity and specificity of CD4/CD8 ratio <1.0 in predicting HIV was 91 and 92% with a negative predicted value (NPV) and positive predicted value (PPV) of 97 and 76%, respectively. CONCLUSION: CD4/CD8 ratio <1.0 is a more sensitive surrogate marker of HIV infection in Indian infants than a CD4 count <1500 cells/µl or CD4% <25%.
Subject(s)
CD4-CD8 Ratio , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , HIV Infections/immunology , Anti-HIV Agents/therapeutic use , Biomarkers/blood , Female , Flow Cytometry , HIV Infections/blood , HIV Infections/diagnosis , HIV Infections/virology , HIV-1 , Humans , India , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical , Lymphocyte Count , Male , Polymerase Chain Reaction , Predictive Value of Tests , Prospective Studies , Sensitivity and Specificity , Sex DistributionABSTRACT
BACKGROUND: Nevirapine is an important component of paediatric combination HIV therapy. Adequate drug exposure is necessary in order to achieve long-lasting viral suppression. OBJECTIVES: To study the influence of age, drug dose and formulation type, nutritional status and CYP2B6 516G>T polymorphism on blood concentrations of nevirapine in children treated with generic antiretroviral drugs. METHODS: A multicentre study was conducted at four sites in India. HIV-infected children receiving generic nevirapine-based fixed-dose combinations were recruited. Trough and 2 h nevirapine plasma concentrations were determined by HPLC. Characterization of the CYP2B6 gene polymorphism was performed using direct sequencing. Clinical and nutritional status was recorded. Groups were compared using the Mann-Whitney U-test and multivariable logistic regression analysis was performed to identify factors contributing to low drug levels. RESULTS: Ninety-four children of median age 78 months were studied; 60% were undernourished or stunted. Stunted children had a significantly lower 2 h nevirapine concentration compared with non-stunted children (Pâ<â0.05); there were no significant differences in trough concentrations between different nutritional groups. Nevirapine levels were significantly higher in children with TT compared with GG and GT CYP2B6 genotypes (Pâ<â0.01). Children ≤ 3 years had a 3.2 (95% confidence interval 1.07-9.45) times higher risk of having sub-therapeutic nevirapine concentrations. CONCLUSIONS: Nevirapine blood concentrations are affected by many factors, most notably age ≤ 3 years; a combination of young age, stunting and CYP2B6 GG or GT genotype could potentially result in sub-therapeutic nevirapine concentrations. Dosing recommendations for children should be reviewed in the light of these findings.
