Nevirapine concentrations in HIV-infected children treated with divided fixed-dose combination antiretroviral tablets in Malawi and Zambia.

OBJECTIVE: To investigate nevirapine concentrations in African HIV-infected children receiving divided Triomune tablets (stavudine+lamivudine+nevirapine). DESIGN: Cross-sectional study. METHODS: Steady-state plasma nevirapine concentrations were determined in Malawian and Zambian children aged 8 months to 18 years receiving Triomune in routine outpatient settings. Predictors from height-for-age, body mass index (BMI)-for-age, age, sex, post-dose sampling time and dose/m2/day were investigated using centre-stratified regression with backwards elimination (P<0.1). RESULTS: Of the 71 Malawian and 56 Zambian children (median age 8.4 vs 8.5 years, height-for-age -3.15 vs -1.84, respectively), only 1 (3%) of those prescribed > or =300 mg/m2/day nevirapine had subtherapeutic concentrations (<3 mg/l) compared with 22 (23%) of those prescribed <300 mg/m2/day; most children with subtherapeutic nevirapine concentrations were taking half or quarter Triomune tablets. Lower nevirapine concentrations were independently associated with lower height-for-age (indicating stunting) (0.37 mg/l per unit higher [95% confidence interval (CI): -0.003, +0.74]; P=0.05), lower prescribed dose/m2 (+0.89 mg/l per 50 mg/m2 higher [95% CI: 0.32, 1.46]; P=0.002) and higher BMI-for-age (indicating lack of wasting) (-0.42 mg/l per unit higher [95% CI: -0.80, -0.04]; P=0.03). CONCLUSIONS: Currently available adult fixed-dose combination tablets are not well suited to children, particularly at younger ages: Triomune 30 is preferable to Triomune 40 because of the higher dose of nevirapine relative to stavudine. Further research is required to confirm that concentrations are reduced in stunted children but increased in wasted children. Development of appropriate paediatric fixed-dose combination tablets is essential if antiretroviral therapy is to be made widely available to children in resource-limited settings.

Healthy Neonates Possess a CD56-Negative NK Cell Population with Reduced Anti-Viral Activity.

BACKGROUND: Neonatal Natural Killer (NK) cells show functional impairment and expansion of a CD56 negative population of uncertain significance. METHODS: NK cells were isolated from cord blood and from adult donors. NK subpopulations were identified as positive or negative for the expression of CD56 and characterized for expression of granzyme B and surface markers by multi-parameter flow cytometry. Cell function was assessed by viral suppression and cytokine production using autologous lymphocytes infected with HIV. Activating (NKp30, NKp46) and inhibitory (Siglec-7) markers in healthy infants and adults were compared with viremic HIV-infected adults. RESULTS: Cord blood contained increased frequencies of CD56 negative (CD56neg) NK cells with reduced expression of granzyme B and reduced production of IFNγ and the CC-class chemokines RANTES, MIP1α and MIP1ß upon stimulation. Both CD56pos and CD56neg NK subpopulations showed impaired viral suppression in cord blood, with impairment most marked in the CD56neg subset. CD56neg NK cells from cord blood and HIV-infected adults shared decreased inhibitory and activating receptor expression when compared with CD56pos cells. CONCLUSIONS: CD56neg NK cells are increased in number in normal infants and these effectors show reduced anti-viral activity. Like the expanded CD56neg population described in HIV-infected adults, these NK cells demonstrate functional impairments which may reflect inadequate development or activation.

Utility of red cell distribution width in screening for iron deficiency.

AIMS: To assess the sensitivity of an adult-derived red cell distribution width (RDW) reference limit in the detection of iron deficiency in young children. METHODS: Haematological analysis performed on a cohort of 13-month-old healthy term infants of North European ancestry. RESULTS: 21/98 infants were iron-deficient (>2.5% hypochromic red cells). Of the remaining 77, 35 with RDW >13.9% also had evidence of incipient iron deficiency on the basis of significantly lower haemoglobin (11.5 vs 11.8 g/dl, p=0.046), mean cell volume (75.6 vs 77.8 fl, p=0.002) and mean cell haemoglobin (25.4 vs 26.2 pg, p=0.002) values and higher zinc protoporphyrin (55 vs 44 µmol/molhaem, p<0.001) values than those of the 42 with RDW ≤13.9%. CONCLUSIONS: An adult-derived RDW reference limit has utility in screening for iron deficiency at the age of 13 months. The incidence of non-anaemic iron deficiency in this group was 52.8%.