Virological response and resistances over 12 months among HIV-infected children less than two years receiving first-line lopinavir/ritonavir-based antiretroviral therapy in Cote d'Ivoire and Burkina Faso: the MONOD ANRS 12206 cohort.

INTRODUCTION: Lopinavir/ritonavir-based antiretroviral therapy (ART) is recommended for all HIV-infected children less than three years. However, little is known about its field implementation and effectiveness in West Africa. We assessed the 12-month response to lopinavir/ritonavir-based antiretroviral therapy in a cohort of West African children treated before the age of two years. METHODS: HIV-1-infected, ART-naive except for a prevention of mother-to-child transmission (PMTCT), tuberculosis-free, and less than two years of age children with parent's consent were enrolled in a 12-month prospective therapeutic cohort with lopinavir/ritonavir ART and cotrimoxazole prophylaxis in Ouagadougou and Abidjan. Virological suppression (VS) at 12 months (viral load [VL] <500 copies/mL) and its correlates were assessed. RESULTS: Between May 2011 and January 2013, 156 children initiated ART at a median age of 13.9 months (interquartile range: 7.8-18.4); 63% were from Abidjan; 53% were girls; 37% were not exposed to any PMTCT intervention or maternal ART; mother was the main caregiver in 81%; 61% were classified World Health Organization Stage 3 to 4. After 12 months on ART, 11 children had died (7%), 5 were lost-to-follow-up/withdrew (3%), and VS was achieved in 109: 70% of children enrolled and 78% of those followed-up. When adjusting for country and gender, the access to tap water at home versus none (adjusted odds ratio (aOR): 2.75, 95% confidence interval (CI): 1.09-6.94), the mother as the main caregiver versus the father (aOR: 2.82, 95% CI: 1.03-7.71), and the increase of CD4 percentage greater than 10% between inclusion and 6 months versus <10% (aOR: 2.55, 95% CI: 1.05-6.18) were significantly associated with a higher rate of VS. At 12 months, 28 out of 29 children with VL ≥1000 copies/mL had a resistance genotype test: 21 (75%) had ≥1 antiretroviral (ARV) resistance (61% to lamivudine, 29% to efavirenz, and 4% to zidovudine and lopinavir/ritonavir), of which 11 (52%) existed before ART initiation. CONCLUSION: Twelve-month VS rate on lopinavir/ritonavir-based ART was high, comparable to those in Africa or high-income countries. The father as the main child caregiver and lack of access to tap water are risk factors for viral failure and justify a special caution to improve adherence in these easy-to-identify situations before ART initiation. Public health challenges remain to optimize outcomes in children with earlier ART initiation in West Africa.

Modeling the variability of creatinine measurements improves estimates of the glomerular filtration rate.

BACKGROUND: The precision of the formulae used to estimate glomerular filtration rate (GFR) decreases when the serum creatinine (SCr) assay is biased compared with the assay used during the development of the formulae. METHODS: For 100 children referred for 51Cr-EDTA clearance (CLEDTA), SCr was measured with a JAFFE (classic Jaffe colorimetric creatinine assay), a compensated Jaffe (COMP), an enzymatic (ENZ) and an HPLC assay. A population pharmacokinetics approach based on a non-linear mixed effects model (NONMEM) was used to model the relationships between the CLEDTA and physiopathological/analytical variables. RESULTS: Unlike JAFFE values, COMP and ENZ SCr gave a high bias using the Schwartz formula for the GFR calculation (median +27.0% and +39.1%, respectively). The best equation obtained from the analysis of the curves of [51Cr-EDTA]plasma vs. time was (n=67): CLEDTA (mL/min)=61.9 x [SCr (microM)/Theta]Psi x [age (years)/13.4]0.522 x (weight (kg)/44.2)0.233. The SCr assay-related coefficients and exponents were Theta=97.4, Psi=-0.757 (-0.922; -0.592) for JAFFE; Theta=85.3, Psi=-0.579 (-0.681; -0.477) for COMP; and Theta=82.6, Psi=-0.560 (-0.659; -0.460) for ENZ. When applied to 33 children, this equation estimated CL(EDTA) without any significant bias: +3.1% (-11.8; +11.4) for COMP and +5.3% (-7.2; +16.4) for ENZ. CONCLUSIONS: As long as there is no standardization of SCr measurements, population pharmacokinetics may be a powerful tool to model inter-assay variability.