After 6 months of breast-feeding, no child out of the 13 had been infected with HIV and all had good psychomotor and growth development. Our results suggest that EFV may be an alternative to nevirapine (NVP) during the third trimester of pregnancy and during the breast-feeding period. Further studies on larger groups of newborns will be necessary to get a better understanding of possible prophylactic protection of the newborns by highly active antiretroviral therapy with EFV given to the mothers.

Cytochrome P450 CYP2B6 is a highly polymorphic enzyme that metabolizes numerous drugs, pesticides, and environmental toxins. Sequence analysis of a Rwandese population identified eight functionally uncharacterized nonsynonymous variants c.329G>T (p.G110V), c.341T>C (p.I114T), c.444G>T (p.E148D), c.548T>G (p.V183G), c.637T>C (p.F213L), c.758G>A (p.R253H), c.835G>C (p.A279P), and c.1459C>A (p.R487S), and five novel alleles termed CYP2B6*33 to CYP2B6*37 were assigned. Recombinant expression in COS-1 cells and functional characterization using the antidepressant bupropion and the antiretroviral efavirenz (EFV) as substrates demonstrated complete or almost complete loss-of-function for variants p.G110V, p.I114T, p.V183G, and p.F213L, whereas p.E148D, p.R253H, p.A279P, and p.R487S variants were functional. The data were used to assess the predictive power of eight online available functional prediction programs for amino-acid changes. Although none of the programs correctly predicted the functionality of all variants, substrate docking simulation analyses indicated similar conformational changes by all four deleterious mutations within the enzyme's active site, thus explaining lack of enzymatic function for both substrates. Because low-activity alleles of CYP2B6 are associated with impaired EFV metabolism and adverse drug response, these results are of potential utility for personalized treatment strategies in HIV/AIDS therapy.

Saliva may provide interesting advantages as matrix for compliance measurements, pharmacokinetic studies and therapeutic drug monitoring in resource limited countries. We investigated the feasibility of using saliva for compliance monitoring of zidovudine (ZDV), lamivudine (3TC) and nevirapine (NVP) in 29 HIV-1 infected patients from Rwanda. ZDV, 3TC and NVP drug levels were quantified by an LC/MS-MS method in plasma and stimulated saliva samples and compared using Bland-Altman analysis. Seven patients demonstrated undetectable saliva ZDV levels while five out of these seven also showed no 3TC salivary concentrations. For the other samples, we observed a good agreement between salivary and plasma concentrations of each antiretroviral drug. A significant relation between the difference in saliva and plasma ZDV concentrations and the average ZDV concentration in the two matrices was deduced as follows: y = -380.15 + 1.79 x. The log saliva and plasma concentration difference of both 3TC and NVP was consistent across the range of average log concentration. Overall, we showed large agreement limits suggesting a wide inter patient variability that may result in non-reliable plasma level predictions from saliva drug measurements. Therefore, our results indicate that saliva may serve as a valuable tool only for NVP compliance testing because of its high salivary concentration.

-Purpose: Recent improvements to the availability of antiretroviral therapy in Sub-Saharan Africa can be attributed to the generic formulation of antiretroviral drugs. Quality drug surveillance, routine supervision and adherence data are however restricted owing to a fundamental lack of resources in the area. Accordingly we have developed an affordable micellar electrokinetic capillary chromatography (MEKC) method for the simultaneous detection and quantification of zidovudine, stavudine, lamivudine and nevirapine in plasma. Methods: The antiretroviral drugs were extracted by solid phase extraction. Various factors influencing separation of the four drugs have been optimized. A buffer consisting of 5 mM sodium tetraborate at pH 9.8, containing 50 mM SDS, 30% methanol and 5% ethanol was found to be particularly suitable and the MEKC method was validated. Results: All validation parameters were within the 20% acceptation limit, except for the interday precision of stavudine which required a daily calibration curve. The limit of quantification (LOQ) for zidovudine, stavudine, lamivudine and nevirapine were 0.037, 0.051, 0.029 and 0.028 mg/L respectively and were below the therapeutic concentration ranges of each drug. The optimized MEKC method was successfully applied to 16 human plasma samples. Conclusion: Our sensitive and validated method was demonstrated to be suitable for simultaneous detection and quantification of zidovudine, stavudine, lamivudine and nevirapine. This cost-effective method could be of interest for resource limited countries not only for adherence or therapeutic monitoring but also for steady-state pharmacokinetic studies of generic ARV drugs.Key words: Capillary electrophoresis, drug monitoring, highly active antiretroviral therapy, Micellar Electrokinetic Capillary Chromatography, plasma Résumé -Objectif : L'accès aux thérapies antirétrovirales en Afrique sub-saharienne s'est récemment nettement amélioré grâce à l'apparition des antirétroviraux sous la forme de génériques. Cependant, la surveillance de la qualité des médicaments, le suivi thérapeutique de routine et les données concernant l'observance restent limités dans ces régions du fait du manque de ressources. Par conséquent, nous avons développé une méthode de chromatographie électrocinétique micellaire (CEM) à faible coût permettant la détection et la quantification simultanée de zidovudine, stavudine, lamivudine et névirapine dans le plasma. Méthodes : Une extraction en phase solide a été réalisée afin d'isoler les médicaments antirétroviraux. Différents facteurs influençant la séparation des quatre composants ont été optimisés. Un tampon constitué de tétraborate de sodium 5 mM à pH 9,8, contenant 50 mM de SDS, 30 % méthanol et 5 % éthanol s'avérait le plus adéquat et la méthode CEM a été validée. zidovudine, de la stavudine, de la lamivudine et de la névirapine étaient respectivement de 0,037, 0,051, 0,029 et 0,028 mg/L, par conséquent, inférieures aux concentrations thérapeutiques de chaque médicament. Seize plasmas huma...