Désiré Lucien Dahourou

Pharmacokinetics of Efavirenz at a High Dose of 25 Milligrams per Kilogram per Day in Children 2 to 3 Years Old

ABSTRACT The MONOD ANRS 12206 trial was designated to assess simplification of a successful lopinavir (LPV)-based antiretroviral treatment in HIV-infected children younger than 3 years of age using efavirenz (EFV; 25 mg/kg of body weight/day) to preserve the class of protease inhibitors for children in that age group. In this substudy, EFV concentrations were measured to check the consistency of an EFV dose of 25 mg/kg and to compare it with the 2016 FDA recommended dose. Fifty-two children underwent blood sampling for pharmacokinetic study at 6 months and 12 months after switching to EFV. We applied a Bayesian approach to derive EFV pharmacokinetic parameters using the nonlinear mixed-effect modeling (NONMEM) program. The proportion of midinterval concentrations 12 h after drug intake (C12 h) corresponding to the EFV therapeutic pharmacokinetic thresholds (1 to 4 mg/liter) was assessed according to different dose regimens (25 mg/kg in the MONOD study versus the 2016 FDA recommended dose). With both the 25 mg/kg/day dose and the 2016 FDA recommended EFV dose, simulations showed that the majority of C12 h values were within the therapeutic range (62.6% versus 62.8%). However, there were more children underexposed with the 2016 FDA recommended dose (11.6% versus 1.2%). Conversely, there were more concentrations above the threshold of toxicity with the 25 mg/kg dose (36.2% versus 25.6%), with C12 h values of up to 15 mg/liter. Only 1 of 52 children was switched back to LPV because of persistent sleeping disorders, but his C12 h value was within therapeutic ranges. A high EFV dose of 25 mg/kg per day in children under 3 years old achieved satisfactory therapeutic effective levels. However, the 2016 FDA recommended EFV dose appeared to provide more acceptable safe therapeutic profiles. (This study has been registered at ClinicalTrials.gov under identifier NCT01127204.)

Knowledge, Attitudes and Practices of HIV Positive Breastfeeding Mothers in Prevention of Mother to Child Transmission of HIV in Ouagadougou (Burkina Faso) and Associated Factors

World Health Organization (WHO) places strong emphasis on exclusive breastfeeding of HIV exposed infants during the first 6 months, combined to antiretroviral treatment for mothers and prophylaxis for infants. However, adherence to safe breastfeeding among HIV infected mothers is still a major challenge in Burkina Faso. We conducted a cross sectional study in four hospitals in Ouagadougou, Burkina Faso in order to explore knowledge, attitudes and practices of HIV infected breastfeeding mothers attending selected clinics for Prevention of Mother to Child Transmission of HIV (PMTCT). Two hundred and one HIV infected mothers attended the clinics for their children’s routine medical visit, among them 162 (81%) had chosen breastfeeding. The majority of women (95%) were familiar with PMTCT measures required during pregnancy and childbirth, whereas prevention measures required during breastfeeding period were less mentioned: mothers strict adherence to antiretroviral treatment (48.1%), safe sexual practices (1.85%), cessation of breastfeeding in case of breast infection (6.2%), avoiding traditional enema (36.4%) and stopping breastfeeding at the age of 12 months after 6 months of exclusive breastfeeding along with the introduction of other foods and fluids (43.2%). Moreover, 52.2% of women did not practice exclusive breastfeeding during the first six months. Factors associated with poor breastfeeding practices were: infant feeding option decided solely by the mother, living in well serviced areas and having a low score (≤ 3) of knowledge on how to prevent HIV transmission during breastfeeding. There is a need for urgent interventions in support of safe breastfeeding in HIV exposed infants in Ouagadougou.

Factors associated with tuberculosis treatment failure in the Central East Health region of Burkina Faso

Introduction Tuberculosis treatment failure results in increased risk of morbidity, drug resistance, transmission and mortality. There are few data about tuberculosis treatment outcomes in Burkina Faso. The current study investigated the factors associated with tuberculosis treatment failure in the central east health region of Burkina Faso. Methods We conducted a case-control study. All cases of pulmonary tuberculosis failing first-line treatment matched to those who were cured (controls) in the Central Eastern Region were sampled from January 2010 to December 2014. Predictors of treatment failure were determined using multiple conditional logistic regression. Results A total of 381 patients with positive microscopic pulmonary tuberculosis were included. Of these 76 cases failed first-line treatment while 305 controls were cured. Weight loss between diagnosis and first sputum-smear examination was significantly associated with the tuberculosis treatment failure [aOR: 2.5, 95% CI: 1.3-4.7]. In addition, the delay from between treatment initiation to first sputum-smear examination, and high bacillary load at the first sputum-smear examination were significantly associated with treatment failure (p<0.001). Conclusion Strengthening the relationship between health care services and local communities to improve the follow-up of tuberculosis patients, and improving adherence to tuberculosis treatment among tuberculosis patients with weight loss between treatment initiation and 2-month sputum-smear examination could be useful to reduce the risk of unsuccessful outcome.