HIV stigma limits the effectiveness of PMTCT in Guinea: the ANRS 12344-DIAVINA study.

BACKGROUND: Nearly half of HIV-infected children worldwide are born in West and Central African countries where access to prevention of mother-to-child transmission of HIV (PMTCT) programmes is still limited. WHO recommends reinforced antiretroviral prophylaxis for infants at high risk of mother-to-child transmission of HIV (MTCT) but its implementation needs further investigation in the field. METHODS: The prospective ANRS 12344-DIAVINA study evaluated the feasibility of a strategy combining early infant diagnosis (EID) and reinforced antiretroviral prophylaxis in high-risk infants as identified by interviews with mothers at Ignace Deen Hospital, Conakry, Guinea. RESULTS: 6493 women were admitted for delivery, 6141 (94.6%) accepted HIV testing and 114 (1.9%) were HIV positive. Among these, 51 high-risk women and their 56 infants were included. At birth, a blood sample was collected for infant EID and reinforced antiretroviral prophylaxis was initiated in 48/56 infants (86%, 95% CI 77%-95%). Iron supplementation was given to 35% of infants for non-severe anaemia. Retrospective measurement of maternal plasma viral load (pVL) at delivery revealed that 52% of women had pVL < 400 copies/mL attributable to undisclosed HIV status and/or antiretroviral intake. Undisclosed HIV status was associated with self-stigmatization (85% versus 44%, P = 0.02). Based on the results of maternal pVL at delivery, 'real' high-risk infants were more frequently lost to follow-up (44% versus 8%, P < 0.01) in comparison with low-risk infants, and this was associated with mothers' stigmatization (69% versus 31%, P < 0.01). CONCLUSIONS: Reinforced antiretroviral prophylaxis and EID at birth are widely feasible. However, mothers' self-disclosure of HIV status and antiretroviral intake do not allow adequate evaluation of MTCT risk, which argues for maternal pVL measurement near delivery. Furthermore, actions against stigmatization are crucial to improve PMTCT.

Early Bacterial Infections After Pediatric Liver Transplantation in the Era of Multidrug-resistant Bacteria: Nine-year Single-center Retrospective Experience.

BACKGROUND: Early bacterial infection is a major and severe complication after liver transplantation (LT). The rise of antimicrobial resistance, especially extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE), is a growing concern for these patients. This study aimed to assess the epidemiology of early bacterial infections in a pediatric population, including those caused by multidrug-resistant (MDR) pathogens, and to identify risk factors for infection. METHODS: We conducted a monocentric retrospective study including 142 consecutive LTs performed in 137 children between 2009 and 2017. RESULTS: Ninety-three bacterial infections occurred after 67 (47%) LTs. Among the 82 isolated pathogens, the most common was Klebsiella pneumoniae (n = 19, 23%). Independent risk factors for early bacterial infection were low weight [odds ratio (OR) = 0.96; 95% confidence interval (CI): 0.9-0.99; P = 0.03] and the presence of a prosthetic mesh (OR = 2.4; 95% CI: 1.1-5.4; P = 0.046). Sixty-one children (45%) carried MDR bacteria and 16 infections were caused by MDR pathogens, especially ESBL-producing K. pneumoniae (n = 12). ESBL-PE stool carriage was associated with ESBL-PE infection (OR = 4.5; 95% CI: 1.4-17.4; P = 0.02). Four children died from an infection, three due to ESBL-producing K. pneumoniae. CONCLUSIONS: This study confirmed a shift toward a predominance of Gram-negative early bacterial infections after pediatric LT. The risk factors for infection were low weight and the presence of a prosthetic mesh. ESBL-PE stool carriage was associated with ESBL-PE infection. Adapted antimicrobial prophylaxis and personalized antibiotherapy are mandatory to reduce infection prevalence and mortality.

Determination of optimal vitamin D3 dosing regimens in HIV-infected paediatric patients using a population pharmacokinetic approach.

AIMS: To investigate 25-hydroxycholecalciferol [25(OH)D] population pharmacokinetics in children and adolescents, to establish factors that influence 25(OH)D pharmacokinetics and to assess different vitamin D3 dosing schemes to reach sufficient 25(OH)D concentrations (>30 ng ml(-1) ). METHODS: This monocentric prospective study included 91 young HIV-infected patients aged 3 to 24 years. Patients received a 100 000 IU vitamin D3 supplementation. A total of 171 25(OH)D concentrations were used to perform a population pharmacokinetic analysis. RESULTS: At baseline 28% of patients had 25(OH)D concentrations below 10 ng ml(-1) , 69% between 10 and 30 ng ml(-1) and 3% above 30 ng ml(-1) . 25(OH)D pharmacokinetics were best described by a one compartment model with an additional production parameter reflecting the input from diet and sun exposure. The effects of skin phototype and bodyweight were significant on 25(OH)D production before any supplementation. The basal level was 27% lower in non-white skin phototype patients and was slightly decreased with bodyweight. No significant differences in 25(OH)D concentrations were related to antiretroviral drugs. To obtain concentrations between 30 and 80 ng ml(-1) , patients with baseline concentrations between 10 and 30 ng ml(-1) should receive 100 000 IU per 3 months. However, vitamin D deficient patients (<10 ng ml(-1) ) would need an intensive phase of 100 000 IU per 2 weeks (two times) followed 2 weeks later by a maintenance phase of 100 000 IU per 3 months. CONCLUSIONS: Skin phototype and bodyweight had an influence on the basal production of 25(OH)D. According to 25(OH)D baseline concentrations, dosing schemes to reach sufficient concentrations are proposed.

French multicenter 22-year experience in stem cell transplantation for beta-thalassemia major: lessons and future directions.

Although hematopoietic stem cell transplantation (HSCT) offers curative potential for beta-thalassemia major (beta-TM), it is associated with a variable but significant incidence of graft rejection. We studied the French national experience for improvement over time and the potential benefit of antithymocyte globulin (ATG). Between December 1985 and December 2007, 108 patients with beta-TM underwent HSCT in 21 different French transplantation centers. The majority of patients received a matched sibling transplant (n = 96) and a busulfan- and cyclophosphamide-based conditioning regimen (n = 95), also with ATG in 57 cases. Ninety-five of the 108 patients survived, with a median follow-up of 12 years. Probabilities of 15-year survival and thalassemia-free survival after first HSCT were 86.8% and 69.4%, respectively. Graft failure occurred in 24 patients, 11 of whom underwent a second HSCT. The use of ATG was associated with a decrease in rejection rate from 35% to 10%. Thalassemia-free survival improved significantly with time, reaching 83% in the 54 patients undergoing HSCT after 1994 (median time of HSCT). In view of the increased risk of graft rejection after matched sibling HSCT, current French national guidelines recommend, for all children at risk for beta-TM, the systematic addition of ATG to the myeloablative conditioning regimen and special attention to optimize transfusion and chelation therapy in the pretransplantation period.