High Rates of Drug Resistance Among Newly Diagnosed HIV-infected Children in the National Prevention of Mother-to-child Transmission Program in Togo.

BACKGROUND: Prevention of mother-to-child transmission (PMTCT) programs have been largely scaled-up, but data on infant HIV drug resistance from PMTCT programs implemented in resource-limited countries are lacking. METHODS: Remnant dried blood spots from HIV-infected children (aged <18 months) tested through the Togo national early infant diagnosis program during 2012 and 2013 were collected and assessed for HIV drug resistance. Pol-RT (reverse transcriptase) region was amplified, sequenced and analyzed for the presence of drug resistance mutations (DRMs). RESULTS: Overall, 121 of 201 (60.2%) newly diagnosed children had detectable DRMs. Among the 131 of 201 (65.2%) children with reported exposure to maternal and/or infant antiretrovirals (ARVs), DRMs were detected in 99 children (75.6%). Importantly, in 41 of 201 children for whom no exposure to ARVs was reported, DRMs were detected in 11 children (26.8%). For 29 children, no data on ARV exposure were available. For the 121 of 201 children with DRMs, 99 of 121 (81.8%) had only nonnucleoside reverse transcriptase inhibitor DRMs detected but 21 of 121 (17.3%) had both nonnucleoside reverse transcriptase inhibitor and nucleoside reverse transcriptase inhibitor (NRTI) DRMs. Among breast-fed children, drug resistance was more frequent when mothers were on antiretroviral therapy (ART), 61 of 75 (81.3%) versus 14 of 39 (35.9%) when mothers were not on ART (P < 0.001). Nucleoside reverse transcriptase inhibitor resistance was more common when mothers were on ART. CONCLUSIONS: Scale-up and improvement of PMTCT strategies resulted in a global decrease of pediatric HIV infections, but our study shows high rates of drug resistance in infants for whom prevention failed.

Effect of Age at Antiretroviral Therapy Initiation on Catch-up Growth Within the First 24 Months Among HIV-infected Children in the IeDEA West African Pediatric Cohort.

BACKGROUND: We described malnutrition and the effect of age at antiretroviral therapy (ART) initiation on catch-up growth over 24 months among HIV-infected children enrolled in the International epidemiologic Databases to Evaluate Aids West African paediatric cohort. METHODS: Malnutrition was defined at ART initiation (baseline) by a Z score <-2 standard deviations, according to 3 anthropometric indicators: weight-for-age (WAZ) for underweight, height-for-age (HAZ) for stunting and weight-for-height/BMI-for-age (WHZ/BAZ) for wasting. Kaplan-Meier estimates for catch-up growth (Z score ≥-2 standard deviations) on ART, adjusted for gender, immunodeficiency and malnutrition at ART initiation, ART regimen, time period and country, were compared by age at ART initiation. Cox proportional hazards regression models determined predictors of catch-up growth on ART over 24 months. RESULTS: Between 2001 and 2012, 2004 HIV-infected children <10 years of age were included. At ART initiation, 51% were underweight, 48% were stunted and 33% were wasted. The 24-month adjusted estimates for catch-up growth were 69% [95% confidence interval (CI): 57-80], 61% (95% CI: 47-70) and 90% (95% CI: 76-95) for WAZ, HAZ and WHZ/BAZ, respectively. Adjusted catch-up growth was more likely for children <5 years of age at ART initiation compared with children ≥5 years for WAZ, HAZ (P < 0.001) and WHZ/BAZ (P = 0.026). CONCLUSIONS: Malnutrition among these children is an additional burden that has to be urgently managed. Despite a significant growth improvement after 24 months on ART, especially in children <5 years, a substantial proportion of children still never achieved catch-up growth. Nutritional care should be part of the global healthcare of HIV-infected children in sub-Saharan Africa.

Association between age at antiretroviral therapy initiation and 24-month immune response in West-African HIV-infected children.

OBJECTIVE: We describe the association between age at antiretroviral therapy (ART) initiation and 24-month CD4 cell response in West African HIV-infected children. METHODS: All HIV-infected children from the IeDEA paediatric West African cohort, initiating ART, with at least two CD4 cell count measurements, including one at ART initiation (baseline) were included. CD4 cell gain on ART was estimated using a multivariable linear mixed model adjusted for baseline variables: age, CD4 cell count, sex, first-line ART regimen. Kaplan-Meier survival curves and a Cox proportional hazards regression model compared immune recovery for age within 24 months post-ART. RESULTS: Of the 4808 children initiated on ART, 3014 were enrolled at a median age of 5.6 years; 61.2% were immunodeficient. After 12 months, children at least 4 years at baseline had significantly lower CD4 cell gains compared with children less than 2 years, the reference group (P<0.001). However, by 24 months, we observed higher CD4 cell gain in children who initiated ART between 3 and 4 years compared with those less than 2 years (P<0.001). The 24-month CD4 cell gain was also strongest in immunodeficient children at baseline. Among these children, 75% reached immune recovery: 12-month rates were significantly highest in all those aged 2-5 years at ART initiation compared with those less than 2 years. Beyond 12 months on ART, immune recovery was significantly lower in children initiated more than 5 years (adjusted hazard ratio: 0.69, 95% confidence interval: 0.56-0.86). CONCLUSION: These results suggest that both the initiation of ART at the earliest age less than 5 years and before any severe immunodeficiency is needed for improving 24-month immune recovery on ART.

[Diabetes mellitus in children in Lomé (Togo)]. / Le diabète sucré de l'enfant à Lomé (Togo).

AIM: Describe clinical aspects and outcome of children with diabetes mellitus in Lomé (Togo). METHODS: This work concern eighteen children consecutively admitted between 1997 and 2004 for diabetes mellitus. Diagnosis of type 2 diabetes mellitus (T2DM) were done on the presentation of at least one of T2DM risk factors: obesity, familial history of T2DM, acanthosis nigricans, polycystic ovary syndrome, dislipidemia, high blood pressure. RESULTS: Twelve children presented type 1 diabetes mellitus (T1DM), 5 T2DM and one, corticosteroids induced diabetes. At least one of the first degree parent suffered from diabetes in 4 of the 5 children with T2DM and 4 of the 12 patients with T1DM. Most patients (with T1DM or T2DM) presented polyuria, polydypsia and ketonuria at admission. All patients with T2DM were obese and had lifestyles characterised by high fat intake, sedentary attitudes, and physical inactivity. The corticosteroid induced diabetes cessed when corticosteroid stopped. The other patients were successfully treated with insulin (T1DM) or insulin then exercises and diets (T2DM). CONCLUSION: Clinical presentation of diabetes mellitus is now characterised in Togo by the emergence of T2DM which principal risks factors are obesity and familial history of T2DM.

[Management of priapism in sickle-cell diseases with alpha-adrenergic agonists]. / Prise en charge du priapisme drépanocytaire par médications alpha-adrénergiques.

Priapism is a common complication of sickle cell anemia. Two different patterns are described: acute priapism, a prolonged painful erection generally lasting more than 6 hours, and stuttering priapism, which consist of brief repeated self-resolving episodes. Until 1990, priapism in sickle-cell patients has relied on measures aimed at lowering blood viscosity and acidosis and reducing the level of circulating hemoglobin S (alcalinization, hyperhydration, exsanguinotransfusion). But these means are not consistently successful. Surgical cavernous-venous shunt was proposed after 12 to 24 hours when conservative treatment failed. These therapeutic modalities are based on the pathophysiology of sickle-cell priapism. Priapism in sickle-cell disease may be due to sequestered sickled red cells in the corpus cavernosum with venous outflow obstruction. For some years, the treatment of priapism in sickle-cell anemia was changed by the use of alpha-adrenergic agonists. These therapeutics (mainly etilefrine and epinephrine) were first reserved for priapism resulting from intrapenile injections of vasoactive drugs which are used for the treatment of impotence. In acute priapism, alpha-adrenergic agonists are used in intracavernous injections (ICI). In stuttering priapism, treatment consists in an oral administration associated, if necessary, with self-administered ICI. ICI results mainly depend on when treatment occurs. Detumescence is achieved in patients treated within 30 hours, as opposed to the few patients treated beyond this delay. This finding is in agreement with experimental findings demonstrating histological evidence of necrosis of endothelial cells and cavernous smooth muscle fibers after 24 hours. Surgery is only used after failure of ICI. The result of oral treatment is not very satisfactory because many patients do not respond well or are dependent on ICI. However, self-administered ICI associated with the oral treatment protects patients with stuttering priapism against acute strokes. The safety of alpha-adrenergic agonists is good as both oral and ICI have few side-effects. The excellent efficacy of ICI in sickle-cell priapism leads to suggest that the pathogenic mechanism could involve a neuromuscular dysfunction.