Neurocognition and quality of life after reinitiating antiretroviral therapy in children randomized to planned treatment interruption

Objective: Understanding the effects of antiretroviral treatment (ART) interruption on neurocognition and quality of life (QoL) are important for managing unplanned interruptions and planned interruptions in HIV cure research. Design: Children previously randomized to continuous (continuous ART, n=41) vs. planned treatment interruption (PTI, n=47) in the Pediatric European Network for Treatment of AIDS (PENTA) 11 study were enrolled. At study end, PTI children resumed ART. At 1 and 2 years following study end, children were assessed by the coding, symbol search and digit span subtests of Wechsler Intelligence Scale for Children (6-16 years old) or Wechsler Adult Intelligence Scale ( 6517 years old) and by Pediatrics QoL questionnaires for physical and psychological QoL. Transformed scaled scores for neurocognition and mean standardized scores for QoL were compared between arms by t-test and Mann-Whitney U test, respectively. Scores indicating clinical concern were compared (<7 for neurocognition and <70 for QoL tests). Results: Characteristics were similar between arms with a median age of 12.6 years, CD4 + of 830 cells/\u3bcl and HIV RNA of 1.7 log 10 copies/ml. The median cumulative ART exposure was 9.6 in continuous ART vs. 7.7 years in PTI (P=0.02). PTI children had a median of 12 months off ART and had resumed ART for 25.2 months at time of first assessment. Neurocognitive scores were similar between arms for all tests. Physical and psychological QoL scores were no different. About 40% had low neurocognitive and QoL scores indicating clinical concern. Conclusion: No differences in information processing speed, sustained attention, short-term memory and QoL functioning were observed between children previously randomized to continuous ART vs. PTI in the PENTA 11 trial

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

Laparoscopic treatment of gastroesophageal reflux disease. Personal experience

The aim of this paper was to prospectively evaluate immediate and late results of laparoscopic fundoplicature for Gastroesophageal Reflux Disease (GERD). Patients presenting with a GERD having previously had a long-term medical treatment were included; exclusion criteria were represented by controindications to laparoscopy and GERD reoperation surgery. Preoperative evaluation included upper GI tract endoscopy, ecography, esophageal manometry and 24-hour pHmetry. Standard surgical procedure was a Nissen-Rossetti 360-degree fundoplication: short vessel division (Nissen operation) was performed in cases of excessive tension of the wrap and a partial 270-degree fundoplication (Toupet) in cases of motility disorders of the esophagus. Postoperative morbidity and late results were evaluated, with a clinical evaluation at 1, 3, 12 and 22 months and a 3-month manometry and pHmetry. Two hundred and twelve patients were observed, and 201 included: 123 men and 78 women. Nissen-Rossetti fundoplication was performed in 158 cases, Nissen in 23 and Toupet in 10. In 9 patients laparoscopic fundoplication was converted to an open Nissen Rossetti procedure. There was no hospital mortality and three cases of complications: two pneumonia and one gastroplegia. Mean hospital stay was 7 days. At late follow up 94% of patients had a Visick score of I or II, with, however, slight dysphagia (without any modification in alimentary habits) in 25% of cases. Fourteen patients had a relapse or a sporadic relapse of GERD, and two were reoperated on for a slipped Nissen and for a stenosis. On the basis of our experience, laparoscopic fundoplication for GERD is a safe and effective operation, with good long-term functional results: slight sequelae, not affecting quality of life, could, however, be present