ABSTRACT
BACKGROUND: Brainstem encephalitis is a serious complication of hand foot and mouth disease (HFMD) in children. Autonomic nervous system (ANS) dysregulation and hypertension may occur, sometimes progressing to cardiopulmonary failure and death. Vietnamese national guidelines recommend use of milrinone if ANS dysregulation with Stage 2 hypertension develops. We wished to investigate whether magnesium sulfate (MgSO4) improved outcomes in children with HFMD if used earlier in the evolution of the ANS dysregulation (Stage 1 hypertension). METHODS: During a regional epidemic we conducted a randomized, double-blind, placebo-controlled trial of MgSO4 in children with HFMD, ANS dysregulation and Stage 1 hypertension, at the Hospital for Tropical Diseases in Ho Chi Minh city. Study participants received an infusion of MgSO4 or matched placebo for 72 h. We also reviewed data from non-trial HFMD patients in whom milrinone failed to control hypertension, some of whom received MgSO4 as second line therapy. The primary outcome for both analyses was a composite of disease progression within 72 h - addition of milrinone (trial participants only), need for ventilation, shock, or death. RESULTS: Between June 2014 and September 2016, 14 and 12 participants received MgSO4 or placebo respectively, before the trial was stopped due to futility. Among 45 non-trial cases with poorly controlled hypertension despite high-dose milrinone, 33 received MgSO4 while 12 did not. There were no statistically significant differences in the composite outcome between the MgSO4 and the placebo/control groups in either study (adjusted relative risk (95%CI) of [6/14 (43%) vs. 6/12 (50%)], 0.84 (0.37, 1.92), p = 0.682 in the trial and [1/33 (3%) vs. 2/12 (17%)], 0.16 (0.01, 1.79), p = 0.132 in the observational cohort). The incidence of adverse events was similar between the groups. Potentially toxic magnesium levels occurred very rarely with the infusion regime used. CONCLUSION: Although we could not demonstrate efficacy in these studies, there were no safety signals associated with use of 30-50 mg/kg/hr. MgSO4 in severe HFMD. Intermittent outbreaks of HFMD are likely to continue across the region, and an adequately powered trial is still needed to evaluate use of MgSO4 in controlling hypertension in severe HFMD, potentially involving a higher dose regimen. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01940250 (Registered 22 AUG 2013). Trial sponsor: University of Oxford.
Subject(s)
Autonomic Nervous System Diseases/drug therapy , Hand, Foot and Mouth Disease/drug therapy , Magnesium Sulfate/therapeutic use , Animals , Autonomic Nervous System/drug effects , Autonomic Nervous System/physiology , Autonomic Nervous System Diseases/etiology , Child , Child, Preschool , Cohort Studies , Disease Progression , Double-Blind Method , Female , Hand, Foot and Mouth Disease/complications , Hand, Foot and Mouth Disease/physiopathology , Hemodynamics/drug effects , Humans , Infant , Magnesium Sulfate/adverse effects , Male , PlacebosABSTRACT
PURPOSE: To assess the incidence and predictors of postsuppression virologic rebound (VR) among adolescents on stable combination antiretroviral therapy in Asia. METHODS: Perinatally HIV-infected Asian adolescents (10-19 years) with documented virologic suppression (two consecutive viral loads [VLs] <400 copies/mL ≥6 months apart) were included. Baseline was the date of the first VL <400 copies/mL at age ≥10 years or the 10th birthday for those with prior suppression. Cox proportional hazards models were used to identify predictors of postsuppression VR (VL >1,000 copies/mL). RESULTS: Of 1,379 eligible adolescents, 47% were males. At baseline, 22% were receiving protease inhibitor-containing regimens; median CD4 cell count (interquartile range [IQR]) was 685 (448-937) cells/mm3; 2% had preadolescent virologic failure (VF) before subsequent suppression. During adolescence, 180 individuals (13%) experienced postsuppression VR at a rate of 3.4 (95% confidence interval: 2.9-3.9) per 100 person-years, which was consistent over time. Median time to VR during adolescence (IQR) was 3.3 (2.1-4.8) years. Wasting (weight-for-age z-score <-2.5), being raised by grandparents, receiving second-line protease inhibitor-based regimens, starting combination antiretroviral therapy after 2005, and having preadolescent VF were independent predictors of adolescent VR. At VR, median age, CD4 cell count, and VL (IQR) were 14.8 (13.2-16.4) years, 507 (325-723) cells/mm3, and 4.1 (3.5-4.7) log10 copies/mL, respectively. CONCLUSIONS: A modest and consistent incidence of postsuppression VR was documented during adolescence in our cohort. Having poor weight, receiving second-line regimens, and prior VF were associated with an increased VR rate. Adolescents at higher risk of VR may benefit from more intensive VL monitoring to enhance adherence management.
Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/virology , Viral Load , Adolescent , Asia, Southeastern , Child , Female , HIV/isolation & purification , HIV Infections/drug therapy , Humans , Incidence , Kaplan-Meier Estimate , Male , RecurrenceABSTRACT
A molecular epidemiological study was conducted on 104 HIV-1 strains isolated from HIV-infected children hospitalized in Children Hospital 1 in Ho Chi Minh City, Vietnam during 2004-2005. Genetic subtyping based on env C2/V3 sequences revealed that CRF01-AE was the sole circulating recombinant form found in this study. Sequence analysis of the V3 loop showed that GPGQ tetramer was the most common V3 loop core motif identified in the HIV-1 strains studied (89.5%). The findings raise great concern about HIV-infected children in Vietnam and provide up-to-date molecular epidemiological information of HIV-1 circulating in Vietnam during the study period.
