Randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir-antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam.

BACKGROUND: Rifampicin and protease inhibitors are difficult to use concomitantly in patients with HIV-associated tuberculosis because of drug-drug interactions. Rifabutin has been proposed as an alternative rifamycin, but there is concern that the current recommended dose is suboptimal. The principal aim of this study was to compare bioavailability of two doses of rifabutin (150 mg three times per week and 150 mg daily) in patients with HIV-associated tuberculosis who initiated lopinavir/ritonavir-based antiretroviral therapy in Vietnam. Concentrations of lopinavir/ritonavir were also measured. METHODS: This was a randomized, open-label, multi-dose, two-arm, cross-over trial, conducted in Vietnamese adults with HIV-associated tuberculosis in Ho Chi Minh City (Clinical trial registry number NCT00651066). Rifabutin pharmacokinetics were evaluated before and after the introduction of lopinavir/ritonavir -based antiretroviral therapy using patient randomization lists. Serial rifabutin and 25-O-desacetyl rifabutin concentrations were measured during a dose interval after 2 weeks of rifabutin 300 mg daily, after 3 weeks of rifabutin 150 mg daily with lopinavir/ritonavir and after 3 weeks of rifabutin 150 mg three times per week with lopinavir/ritonavir. RESULTS: Sixteen and seventeen patients were respectively randomized to the two arms, and pharmacokinetic analysis carried out in 12 and 13 respectively. Rifabutin 150 mg daily with lopinavir/ritonavir was associated with a 32% mean increase in rifabutin average steady state concentration compared with rifabutin 300 mg alone. In contrast, the rifabutin average steady state concentration decreased by 44% when rifabutin was given at 150 mg three times per week with lopinavir/ritonavir. With both dosing regimens, 2 - 5 fold increases of the 25-O-desacetyl- rifabutin metabolite were observed when rifabutin was given with lopinavir/ritonavir compared with rifabutin alone. The different doses of rifabutin had no significant effect on lopinavir/ritonavir plasma concentrations. CONCLUSIONS: Based on these findings, rifabutin 150 mg daily may be preferred when co-administered with lopinavir/ritonavir in patients with HIV-associated tuberculosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00651066

Assessment and Simplification of Treatment Eligibility Among Patients With Chronic Hepatitis B Infection in Vietnam

Background Treatment eligibility and the accuracy of its simplified criteria have been poorly documented in patients with chronic hepatitis B virus (HBV) infection worldwide, especially in low- and middle-income countries. Methods From a cohort of HBV-infected patients in Vietnam, we assessed the proportion of patients eligible for treatment using the national guidelines based on reference tests (HBV DNA quantification and FibroScan); and the accuracy of simplified treatment criteria free from HBV DNA and FibroScan (Treatment Eligibility in Africa for the Hepatitis B Virus [TREAT-B] score and simplified World Health Organization [WHO] criteria) to select patients for antiviral therapy using the national guidelines as a reference. Results We analyzed 400 consecutive treatment-naïve HBV-monoinfected patients: 49% males, median age 38 years (range, 18–86), 32% hepatitis B e antigen-positive, median HBV DNA 4.8 log10 IU/mL (undetectable −8.4), median FibroScan 5.3 kPa (3.0–67.8), and 25% having significant liver fibrosis including 12% with cirrhosis. Of these, 167 (42%) fulfilled treatment criteria according to national guidelines. Using the national criteria as a reference, the performance of TREAT-B to select patients for treatment was high (area under the receiver operating characteristic [AUROC], 0.89 [95% confidence interval 0.87-0.92]) with a sensitivity of 74.3% and a specificity of 88.4%. In a subset of patients with 2 alanine aminotransferase measurements over a 6-month period (n = 89), the AUROC of TREAT-B was significantly higher than that of the simplified WHO criteria (P < .001). Conclusions Our study suggests that a large proportion of patients with chronic HBV infection require antiviral therapy in Vietnam. Compared with the simplified WHO criteria free from HBV DNA quantification, TREAT-B is a better alternative to easily indicate treatment eligibility and might help scale up treatment intervention in Vietnam

Neurological manifestations of COVID-19 in adults and children

Different neurological manifestations of coronavirus disease 2019 (COVID-19) in adults and children and their impact have not been well characterized. We aimed to determine the prevalence of neurological manifestations and in-hospital complications among hospitalized COVID-19 patients and ascertain differences between adults and children. We conducted a prospective multicentre observational study using the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) cohort across 1507 sites worldwide from 30 January 2020 to 25 May 2021. Analyses of neurological manifestations and neurological complications considered unadjusted prevalence estimates for predefined patient subgroups, and adjusted estimates as a function of patient age and time of hospitalization using generalized linear models. Overall, 161 239 patients (158 267 adults; 2972 children) hospitalized with COVID-19 and assessed for neurological manifestations and complications were included. In adults and children, the most frequent neurological manifestations at admission were fatigue (adults: 37.4%; children: 20.4%), altered consciousness (20.9%; 6.8%), myalgia (16.9%; 7.6%), dysgeusia (7.4%; 1.9%), anosmia (6.0%; 2.2%) and seizure (1.1%; 5.2%). In adults, the most frequent in-hospital neurological complications were stroke (1.5%), seizure (1%) and CNS infection (0.2%). Each occurred more frequently in intensive care unit (ICU) than in non-ICU patients. In children, seizure was the only neurological complication to occur more frequently in ICU versus non-ICU (7.1% versus 2.3%, P &lt; 0.001). Stroke prevalence increased with increasing age, while CNS infection and seizure steadily decreased with age. There was a dramatic decrease in stroke over time during the pandemic. Hypertension, chronic neurological disease and the use of extracorporeal membrane oxygenation were associated with increased risk of stroke. Altered consciousness was associated with CNS infection, seizure and stroke. All in-hospital neurological complications were associated with increased odds of death. The likelihood of death rose with increasing age, especially after 25 years of age. In conclusion, adults and children have different neurological manifestations and in-hospital complications associated with COVID-19. Stroke risk increased with increasing age, while CNS infection and seizure risk decreased with age

Zooplankton nutrition, storage and fecal lipid composition in different water masses associated with the Agulhas and Subtropical Fronts

Fecal pellets of zooplankton can be important carriers of organic matter from surface to deep waters of the oceans, The summer cruise ANTARES 4 gave us the opportunity to collect zooplankton from the frontal subantarctic zone (station 7 or s-ant) and adjacent subtropical waters (station 8 or s-trop). Triglyceride fatty acid profiles were used to assess the trophic position of two copepods (Metridia lucens and Pleuromamma spp.), three euphausiids (Euphausia spinifera, Nematoscelis megalops, and Thysanoessa sp) and a decapod Acanthephyra sp. The euphausiid E. spinifera was studied at the two sites and its reaction to contrasting trophic environments and hydrology was highlighted by variations in its lipid composition. Most species showed various degree of omnivory: E. spinifera from subantarctic showed the highest degree of herbivory on phytoplankton (high proportion of 16:4(n-1), 18:5(n-3), 16:1(n-7)), while the same species at the subtropical station, as well as Thysanoessa sp and M lucens from the subantarctic station displayed more omnivorous feeding characteristics, partly linked to the abundance of microzooplankton cells. Acanthephirasp, N. megalops and Pleuromammasp from station 8 (s-trop) appear to be essentially carnivorous (high 18:1 n-9/18:1n-7 ratio, high levels of 20: 1 (n-9) or 22: 1 (n-11)). The trophic position influenced the composition of feces, with higher PUFA percentages in fecal pellets from carnivorous species. Hence, the surface faunal assemblage and the season controlled not only the quantity but also the quality of the food supply as PUFA exported towards the benthic domain. (c) 2007 Elsevier B.V. All rights reserved