Genomic characterisation of multidrug-resistant Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii in two intensive care units in Hanoi, Viet Nam: a prospective observational cohort study.

BACKGROUND: Viet Nam has high rates of antimicrobial resistance (AMR) but little capacity for genomic surveillance. This study used whole genome sequencing to examine the prevalence and transmission of three key AMR pathogens in two intensive care units (ICUs) in Hanoi, Viet Nam. METHODS: A prospective surveillance study of all adults admitted to ICUs at the National Hospital for Tropical Diseases and Bach Mai Hospital was done between June 19, 2017, and Jan 16, 2018. Clinical and environmental samples were cultured on selective media, characterised with MALDI TOF mass spectrometry, and sequenced with Illumina. Phylogenies based on the de-novo assemblies (SPAdes) were constructed with MAFFT (PARsnp), Gubbins, and RAxML. Resistance genes were detected with Abricate against the US National Center for Biotechnology Information database. FINDINGS: 3153 Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii isolates from 369 patients were analysed. Phylogenetic analysis revealed predominant lineages within A baumannii (global clone 2, sequence types ST2 and ST571) and K pneumoniae (ST15, ST16, ST656, ST11, and ST147) isolates. Isolation from stool was most common with E coli (87·0%) followed by K pneumoniae (62·5%). Of the E coli, 85·0% carried a blaCTX-M variant, while 81·8% of K pneumoniae isolates carried blaNDM (54·4%), or blaKPC (45·1%), or both. Transmission analysis with single nucleotide polymorphisms identified 167 clusters involving 251 (68%) of 369 patients, in some cases involving patients from both ICUs. There were no clear differences between the lineages or AMR genes recovered between the two ICUs. INTERPRETATION: This study represents the largest prospective surveillance study of key AMR pathogens in Vietnamese ICUs. Clusters of closely related isolates in patients across both ICUs suggests recent transmission before ICU admission in other health-care settings or in the community. FUNDING: UK Medical Research Council Newton Fund, Viet Nam Ministry of Science and Technology, Wellcome Trust, Academy of Medical Sciences, Health Foundation, and UK National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Systematic Surveillance of Rickettsial Diseases in 27 Hospitals from 26 Provinces throughout Vietnam.

In Vietnam, the public health burden of rickettsial infections continues to be underestimated due to knowledge gaps in the epidemiology of these diseases. We conducted a systematic study among 27 hospitals from 26 provinces in eight ecological regions throughout Vietnam to investigate the prevalence, distribution, and clinical characteristics of rickettsial diseases. We recruited 1834 patients in the study from April 2018 to October 2019. The findings showed that rickettsial diseases were common among undifferentiated febrile patients, with 564 (30.8%) patients positive by qPCR for scrub typhus, murine typhus or spotted fever. Scrub typhus (484, 85.8%) was the most common rickettsial disease, followed by murine typhus (67, 11.9%) and spotted fever (10, 1.8%). Rickettsial diseases were widely distributed in all regions of Vietnam and presented with nonspecific clinical manifestations.

Viral hepatitis and the cascade of care among people living with HIV in the Asia-Pacific.

BACKGROUND: Although the prevalence and mortality of hepatitis is high in the Asia-Pacific region, few studies are available on the diagnosis, treatment, and cure rates for viral hepatitis among people living with HIV in this area. This study aims to report the cascade of care (CoC) for hepatitis B (HBV) and C (HCV) among people living with HIV receiving combined antiretroviral therapy (ART). METHODS: Patients enrolled in the TREAT Asia HIV Observational Database Low Intensity Transfer (TAHOD-LITE) cohort, on ART, and with follow-up data from 2010 to 2019 were included. Patients were determined as positive for HCV or HBV co-infection if they ever tested positive for HCV antibody (anti-HCV) or HBV surface antigen (HBsAg), respectively. RESULTS: In total, 39% (8612/22 340) of the adult HIV cohort had undergone HBsAg testing, with 8% (672/8612) testing positive. HBV CoC demonstrated that 71% (474/672) of those with HBsAg positive results initiated treatment, 67% (318/474) of those on treatment had HBV DNA testing to evaluate treatment progression, and 18% (58/318) of those tested reached viral suppression. Of the cohort, 37% (8231/22 340) had anti-HCV testing, of whom 10% (779/8231) tested positive. The HCV CoC showed that 68% (526/779) of those with positive anti-HCV tests had HCV RNA tests, of whom 51% (267/526) had detectable HCV RNA. Among those with detectable HCV RNA, 65% (174/267) initiated HCV treatment. Of the 40% (69/174) who initiated HCV treatment, 90% (62/69) reached sustained virological response. CONCLUSION: Our findings identified less frequent testing in the healthcare system and limited access to treatment as gaps in the CoC for viral hepatitis. More routine HCV RNA and HBV DNA testing is required for patients with positive screening tests to identify those in need of treatment.

Improving antimicrobial use through antimicrobial stewardship in a lower-middle income setting: a mixed-methods study in a network of acute-care hospitals in Viet Nam.

OBJECTIVES: This study aimed to analyse the current state of antimicrobial stewardship (AMS) in hospitals in Viet Nam, a lower-middle income country (LMIC), to identify factors determining success in AMS implementation and associated challenges to inform planning and design of future programmes. METHODS: We conducted a mixed-methods study in seven acute-care hospitals in the antimicrobial resistance (AMR) surveillance network in Viet Nam. Data collection included 7 focus group discussions, 40 in-depth interviews and a self-administered quantitative survey of staff on AMR and AMS programmes. We summarised qualitative data by reporting the most common themes according to the core AMS elements, and analysed quantitative data using proportions and a linear mixed-effects model. RESULTS: The findings reveal a complex picture of factors and actors involved in AMS implementation from the national level to the departmental and individual level within each hospital. The level of implementation varied, starting from the formation of an AMS committee, with or without active delivery of specific interventions. Development of treatment guidelines, pre-authorisation of antimicrobial drug classes, and post-prescription audit and feedback to doctors in selected clinical departments were the main interventions reported. A higher level of leadership support and commitment to AMS led to a higher level of engagement with AMS activities from the AMS team and effective collaboration between departments involved. CONCLUSION: Establishing country-specific guidelines on AMS staffing and adapting standards for AMS education and training from international resources are needed to support capacity building to implement AMS programmes effectively in LMICs such as Viet Nam.

Prevalence of Advanced HIV Disease, Cryptococcal Antigenemia, and Suboptimal Clinical Outcomes Among Those Enrolled in Care in Vietnam.

BACKGROUND: People living with advanced HIV disease are at high risk of morbidity and mortality. We assessed the prevalence of cryptococcal antigenemia (CrAg) and clinical outcomes among patients newly presenting with CD4 ≤100 cells/µL in Vietnam. SETTING: Twenty-two public HIV clinics in Vietnam. METHODS: During August 2015-March 2017, antiretroviral therapy (ART)-naïve adults presenting for care with CD4 ≤100 cells/µL were screened for CrAg. Those who consented to study enrollment were followed up for up to 12 months and assessed for clinical outcomes. RESULTS: Of 3504 patients with CD4 results, 1354 (38.6%) had CD4 ≤100 cells/µL, of whom 1177 (86.9%) enrolled in the study. The median age was 35 years (interquartile range 30-40); 872 (74.1%) of them were men, and 892 (75.8%) had CD4 <50 cells/µL. Thirty-six patients (3.1%) were CrAg-positive. Overall, 1151 (97.8%) including all who were CrAg-positive initiated ART. Of 881 patients (76.5%) followed up for ≥12 months, 623 (70.7%) were still alive and on ART at 12 months, 54 (6.1%) had transferred to nonstudy clinics, 86 (9.8%) were lost to follow-up, and 104 (11.8%) had died. Among all 1177 study participants, 143 (12.1%) died, most of them (123, 86.0%) before or within 6 months of enrollment. Twenty-seven patients (18.9%) died of pulmonary tuberculosis, 23 (16.1%) died of extrapulmonary tuberculosis, 8 (5.6%) died of Talaromyces marneffei infection, and 6 (4.2%) died of opioid overdose. Eight deaths (5.8%) occurred among the 36 CrAg-positive individuals. CONCLUSIONS: Late presentation for HIV care was common. The high mortality after entry in care calls for strengthening of the management of advanced HIV disease.

Initial success from a public health approach to hepatitis C testing, treatment and cure in seven countries: the road to elimination.

With political will, modest financial investment and effective technical assistance, public sector hepatitis C virus (HCV) programmes can be established in low- and middle-income countries as a first step towards elimination. Seven countries, with support from the Clinton Health Access Initiative (CHAI) and partners, have expanded access to HCV treatment by combining programme simplification with market shaping to reduce commodity prices. CHAI has supported a multipronged approach to HCV programme launch in Cambodia, India, Indonesia, Myanmar, Nigeria, Rwanda and Vietnam including pricing negotiations with suppliers, policy development, fast-track registrations of quality-assured generics, financing advocacy and strengthened service delivery. Governments are leading programme implementation, leveraging HIV programme infrastructure/financing and focusing on higher-HCV prevalence populations like people living with HIV, people who inject drugs and prisoners. This manuscript aims to describe programme structure and strategies, highlight current commodity costs and outline testing and treatment volumes across these countries. Across countries, commodity costs have fallen from >US$100 per diagnostic test and US$750-US$900 per 12-week pan-genotypic direct-acting antiviral regimen to as low as US$80 per-cure commodity package, including WHO-prequalified generic drugs (sofosbuvir + daclatasvir). As of December 2019, 5900+ healthcare workers were trained, 2 209 209 patients were screened, and 120 522 patients initiated treatment. The cure (SVR12) rate was >90%, including at lower-tier facilities. Programmes are successfully implementing simplified, decentralised public health approaches. Combined with political will and affordable pricing, these efforts can translate into commitments to achieve global targets. However, to achieve elimination, additional investment in scale-up is required.

Dyslipidemia and cardiovascular disease in Vietnamese people with HIV on antiretroviral therapy.

With expanding antiretroviral therapy (ART) in Vietnam, the use of second-line ART with ritonavir-boosted lopinavir (LPV/r) is increasing. However, little is known regarding the effect of LPV/r on dyslipidemia (DL) and cardiovascular disease (CVD) in people with HIV in Vietnam. A cross-sectional study was performed in a cohort of HIV-infected Vietnamese patients on ART at the National Hospital for Tropical Diseases in Hanoi, Vietnam. In addition to DL, we included hypertension (HT) and hyperglycemia (HG) as non-communicable diseases. Blood pressure, casual blood sugar levels, and the lipid profile were evaluated cross-sectionally in October and November 2016. The incidence of CVD was calculated in the cohort. We determined factors associated with diseases by univariate and multivariate analyses. A total of 1,346 subjects were evaluated for their non-communicable diseases. The subjects' mean age was 39.2 years and 41.8% were women. A total of 10.5% of the subjects had exposure to LPV/r. DL, HT, and HG was diagnosed in 53.5%, 24.4%, and 0.8% of the subjects, respectively. In multivariate analysis, age (OR = 1.040; 95% CI, 1.025-1.055), female sex (OR = 0.335; 95% CI, 0.264-0.424), and LPV/r exposure (OR = 3.251; 95% CI, 2.030-5.207) were significantly associated with DL. The incidence rate of CVD was 1.87/1,000 person-years (15 incidental cases in 8,013 person-years). LPV/r exposure was not a risk factor for the incidence of CVD. Although a causative relation with LPV/r and CVD was not identified in this study, attention should be paid to CVD for patients on LPV/r in the future.

Building HIV healthcare worker capacity through telehealth in Vietnam.

Development of a robust technical assistance system is an essential component of a sustainable HIV response. Vietnam's National HIV Program is transitioning from a largely donor-funded programme to one primarily supported by domestic resources. Telehealth interventions are increasingly being used for training, mentoring and expert consultation in high-resource settings and hold significant potential for use as a tool to build HIV health worker capacity in low and middle-income countries. We designed, implemented and scaled up a novel HIV telehealth programme for Vietnam, with the goal of building a sustainable training model to support the country's HIV workforce needs. Over a 4-year period, HIV telehealth programmes were initiated in 17 public institutions with participation of nearly 700 clinical sites across 62 of the 63 provinces in the country. The telehealth programme was used to deliver certificate training courses, provide clinical mentoring and case-based learning, support programme implementation, provide coaching in quality improvement and disseminate new guidelines and policies. Programme evaluation demonstrated improved health worker self-reported competence in HIV care and treatment and high satisfaction among the programme participants. Lessons learnt from Vietnam's experience with telehealth can inform country programmes looking to develop a sustainable approach to HIV technical assistance and health worker capacity building.

Burden of disease and economic impact of human Streptococcus suis infection in Viet Nam.

BACKGROUND: Streptococcus suis is a zoonotic disease mainly affecting men of working age and can result in death or long-term sequelae, including severe hearing loss and vestibular dysfunction. We aimed to quantify the burden of disease and economic impact of this infection in Viet Nam. METHODS: The annual disease incidence for the period 2011-2014 was estimated based on surveillance data using a multiple imputation approach. We calculated disease burden in disability-adjusted life years (DALYs) and economic costs using an incidence-based approach from a patient's perspective and including direct and indirect impacts of S. suis infection and its long-term sequelae. RESULTS: The estimated annual incidence rate was 0.318, 0.324, 0.255 and 0.249 cases per 100 000 population in 2011, 2012, 2013 and 2014, respectively. The corresponding DALYs lost were 1832, 1866, 1467 and 1437. The mean direct cost per episode was US$1635 (95% confidence interval 1352-1923). The annual direct cost was US$370 000-500 000 and the indirect cost was US$2.27-2.88 million in this time period. CONCLUSIONS: This study showed a large disease burden and high economic impact of S. suis infection and provides important data for disease monitoring and control.

Clinical characteristics, organ failure, inflammatory markers and prediction of mortality in patients with community acquired bloodstream infection.

BACKGROUND: Community acquired bloodstream infection (CABSI) in low- and middle income countries is associated with a high mortality. This study describes the clinical manifestations, laboratory findings and correlation of SOFA and qSOFA with mortality in patients with CABSI in northern Vietnam. METHODS: This was a retrospective study of 393 patients with at least one positive blood culture with not more than one bacterium taken within 48 h of hospitalisation. Clinical characteristic and laboratory results from the first 24 h in hospital were collected. SOFA and qSOFA scores were calculated and their validity in this setting was evaluated. RESULTS: Among 393 patients with bacterial CABSI, approximately 80% (307/393) of patients had dysfunction of one or more organ on admission to the study hospital with the most common being that of coagulation (57.1% or 226/393). SOFA performed well in prediction of mortality in those patients initially admitted to the critical care unit (AUC 0.858, 95%CI 0.793-0.922) but poor in those admitted to medical wards (AUC 0.667, 95%CI 0.577-0.758). In contrast qSOFA had poor predictive validity in both settings (AUC 0.692, 95%CI 0.605-0.780 and AUC 0.527, 95%CI 0.424-0.630, respectively). The overall case fatality rate was 28%. HIV infection (HR = 3.145, p = 0.001), neutropenia (HR = 2.442, p = 0.002), SOFA score 1-point increment (HR = 1.19, p < 0.001) and infection with Enterobacteriaceae (HR = 1.722, p = 0.037) were independent risk factors for in-hospital mortality. CONCLUSIONS: Organ dysfunction was common among Vietnamese patients with CABSI and associated with high case fatality. SOFA and qSOFA both need to be further validated in this setting.

Elbasvir/grazoprevir in Asia-Pacific/Russian participants with chronic hepatitis C virus genotype 1, 4, or 6 infection.

The prevalence of hepatitis C virus (HCV) infection in Asian countries is high. This study assessed the efficacy and safety of elbasvir/grazoprevir (EBR/GZR) in participants with HCV infection from Asia-Pacific countries and Russia. In this phase 3, randomized, placebo-controlled, double-blind study, treatment-naive participants with HCV genotype (GT) 1, 4, or 6 infection were randomized to EBR 50 mg/GZR 100 mg (immediate-treatment group [ITG]) or placebo (deferred-treatment group [DTG]) once daily for 12 weeks (Protocol PN-5172-067, NCT02251990). The primary efficacy variable was a nonrandomized comparison of sustained virologic response at 12 weeks after the end of therapy (SVR12) for the ITG with a historical control. The primary safety outcome was a randomized comparison between the ITG and DTG. Three hundred thirty-seven participants were randomized to the ITG (n = 251) or DTG (n = 86); 199 (59.2%) participants were Asian, and 250 (74.4%) had HCV GT1b infection. Overall, 232/250 (92.8%) participants in the ITG achieved SVR12 (97.5% confidence interval, 89.1, 96.5). Of the 18 participants who failed to attain SVR12, 1 was lost to follow-up and 17 had virologic failure, 13 of whom had HCV GT6 infection. The incidence of adverse events was similar between participants receiving EBR/GZR and placebo (50.8% versus 51.2%; difference, -0.3%; 95% confidence interval, -12.3, 11.9). Conclusion: EBR/GZR for 12 weeks provides an effective and well-tolerated regimen for chronic HCV GT1 infection in treatment-naive people from Asia-Pacific countries and Russia, particularly for the large population with GT1b infection. EBR/GZR is not recommended for the treatment of individuals with HCV GT6 infection. (Hepatology Communications 2018;2:595-606).

Continuous versus intermittent endotracheal cuff pressure control for the prevention of ventilator-associated respiratory infections in Vietnam: study protocol for a randomised controlled trial.

BACKGROUND: Ventilator-associated respiratory infection (VARI) comprises ventilator-associated pneumonia (VAP) and ventilator-associated tracheobronchitis (VAT). Although their diagnostic criteria vary, together these are the most common hospital-acquired infections in intensive care units (ICUs) worldwide, responsible for a large proportion of antibiotic use within ICUs. Evidence-based strategies for the prevention of VARI in resource-limited settings are lacking. Preventing the leakage of oropharyngeal secretions into the lung using continuous endotracheal cuff pressure control is a promising strategy. The aim of this study is to investigate the efficacy of automated, continuous endotracheal cuff pressure control in preventing the development of VARI and reducing antibiotic use in ICUs in Vietnam. METHODS/DESIGN: This is an open-label randomised controlled multicentre trial. We will enrol 600 adult patients intubated for ≤ 24 h at the time of enrolment. Eligible patients will be stratified according to admission diagnosis (180 tetanus, 420 non-tetanus) and site and will be randomised in a 1:1 ratio to receive either (1) automated, continuous control of endotracheal cuff pressure or (2) intermittent measurement and control of endotracheal cuff pressure using a manual cuff pressure meter. The primary outcome is the occurrence of VARI, defined as either VAP or VAT during the ICU admission up to a maximum of 90 days after randomisation. Patients in both groups who are at risk for VARI will receive a standardised battery of investigations if their treating physician feels a new infection has occurred, the results of which will be used by an endpoint review committee, blinded to the allocated arm and independent of patient care, to determine the primary outcome. All enrolled patients will be followed for mortality and endotracheal tube cuff-related complications at 28 days and 90 days after randomisation. Other secondary outcomes include antibiotic use; days ventilated, in ICU and in hospital; inpatient mortality; costs of antibiotics in ICU; duration of ICU stay; and duration of hospital stay. DISCUSSION: This study will provide high-quality evidence concerning the use of continuous endotracheal cuff pressure control as a method to reduce VARI, antibiotic use and hospitalisation costs and to shorten stay. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02966392 . Registered on November 9, 2016. Protocol version: 2.0; issue date March 3, 2017.

Long-term viral suppression and immune recovery during first-line antiretroviral therapy: a study of an HIV-infected adult cohort in Hanoi, Vietnam.

INTRODUCTION: Achieving viral suppression is key in the global strategy to end the HIV epidemic. However, the levels of viral suppression have yet to be described in many resource-limited settings. METHODS: We investigated the time to virologic failure (VF; defined as a viral load of ≥1000 copies/ml) and changes in CD4 counts since starting antiretroviral therapy (ART) in a cohort of HIV-infected adults in Hanoi, Vietnam. Factors related to the time to VF and impaired early immune recovery (defined as not attaining an increase in 100 cells/mm3 in CD4 counts at 24 months) were further analysed. RESULTS: From 1806 participants, 225 were identified as having VF at a median of 50 months of first-line ART. The viral suppression rate at 12 months was 95.5% and survival without VF was maintained above 90% until 42 months. An increase in CD4 counts from the baseline was greater in groups with lower baseline CD4 counts. A younger age (multivariate hazard ratio (HR) 0.75, vs. <30), hepatitis C (HCV)-antibody positivity (HR 1.43), and stavudine (d4T)-containing regimens (HR 1.4, vs. zidovudine (AZT)) were associated with earlier VF. Factors associated with impaired early immune recovery included the male sex (odds ratio (OR) 1.78), HCV-antibody positivity (OR 1.72), d4T-based regimens (OR 0.51, vs. AZT), and nevirapine-based regimens (OR 0.53, vs. efavirenz) after controlling for baseline CD4 counts. CONCLUSION: Durable high-rate viral suppression was observed in the cohort of patients on first-line ART in Vietnam. Our results highlight the need to increase adherence support among injection drug users and HCV co-infected patients.

A Trial of Itraconazole or Amphotericin B for HIV-Associated Talaromycosis.

BACKGROUND: Talaromyces marneffei infection is a major cause of human immunodeficiency virus (HIV)-related death in South and Southeast Asia. Guidelines recommend initial treatment with amphotericin B deoxycholate, but this drug has substantial side effects, a high cost, and limited availability. Itraconazole is available in oral form, is associated with fewer unacceptable side effects than amphotericin, and is widely used in place of amphotericin; however, clinical trials comparing these two treatments are lacking. METHODS: In this open-label, noninferiority trial, we randomly assigned 440 HIV-infected adults who had talaromycosis, confirmed by either microscopy or culture, to receive either intravenous amphotericin B deoxycholate (amphotericin) (219 patients), at a dose of 0.7 to 1.0 mg per kilogram of body weight per day, or itraconazole capsules (221 patients), at a dose of 600 mg per day for 3 days, followed by 400 mg per day, for 11 days; thereafter, all the patients received maintenance therapy with itraconazole. The primary outcome was all-cause mortality at week 2. Secondary outcomes included all-cause mortality at week 24, the time to clinical resolution of talaromycosis, early fungicidal activity, relapse of talaromycosis, development of the immune reconstitution inflammatory syndrome (IRIS), and the side-effect profile. RESULTS: The risk of death at week 2 was 6.5% in the amphotericin group and 7.4% in the itraconazole group (absolute risk difference, 0.9 percentage points; 95% confidence interval [CI], -3.9 to 5.6; P<0.001 for noninferiority); however, the risk of death at week 24 was 11.3% in the amphotericin group and 21.0% in the itraconazole group (absolute risk difference, 9.7 percentage points; 95% CI, 2.8 to 16.6; P=0.006). Treatment with amphotericin was associated with significantly faster clinical resolution and fungal clearance and significantly lower rates of relapse and IRIS than itraconazole. The patients who received amphotericin had significantly higher rates of infusion-related reactions, renal failure, hypokalemia, hypomagnesemia, and anemia than patients in the itraconazole group. CONCLUSIONS: Amphotericin was superior to itraconazole as initial treatment for talaromycosis with respect to 6-month mortality, clinical response, and fungicidal activity. (Funded by the Medical Research Council and others; IVAP Current Controlled Trials number, ISRCTN59144167 .).

Seroprevalence of Scrub Typhus, Typhus, and Spotted Fever Among Rural and Urban Populations of Northern Vietnam.

AbstractRickettsial infections are recognized as important causes of fever throughout southeast Asia. Herein, we determined the seroprevalence to rickettsioses within rural and urban populations of northern Vietnam. Prevalence of individuals with evidence of prior rickettsial infections (IgG positive) was surprisingly low, with 9.14% (83/908) testing positive to the three major rickettsial serogroups thought to circulate in the region. Prevalence of typhus group rickettsiae (TG)-specific antibodies (6.5%, 58/908) was significantly greater than scrub typhus group orientiae (STG)- or spotted fever group rickettsiae (SFG)-specific antibodies (P < 0.05). The majority of TG seropositives were observed among urban rather than rural residents (P < 0.05). In contrast, overall antibody prevalence to STG and SFG were both very low (1.1%, 10/908 for STG; 1.7%, 15/908 for SFG), with no significant differences between rural and urban residents. These results provide data on baseline population characteristics that may help inform development of Rickettsia serological testing criteria in future clinical studies.

High Plasma Concentrations of Zidovudine (AZT) Do Not Parallel Intracellular Concentrations of AZT-Triphosphates in Infants During Prevention of Mother-to-Child HIV-1 Transmission.

OBJECTIVES: Zidovudine (AZT) is mainly used to prevent mother-to-child HIV-1 transmission (PMTCT). Despite serious concerns on AZT-associated toxicity, there is little information on pharmacokinetics of intracellular AZT metabolites in infants. METHODS: We conducted a prospective study in 31 HIV-uninfected infants who received AZT for PMTCT. Blood samples were obtained from 14 infants on postdelivery days (PDD) 1, 7, 14, and 28 and from 17 infants at 0 and 4 hours after dosing on PDD-1. Plasma AZT concentrations (pAZT) and intracellular concentrations of AZT-monophosphate (icAZT-MP), diphosphate (icAZT-DP), and triphosphate (icAZT-TP) were determined. RESULTS: Plasma AZT and icAZT-MP concentrations were 2713 nmol/L and 79 fmol/10 cells in PDD-1, but decreased to 1437 nmol/L and 31 fmol/10 cells by PDD-28 (P = 0.02 and P = 0.07 for all PDDs, respectively), whereas those of icAZT-DP and icAZT-TP remained low throughout the sampling period (P = 0.29 and P = 0.61 for all PDDs, respectively) There were no differences in icAZT-TP between infants of the 2 mg/kg 4 times a day dose and 4 mg/kg twice daily dose (P = 0.25), whereas pAZT and icAZT-MP levels were higher in the latter (P < 0.01 and <0.01, respectively). The pAZT and icAZT-MP significantly increased from 0 to 4 hours after dosing (P < 0.001 and <0.001, respectively), whereas icAZT-DP, icAZT-TP levels were not changed (P = 0.41 and 0.33, respectively). CONCLUSIONS: The level of icAZT-TP did not change with age, time, or a single dose despite the wide range of pAZT concentration. A safer dosage needs to be determined because high pAZT levels do not parallel those of icAZT-TP.

Trust, Respect, and Reciprocity: Informing Culturally Appropriate Data-Sharing Practice in Vietnam.

International science funders and publishers are driving a growing trend in data sharing. There is mounting pressure on researchers in low- and middle-income settings to conform to new sharing policies, despite minimal empirically grounded accounts of the ethical challenges of implementing the policies in these settings. This study used in-depth interviews and focus group discussions with 48 stakeholders in Vietnam to explore the experiences, attitudes, and expectations that inform ethical and effective approaches to sharing clinical research data. Distinct views on the role of trust, respect, and reciprocity were among those that emerged to inform culturally appropriate best practices. We conclude by discussing the challenges that authors of data-sharing policies should consider in this unique context.