Association between recent methamphetamine use, antiretroviral therapy and HIV viral load; a mediation analysis from a cohort of HIV positive persons who inject drugs in Hai Phong, Vietnam.

BACKGROUND: There has been a significant increase in methamphetamine use among persons who use drugs in Vietnam in the last 5-10 years. We examined the degree to which adherence to antiretroviral therapy (ART) mediates the relationship between recent methamphetamine use and unsuppressed HIV viral load among people who inject drugs (PWID) in Hai Phong, Vietnam. METHODS: We recruited PWID from October 2016-October 2018 and enrolled HIV positive PWID into a cohort, with up to three years of total follow-up. We assessed relationships among recent methamphetamine use frequency, ART adherence and unsuppressed HIV viral load. Mediation analysis was used to estimate the total and natural direct effects of recent methamphetamine use on unsuppressed HIV viral load and the indirect effect proportion. RESULTS: We enrolled 792 HIV seropositive PWID into the cohort; approximately 75.9% reported high/perfect ART adherence at baseline and 81.3% were virally suppressed. In mediation analysis, the total effect for the association between methamphetamine use and unsuppressed HIV viral load (1000 copies/mL) was 3.94 (95% CI: 1.95, 7.96); the natural direct effect was 2.14 (95% CI: 1.29, 3.55); the proportion mediated by self-reported ART adherence was 0.444. Similar results were found when examining lower unsuppressed HIV viral load cutpoints of 250 copies/mL and 500 copies/mL. CONCLUSIONS: Methamphetamine use is associated with unsuppressed HIV viral load among PWID despite high levels of ART adherence. Further research is needed to better understand these relationships, with emphasis on potential biological pathways that may interact with ART.

Towards HCV elimination among people who inject drugs in Hai Phong, Vietnam: study protocol for an effectiveness-implementation trial evaluating an integrated model of HCV care (DRIVE-C: DRug use & Infections in ViEtnam-hepatitis C).

INTRODUCTION: In Vietnam, people who inject drugs (PWID), who are the major population infected by hepatitis C virus (HCV), remain largely undiagnosed and unlinked to HCV prevention and care despite recommended universal hepatitis C treatment. The data on the outcomes of HCV treatment among PWID also remain limited in resource-limited settings. The DRug use & Infections in ViEtnam-hepatitis C (DRIVE-C) study examines the effectiveness of a model of hepatitis C screening and integrated care targeting PWID that largely uses community-based organisations (CBO) in Hai Phong, Vietnam. In a wider perspective, this model may have the potential to eliminate HCV among PWID in this city. METHODS AND ANALYSIS: The model of care comprises large community-based mass screening, simplified treatment with direct-acting antivirals (DAAs) and major involvement of CBO for PWID reaching out, linkage to care, treatment adherence and prevention of reinfection. The effectiveness of DAA care strategy among PWID, the potential obstacles to widespread implementation and its impact at population level will be assessed. A cost-effectiveness analysis is planned to further inform policy-makers. The enrolment target is 1050 PWID, recruited from the DRIVE study in Hai Phong. After initiation of pan-genotypic treatment consisting of sofosbuvir and daclatasvir administrated for 12 weeks, with ribavirin added in cases of cirrhosis, participants are followed-up for 48 weeks. The primary outcome is the proportion of patients with sustained virological response at week 48, that will be compared with a theoretical expected rate of 70%. ETHICS AND DISSEMINATION: The study was approved by Haiphong University of Medicine and Pharmacy's Ethics Review Board and the Vietnamese Ministry of Health. The sponsor and the investigators are committed to conducting this study in accordance with ethics principles contained in the World Medical Association's Declaration of Helsinki (Ethical Principles for Medical Research Involving Human Subjects). Informed consent is obtained before study enrolment. The data are anonymised and stored in a secure database. The study is ongoing. Results will be presented at international conferences and submitted to international peer-review journals. TRIAL REGISTRATION NUMBER: NCT03537196.

Daily heroin injection and psychiatric disorders: A cross-sectional survey among People Who Inject Drugs (PWID) in Haiphong, Vietnam.

BACKGROUND: Psychiatric comorbidities are frequent among people who inject drugs, they are associated with a poorer prognosis and need to be addressed. Their interaction with daily heroin injection requires clarification. METHODS: A cross-sectional survey was conducted among PWID recruited in the city of Haiphong, Vietnam, by respondent-driven sampling. The inclusion criteria were age 18 or older and current injection drug use, verified by skin marks and positive urine tests for heroin or methamphetamine. Data on socio-demographic characteristics, drug use, sexual behaviour and access to treatment were collected using face-to-face questionnaires by trained interviewers. PWID were screened by trained psychiatrists for depression, psychotic disorder and suicidality, using the MINI questionnaire. RESULTS: 418 participants were included in the analyses. All were injected heroin users, 21 % were diagnosed with a current major depressive disorder, 15 % with a current psychotic disorder and 12 % presented a suicide risk. In the bivariate analyses, regular meth use, cannabis use and ketamine use were positively associated with presenting at least one psychiatric condition while daily heroin injection and being currently treated with methadone were negatively associated. In the multivariate model, poly-substance use was positively associated with depression (methamphetamine and drinking in addition to heroin) and psychotic disorder (methamphetamine and/or hazardous drinking in addition to heroin) while daily heroin injection and current methadone treatment were negatively and independently associated with depression and psychotic syndrome. CONCLUSIONS: Our survey confirms the burden of methamphetamine use and the protective effect of methadone but also a possible protective effect of daily heroin injection.

Psychiatric Comorbidities among People Who Inject Drugs in Hai Phong, Vietnam: The Need for Screening and Innovative Interventions.

The objective of this study is to describe psychiatric comorbidities, associated factors, and access to psychiatric assessment and care in a cohort of people who inject drugs (PWID) in Hai Phong, Vietnam. Mental health was assessed after 12 months' follow-up using the Mini International Neuropsychiatric Interview questionnaire (MINI 5.0.0). PWID medical history, drug use, and sociodemographic and clinical characteristics were also collected. Among 188 PWID who participated in the assessment, 48 (25.5%) had at least one psychiatric disorder and 19 (10.1%) had 2 or more psychiatric disorders. The most common current psychiatric disorders were major depressive episode (12.2%) and psychotic disorder (4.8%), reaching 10.1% for the latter when lifetime prevalence was considered. Females were more likely than males to have at least one psychiatric disorder, a major depressive disorder, or an anxiety disorder. Methamphetamine use was associated with an increased risk of presenting a lifetime psychotic syndrome. Problematic alcohol consumption was associated with an increased risk of having at least one psychiatric disorder. Psychiatric comorbidities are frequent among PWID in Vietnam. These results highlight the need for routine assessment and innovative interventions to address mental health needs among PWID. Community-based interventions targeting mental health prevention and care should be strongly supported.

Increased Methamphetamine Use among Persons Who Inject Drugs in Hai Phong, Vietnam, and the Association with Injection and Sexual Risk Behaviors.

Methamphetamine use has increased significantly in Southeast Asia in the last 5-10 years, but there is little research on risk behaviors associated with the increase in this region. We evaluate injection and sexual risk behaviors associated with current methamphetamine use among heterosexual persons who inject drugs (PWID) in Hai Phong, Vietnam. We recruited 1336 PWID and assessed associations between methamphetamine use, injection and sexual risk behaviors, stratified by HIV serostatus. There were several statistically significant associations between methamphetamine use and sexual risk behaviors among HIV-positive PWID, but we did not find any associations between methamphetamine use and injection risk behaviors. Methamphetamine may increase the likelihood of PWID transmitting HIV to non-injecting primary sexual partners, as it can reduce ART adherence and can lead to weakening of the immune system and increased HIV viral loads. All participants were injecting heroin, and methamphetamine use may interfere with opiate use treatment. Public health efforts should focus on the large increase in methamphetamine use and the associated sexual risk behaviors. Emphasis on sexual risk behavior, particularly among those who are HIV-positive, in conjunction with continued monitoring of ART adherence and HIV viral loads, is critical.

Intravenous heroin use in Haiphong, Vietnam: Need for comprehensive care including methamphetamine use-related interventions.

BACKGROUND: The aim of this study was to describe patterns among people who inject drugs (PWID), risk-related behaviours and access to methadone treatment, in order to design a large-scale intervention aiming to end the HIV epidemic in Haiphong, Vietnam. METHODS: A respondent-driven sampling (RDS) survey was first conducted to identify profiles of drug use and HIV risk-related behaviour among PWID. A sample of PWID was then included in a one-year cohort study to describe access to methadone treatment and associated factors. RESULTS: Among the 603 patients enrolled in the RDS survey, 10% were female, all were injecting heroin and 24% were using methamphetamine, including 3 (0.5%) through injection. Different profiles of risk-related behaviours were identified, including one entailing high-risk sexual behaviour (n=37) and another involving drug-related high-risk practices (n=22). High-risk sexual activity was related to binge drinking and methamphetamine use. Among subjects with low sexual risk, sexual intercourse with a main partner with unknown serostatus was often unprotected. Among the 250 PWID included in the cohort, 55.2% initiated methadone treatment during the follow-up (versus 4.4% at RDS); methamphetamine use significantly increased. The factors associated with not being treated with methadone after 52 weeks were fewer injections per month and being a methamphetamine user at RDS. CONCLUSION: Heroin is still the main drug injected in Haiphong. Methamphetamine use is increasing markedly and is associated with delay in methadone initiation. Drug-related risks are low but sexual risk behaviours are still present. Comprehensive approaches are needed in the short term.

High Proportion of HIV-HCV Coinfected Patients with Advanced Liver Fibrosis Requiring Hepatitis C Treatment in Haiphong, Northern Vietnam (ANRS 12262).

RATIONALE AND AIMS: Screening and treatment for chronic hepatitis C are very limited in Vietnam and clinical data on HCV-related liver disease in HIV-coinfected people are almost inexistent. This study aimed to assess the severity of liver fibrosis and its risk factors in HIV-HCV coinfected patients in Haiphong, Northern Vietnam. METHODS: A cross-sectional study was conducted at a HIV outpatient clinic. Consecutive HIV treated adults with positive HCV serology completed a standardised epidemiological questionnaire and had a comprehensive liver assessment including hepatic elastography (Fibroscan®, Echosens). RESULTS: From February to March 2014, 104 HIV-HCV coinfected patients receiving antiretroviral therapy (ART) were prospectively enrolled (99 males, median age: 35.8 (32.7-39.6) years, median CD4 count: 504 (361-624) /mm3. Of them, 93 (89.4%) had detectable HCV RNA (median 6.19 (4.95-6.83 Log10 IU/mL). Patients were mainly infected with genotypes 1a/1b (69%) and genotypes 6a/6e (26%). Forty-three patients (41.3%) had fibrosis ≥F2 including 24 patients (23.1%) with extensive fibrosis (F3) and/or cirrhosis (F4). In univariate analysis, excessive alcohol consumption, estimated time duration from HCV infection, nevirapine and lopinavir-based ARV regimen and CD4 nadir were associated factors of extensive fibrosis/cirrhosis. Alcohol abuse was the only independent factor of extensive fibrosis in multivariate analysis. Using Fibroscan® as a gold standard, the high thresholds of AST-to-platelet ratio index (APRI) and fibrosis-4 score (FIB-4) had very good performances for the diagnosis of extensive fibrosis/cirrhosis (Se: 90 and 100%, Sp:84 and 81%, AUROCs = 0.93, 95%CI: 0.86-0.99 and 0.96 (0.92-0.99), respectively). CONCLUSION: In this study, nearly 25% of HIV-HCV coinfected patients successfully treated with ART have extensive fibrosis or cirrhosis, and therefore require urgently HCV treatment.

Serum carbohydrate-binding IgM are present in Vietnamese striped catfish (Pangasianodon hypophthalmus) but not in North African catfish (Clarias gariepinus).

Pangasianodon hypophthalmus serum was fractionated by affinity chromatography on 12 different Sepharose-carbohydrate columns and proteins eluted by the corresponding sugar. Binding to the affinity matrices is dependent on Ca(2+) ions. Upon gel filtration using Superose-12, essentially one fraction was obtained, eluting as a protein with a molecular mass of about 900 kDa. SDS-PAGE in reducing conditions revealed the presence of large (72 kDa) subunits (H-chains) and one up to three small (24, 26 and/or 28-29 kDa) subunits (L-chains). The isolated proteins were shown to be IgM since they bind monoclonal anti-P. hypophthalmus IgM antibodies. Rabbit polyclonal anti-galactose-binding IgM only cross-react with some sugar-binding IgM. The H-chains of the anti-carbohydrate IgM are glycosylated. Circular dichroism studies revealed that the IgMs have an "all-ß" type of structure, and that Ca(2+) ions, though essential for carbohydrate-binding activity, are not required for the structural integrity of the molecules. In non-reducing SDS-PAGE, only monomers and halfmers were obtained, showing that there are no disulfide bonds linking the monomers, and that a disulfide bond connecting both H-chains within one monomer is only present in 45% of the molecules. Both the monomers and the halfmers display molecular mass heterogeneity which is indicative for redox forms at the level of the intradomain disulfide bonds. The native carbohydrate-binding IgMs agglutinate erythrocytes from different animals, as well as fish pathogenic bacteria. Similar proteins could not be isolated from another catfish, Clarias gariepinus.