HCV RNA Quantification by a Domestic Commercial Assay: A Case Study among People Who Inject Drugs in Vietnam.

The desired performance of nucleic acid testing (NAT) may vary if used for disease diagnosis or for the evaluation of the therapeutic efficacy of a treatment, although in most cases, the same assay is used. However, these tests may not be affordable in many situations including in low/middle income countries that in response have developed domestic assays. Given the example of HCV NAT among people who inject drugs in Vietnam, we aimed at evaluating a domestic assay versus an FDA- and CE-approved assay. This cross-evaluation revealed that (i) the domestic assay had a poorer sensitivity with a threshold of detection above 104 IU/mL, and (ii) the FDA-approved assay had a percentage of false negative results close to 1%. Together, in the present study, the domestic assay had a performance compatible with diagnosis purposes (given that this population was 70% HCV seropositive) but not compatible with HCV treatment monitoring (given that treatment failures are rare and the observed viremia frequently below the threshold of detection). This study highlights the need for a proper evaluation of HCV RNA domestic assays in order to efficiently contribute to the WHO HCV elimination target by 2030.

A community-based strategy to eliminate hepatitis C among people who inject drugs in Vietnam.

Background: Towards hepatitis C elimination among people who inject drugs (PWID), we assessed the effectiveness of a strategy consisting of a community-based respondent-driven sampling (RDS) as wide screening, a simplified and integrated hospital-based care, and prevention of reinfection supported by community-based organisations (CBO), in Hai Phong, Vietnam. Methods: Adults who injected heroin were enrolled in a RDS survey implemented in two CBO premises. Rapid HIV and HCV tests were done on site, and blood was taken for HCV RNA testing. Those with detectable HCV RNA were referred with CBO support to three public hospitals for 12-week sofosbuvir/daclatasvir, plus ribavirin for patients with cirrhosis. Participants were followed-up 12 weeks post-treatment (SVR12) and 48 weeks after enrolment. The primary endpoint was the rate of undetectable HCV RNA participants at 48 weeks. Findings: Among the 1444 RDS survey participants, 875 had hepatitis C. Their median age was 41 years (IQR 36-47), 96% were males, 36% were HIV-coinfected. Overall, 686 (78.4%) started sofosbuvir/daclatasvirs, and 629 of the 647 (97.2%) patients tested at SVR12 were cured. At week 48 (581/608) 95.6% had undetectable HCV RNA, representing 66.4% of all PWID identified with hepatitis C. The reinfection rate after SVR12 was 4/100 person-years (95% CI: 2-7). Interpretation: Our strategy, involving CBO and addressing all steps from wide HCV screening to prevention of reinfection, stands as a promising approach to eliminate HCV among PWID in low and middle-income countries. Funding: France ANRS|MIE (#ANRS12380). The RDS survey was implemented with grants from the NIDA (#R01DA041978) and ANRS|MIE (#ANRS12353).

Long-Term Persistence of Mitochondrial DNA Instability among HCV-Cured People Who Inject Drugs.

People who inject drugs (PWID) are a population exposed to many genotoxicants and with a high prevalence of HCV infection. Direct-acting antiviral (DAA) regimens are now widely used to treat chronic HCV infection. Although side effects to treatment are currently rare, the long-term effects such as suspicions of de novo hepatocellular carcinoma (HCC) occurrence or HCC recurrence and cardiac defects are still up for debate. Given the structure of DAAs, the molecules have a potential mitochondrial DNA (mtDNA) genotoxicity. We have previously reported acute mtDNA toxicity of three DAA regimens among PWID with a strong impact on the rate of mtDNA deletion, less on the quantity of mtDNA copy per cell at sustained viral response at 12 weeks (SVR12). Herein, we report the mtDNA parameters nine months after drug discontinuation. We observed that the percentage of the deleted mtDNA genome increased over time. No exposure to any other genotoxicants during this period was associated with a high deletion percentage, suggesting that the replicative advantage of the deleted molecules outweighed their elimination processes. Such observation calls for longer-term follow-up and may contribute to the molecular basis of subclinical side effects of DAA treatments.

Mental Disorders Are Associated With Leukocytes Telomere Shortening Among People Who Inject Drugs.

Premature biological aging, assessed by shorter telomere length (TL) and mitochondrial DNA (mtDNA) alterations, has been reported among people with major depressive disorders or psychotic disorders. However, these markers have never been assessed together among people who inject drugs (PWIDs), although mental disorders are highly prevalent in this population, which, in addition, is subject to other aggravating exposures. Diagnosis of mental disorders was performed by a psychiatrist using the Mini International Neuropsychiatric Interview test among active PWIDs in Haiphong, Vietnam. mtDNA copy number (MCN), mtDNA deletion, and TL were assessed by quantitative PCR and compared to those without any mental disorder. We next performed a multivariate analysis to identify risk factors associated with being diagnosed with a major depressive episode (MDE) or a psychotic syndrome (PS). In total, 130 and 136 PWIDs with and without psychiatric conditions were analyzed. Among PWIDs with mental disorders, 110 and 74 were diagnosed with MDE and PS, respectively. TL attrition was significantly associated with hepatitis C virus-infected PWIDs with MDE or PS (adjusted odds ratio [OR]: 0.53 [0.36; 0.80] and 0.59 [0.39; 0.88], respectively). TL attrition was even stronger when PWIDs cumulated at least two episodes of major depressive disorders. On the other hand, no difference was observed in mtDNA alterations between groups. The telomeric age difference with drug users without a diagnosis of psychiatric condition was estimated during 4.2-12.8 years according to the number of MDEs, making this group more prone to age-related diseases.

Alarming Tuberculosis Rate Among People Who Inject Drugs in Vietnam.

BACKGROUND: The tuberculosis (TB) epidemic is not homogeneous in the general population but presents high-risk groups. People who inject drugs (PWID) are such a group. However, TB among PWID remains largely undocumented. Our goal was to assess the prevalence of TB and the risk factors associated with TB among PWID in Vietnam. METHODS: We implemented a cross-sectional survey among 2 community-based cohorts of human immunodeficiency virus (HIV)-positive and HIV-negative PWID in Hai Phong. Participants were screened for TB using questions on TB symptoms. Those who reported any symptom were accompanied by peers to the TB clinic for chest x-ray. If the latter was abnormal, a sputum was collected to perform an Xpert MTB/RIF test. RESULTS: A total of 885 PWID were screened for TB. For both cohorts, most PWID were male (>90.0%), with a median age of 42 years. Beside heroin injection, 52.5% of participants reported smoking methamphetamine, and 63.2% were on methadone. Among HIV-positive PWID (N = 451), 90.4% were on antiretroviral therapy and 81.6% had a viral load <1000 copies/mL. Using a complete-case analysis, the estimated TB prevalence was 2.3% (95% confidence interval [CI], 1.0-4.5) and 2.1% (95% CI, 0.8-4.2) among HIV-positive and HIV-negative people, respectively. Living as a couple, arrest over the past 6 months, homelessness, and smoking methamphetamine were independently associated with TB but not HIV infection. CONCLUSIONS: In the context of very large antiretroviral therapy coverage, this extremely high rate of TB among PWID requires urgent actions.

Mitochondrial Genotoxicity of Hepatitis C Treatment among People Who Inject Drugs.

Antiviral nucleoside analogues (ANA) are newly used therapeutics acting against the hepatitis C virus (HCV). This class of drug is well known to exhibit toxicity on mitochondrial DNA (mtDNA). People who inject drugs (PWID) are particularly affected by HCV infection and cumulated mitotoxic drug exposure from HIV treatments (antiretrovirals, ARV) and other illicit drugs. This study aims to explore the impact of direct-acting antiviral (DAA) treatments on mtDNA among PWID. A total of 470 actively injecting heroin users were included. We used quantitative PCR on whole blood to determine the mitochondrial copy number per cell (MCN) and the proportion of mitochondrial DNA deletion (MDD). These parameters were assessed before and after DAA treatment. MDD was significantly increased after HCV treatment, while MCN did not differ. MDD was even greater when subjects were cotreated with ARV. In multivariate analysis, we identified that poly-exposure to DAA and daily heroin injection or regular consumption of methamphetamines were positively associated with high MCN loss while DAA and ARV treatments or methadone use were identified as risk factors for having mtDNA deletion. These observations deserve attention since they were previously associated with premature cell ageing or cell transformation and therefore call for a long-term follow-up.

Female sexual partners of male people who inject drugs in vietnam have poor knowledge of their male partners' HIV status.

BACKGROUND: Vietnam's HIV epidemic is concentrated among male people who inject drugs (PWID), and their female sexual partners (SPs) may be at risk for infection. HIV prevention interventions for SPs were implemented in Hanoi, Dien Bien Province, and Ho Chi Minh City (HCMC), and data from linked surveys used to evaluate these interventions offered an unusual opportunity to assess knowledge of HIV status within couples. METHODS: Linked surveys (behavioral interviews and HIV testing) among 200 PWID-SP couples in Hanoi, 300 in Dien Bien, and 249 in HCMC. RESULTS: HIV prevalence among male PWID was 53% in Hanoi, 30% in Dien Bien, and 46% in HCMC, and lower among their SPs: 44%, 10%, and 37%, respectively. Comparison of SPs' beliefs regarding male PWID partners' HIV status with the PWIDs' actual test results revealed that 32% of SPs in Dien Bien and 44% in Hanoi and HCMC lacked correct knowledge of their male partners' status. This proportion was slightly lower (21%-33%) among SPs whose PWID partners reported having been previously tested and received HIV+ results. CONCLUSIONS: SP interventions reached HIV-negative women in serodiscordant relationships, and some improvements occurred in condom use and relationship characteristics. Nevertheless, our findings suggest that at least 11,000 SPs in Vietnam may be at high risk for HIV infection because of incorrect knowledge of their partners' HIV status. Interventions should be strengthened in HIV testing, disclosure, and treatment, as well as empowerment of SPs as individuals, within couples, and as communities.