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ABSTRACT In resource-limited settings, alternatives to HIV viral load testing may be necessary to monitor the health of people living with HIV. We assessed the utility of self-report antiretroviral therapy (ART) to screen for HIV viral load among persons who inject drugs in Hai Phong Vietnam, and consider differences by recent methamphetamine use. From 2016 to 2018 we recruited PWID through cross sectional surveys and collected self-report ART adherence and HIV viral load to estimate sensitivity, specificity, positive and negative predictive values (PPV, NPV) and likelihood ratios (LR+, LR-) for self-reported ART adherence as a screening test for HIV viral load. We used three HIV viral load thresholds: < 1000, 500 and 250 copies/mL; laboratory-confirmed HIV viral load was the gold standard. Among 792 PWID recruited, PPV remained above 90% regardless of recent methamphetamine use with slightly higher PPV among those not reporting recent methamphetamine use. The results remained consistent across all three HIV viral load thresholds. Our findings suggest that when HIV viral load testing is not possible, self-reported ART adherence may inform decisions about how to prioritize HIV viral load testing among PWID. The high PPV values suggest self-reported high ART adherence indicates likely HIV viral suppression, irrespective of methamphetamine use.

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 10 4 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.

Background: The co-occurrence of substance use disorder and mental disorder, known as dual diagnosis, has a distressingly high prevalence among individuals grappling with either of these conditions. Mood disorders, especially depression, constitute a substantial burden for People Who Inject Drugs (PWID) and a significant public health concern in Vietnam. Identifying risk factors for depression in PWID is imperative for the development of targeted interventions., Methods: We enrolled PWID into a cohort using the respondent-driven sampling method. Over a 36-month period, we systematically tracked the emergence of depression and employed multiple imputation in conjunction with a mixed nonlinear model to pinpoint risk factors for depression in this demographic. At inclusion, depression was screened using the PHQ-2 questionnaire, and subsequent episodes of depression were assessed semi-annually using the CES-D8., Results: Three hundred and ninety-one PWID (26.6%) were depressed. Major risk factors for depression included being female, not having a permanent residency, having been hospitalized and using methamphetamine more than weekly. Other risk factors included age, being single, not having a health insurance card and not being on methadone., Limitations: The exclusion of missing visits and social desirability could have led to selection and information biases. In this observational study, confusion biases are possible despite our best efforts., Conclusion: Depression is alarmingly frequent in PWID. In this study taking in account the chronological relationship between sociodemographic and clinical factors and depression, risk factors were identified in this specific setting of low-to-middle income country. The findings highlight the need to develop innovative targeted psychiatric interventions with the help of supporting peers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Moulis, Le, Hai, Huong, Minh, Oanh, Rapoud, Quillet, Thi, Vallo, Hoang, Moles, Laureillard, Feelemyer, Des Jarlais, Michel, Nagot and the DRIVE Study Team.)

Background: Understanding drug use and behavior within the PWUD population is crucial to adapt harm reduction and prevention strategies, and provide improved addiction and medical treatment. However, in most countries such as France, the knowledge of drug use behaviors is likely biased as it originates from addiction centers which are attended by only an unknown proportion of PWUD. The objectives of this study were to describe drug use behavior in a population of active PWUD in the urban area of Montpellier, South of France., Methods: We implemented a community-based respondent-driven sampling survey (RDSS), a validated strategy to obtain a representative sample of a population, to recruit PWUD in the city. Adult individuals reporting frequent psychoactive drug use other than cannabis, with confirmation by urine test, were eligible. Beside HCV and HIV testing, trained peers interviewed participants on their drug consumption and behavior using standardized questionnaires. Fifteen seeds launched the RDSS., Results: During the 11 weeks of the RDSS, 554 actives PWUD were consecutively included. They were mostly men (78.8%), had a median age of 39 years, and only 25.6% had a stable living place. On average, participants consumed 4.7 (± 3.1) different drugs, and 42.6% smoked free-base cocaine. Unexpectedly, heroin and methamphetamine were consumed by 46.8% and 21.5% of participants, respectively. Among the 194 participants injecting drugs, 33% declared sharing their equipment., Conclusion: This RDSS highlighted a high consumption of heroin, crack and methamphetamine in this PWUD population. These unexpected results can be explained by low attendance to addiction centers, the source of drug use reports. Despite free care and risk reduction equipment in the city, sharing was very frequent among injectors, challenging the current program of harm reduction., (© 2023. The Author(s).)

We examined gender differences among people who inject drug (PWID) in Hai Phong, Vietnam in term of blood-borne infections, risk behaviors, and access to care. Using respondent-driven-sampling surveys, we recruited 3146 PWID from 2016 to 2018. Inclusion criteria included a positive urine test for heroin and recent injection marks. There were 155 female PWID (4,9%), including 82 at RDS-2016, 32 at RDS-2017 and 38 at RDS-2018. The age mean was 36.3 ± 7.2 years. The majority of female PWID had less than high school education (90.9%) and were unemployed (51.3%). There was no difference in the proportion of HIV and HCV positive by gender. However, women had several significant differences in risk behaviors than men in multivariable logistic regression. Being a woman was independently associated with being unemployed, being a sex worker, having unstable housing, having uses drugs for less than 5 years, more use of methamphetamine, having a partner who ever injected drugs, and less access to methadone treatment. Interventions targeting female PWID are needed, possibly through community organizations and peer educators., (© 2022. The Author(s).)

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)., Competing Interests: ML received fees from Cepheid and Gilead US, as well as consultancy fees from Gilead US, outside the submitted work. KL received grants or contracts from MSD, honoraria from Janssen and Gilead, and travel support from Gilead, outside the submitted work. DDJ received grants and contracts from U.S. Centers for Disease Control, outside the submitted work. PV grants and contracts from Gilead medical Sciences outside the submitted work. Other authors declare no competing interest., (© 2023 The Author(s).)

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.

Background: After the emergence of COVID-19, a one-month strict lockdown was imposed in April 2020 in Vietnam, followed by lighter social distancing restrictions over the year. We investigated whether those measures affected people who inject drugs (PWID) in terms of risk behaviors for HIV and HCV and access to prevention and care in the city of Haiphong, a historic hotspot for HIV and drug use., Methodology: We carried out a 'before-after' study from 2019 to 2020 using respondent-driven sampling method to enroll PWID. They were interviewed on their socioeconomic situation, drug use and sexual behaviors, relations to care services and tested for drugs and methadone in the urine, for HIV, HCV, and HIV plasma viral load when HIV-positive. Changes following the restrictions were assessed by comparing 'before' to 'after' data., Results: 780 PWID were enrolled. Mean age was 44 years; 94% were male. All were actively injecting heroin 'before', versus 56% 'after'. Among those, frequency of consumption decreased from 24 to 17 days per month. No changes were observed in the frequency and practices of methamphetamine smoking. The proportion of PWID on MMT increased from 68.7% to 75.3%, and that of PWID engaging in risky behaviors related to drug injection decreased from 6.0% to 1.5%. No HIV seroconversions were observed; HCV incidence was 2.6/100 person-years (95% CI [0.7-6.7]). 9% of PWID reported a monthly income of less than 130USD 'before' versus 53% 'after'., Conclusion: The case of Hai Phong shows that it is possible, during times of COVID-19 pandemic, to maintain access to harm reduction and care and to prevent HIV and HCV transmission among PWID in a resource-limited setting where severe social distancing restrictions are implemented. Further research is needed to assess the consequences of long-term economic difficulties and the impact of actual spread of SARS-Cov2 that has since emerged in Haiphong., Competing Interests: Declarations of Interest The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022. Published by Elsevier B.V.)

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.

Background: In most low-to-middle-income countries, HIV control at the population level among people who inject drugs (PWID) remains a major challenge. We aimed to demonstrate that an innovative intervention can identify HIV-positive PWID in the community who are not treated efficiently, and get them treated efficiently., Methods: Between 2016 and 2020, we implemented an intervention consisting of mass HIV screening of PWID using three annual respondent-driven sampling surveys (RDSS) and a post-intervention evaluation RDSS in community-based organisation (CBO) sites, coupled with peer support to facilitate/improve access to antiretroviral and methadone therapy in Haiphong, Vietnam. The primary outcome was the proportion of identified uncontrolled HIV-positive PWID who achieved viral control. We also estimated the potential effect of the intervention on the proportion of PWID with HIV RNA >1000 copies/mL among all PWID during the study period., Findings: Over the three RDSS, 3150 different PWID were screened, i.e. two-thirds of the estimated population size. They all injected heroin, their median age was of 39 years, 95% were male, 26.5% were HIV-infected, and 78.6% of the latter had HIV RNA ≤1000 copies/mL. Among the 177 PWID identified with an unsuppressed viral load, 73 (41.2%) achieved viral suppression at the final visit. HIV viremia decreased from 7.2% at baseline to 2.9% at the final RDSS ( p <0.001). Up to 42% of this observed reduction may be explained by the intervention, in the absence of any external intervention targeting PWID during the study period., Interpretation: Mass community-based screening using RDSS coupled with CBO support is a powerful tool to rapidly identify untreated HIV-positive PWID and (re)link them to care., Funding: NIDA (USA) and ANRS (France)., Competing Interests: The authors declare no competing interest., (© 2022 The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Durand, Nagot, Michel, Le, Duong, Vallo, Vizeneux, Rapoud, Giang, Quillet, Thanh, Hai Oanh, Vinh, Feelemyer, Vande Perre, Minh, Laureillard, Des Jarlais and Molès.)

Background: Elimination of hepatitis C virus (HCV) among people who use drugs (PWUD) remains a challenge even in countries in which HCV care is provided free of cost. We assessed whether an innovative community-based, respondent-driven sampling (RDS) survey, coupled with HCV screening and immediate treatment, could be efficient to detect and cure current PWUD with chronic HCV in a large city of Southern France., Methods: At a community site with peers, PWUD (cannabis not included) were enrolled after confirmation by a urine drug test. Participants were then screened for hepatitis B virus, HCV, and human immunodeficiency virus and benefited from onsite HCV treatment evaluation and prescription. Peer support was provided during treatment, and a systematic visit was scheduled 12 weeks after the end of treatment. The cost of the intervention was estimated., Results: Five hundred fifty-four participants were enrolled. Most were male (78.8%) with a median age of 39 years (interquartile range, 33-46). Cocaine (73.1%) and heroine (46.8%) were the main drugs consumed. Overall, 32.6% of PWUD ( N  = 181) were HCV seropositive, 49 (27.1%) of which had detectable HCV ribonucleic acid and were thus eligible for treatment. Ten of these patients had severe fibrosis. Hepatitis C virus treatment was initiated for 37 (75.5%) patients, 30 (81.1%) of whom completed their treatment and 27 (73.0%) achieved sustained viral response at week 12. The total cost was 161 euros € per screened patient and 1816€ per patient needing treatment., Conclusions: A community-based RDS survey approach, involving peers, proved efficient and cost-effective to reach and cure PWUD for HCV. This innovative strategy could be key for the final step of HCV elimination. Clinical trial registration. ClinicalTrials.gov, NCT04008927., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: The prevalence of mental health disorders among people who use drugs is high and well documented. This hard-to-reach population faces a very low awareness and access to mental health care, especially in developing countries. The objectives of this study were to design and assess a quick screening tool (QST) that community-based organisations (CBO) could routinely apply to a Vietnamese population of people who inject drugs (PWID), in order to refer them appropriately to mental health specialists., Methods: We devised a tool that included nine questions covering anxiety, depression, suicide risk and psychotic symptomatology. Its use required no specific background and 2 h training. Specificity and sensitivity of the QST were assessed in a population of 418 PWID recruited via respondent driven sampling, using the Mini International Neuropsychiatric Interview questionnaire plus clinical evaluation as a reference standard. Acceptability was assessed using a self-administered anonymous questionnaire submitted to all CBO members who used the QST., Results: CBO members considered the QST easy to use, relevant and helpful to deal with mental health issues. Area under the curve for detection of any symptom using the QST was 0.770. The maximum sensitivity and specificity were reached with a cut-off of 2 [sensitivity was 71.1% (95% confidence interval 62.4, 78.8), specificity was 75.9% (70.5, 80.7)]., Discussion and Conclusions: The QST appeared to be both efficient and well accepted. Given the burden of mental health problems among hard-to-reach PWID in developing countries, community-based screenings such as this one could be a particularly appropriate response., (© 2021 Australasian Professional Society on Alcohol and other Drugs.)

Background: Access to psychiatric care for people who inject drugs (PWID) is limited/absent and stigmatized in most low-middle-income countries (LMICs). Innovative interventions are needed. We aimed to describe and assess the impact of a community-based psychiatric intervention among PWID in Hai Phong, Vietnam., Methods: In a cohort study with one year psychiatric follow-up, PWID diagnosed with a psychotic disorder, a major depressive episode, or suicide risk, were recruited from the wider Drug-Related Infections in ViEtnam (DRIVE) project in the city of Hai Phong. The community-based psychiatric intervention included specialized follow-up (free consultations with psychiatrists, free medication, referral to mental health department for hospitalization when necessary) and support from community-based organisations (case management, harm reduction, administrative support, linkage to HIV care, methadone maintenance treatment and mental health support). The main outcome was reduction/remission of symptoms. Access to and retention in psychiatric care, quality-of-life and stigmatization were also measured pre and post-intervention., Findings: Among the 1212 participants screened from March to May 2019, 271 met the inclusion criteria, 233 (86.3%) accepted the intervention and 170 completed the follow-up (72.9%). At inclusion, 80.6% were diagnosed with current depression, 44.7% with psychotic disorder and 42.4% with suicide risk. After a one-year follow-up, these proportions dropped to 15.9%, 21.8%, and 22.9% respectively. Quality-of-life and perceived stigma related to mental health were also significantly improved, while drug use decreased only marginally., Interpretation: Community-based psychiatric interventions are both feasible and efficient in the Vietnamese context. Similar interventions should be implemented and evaluated in other, different LMICs., Funding: : This work was supported by grants from NIDA (US) (#DA041978) and ANRS (France) (#13353). The funding agencies had no role in designing the research, data analyses, or preparation of the report., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Aims: To describe the use of large-scale respondent driven sampling (RDS) surveys to demonstrate the "end of an HIV epidemic" (HIV incidence < 0.5/100 person-years) among persons who inject drugs (PWID) in a middle-income country. Large sample sizes are needed to convincingly demonstrate very low incidence rates., Methods: 4 large surveys (Ns approximately 1500 each) were conducted among PWID in Hai Phong, Vietnam in 2016-2019. Respondent driven sampling (RDS) with a modification to add snowball sampling was used for recruiting participants. HIV incidence was measured through recency testing, repeat participants across multiple surveys and in a cohort study of PWID recruited from the surveys. RDS analytics (time to equilibria and homophilies for major variables) were used to assess similarities/differences in RDS only versus RDS plus snowball recruiting. Characteristics were compared among respondents recruited through standard RDS recruitment versus through snowball sampling. An overall assessment of the robustness of RDS to modification was made when adding a snowball sampling recruitment., Results: RDS recruiting was very efficient in the first 5 weeks of each survey with approximately 180 respondents recruited per week. Recruiting then slowed considerably, and snowball sampling (permitting an individual respondent to recruit large numbers of new respondents) was added to the existing RDS recruiting. This led to recruiting within 13-14 weeks of 1383, 1451, 1444 and 1268 respondents, close to the target of 1500 respondents/survey. Comparisons of participants recruited through standard RDS method and respondents recruited through snowball methods showed very few significant differences. RDS analytics (quickly reaching equilibria, low homophilies) were favorable for both RDS recruited and total numbers of participants in each survey. DRug use and Infections in ViEtnam (DRIVE) methods have now been officially adopted in other provinces., Conclusions: RDS appears to be quite robust with respect to adding a modest number of participants recruited through snowball sampling. Large sample sizes can provide compelling evidence for "ending an HIV epidemic" to policy makers in a PWID population in a middle income country setting., Competing Interests: The authors have declared that no competing interests exist.

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Objective: To estimate the residual mortality rate among people who inject drugs (PWID) in a Low-Middle Income Countries context where the HIV epidemic has been controlled and methadone coverage is high., Study Design and Setting: PWID from Haiphong, Vietnam, were recruited through three annual respondent-driven sampling surveys that fueled two cohorts of PWID with HIV (n = 761) and without HIV (n = 897), with bi-annual follow-up. Presumed causes of death were ascertained from medical records and/or interviews of participants family., Results: Among the 1658 participants with a median follow-up of 2 years, 67 and 36 died in the HIV-positive and HIV-negative cohort, respectively, yielding crude mortality rates of 4.3 (95% Confidence interval (CI): 3.3-5.4) per 100 person-years of follow-up (PYFU) and 1.9 (CI: 1.4-2.6) per 100 PYFU. In the HIV-positive cohort, in which 81% of participants had undetectable viral load, the two main causes of death were tuberculosis and HIV-related diseases. In the HIV-negative cohort, the two main causes of death were liver-related diseases and overdose. In a time-dependent multivariable model, "unsuppressed viral load" was associated with increased risk of mortality, whereas "being on methadone" or "being employed" was associated with a lower risk., Conclusion: Despite a very successful HIV and methadone program, the mortality remains high among PWID in Vietnam, largely due to curable infectious diseases such as tuberculosis and viral hepatitis., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

Aims: To describe the current methamphetamine (MA) use epidemic among persons who inject heroin (PWID) in Hai Phong, Vietnam, and consider possibilities for mitigating adverse effects of methamphetamine use., Methods: This study conducted surveys of PWID in 2016, 2017, and 2018 (N = 1383, 1451, and 1445, respectively). Trained interviewers administered structured interviews covering drug use histories, current drug use, and related risk behaviors. The study used urinalysis to confirm current drug use, and conducted HIV and HCV testing., Results: Participants were predominantly male (95%), mean age of 40, and all reported injecting heroin. Respondents' reports of initiating MA use were rare up through early 2000s but increased exponentially through the mid-2010s. MA use was predominantly "smoking," heating the drug and inhaling the vapor using a pipe; injecting MA was rare. Current (past 30 day) MA use appears to have plateaued in 2016-2018 with 53-58% of participants reporting no use in the last 30 days, 37-41% reporting low to moderate use (1 to 19 days in last 30 days), and 5-7% reporting very frequent use (20 or more days in last 30 days). This plateau reflects a rough balance between new users and individuals ceasing use., Conclusions: MA use has become a substantial public health problem among PWID in Hai Phong. Initiation into MA use rose exponentially from 2005 to about 2015. Use of MA will likely continue for a substantial number of PWID. Currently, no medication is approved for treating MA disorders in Vietnam. Current psychosocial treatment requires highly trained counselors and months of treatment, so that psychosocial treatment for all PWID with MA disorders is likely beyond the resources available in a middle-income country such as Vietnam. Harm reduction programs implemented by community-based organization staff may provide a way to rapidly address aspects of the current MA epidemic. Such programs could emphasize social support for reducing use where possible and for avoiding escalation of use among persons continuing to use., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In the ANRS 12174 trial, HIV-exposed uninfected African neonates who received lopinavir-ritonavir (LPV/r) prophylaxis for 1 year exhibited slower growth from birth to week 50 compared with those receiving lamivudine (3TC). We assessed whether this difference in growth persisted over time, and was accompanied by differences in neuropsychological and clinical outcomes. Between February 2017 and February 2018, we conducted a cross-sectional clinical evaluation among former trial participants who completed the 50-week follow-up and who were not HIV-infected. In addition to clinical examination, neuropsychological outcomes were assessed using the tests Kaufman-ABCII, Test of Variables of Attention, Movement Assessment Battery for Children and the Strengths and Difficulties questionnaire, parent version. Of 1101 eligible children, aged 5-7 years, 553 could be traced and analysed (274 in the LPV/r and 279 in the 3TC groups). Growth, clinical and neuropsychological outcomes did not differ between treatment groups. At school age, children exposed to LPV/r and 3TC at birth for 1 year had comparable growth and neuropsychological outcomes without evidence of long-term side-effects of LPV/r. It provides reassuring data on clinical outcomes for all HIV-infected children treated with this antiretroviral drug in early life.

Objective: To determine whether it is possible to 'end an HIV epidemic' among persons who inject drugs (PWID) in a low/middle income country., Design: Serial cross-sectional surveys with a cohort of HIV seronegative participants with 6-month follow-up visits recruited from surveys., Methods: Surveys of PWID using respondent driven and snowball sampling were conducted in 2016, 2017, 2018, and 2019 (N = 1383, 1451, 1444, and 1268). HIV recency testing was used to identify possible seroconversions in the window period prior to study entry. Structured interviews covering drug use histories, current drug use, and use of HIV-related services were administered by trained interviewers. Urinalysis was used to confirm current drug use. HIV and hepatitis C virus testing were conducted. Electronic fingerprint readers were used to avoid multiple participation in each survey and to link participants across surveys. A cohort of HIV seronegative participants with 6-month follow-up visits was recruited from the surveys, 480 from 2016, 233 from 2017, and 213 from 2018., Results: Participants were predominantly male (95%), mean age approximately 40, all reported injecting heroin, HIV prevalence ranged between 26 and 30%. We had three seroconversions in 1483 person-years at risk (PYAR) in the cohort study, and 0 in 696 PYAR among repeat survey participants, and 0 seroconversions in 1344 PYAR in recency testing. Overall HIV incidence was 0.085/100 PYAR, 95% confidence interval 0.02-0.25/100 PYAR., Conclusion: The data from Hai Phong clearly demonstrate that it is possible to achieve very low HIV incidence - 'end an HIV epidemic' - among PWID in a middle-income country.

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We assessed the association between methamphetamine use and lack of viral suppression among a cohort of HIV-seropositive persons who inject drugs (PWID) in Hai Phong, Vietnam., Design: Cohort study with random effects logit modeling and mediation analysis for antiretroviral therapy (ART) adherence., Methods: PWID were recruited from October 2016 to October 2017; HIV-seropositive PWID were enrolled in a cohort to assess HIV viral loads, changes in drug use, risk behaviors, and ART adherence during 24-month follow-up. Methamphetamine use in last 30 days was divided into three categories: 0 days (no use), 1-19 days (intermediate), and 20 or more days (heavy). Bivariate and a multivariable random effects logit models were used to assess the relationship between methamphetamine use and not being virally suppressed. We also assessed self-reported ART adherence as a mediating factor., Results: A total of 645 HIV-seropositive PWID were included at baseline; 95% male, average age 40 (SD = 6.4). At baseline, methamphetamine use in last 30 days was 64% no use, 32% intermediate use, 4% heavy use. Approximately 74% of PWID reported high/complete adherence; 76% were at viral suppression. In random effects analysis, recent methamphetamine use was associated with not being virally suppressed during follow-up (adjusted odds ratio: 1.84, 95% confidence interval: 1.06, 3.17); the effect was not explained by a mediating effect of self-reported adherence to ART., Conclusion: Recent methamphetamine use is associated with not being virally suppressed among PWID. The results of this study indicate the need for targeted interventions for methamphetamine use with special focus on those with HIV infection.

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., (Copyright © 2020 Elsevier B.V. All rights reserved.)

People who inject drugs (PWID) are a dominant risk group afflicted by blood-borne viruses, mental health disorders, and social precariousness. Risk reduction interventions are administered to PWID regardless of their characteristics or specific risks. The objective of this cross-sectional analysis was to empirically identify profiles of PWID regarding their drug use, risk behaviors, and mental health in order to tailor adapted interventions taking into account limited access to comprehensive care in middle-income countries. PWID were recruited using respondent-driven sampling. PWID with urine testing positive for heroin or methamphetamine and manifesting recent skin injection marks were enrolled. Classification of participants was based on drug use, injection, risky sexual behavior, and mental health data. This was subjected to multiple correspondence analysis followed by hierarchical cluster analysis combined with K -means methodology. From October 2016 to January 2017, 1490 participants were recruited of which 1383 were eligible and enrolled. HCV prevalence was 70.5% and HIV prevalence 29.4%. The cluster analysis identified five distinct profiles: profile 1: recent injection practices and high alcohol consumption, profile 2: at-risk injection and sexual behaviors with precarious situations, profile 3: no sexual activity and older age, profile 4: frequent injections with high methamphetamine use, and profile 5: stable partnerships and less frequent injections. Our study has identified profiles of PWID at particularly high risks, and they should thus be targeted for interventions tailored to their specific risks., Competing Interests: The authors have no conflicts to declare., (Copyright © 2020 Adeline Riondel et al.)

In Vietnam, harm reduction programs to control HIV among people who inject drugs (PWID) were implemented approximately 10 years ago. Since then, the HIV prevalence has declined in this population, however, the impact of these programs on the rate of new HIV and Hepatitis C (HCV) infections remains unknown as high mortality can exceed the rate of new infections. We evaluated HIV and HCV incidences in a cohort of active PWID in HaiPhong in 2014, who were recruited from a community-based respondent driven sampling (RDS) survey and followed for 1 year. Only HIV-negative or HCV-negative participants not on medication assisted treatment (MAT) were eligible. HIV/HCV serology was tested at enrollment and at 32- and 64-week follow-up visits. Among 603 RDS participants, 250 were enrolled in the cohort, including 199 HIV seronegative and 99 HCV seronegative PWID. No HIV seroconversion was reported during the 206 person-years (PY) of follow-up (HIV incidence of 0/100PY, one-sided 97.5%CI:0-1.8/100 PY). Eighteen HCV seroconversions were reported for an incidence of 19.4/100 PY (95%CI;11.5-30.7). In multivariate analysis, "Injecting more than twice daily" was associated with HCV seroconversion with an adjusted odds ratio of 5.8 (95%CI;1.8-18.1). In Hai Phong, in a context that demonstrates the effectiveness of HIV control programs, the HCV incidence remains high. New strategies such as mass access to HCV treatment should be evaluated in order to tackle HCV transmission among PWID.

Background: Diagnosis of tuberculosis should be improved in children infected with HIV to reduce mortality. We developed prediction scores to guide antituberculosis treatment decision in HIV-infected children with suspected tuberculosis., Methods: HIV-infected children with suspected tuberculosis enrolled in Burkina Faso, Cambodia, Cameroon, and Vietnam (ANRS 12229 PAANTHER 01 Study), underwent clinical assessment, chest radiography, Quantiferon Gold In-Tube (QFT), abdominal ultrasonography, and sample collection for microbiology, including Xpert MTB/RIF (Xpert). We developed 4 tuberculosis diagnostic models using logistic regression: (1) all predictors included, (2) QFT excluded, (3) ultrasonography excluded, and (4) QFT and ultrasonography excluded. We internally validated the models using resampling. We built a score on the basis of the model with the best area under the receiver operating characteristic curve and parsimony., Results: A total of 438 children were enrolled in the study; 251 (57.3%) had tuberculosis, including 55 (12.6%) with culture- or Xpert-confirmed tuberculosis. The final 4 models included Xpert, fever lasting >2 weeks, unremitting cough, hemoptysis and weight loss in the past 4 weeks, contact with a patient with smear-positive tuberculosis, tachycardia, miliary tuberculosis, alveolar opacities, and lymph nodes on the chest radiograph, together with abdominal lymph nodes on the ultrasound and QFT results. The areas under the receiver operating characteristic curves were 0.866, 0.861, 0.850, and 0.846, for models 1, 2, 3, and 4, respectively. The score developed on model 2 had a sensitivity of 88.6% and a specificity of 61.2% for a tuberculosis diagnosis., Conclusions: Our score had a good diagnostic performance. Used in an algorithm, it should enable prompt treatment decision in children with suspected tuberculosis and a high mortality risk, thus contributing to significant public health benefits., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2019 by the American Academy of Pediatrics.)

Objective: To assess the prevalence of menstrual hygiene management (MHM) knowledge and practices among adolescent schoolgirls in Indonesia, and assess factors associated with poor MHM and school absenteeism due to menstruation., Methods: A cross-sectional survey enrolled a representative sample of urban and rural school-going girls aged 12-19 years in four provinces of Indonesia. A semi-structured, self-administered questionnaire obtained socio-demographic characteristics, knowledge, practices and attitudes related to menstruation, MHM and school absenteeism. School water, sanitation and hygiene (WASH) facilities were also assessed. Univariate weighted population prevalence was estimated and multivariable logit regression analyses applied to explore associations., Results: A total of 1159 adolescent girls with a mean age of 15 years (SD = 1.8) participated. Most girls (90.8%, 95% confidence interval (95% CI) = 79.7-96.1) had reached menarche. Over half (64.1%, 95% CI = 49.9-76.2) reported poor MHM practices, and 11.1% (95% CI = 8.1-15.2) had missed one or more days of school during their most recent menstrual period. Poor MHM practices were associated with rural residence (Adjusted odds ratio (AOR) = 1.73, 95% CI = 1.13-2.64), province (various AOR), lower school grade (AOR = 1.69, 95% CI = 1.05-2.74) and low knowledge of menstruation (AOR = 3.49, 95% CI = 1.61-7.58). Absenteeism was associated with living in rural areas (AOR = 3.96, 95% CI = 3.02-5.18), province (various AOR), higher school grade (AOR = 3.02, 95% CI = 2.08-4.38), believing menstruation should be kept secret (AOR = 1.47, 95% CI = 1.03-2.11), experiencing serious menstrual pain (AOR = 1.68, 95% CI = 1.06-2.68) and showed mixed associations with school WASH facilities., Conclusions: High prevalence of poor MHM and considerable school absenteeism due to menstruation among Indonesian girls highlight the need for improved interventions that reach girls at a young age and address knowledge, shame and secrecy, acceptability of WASH infrastructure and menstrual pain management., (© 2018 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

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.

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.

Background: Good estimates of key population sizes are critical for appropriating resources to prevent HIV infection. We conducted two capture/recapture studies to estimate the number of PWID currently in Hai Phong, Vietnam., Methods: A 2014 respondent-driven sampling (RDS) survey served as one capture, and distribution of cigarette lighters at drug use "hotspots" in 2016 served as another "capture." A 2016 survey using RDS, conducted 1 week after lighter distribution, served as "recapture" for both captures. Recaptured participants in the two surveys were identified with a computerized fingerprint reader. Recaptured participants from the lighter distribution were asked to show their lighters., Results: 1385 participants were included in the "recapture" survey. They were 94% male and had a median age of 39. All (100%) injected heroin, and HIV prevalence was 30%. 144 of the 603 participants in the 2014 survey and 152 of the 600 PWID who had received lighters were "recaptured" in the 2016 survey. After adjusting for police suppression of drug use hotspots and conducting sensitivity analyses, our best estimate of the population size from the lighter recapture was 4617 (95% CI: 4090-5143), and our best estimate from the 2014 survey recapture was 5220 (95% CI: 4568-5872). A combined best estimate of the PWID population in Hai Phong is 5000, range 4000-6000., Conclusions: The capture/recapture studies produced consistent estimates. Adding a lighter/token distribution to planned RDS surveys may provide an inexpensive method for estimating PWID population size. Analyses of the estimates should include contextual information about the local drug scene., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.

Background: Cryptococcal infection is a frequent cause of mortality in Cambodian HIV-infected patients with CD4+ count ≤100 cells/µl. This study assessed the cost-effectiveness of three strategies for cryptococcosis prevention in HIV-infected patients., Methods: A MARKOV DECISION TREE WAS USED TO COMPARE THE FOLLOWING STRATEGIES AT THE TIME OF HIV DIAGNOSIS: no intervention, one time systematic serum cryptococcal antigen (CRAG) screening and treatment of positive patients, and systematic primary prophylaxis with fluconazole. The trajectory of a hypothetical cohort of HIV-infected patients with CD4+ count ≤100 cells/µl initiating care was simulated over a 1-year period (cotrimoxazole initiation at enrollment; antiretroviral therapy within 3 months). Natural history and cost data (US$ 2009) were from Cambodia. Efficacy data were from international literature., Results: In a population in which 81% of patients had a CD4+ count ≤50 cells/ µl and 19% a CD4+ count between 51-100 cells/µl, the proportion alive 1 year after enrollment was 61% (cost $ 472) with no intervention, 70% (cost $ 483) with screening, and 72% (cost $ 492) with prophylaxis. After one year of follow-up, the cost-effectiveness of screening vs. no intervention was US$ 180/life year gained (LYG). The cost-effectiveness of prophylaxis vs. screening was $ 511/LYG. The cost-effectiveness of prophylaxis vs. screening was estimated at $1538/LYG if the proportion of patients with CD4+ count ≤50 cells/µl decreased by 75%., Conclusion: In a high endemic area of cryptococcosis and HIV infection, serum CRAG screening and prophylaxis are two cost effective strategies to prevent AIDS associated cryptococcosis in patients with CD4+ count ≤100 cells/µl, at a short-term horizon, screening being more cost-effective but less effective than prophylaxis. Systematic primary prophylaxis may be preferred in patients with CD4+ below 50 cells/µl while systematic serum CRAG screening for early targeted treatment may be preferred in patients with CD4+ between 51-100 cells/µl.

Background: The long-term maintenance of antiretroviral therapy (ART) remains an important issue, especially in limited-resource settings where additional barriers exist. A cross-sectional study was performed 24 months after ART initiation for patients treated in Cambodia in order to estimate the prevalence and identify determinants of non-adherence., Methods: Adults receiving ART for 24 +/- 2 months were considered eligible for the study. Self-reported non-adherence was defined according to an algorithm based on six items. The questionnaire also assessed ART-related side effects and HIV disclosure. HIV-1 RNA plasma viral load was measured using real-time PCR. Multivariate rare events logistic regression analysis was used to identify independent factors associated with non-adherence., Results: A total of 346 patients participated in the study. At 24 months, 95% of patients were adherent, 80% had HIV RNA <40 copies/ml and 75% had CD4+ T-cell counts >200 cells/mm3. Virological success was significantly higher in adherent patients than in non-adherent patients (81% versus 56%, P=0.021). Living in a rural area, limited HIV disclosure and perceived lipodystrophy were independently associated with non-adherence., Conclusions: At 24 months, adherence to ART was high and explained positive virological outcomes. In order to maintain adherence and long-term virological benefits, special attention should be given to patients living in rural areas, those with lipodystrophy-related symptoms and others who express difficulties disclosing their condition to close family members.

Objectives: African and Asian cohort studies have demonstrated the feasibility and efficacy of HAART in resource-poor settings. The long-term virological outcome and clinico-immunological criteria of success remain important questions. We report the outcomes at 24 months of antiretroviral therapy (ART) in patients treated in a Médecins Sans Frontières/Ministry of Health programme in Cambodia., Methods: Adults who started HAART 24 +/- 2 months ago were included. Plasma HIV-RNA levels were assessed by real-time polymerase chain reaction. Factors associated with virological failure were analysed using logistic regression., Results: Of 416 patients, 59.2% were men; the median age was 33.6 years. At baseline, 95.2% were ART naive, 48.9% were at WHO stage IV, and 41.6% had a body mass index less than 18 kg/m. The median CD4 cell count was 11 cells/microl. A stavudine-lamivudine-efavirenz-containing regimen was initiated predominantly (81.0%). At follow-up (median 23.8 months), 350 (84.1%) were still on HAART, 53 (12.7%) had died, six (1.4%) were transferred, and seven (1.7%) were lost to follow-up. Estimates of survival were 85.5% at 24 months. Of 346 tested patients, 259 (74.1%) had CD4 cell counts greater than 200 cells/microl and 306 (88.4%) had viral loads of less than 400 copies/ml. Factors associated with virological failure at 24 months were non-antiretroviral naive, an insufficient CD4 cell gain of less than 350 cells/microl or a low trough plasma ART concentration. In an intention-to-treat analysis, 73.6% of patients were successfully treated., Conclusion: Positive results after 2 years of advanced HIV further demonstrate the efficacy of HAART in the medium term in resource-limited settings.

Background: HAART efficacy was evaluated in a real-life setting in Phnom Penh (Médecins Sans Frontières programme) among severely immuno-compromised patients., Methods: Factors associated with mortality and immune reconstitution were identified using Cox proportional hazards and logistic regression models, respectively., Results: From July 2001 to April 2005, 1735 patients initiated HAART, with median CD4 cell count of 20 (inter-quartile range, 6-78) cells/microl. Mortality at 2 years increased as the CD4 cell count at HAART initiation decreased, (4.4, 4.5, 7.5 and 24.7% in patients with CD4 cell count > 100, 51-100, 21-50 and < or = 20 cells/microl, respectively; P < 10). Cotrimoxazole and fluconazole prophylaxis were protective against mortality as long as CD4 cell counts remained < or = 200 and < or = 100 cells/microl, respectively. The proportion of patients with successful immune reconstitution (CD4 cell gain > 100 cells/microl at 6 months) was 46.3%; it was lower in patients with previous ART exposure [odds ratio (OR), 0.16; 95% confidence interval (CI), 0.05-0.45] and patients developing a new opportunistic infection/immune reconstitution infection syndromes (OR, 0.71; 95% CI, 0.52-0.98). Similar efficacy was found between the stavudine-lamivudine-nevirapine fixed dose combination and the combination stavudine-lamivudine-efavirenz in terms of mortality and successful immune reconstitution. No surrogate markers for CD4 cell change could be identified among total lymphocyte count, haemoglobin, weight and body mass index., Conclusion: Although CD4 cell count-stratified mortality rates were similar to those observed in industrialized countries for patients with CD4 cell count > 50 cells/microl, patients with CD4 cell count < or = 20 cells/microl posed a real challenge to clinicians. Widespread voluntary HIV testing and counselling should be encouraged to allow HAART initiation before the development of severe immuno-suppression.