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Background: Studying human immunodeficiency virus type 1 (HIV-1) superinfection is important to understand virus transmission, disease progression, and vaccine design. But detection remains challenging, with low sampling frequencies and insufficient longitudinal samples., Methods: Using the Swiss HIV Cohort Study (SHCS), we developed a molecular epidemiology screening for superinfections. A phylogeny built from 22 243 HIV-1 partial polymerase sequences was used to identify potential superinfections among 4575 SHCS participants with longitudinal sequences. A subset of potential superinfections was tested by near-full-length viral genome sequencing (NFVGS) of biobanked plasma samples., Results: Based on phylogenetic and distance criteria, 325 potential HIV-1 superinfections were identified and categorized by their likelihood of being detected as superinfections due to sample misidentification. NFVGS was performed for 128 potential superinfections; of these, 52 were confirmed by NFVGS, 15 were not confirmed, and for 61 sampling did not allow confirming or rejecting superinfection because the sequenced samples did not include the relevant time points causing the superinfection signal in the original screen. Thus, NFVGS could support 52 of 67 adequately sampled potential superinfections., Conclusions: This cohort-based molecular approach identified, to our knowledge, the largest population of confirmed superinfections, showing that, while rare with a prevalence of 1%-7%, superinfections are not negligible events., Competing Interests: Potential conflicts of interest. The institution of E. B. received fees for E. B. participation in advisory boards and travel grants from Gilead Sciences, MSD, ViiV Healthcare, Pfizer, AbbVie, and Sandoz. K. J. M. has received advisory board honoraria from Gilead Sciences; has received travel grants and honoraria from Gilead Sciences, Roche Diagnostics, GlaxoSmithKline, Merck Sharp & Dohme, Bristol-Myers Squibb, ViiV, and Abbott; the University of Zurich received research grants from Gilead Science, Novartis, Roche, and Merck Sharp & Dohme for studies for which K. J. M. serves as principal investigator. H. F. G. has received unrestricted research grants from Gilead Sciences and Roche; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Merck, and ViiV Healthcare; and grants from SystemsX, and the National Institutes of Health. The institution of H. F. G. received educational grants from Gilead Sciences, ViiV, MSD, AbbVie, and Sandoz. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Phylogenetic analyses of 2 or more countries allow to detect differences in transmission dynamics of local HIV-1 epidemics beyond differences in demographic characteristics., Methods: A maximum-likelihood phylogenetic tree was built using pol -sequences of the Swiss HIV Cohort Study (SHCS) and the Austrian HIV Cohort Study (AHIVCOS), with international background sequences. Three types of phylogenetic cherries (clusters of size 2) were analyzed further: (1) domestic cherries; (2) international cherries; and (3) SHCS/AHIVCOS-cherries. Transmission group and ethnicities observed within the cherries were compared with the respective distribution expected from a random distribution of patients on the phylogeny., Results: The demographic characteristics of the AHIVCOS (included patients: 3'141) and the SHCS (included patients: 12'902) are very similar. In the AHIVCOS, 36.5% of the patients were in domestic cherries, 8.3% in international cherries, and 7.0% in SHCS/AHIVCOS cherries. Similarly, in the SHCS, 43.0% of the patients were in domestic cherries, 8.2% in international cherries, and 1.7% in SHCS/AHIVCOS cherries. Although international cherries in the SHCS were dominated by heterosexuals with men who have sex with men being underrepresented, the opposite was the case for the AHIVCOS. In both cohorts, cherries with one patient belonging to the transmission group intravenous drug user and the other one non-intravenous drug user were underrepresented., Conclusions: In both cohorts, international HIV transmission plays a major role in the local epidemics, mostly driven by men who have sex with men in the AHIVOS, and by heterosexuals in the SHCS, highlighting the importance of international collaborations to understand global HIV transmission links on the way to eliminate HIV., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: As trans women are disproportionately affected by the HIV epidemic, and are still understudied, we aimed to identify and characterize the trans women in the Swiss HIV Cohort Study (SHCS)., Methods: A combination of criteria from pre-existing cohort data was used to identify trans women. Information on socioeconomic factors, clinical data, risk behaviors, and mental health was collected. We also described their phylogenetic patterns within HIV transmission networks in relation to other risk groups., Results: We identified 89 trans women of a total 20 925 cohort participants. Trans women were much more likely to be Asian (30.3%) and Hispanic (15.7%) than men who have sex with men (MSM) (2.5% and 4.1%; P < .001) and cis heterosexual (HET) women (7.0% and 3.3%; P < .001). Trans women were more similar to cis HET women in some measures like educational level (postsecondary education attainment: 22.6% and 20.7% [P = .574] vs 46.5% for MSM [P < .001]), while being more similar to MSM for measures like prior syphilis diagnosis (36.0% and 44.0% [P = .170] vs 6.7% for cis HET women [P < .001]). 11.2% of trans women have been previously hospitalized for psychological reasons compared with 4.2% of MSM (P = .004) and 5.1% of cis HET women (P = .025). Analysis of transmission clusters containing trans women suggested greater affinity within the transmission networks to MSM compared with cis HET women., Conclusions: Trans women are epidemiologically distinct in the setting of the Swiss HIV epidemic, warranting better identification and study to better serve this underserved risk group., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: In Switzerland, HIV-1 transmission among men who have sex with men (MSM) has been dominated by subtype B, whilst non-B subtypes are commonly attributed to infections acquired abroad among heterosexuals. Here, we evaluated the temporal trends of non-B subtypes and the characteristics of molecular transmission clusters (MTCs) among MSM., Methods: Sociodemographic and clinical data and partial pol sequences were obtained from participants enrolled in the Swiss HIV Cohort Study. For non-B subtypes, maximum likelihood trees were constructed, from which Swiss MTCs were identified and analyzed by transmission group., Results: Non-B subtypes were identified in 8.1% (416/5116) of MSM participants. CRF01&#95;AE was the most prevalent strain (3.5%), followed by subtype A (1.2%), F (1.1%), CRF02&#95;AG (1.1%), C (0.9%), and G (0.3%). Between 1990 and 2019, an increase in the proportion of newly diagnosed individuals (0/123 [0%] to 11/32 [34%]) with non-B subtypes in MSM was found. Across all non-B subtypes, the majority of MSM MTCs were European. Larger MTCs were observed for MSM than heterosexuals., Conclusions: We found a substantial increase in HIV-1 non-B subtypes among MSM in Switzerland and the occurrence of large MTCs, highlighting the importance of molecular surveillance in guiding public health strategies targeting the HIV-1 epidemic., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: In 2016, the World Health Organization (WHO) introduced global targets for the elimination of hepatitis C virus (HCV) by 2030. We conducted a nationwide HCV micro-elimination program among men who have sex with men (MSM) living with human immunodeficiency virus (HIV) from the Swiss HIV Cohort Study (SHCS) to test whether the WHO goals are achievable in this population., Methods: During phase A (10/2015-06/2016), we performed a population-based and systematic screening for HCV-RNA among MSM from the SHCS. During phase B (06/2016-02/2017) we offered treatment with HCV direct-acting antiviral (DAA) agents to MSM identified with a replicating HCV infection. During phase C (03/2017-11/2017), we offered rescreening to all MSM for HCV-RNA and initiated DAA treatment in MSM with replicating infections., Results: We screened 3715/4640 (80%) MSM and identified 177 with replicating HCV infections (4.8%); 150 (85%) of whom started DAA treatment and 149 (99.3%) were cured. We rescreened 2930/3538 (83%) MSM with a prior negative HCV-RNA and identified 13 (0.4%) with a new HCV infection. At the end of the micro-elimination program, 176/190 MSM (93%) were cured, and the HCV incidence rate declined from .53 per 100 patient-years (95% CI, .35-.83) prior to the intervention to .12 (95% CI, .03-.49) by the end of 2019., Conclusions: A systematic, population-based HCV micro-elimination program among MSM living with HIV was feasible and resulted in a strong decline in HCV incidence and prevalence. Our study can serve as a model for other countries aiming to achieve the WHO HCV elimination targets., Clinical Trials Registration: NCT02785666., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Identifying local outbreaks and their drivers is a key step toward curbing human immunodeficiency virus (HIV) transmission and potentially achieving HIV elimination. Such outbreaks can be identified as transmission clusters extracted from phylogenetic trees constructed of densely sampled viral sequences. In this study, we combined phylogenetic transmission clusters with extensive data on virological suppression and behavioral risk of cluster members to quantify the drivers of ongoing transmission over 10 years., Methods: Using the comprehensive Swiss HIV Cohort Study and its drug-resistance database, we reconstructed phylogenetic trees for each year between 2007 and 2017. We identified HIV transmission clusters dominated by men who have sex with men (MSM) and determined their annual growth. We used Poisson regression to assess if cluster growth was associated with a per-cluster infectivity and behavioral risk score., Results: Both infectivity and behavioral risk scores were significantly higher in growing MSM transmission clusters compared to nongrowing clusters (P ≤ .01). The fraction of transmission clusters without infectious members acquiring new infections increased significantly over the study period. The infectivity score was significantly associated with per-capita incidence of MSM transmission clusters in 8 years, while the behavioral risk score was significantly associated with per-capita incidence of MSM transmission clusters in 3 years., Conclusions: We present a phylogenetic method to identify hotspots of ongoing transmission among MSM. Our results demonstrate the effectiveness of treatment as prevention at the population level. However, the significantly increasing number of new infections among transmission clusters without infectious members highlights a relative shift from diagnosed to undiagnosed individuals as drivers of HIV transmission in Swiss MSM., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Considering the remaining threat of drug-resistantmutations (DRMs) to antiretroviral treatment (ART) efficacy, we investigated how the selective pressure of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes drives certain DRMs' emergence and retention., Methods: We systematically screened DRM:HLA class I allele combinations in 3997 ART-naïve Swiss HIV Cohort Study (SHCS) patients. For each pair, a logistic regression model preliminarily tested for an association with the DRM as the outcome. The three HLA:DRM pairs remaining after multiple testing adjustment were analyzed in three ways: cross-sectional logistic regression models to determine any HLA/infection time interaction, survival analyses to examine if HLA type correlated with developing specific DRMs, and via NetMHCpan to find epitope binding evidence of immune escape., Results: Only one pair, RT-E138:HLA-B18, exhibited a significant interaction between infection duration and HLA. The survival analyses predicted two pairs with an increased hazard of developing DRMs: RT-E138:HLA-B18 and RT-V179:HLA-B35. RT-E138:HLA-B18 exhibited the greatest significance in both analyses (interaction term odds ratio [OR] 1.169 [95% confidence interval (CI) 1.075-1.273]; p-value<0.001; survival hazard ratio 12.211 [95% CI 3.523-42.318]; p-value<0.001). The same two pairs were also predicted by netMHCpan to have epitopic binding., Conclusions: We identified DRM:HLA pairs where HLA presence is associated with the presence or emergence of the DRM, indicating that the selective pressure for these mutations alternates direction depending on the presence of these HLA alleles., Funding: Funded by the Swiss National Science Foundation within the framework of the SHCS, and the University of Zurich, University Research Priority Program: Evolution in Action: From Genomes Ecosystems, in Switzerland., Competing Interests: HN, CT, JF, JB, SY, MP, HH, KK, MT, MB, CK, RK No competing interests declared, MC has received research and travel grants for his institution from ViiV and Gilead. EB has received fees for his institution for participation to advisory board from MSD, Gilead Sciences, ViiV Healthcare, Abbvie and Janssen. HG HFG has received unrestricted research grants from Gilead Sciences and Roche; fees for data and safety monitoring board membership from Merck; consulting/advisory board membership fees from Gilead Sciences, Sandoz and Mepha; and travel reimbursement from Gilead., (© 2021, Nguyen et al.)

This study aims to characterize trends and changes in the prevalence of knowledge of mother-to-child transmission (MTCT) means of HIV as well as to identify its associated socioeconomic factors among Vietnamese women. This is a repeated cross-sectional study using data from the Vietnam Multiple Indicator Cluster Surveys 2000, 2006, 2011 and 2014. We found that a slow increase was found in the trend of adequate knowledge of HIV transmission means from mother to child among women between 2000 and 2014 (41.81% in 2000, 45.66% in 2006, 49.58% in 2011, and 46.83% in 2014). Most women knew that HIV could be transmitted during pregnancy, however, more than half of women did not know all three ways of MTCT. Socioeconomic factors including age, ethnicity, education level, and economic status as factors that affected full knowledge of MTCT means. The study helps to design public health programs to raise 15-49-year-old women's knowledge in HIV transmission means from mother to child as well as can provide a quite strong case for policy adaptation to improve women's health in the time to come.

Background: People living with HIV who were diagnosed before highly active antiretroviral therapy became available in 1996 and who survived at least 15 years after HIV diagnosis, termed long-term survivors (LTS), form a particularly vulnerable population. We study social, clinical and mental factors of LTS in the Swiss HIV Cohort Study, with a particular focus on people who inject drugs (PWID)., Methods: We quantified differences between PWID LTS, and men who have sex with men (MSM) and heterosexual (HET) LTS. Using phylogenetic methods, we distinguished between heterosexual LTS who most likely shared a social network with PWID at the time of infection, termed clusteredHET, and those who did not, termed HET not clustered (HETnc). The analysis was performed using data collected at least 15 years post diagnosis., Results: Overall, 1,663 of 5,686 (29.2%) PWID were LTS. We found significant differences between PWID LTS and MSM/HETnc LTS regarding self-reported depression (59.4% versus 43.3%; odds ratio [OR]=1.8; P<0.001), incarceration (30.6% versus 7.0%; OR=6.9; P<0.001) and full work ability (25.4% versus 59.0%; OR=0.27; P<0.001). ClusteredHET were less vulnerable with respect to these variables than PWID LTS but more at risk compared with MSM/HETnc LTS, indicating that clusteredHET are closer to PWID with regard to social and mental aspects compared with all MSM/HETnc., Conclusions: Even more than 15 years post HIV diagnosis, special care for HIV-positive PWID is needed, with emphasis on mental health and social integration of PWID LTS.

Background: Hepatitis C virus (HCV) is common in men who have sex with men (MSM) with HIV. The Swiss HCVree Trial targeted a micro-elimination by using a treat and counsel strategy. Self-reported condomless anal intercourse with non-steady partners was used as the selection criterion for participation in a counselling intervention designed to prevent HCV re-infection. The purpose of this study was to assess the ability of this criterion to identify men who engaged in other sexual risk behaviours associated with HCV re-infection., Methods: Men who disclosed their sexual and drug- use behaviours during the prior 6 months, at study baseline, were included in the current study. Using a descriptive comparative study design, we explored self-reported sexual and drug-use risk behaviours, compared the odds of reporting each behaviour in men who reported and denied condomless anal intercourse with non-steady partners during the prior year and calculated the sensitivity/specificity (95% CI) of the screening question in relation to the other at-risk behaviours., Results: Seventy-two (61%) of the 118 men meeting eligibity criteria reported condomless anal intercourse with non-steady partners during the prior year. Many also engaged in other potential HCV transmission risk behaviours, e.g., 52 (44%) had used drugs. In participants disclosing drug use, 44 (37%) reported sexualised drug use and 17 (14%) injected drugs. Unadjusted odds ratios (95% CI) for two well-known risk behaviours were 2.02 (0.80, 5.62) for fisting and 5.66 (1.49, 37.12) for injecting drug use. The odds ratio for sexualised drug use - a potential mediator for increased sexual risk taking - was 5.90 (2.44, 16.05). Condomless anal intercourse with non-steady partners showed varying sensitivity in relation to the other risk behaviours examined (66.7-88.2%)., Conclusions: Although condomless anal intercourse with non-steady partners was fairly sensitive in detecting other HCV relevant risk behaviours, using it as the only screening criterion could lead to missing a proportion of HIV-positive men at risk for HCV re-infection due to other behaviours. This work also points to the importance of providing access to behavioral interventions addressing other sexual and drug use practices as part of HCV treatment., Trial Registration: Clinical Trial Number: NCT02785666 , 30.05.2016.

Background: HIV's capacity to escape immune recognition by human leukocyte antigen (HLA) is a core component of HIV pathogenesis. A better understanding of the distribution of HLA class I in HIV-infected patients would improve our knowledge of pathogenesis in relation to the host HLA type and could better improve therapeutic strategies against HIV., Materials and Methods: Three hundred one to 325 transmission pairs and 469-496 clusters were identified for analysis among Swiss HIV Cohort Study (SHCS) participants using HIV pol sequences from the drug resistance database. HLA class I data were compiled at 3 specificity levels: 4-digit, 2-digit alleles, and HLA-B supertype. The analysis tabulated HLA-I homogeneity as 2 measures: the proportion of transmission pairs, which are HLA concordant, and the average percentage of allele matches within all clusters. These measures were compared with the mean value across randomizations with randomly assorted individuals., Results: We repeated the analysis for different HLA classification levels and separately for HLA-A, -B, and -C. Subanalyses by the risk group were performed for HLA-B. HLA-B showed significantly greater homogeneity in the transmission chains (2-digit clusters: 0.291 vs. 0.251, P value = 0.009; supertype clusters: 0.659 vs. 0.611, P value = 0.002; supertype pairs: 0.655 vs. 0.608, P value = 0.014). Risk group restriction caused the effect to disappear for men-who-have-sex-with-men but not for other risk groups. We also examined if protective HLA alleles B27 and B57 were under- or overrepresented in the transmission chains, although this yielded no significant pattern., Conclusions: The HLA-B alleles of patients within HIV-1 transmission chains segregate in homogenous clusters/pairs, potentially indicating preferential transmission among HLA-B concordant individuals.

To systematically test whether coinfections spread along the HIV-1 transmission network and whether similarities in HIV-1 genomes predict AIDS-defining illnesses and comorbidities, we analyzed the distribution of these variables on the HIV phylogeny of the densely sampled Swiss HIV Cohort Study. By combining different statistical methods, we could detect, quantify, and explain the clustering of diseases. Infectious conditions such as hepatitis C, but also Kaposi sarcoma, clustered significantly, suggesting transmission of these infections along the HIV-1 transmission network. The clustering of patients with neurocognitive complaints could not be completely explained by the clustering of patients with similar demographic risk factors, which suggests a potential impact of viral genetics. In summary, the consistent and robust signal for coinfections and comorbidities highlights the strong interaction of HIV-1 and other infections and shows the potential of combining phylogenetic methods to identify disease traits that are likely to be related to virus genetic factors., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objectives: Currently, HIV testing and counseling (HTC) services in Vietnam are primarily funded by international sources. However, international funders are now planning to withdraw their support and the Government of Vietnam (GVN) is seeking to identify domestic funding and generate client fees to continue services. A clear understanding of the cost to sustain current HTC services is becoming increasingly important to facilitate planning that can lead to making HTC and other HIV services more affordable and sustainable in Vietnam. The objectives of this analysis were to provide a snapshot of current program costs to achieve key program outcomes including 1) testing and identifying PLHIV unaware of their HIV status and 2) successfully enrolling HIV (+) clients in care., Methods: We reviewed expenditure data reported by 34 HTC sites in nine Vietnamese provinces over a one-year period from October 2012 to September 2013. Data on program outcomes were extracted from the HTC database of 42,390 client records. Analysis was carried out from the service providers' perspective., Results: The mean expenditure for a single client provided HTC services (testing, receiving results and referral for care/treatment) was US $7.6. The unit expenditure per PLHIV identified through these services varied widely from US $22.8 to $741.5 (median: $131.8). Excluding repeat tests, the range for expenditure to newly diagnose a PLHIV was even wider (from US $30.8 to $1483.0). The mean expenditure for one successfully referred HIV client to care services was US $466.6. Personnel costs contributed most to the total cost., Conclusions: Our analysis found a wide range of expenditures by site for achieving the same outcomes. Re-designing systems to provide services at the lowest feasible cost is essential to making HIV services more affordable and treatment for prevention programs feasible in Vietnam. The analysis also found that understanding the determinants and reasons for variance in service costs by site is an important enhancement to the cascade of HIV services framework now adapted for and extensively used in Vietnam for planning and evaluation.

Rapid economic and social development in Vietnam has resulted in increased opportunities for travel and new potential routes of HIV transmission. We conducted a cross-sectional study examining demographics, knowledge, and sexual risk behaviour amongst 100 Vietnamese men who have sex with men who traveled abroad in the previous 12 months. Men who have sex with men surveyed were mostly university-educated, single, and under 30. Most travel (73%) was within Southeast Asia and was undertaken for tourism (51%) or for work (29%). Casual sex with a foreign partner occurred on 39% of trips. Only four were reported to have involved in unsafe sex with a casual partner. Four reported illicit drug use. Alcohol was widely consumed. Multivariate analysis showed that two variables, travelling alone (OR = 5.26,p < 0.001) and a university education (OR = 4.05,p = 0.004), were significantly associated with casual sex abroad. More HIV prevention education on the risks of sex while travelling abroad is needed for men who have sex with men in Vietnam., (© The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Background This study was performed to investigate the efficacy and safety of grazoprevir-elbasvir guided by baseline resistance-associated substitutions (RASs) in the Swiss HCVree Trial. Methods We performed hepatitis C virus (HCV) RNA screening among all men who have sex with men (MSM) enrolled in the Swiss HIV Cohort Study. Individuals with replicating HCV genotype 1 or 4 infection were eligible for grazoprevir-elbasvir treatment. Genotype 1a–infected individuals with baseline RASs and genotype 4–infected individuals with prior failure of HCV treatment received 16 weeks of grazoprevir-elbasvir combined with ribavirin. All other individuals received 12 weeks of grazoprevir-elbasvir alone. Patients reporting unprotected sex with occasional partners were offered a HCV risk reduction–oriented behavioral intervention. Results We screened 3722 MSM and identified 177 (4.8%) with replicating infection. A total of 122 individuals (3.3%) were eligible for study treatment. Six of 76 patients infected with genotype 1a (7.3%) harbored baseline RASs. Sustained virological response after 12 weeks of follow-up was achieved in 121 patients (99%), including all with genotype 1a infection. Overall, 8 serious adverse events occurred, none of which was related to the study drug. Seventy-five percent of eligible MSM participated in the risk counseling program. Conclusions Grazoprevir-elbasvir for 12 or 16 weeks, with or without ribavirin, achieved high cure rates and had an excellent safety profile. Unique to other studies, the treatment duration was guided by the presence of baseline RASs among genotype 1a–infected individuals, and the treatment phase was accompanied by an HCV risk reduction–oriented behavioral intervention. This successful population-wide treatment approach lays the groundwork to achieve HCV elimination in coinfected MSM. Clinical Trials Registration NCT02785666 [ABSTRACT FROM AUTHOR]

Monitoring for drug-induced liver injury (DILI) via serial transaminase measurements in patients on potentially hepatotoxic medications (e.g., for HIV and tuberculosis) is routine in resource-rich nations, but often unavailable in resource-limited settings. Towards enabling universal access to affordable point-of-care (POC) screening for DILI, we have performed the first field evaluation of a paper-based, microfluidic fingerstick test for rapid, semi-quantitative, visual measurement of blood alanine aminotransferase (ALT). Our objectives were to assess operational feasibility, inter-operator variability, lot variability, device failure rate, and accuracy, to inform device modification for further field testing. The paper-based ALT test was performed at POC on fingerstick samples from 600 outpatients receiving HIV treatment in Vietnam. Results, read independently by two clinic nurses, were compared with gold-standard automated (Roche Cobas) results from venipuncture samples obtained in parallel. Two device lots were used sequentially. We demonstrated high inter-operator agreement, with 96.3% (95% C.I., 94.3–97.7%) agreement in placing visual results into clinically-defined “bins” (<3x, 3–5x, and >5x upper limit of normal), >90% agreement in validity determination, and intraclass correlation coefficient of 0.89 (95% C.I., 0.87–0.91). Lot variability was observed in % invalids due to hemolysis (21.1% for Lot 1, 1.6% for Lot 2) and correlated with lots of incorporated plasma separation membranes. Invalid rates <1% were observed for all other device controls. Overall bin placement accuracy for the two readers was 84% (84.3%/83.6%). Our findings of extremely high inter-operator agreement for visual reading–obtained in a target clinical environment, as performed by local practitioners–indicate that the device operation and reading process is feasible and reproducible. Bin placement accuracy and lot-to-lot variability data identified specific targets for device optimization and material quality control. This is the first field study performed with a patterned paper-based microfluidic device and opens the door to development of similar assays for other important analytes. [ABSTRACT FROM AUTHOR]