Integrating HIV Cluster Analysis in Everyday Public Health Practice: Lessons Learned From a Public Health--Academic Partnership.

BACKGROUND: The use of molecular HIV cluster analysis to supplement public health contact tracing has shown promise in addressing HIV outbreaks. However, the potential of HIV cluster analysis as an adjunct to daily, person-by-person HIV prevention efforts remains unknown. We documented lessons learned within a unique public health-academic partnership while guiding workaday HIV prevention efforts with near-real-time molecular cluster analysis. SETTING: A public health-academic partnership in the State of Rhode Island, the United States. METHODS: We recorded perceptions of our team of academicians and public health practitioners that were encountered in an 18-month study evaluating the integration of molecular cluster analysis with HIV contact tracing for public health benefit. The focus was on monthly conferences where molecular clustering of each new statewide diagnosis was discussed to facilitate targeted interventions and on attempted reinterviews of all newly HIV-diagnosed persons statewide whose HIV sequences clustered to increase partner naming. RESULTS: Three main themes emerged: First, multidisciplinary conferences are substantially beneficial for gleaning actionable inferences from integrating molecular cluster analysis and public health data. Second, universal reinterviews were perceived to potentially have negative consequences but may be selectively beneficial. Third, the translation of cluster analysis into public health action is hampered by jurisdictional surveillance boundaries and within-jurisdictional data silos, across which data sharing is problematic. CONCLUSIONS: Insights from a statewide public health-academic partnership support integration of molecular HIV cluster analyses with public health efforts, which can guide public health activities to prevent transmission while identifying substantial barriers to integration, informing continued research.

Acquired Human Immunodeficiency Virus Type 1 Drug Resistance in Rhode Island, USA, 2004-2021.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) acquired drug resistance (ADR) compromises antiretroviral therapy (ART). METHODS: We aggregated all HIV-1 protease-reverse transcriptase-integrase sequences over 2004-2021 at the largest HIV center in Rhode Island and evaluated ADR extent, trends, and impact using Stanford Database tools. Trends were measured with Mann-Kendall statistic, and multivariable regressions evaluated resistance predictors. RESULTS: Sequences were available for 914 ART-experienced persons. Overall ADR to any drug decreased from 77% to 49% (-0.66 Mann-Kendall statistic); nucleoside reverse transcriptase inhibitors 65% to 32%, nonnucleoside reverse transcriptase inhibitors 53% to 43%, and protease inhibitors 28% to 7% (2004-2021), and integrase strand transfer inhibitors 16% to 13% (2017-2021). Multiclass resistance decreased from 44% to 12% (2-class) and 12% to 6% (3-class). In 2021, 94% had at least one 3-drug or 2-drug one-pill-once-daily (OPOD) option. Males and those exposed to more ART regimens were more likely to have ≥2-class resistance, and higher regimen exposure was also associated with fewer OPOD options. CONCLUSIONS: Comprehensive analyses within a densely-sampled HIV epidemic over 2004-2021 demonstrated decreasing ADR. Continued ADR monitoring is important to maintain ART success, particularly with rising INSTI use in all lines of therapy and 2-drug and long-acting formulations.

Risk of HIV Viral Rebound in the Era of Universal Treatment in a Multicenter Sample of Persons With HIV in Primary Care.

Background: Antiretroviral therapy (ART) is recommended for people with HIV (PWH), irrespective of CD4 cell count, to improve their health and reduce the risk of transmission to sexual partners through long-term viral suppression. We identified risk factors for viral rebound among patients with a period of stable viral suppression to inform counseling and monitoring. Methods: We conducted a multisite, retrospective study of PWH with a 2-year period of sustained viral suppression in the United States using the Centers for AIDS Research Network of Integrated Clinical Systems cohort. We used multivariable logistic regression to identify characteristics independently associated with any viral rebound (viral load [VL] ≥200 copies/mL) and sustained viral rebound (VL ≥200 copies/mL followed by a VL that was also ≥200 copies/mL within 6 months), within 2 years of follow-up. Results: Among 3496 eligible patients with a 2-year period of sustained viral suppression, most (90%) continued to have viral suppression over 2 additional years; 10% experienced viral rebound, and 4% experienced sustained viral rebound. In multivariable analyses, Black race, current smoking, integrase strand transfer inhibitor use, and 5- to 9-year duration of ART were positively associated, and being age ≥50 years was negatively associated, with any viral rebound. Only current smoking and 5- to 9-year (vs 2- to 4-year) duration of ART were positively associated, and being age ≥60 years was negatively associated, with sustained viral rebound. Conclusions: Most people retained in clinical care and with HIV viral suppression on ART will have persistent viral suppression. However, some patients may benefit from additional treatment adherence support.

An Automated Bioinformatics Pipeline Informing Near-Real-Time Public Health Responses to New HIV Diagnoses in a Statewide HIV Epidemic.

Molecular HIV cluster data can guide public health responses towards ending the HIV epidemic. Currently, real-time data integration, analysis, and interpretation are challenging, leading to a delayed public health response. We present a comprehensive methodology for addressing these challenges through data integration, analysis, and reporting. We integrated heterogeneous data sources across systems and developed an open-source, automatic bioinformatics pipeline that provides molecular HIV cluster data to inform public health responses to new statewide HIV-1 diagnoses, overcoming data management, computational, and analytical challenges. We demonstrate implementation of this pipeline in a statewide HIV epidemic and use it to compare the impact of specific phylogenetic and distance-only methods and datasets on molecular HIV cluster analyses. The pipeline was applied to 18 monthly datasets generated between January 2020 and June 2022 in Rhode Island, USA, that provide statewide molecular HIV data to support routine public health case management by a multi-disciplinary team. The resulting cluster analyses and near-real-time reporting guided public health actions in 37 phylogenetically clustered cases out of 57 new HIV-1 diagnoses. Of the 37, only 21 (57%) clustered by distance-only methods. Through a unique academic-public health partnership, an automated open-source pipeline was developed and applied to prospective, routine analysis of statewide molecular HIV data in near-real-time. This collaboration informed public health actions to optimize disruption of HIV transmission.

Not all clusters are equal: dynamics of molecular HIV-1 clusters in a statewide Rhode Island epidemic.

OBJECTIVES: Molecular epidemiology is a powerful tool to characterize HIV epidemics and prioritize public health interventions. Typically, HIV clusters are assumed to have uniform patterns over time. We hypothesized that assessment of cluster evolution would reveal distinct cluster behavior, possibly improving molecular epidemic characterization, towards disrupting HIV transmission. DESIGN: Retrospective cohort. METHODS: Annual phylogenies were inferred by cumulative aggregation of all available HIV-1 pol sequences of individuals with HIV-1 in Rhode Island (RI) between 1990 and 2020, representing a statewide epidemic. Molecular clusters were detected in annual phylogenies by strict and relaxed cluster definition criteria, and the impact of annual newly-diagnosed HIV-1 cases to the structure of individual clusters was examined over time. RESULTS: Of 2153 individuals, 31% (strict criteria) - 47% (relaxed criteria) clustered. Longitudinal tracking of individual clusters identified three cluster types: normal, semi-normal and abnormal. Normal clusters (83-87% of all identified clusters) showed predicted growing/plateauing dynamics, with approximately three-fold higher growth rates in large (15-18%) vs. small (∼5%) clusters. Semi-normal clusters (1-2% of all clusters) temporarily fluctuated in size and composition. Abnormal clusters (11-16% of all clusters) demonstrated collapses and re-arrangements over time. Borderline values of cluster-defining parameters explained dynamics of non-normal clusters. CONCLUSIONS: Comprehensive tracing of molecular HIV clusters over time in a statewide epidemic identified distinct cluster types, likely missed in cross-sectional analyses, demonstrating that not all clusters are equal. This knowledge challenges current perceptions of consistent cluster behavior over time and could improve molecular surveillance of local HIV epidemics to better inform public health strategies.

Beyond HIV outbreaks: protocol, rationale and implementation of a prospective study quantifying the benefit of incorporating viral sequence clustering analysis into routine public health interventions.

INTRODUCTION: HIV continues to have great impact on millions of lives. Novel methods are needed to disrupt HIV transmission networks. In the USA, public health departments routinely conduct contact tracing and partner services and interview newly HIV-diagnosed index cases to obtain information on social networks and guide prevention interventions. Sequence clustering methods able to infer HIV networks have been used to investigate and halt outbreaks. Incorporation of such methods into routine, not only outbreak-driven, contact tracing and partner services holds promise for further disruption of HIV transmissions. METHODS AND ANALYSIS: Building on a strong academic-public health collaboration in Rhode Island, we designed and have implemented a state-wide prospective study to evaluate an intervention that incorporates real-time HIV molecular clustering information with routine contact tracing and partner services. We present the rationale and study design of our approach to integrate sequence clustering methods into routine public health interventions as well as related important ethical considerations. This prospective study addresses key questions about the benefit of incorporating a clustering analysis triggered intervention into the routine workflow of public health departments, going beyond outbreak-only circumstances. By developing an intervention triggered by, and incorporating information from, viral sequence clustering analysis, and evaluating it with a novel design that avoids randomisation while allowing for methods comparison, we are confident that this study will inform how viral sequence clustering analysis can be routinely integrated into public health to support the ending of the HIV pandemic in the USA and beyond. ETHICS AND DISSEMINATION: The study was approved by both the Lifespan and Rhode Island Department of Health Human Subjects Research Institutional Review Boards and study results will be published in peer-reviewed journals.

Police abuse and care engagement of people with HIV who inject drugs in Ukraine.

Police abuse affects people who inject drugs (PWID), including those with HIV, and negatively impacts care engagement. This cross-sectional study evaluated police abuse among PWID receiving MOUD (medication for opioid use disorder) living with HIV and associations with HIV treatment adherence and receipt of NGO services. We assessed lifetime and past six-month rates of police abuse among a cohort of Ukrainian PWID with HIV receiving MOUD (n = 190) from August to September 2017. Logistic regression models evaluated associations between past six-month police abuse and past 30-day antiretroviral therapy (ART) adherence, and past six-month NGO service receipt. Almost all (90%) participants reported lifetime police abuse: 77% reported physical violence and 75% reported paying the police to avoid arrest. One in four females (25%) reported police-perpetrated sexual violence. Recent police abuse was reported by 16% of males and 2% of females and was not associated with ART adherence (aOR: 1.1; 95% CI:0.3-5.0) or NGO service receipt (aOR: 3.4; 95% CI:0.6-18.3). While lifetime police abuse rates were high, few participants reported recent police abuse, which was not linked to care engagement. These trends should encourage the Ukrainian government for public health-public safety partnerships and legal interventions to eliminate human rights violations against PWID living with HIV.

DirectDetect SARS-CoV-2 Direct Real-Time RT-PCR Study Using Patient Samples.

COVID-19 is an infectious disease that caused a global pandemic affecting people worldwide. As disease detection and vaccine rollout continue to progress, there is still a need for efficient diagnostic tools to satisfy continued testing needs. This preliminary study evaluated a novel SARS-CoV-2 diagnostic test called DirectDetect SARS-CoV-2 Direct Real-time reverse transcriptase polymerase chain reaction (RT-PCR) based on a limited sample size of 24 respiratory samples from 14 SARS-CoV-2-positive patients. The test is advantageous compared to others on the market since it does not require viral transport medium or viral RNA extraction prior to nucleic acid amplification and detection. This capability transforms the hours-long sample preparation time into a minutes-long procedure while also eliminating the need for many costly reagents which may be difficult to obtain during the surge in nucleic acid-based testing during the pandemic. The results show a positive agreement of 94.7, 100, and 94.7% between dry sample swabs, treated samples, and untreated samples tested using the DirectDetect SARS-CoV-2 Direct Real-time RT-PCR compared to tests used in a clinical laboratory, respectively. The findings indicate that DirectDetect can be used for multiple different sample types while reducing the number of reagents and time needed for diagnosis. Although this study shows promising results using the DirectDetect results, further validation of this test using a larger sample set is required to assess the true performance of this test.

Statewide Longitudinal Trends in Transmitted HIV-1 Drug Resistance in Rhode Island, USA.

BACKGROUND: HIV-1 transmitted drug resistance (TDR) remains a global challenge that can impact care, yet its comprehensive assessment is limited and heterogenous. We longitudinally characterized statewide TDR in Rhode Island. METHODS: Demographic and clinical data from treatment-naïve individuals were linked to protease, reverse transcriptase, and integrase sequences routinely obtained over 2004-2020. TDR extent, trends, impact on first-line regimens, and association with transmission networks were assessed using the Stanford Database, Mann-Kendall statistic, and phylogenetic tools. RESULTS: In 1123 individuals, TDR to any antiretroviral increased from 8% (2004) to 26% (2020), driven by non-nucleotide reverse transcriptase inhibitor (NNRTI; 5%-18%) and, to a lesser extent, nucleotide reverse transcriptase inhibitor (NRTI; 2%-8%) TDR. Dual- and triple-class TDR rates were low, and major integrase strand transfer inhibitor resistance was absent. Predicted intermediate to high resistance was in 77% of those with TDR, with differential suppression patterns. Among all individuals, 34% were in molecular clusters, some only with members with TDR who shared mutations. Among clustered individuals, people with TDR were more likely in small clusters. CONCLUSIONS: In a unique (statewide) assessment over 2004-2020, TDR increased; this was primarily, but not solely, driven by NNRTIs, impacting antiretroviral regimens. Limited TDR to multiclass regimens and pre-exposure prophylaxis are encouraging; however, surveillance and its integration with molecular epidemiology should continue in order to potentially improve care and prevention interventions.

Predictors of severity and mortality among patients hospitalized with COVID-19 in Rhode Island.

BACKGROUND: In order for healthcare systems to prepare for future waves of COVID-19, an in-depth understanding of clinical predictors is essential for efficient triage of hospitalized patients. METHODS: We performed a retrospective cohort study of 259 patients admitted to our hospitals in Rhode Island to examine differences in baseline characteristics (demographics and comorbidities) as well as presenting symptoms, signs, labs, and imaging findings that predicted disease progression and in-hospital mortality. RESULTS: Patients with severe COVID-19 were more likely to be older (p = 0.02), Black (47.2% vs. 32.0%, p = 0.04), admitted from a nursing facility (33.0% vs. 17.9%, p = 0.006), have diabetes (53.9% vs. 30.4%, p<0.001), or have COPD (15.4% vs. 6.6%, p = 0.02). In multivariate regression, Black race (adjusted odds ratio [aOR] 2.0, 95% confidence interval [CI]: 1.1-3.9) and diabetes (aOR 2.2, 95%CI: 1.3-3.9) were independent predictors of severe disease, while older age (aOR 1.04, 95% CI: 1.01-1.07), admission from a nursing facility (aOR 2.7, 95% CI 1.1-6.7), and hematological co-morbidities predicted mortality (aOR 3.4, 95% CI 1.1-10.0). In the first 24 hours, respiratory symptoms (aOR 7.0, 95% CI: 1.4-34.1), hypoxia (aOR 19.9, 95% CI: 2.6-152.5), and hypotension (aOR 2.7, 95% CI) predicted progression to severe disease, while tachypnea (aOR 8.7, 95% CI: 1.1-71.7) and hypotension (aOR 9.0, 95% CI: 3.1-26.1) were associated with increased in-hospital mortality. CONCLUSIONS: Certain patient characteristics and clinical features can help clinicians with early identification and triage of high-risk patients during subsequent waves of COVID-19.

Longitudinal typing of molecular HIV clusters in a statewide epidemic.

BACKGROUND: HIV molecular epidemiology is increasingly integrated into public health prevention. We conducted cluster typing to enhance characterization of a densely sampled statewide epidemic towards informing public health. METHODS: We identified HIV clusters, categorized them into types, and evaluated their dynamics between 2004 and 2019 in Rhode Island. We grouped sequences by diagnosis year, assessed cluster changes between paired phylogenies, t0 and t1, representing adjacent years and categorized clusters as stable (cluster in t0 phylogeny = cluster in t1 phylogeny) or unstable (cluster in t0 ≠ cluster in t1). Unstable clusters were further categorized as emerging (t1 phylogeny only) or growing (larger in t1 phylogeny). We determined proportions of each cluster type, of individuals in each cluster type, and of newly diagnosed individuals in each cluster type, and assessed trends over time. RESULTS: A total of 1727 individuals with available HIV-1 subtype B pol sequences were diagnosed in Rhode Island by 2019. Over time, stable clusters and individuals in them dominated the epidemic, increasing over time, with reciprocally decreasing unstable clusters and individuals in them. Conversely, proportions of newly diagnosed individuals in unstable clusters significantly increased. Within unstable clusters, proportions of emerging clusters and of individuals in them declined; whereas proportions of newly diagnosed individuals in growing clusters significantly increased over time. CONCLUSION: Distinct molecular cluster types were identified in the Rhode Island epidemic. Cluster dynamics demonstrated increasing stable and decreasing unstable clusters driven by growing, rather than emerging clusters, suggesting consistent in-state transmission networks. Cluster typing could inform public health beyond conventional approaches and direct interventions.

Evaluation of a Next-Generation Sequencing Metagenomics Assay to Detect and Quantify DNA Viruses in Plasma from Transplant Recipients.

Viral infections are major causes of morbidity and mortality in solid-organ and hematopoietic stem cell transplant recipients. This study evaluated the performance of the Galileo Pathogen Solution metagenomics Next-Generation sequencing assay to detect and quantify 11 DNA viruses (cytomegalovirus, Epstein-Barr virus, BK virus, human adenovirus, JC virus, herpes simplex virus 1 and 2, varicella zoster virus, human herpesvirus 6A and 6B, and parvovirus B19) and to qualitatively detect torque teno virus. DNA extracted from 47 plasma samples of viremic transplant recipients were subjected to DNA library preparation with pathogen enrichment/human background depletion, sequencing, and automated data analysis. The viral loads were determined with the Galileo assay using a standard curve generated from a calibration panel. All of the samples tested had a 100% agreement with the real-time quantitative PCR (qPCR) assays in detecting the primary virus targets and the majority of the quantified samples had a viral load difference within 0.46 log10 IU/mL or copies/mL. The mean difference for cytomegalovirus between the Galileo and qPCR assays was 0.21 log10 IU/mL (SD, ±0.43 log10 IU/mL). The mean difference for BK virus between the Galileo and qPCR assays was 0.17 log10 cp/mL (SD, ±0.67 log10 cp/mL). Additionally, 75 co-infections were detected in 31 samples by the Galileo assay. The study findings show that the Galileo assay can simultaneously detect and quantify multiple viruses in transplant recipients with results that are comparable with standard-of-care qPCR assays.

Evaluating HIV Viral Rebound Among Persons on Suppressive Antiretroviral Treatment in the Era of "Undetectable Equals Untransmittable (U†=†U)".

BACKGROUND: Studies have demonstrated that persons with HIV (PWH) maintaining viral suppression do not transmit HIV to HIV-negative partners through condomless sex, leading to the "Undetectable = Untransmittable (U = U)" prevention campaign. However, few studies have examined the durability of suppression in the era of U = U. METHODS: This retrospective cohort study was conducted in Providence, Rhode Island. PWH aged ≥18 years with documented viral suppression (defined as at least 1 viral load [VL] <200 copies/mL and no VL ≥200 copies/mL) in 2015 were included in the baseline cohort. Primary outcomes were viral suppression, viral rebound (at least 1 VL ≥200 copies/mL), or gap in VL monitoring assessed annually from 2016 to 2019. Those with viral rebound were assessed for resuppression within 6 months. Demographic and clinical characteristics associated with viral rebound or gaps in VL monitoring were investigated by bivariate analysis and logistic regression. RESULTS: A total of 1242 patients with viral suppression were included in the baseline cohort. In each follow-up year, 85%-90% maintained viral suppression, 2%-5% experienced viral rebound, and 8%-10% had a gap in VL monitoring. Among those with viral rebound, approximately one-half were suppressed again within 6 months. In the logistic regression models, retention in care was significantly associated with viral suppression, while younger age, black race, high school or equivalent education, non-men who have sex with men, and history of incarceration were significantly associated with viral rebound. CONCLUSIONS: In the U = U era, most patients with viral suppression who are retained in care are likely to maintain viral suppression over time. Some patients require additional support for regular VL monitoring.

Empirical comparison of analytical approaches for identifying molecular HIV-1 clusters.

Public health interventions guided by clustering of HIV-1 molecular sequences may be impacted by choices of analytical approaches. We identified commonly-used clustering analytical approaches, applied them to 1886 HIV-1 Rhode Island sequences from 2004-2018, and compared concordance in identifying molecular HIV-1 clusters within and between approaches. We used strict (topological support ≥ 0.95; distance 0.015 substitutions/site) and relaxed (topological support 0.80-0.95; distance 0.030-0.045 substitutions/site) thresholds to reflect different epidemiological scenarios. We found that clustering differed by method and threshold and depended more on distance than topological support thresholds. Clustering concordance analyses demonstrated some differences across analytical approaches, with RAxML having the highest (91%) mean summary percent concordance when strict thresholds were applied, and three (RAxML-, FastTree regular bootstrap- and IQ-Tree regular bootstrap-based) analytical approaches having the highest (86%) mean summary percent concordance when relaxed thresholds were applied. We conclude that different analytical approaches can yield diverse HIV-1 clustering outcomes and may need to be differentially used in diverse public health scenarios. Recognizing the variability and limitations of commonly-used methods in cluster identification is important for guiding clustering-triggered interventions to disrupt new transmissions and end the HIV epidemic.

SARS-CoV-2 and HIV coinfection: clinical experience from Rhode Island, United States.

INTRODUCTION: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has infected >6 million people worldwide since December 2019. Global reports of HIV/SARS-CoV-2 coinfection are limited. To better understand the impact of the coronavirus disease 2019 (COVID-19) pandemic on persons with HIV and improve their care, we present an outpatient and inpatient clinical experience of HIV/SARS-CoV-2 coinfection from Rhode Island, US. METHODS: We describe outpatient and inpatient preparedness for the COVID-19 pandemic, and present a case series of all known patients with HIV/SARS-CoV-2 coinfection at The Miriam Hospital and Rhode Island Hospital, and The Miriam Hospital Infectious Diseases and Immunology Center, in Providence, Rhode Island, US. RESULTS AND DISCUSSION: The Infectious Diseases and Immunology Center rapidly prepared for outpatient and inpatient care of persons with HIV and SARS-CoV-2. Between 30 March and 20 May 2020, 27 patients with HIV were diagnosed with SARS-CoV-2. Twenty were male, six female and one transgender female; average age was 49 years; 13/27 were Hispanic and 6/27 were African American. All had HIV viral load <200 copies/mL and were on antiretroviral therapy with CD4 count range 87 to 1441 cells/µL. Twenty-six of the 27 had common COVID-19 symptoms for one to twenty-eight days and most had other co-morbidities and/or risk factors. Nine of the 27 were hospitalized for one to thirteen days; of those, three lived in a nursing home, six received remdesivir through a clinical trial or emergency use authorization and tolerated it well; eight recovered and one died. Overall, 17% of known Center people had HIV/SARS-CoV-2 coinfection, whereas the comparable state-wide prevalence was 9%. CONCLUSIONS: We highlight challenges of outpatient and inpatient HIV care in the setting of the COVID-19 pandemic and present the largest detailed case series to date from the United States on HIV/SARS-CoV-2 coinfection, adding to limited global reports. The aggregated clinical findings suggest that the clinical presentation and outcomes of COVID-19 appear consistent with those without HIV. Whether SARS-CoV-2 infection is more frequent among persons with HIV remains to be determined. More data are needed as we develop our understanding of how HIV and antiretroviral therapy are affected by or have an impact on this pandemic.

Stigma and quality of co-located care for HIV-positive people in addiction treatment in Ukraine: a cross-sectional study.

INTRODUCTION: Co-located treatment for HIV and opioid use disorder has been shown to improve care outcomes for HIV-positive people who inject drugs (PWID) in Ukraine. However, patients continue to be stigmatized for both HIV and substance use. This study aimed to assess whether co-located care for HIV-positive PWID receiving opioid agonist treatment (OAT) services in Ukraine is associated with less stigma and better perceived quality of HIV services. METHODS: This cross-sectional study enrolled 191 HIV-positive PWID who received OAT services at three healthcare facilities providing substance use treatment (OAT only) and at four facilities that provided co-located care (both OAT and HIV treatment) in six regions in Ukraine during July-September, 2017. Primary outcomes were HIV stigma (Berger scale), substance use stigma (Substance Abuse Stigma Scale) and intersectional stigma (both stigma forms above 75th percentile). Secondary outcome was quality of HIV care, a composite score based on a package of received services. Linear and ordinal regressions were used to assess the predictors of selected outcomes. RESULTS: Study participants were 75% male, mean age 40 ± 7 years; 47% received co-located care, and 10.5% had both high HIV and substance use stigma. Co-located care was neither associated with HIV nor substance use stigma but it was linked to better quality of HIV care (adjusted odds ratio: 4.13; 95% CI: 2.31, 7.54). HIV stigma was associated with suicide attempts (adjusted beta (aß): 5.90; 95% CI: 2.05, 9.75), and substance use stigma was linked to poor mental health (aß: -0.26; 95% CI: -0.44, -0.08) and lower likelihood of receipt of services from non-governmental organization (NGO; aß: -6.40; 95% CI: -10.23, -2.57). CONCLUSION: One in ten people with HIV in this cohort who received OAT services experienced high levels of both HIV and substance use stigma, which was associated with poorer mental health and less NGO support. Co-located HIV and OAT services were linked to better perceived quality of HIV care, but did not seem to reduce stigma for this key population. Stigma interventions for PWID, possibly delivered involving NGOs, may be an approach to mitigate this challenge.

Challenges in evaluating the use of viral sequence data to identify HIV transmission networks for public health.

Great efforts are devoted to end the HIV epidemic as it continues to have profound public health consequences in the United States and throughout the world, and new interventions and strategies are continuously needed. The use of HIV sequence data to infer transmission networks holds much promise to direct public heath interventions where they are most needed. As these new methods are being implemented, evaluating their benefits is essential. In this paper, we recognize challenges associated with such evaluation, and make the case that overcoming these challenges is key to the use of HIV sequence data in routine public health actions to disrupt HIV transmission networks.

High Rates of Indeterminate TB Tests Among Hospitalized Patients: Can We Optimize Use of Gamma Interferon Release Assays in Tuberculosis?

In the United States, high concern for iatrogenic reactivation to tuberculosis (TB) disease secondary to prescribed immunosuppression has resulted in increased use of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) to screen for Mycobacterium tuberculosis (Mtb) infection. The aim of our study was to determine indications for QFT-GIT testing and risk factors for indeterminate QFT-GIT results. We retrospectively identified patients with QFT-GIT testing over a six-month period in a tertiary care academic health care system and performed a record review. Inpatients were 11 times more likely to have an indeterminate QFT-GIT result than outpatients (95% CI 7.6-16.2). 61.5% inpatient QFT-GITs were ordered during workup of active TB. Providers treating exogenously or endogenously immunosuppressed patients ordered the most QFT-GITs. We highlight the significant limitations of TB screening tests in the inpatient setting and the need to test earlier in those requiring immunosuppressive therapy to avoid indeterminate results.

Effect of First-Line Antituberculosis Therapy on Nevirapine Pharmacokinetics in Children Younger than Three Years Old.

Nevirapine-based antiretroviral therapy (ART) is one of the limited options in HIV-infected children younger than 3 years old (young children) with tuberculosis (TB) coinfection. To date, there are insufficient data to recommend nevirapine-based therapy during first-line antituberculosis (anti-TB) therapy in young children. We compared nevirapine pharmacokinetics (PK) in HIV-infected young children with and without TB coinfection. In the coinfected group, nevirapine PK was evaluated while on anti-TB therapy and after completing an anti-TB therapy regimen. Of 53 participants, 23 (43%) had TB-HIV coinfection. While the mean difference in nevirapine PK parameters between the two groups was not significant (P > 0.05), 14/23 (61%) of the children with TB-HIV coinfection and 9/30 (30%) with HIV infection had a nevirapine minimum concentration (Cmin) below the proposed target of 3.0 mg/liter (P = 0.03). In multivariate analysis, anti-TB therapy and the CYP2B6 516G>T genotype were joint predictors of nevirapine PK parameters. Differences in nevirapine PK parameters between the two groups were significant in children with CYP2B6 516GG but not the GT or TT genotype. Among 14 TB-HIV-coinfected participants with paired data, the geometric mean Cmin and area under the drug concentration-time curve from time zero to 12 h (AUC0-12) were about 34% lower when patients were taking anti-TB therapy, while the nevirapine apparent oral clearance (CL/F) was about 45% higher. While the induction effect of anti-TB therapy on nevirapine PK in our study was modest, the CYP2B6 genotype-dependent variability in the TB drug regimen effect would complicate any dose adjustment strategy in young children with TB-HIV coinfection. Alternate ART regimens that are more compatible with TB treatment in this age group are needed. (This study has been registered at ClinicalTrials.gov under identifier NCT01699633.).