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1.
Article En | MEDLINE | ID: mdl-38868933

The increased incidence of chronic diseases among people with HIV (PWH) is poised to increase the need for specialty care outside of HIV treatment settings. To reduce outcome disparities for HIV-associated comorbidities in the United States, it is critical to optimize access to and the quality of specialty care for underrepresented racial and ethnic minority (URM) individuals with HIV. We explored the experiences of URM individuals with HIV and other comorbidities in the specialty care setting during their initial and follow-up appointments. We conducted qualitative interviews with participants at three large academic medical centers in the United States with comprehensive health care delivery systems between November 2019 and March 2020. The data were analyzed using applied thematic analysis. A total of 27 URM individuals with HIV were interviewed. The majority were Black or African American and were referred to cardiology specialty care. Most of the participants had positive experiences in the specialty care setting. Facilitators of the referral process included their motivation to stay healthy, referral assistance from HIV providers, access to reliable transportation, and proximity to the specialty care health center. Few participants faced individual, interpersonal, and structural barriers, including the perception of individual and facility stigma toward PWH, a lack of transportation, and a lack of rapport with providers. Future case studies are needed for those URM individuals with HIV who face barriers and negative experiences. Interventions that involve PWH and health care providers in specialty care settings with a focus on individual- and structural-level stigma can support the optimal use of specialty care.

2.
J Natl Cancer Inst ; 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38837335

Squamous cell carcinoma of the anus (SCCA) incidence has been rising in the United States, particularly among older adults (≥65 years). We estimated the impact of this rise on future burden (through 2035) using age-period-cohort modeling. The SCCA burden (cases/year) is expected to rise, reaching ∼2700 among men and ∼7000 among women in 2031-2035 (burden during 2016-2020 among men and women was ∼2150 and ∼4600), with most cases aged ≥65 years (61% in men and 70% in women in 2031-2035; from 40% and 46% in 2016-2020). SCCA incidence (per 100,000) is projected to rise among older men aged 65-74, 75-84, and ≥85 years (5.0, 4.9, and 4.3, in 2031-2035 vs 3.7, 3.8, 3.4 in 2016-2020) and women (11.2, 12.6, 8.0 in 2031-2035 vs 8.2, 6.8, 5.2 in 2016-2020). The projected rise in SCCA burden among older adults is troubling and highlights the importance of improving early detection and clinical care.

3.
AIDS ; 38(8): 1181-1185, 2024 Jul 01.
Article En | MEDLINE | ID: mdl-38489581

OBJECTIVE: The aim of this study was to examine outcomes of follow-up for persons with discordant fourth-generation HIV screening test results. DESIGN: A retrospective chart review. METHODS: We analyzed the electronic health record at the Medical University of South Carolina for a 10-year period spanning 2012-2022 to identify instances of discordant HIV screening test results, wherein initial antigen/antibody screening was positive, but reflex confirmatory testing for HIV-1 and HIV-2 antibodies was negative. We reviewed individual records to evaluate clinical follow-up and determine if the discordant test represented an acute HIV infection, a false-positive result, or was unresolved. RESULTS: We identified 199 testing instances with discordant results. Most discordant results ( n  = 115) were subsequently determined to reflect a false-positive test, while 56 were unresolved without documented follow-up testing. Twenty-eight cases of acute HIV infection were identified of which 26 were linked to care within a month of initial testing. Two acute HIV cases were not identified in real time leading to delay in diagnosis and care. Testing done in the context of infectious symptoms and testing performed in the emergency department were associated with increased odds of a discordant test ultimately reflecting acute HIV infection. CONCLUSION: These results demonstrate the importance of appropriate and timely follow-up for discordant HIV screening test results.


Academic Medical Centers , HIV Infections , HIV Testing , Humans , Retrospective Studies , HIV Infections/diagnosis , Male , Female , Adult , HIV Testing/statistics & numerical data , Middle Aged , South Carolina , Young Adult , Mass Screening/methods , HIV Antibodies/blood , Aged , Adolescent , HIV-1/isolation & purification , HIV-1/immunology , HIV-2/immunology
5.
AIDS Care ; 36(4): 452-462, 2024 Apr.
Article En | MEDLINE | ID: mdl-37139535

Eligible persons with HIV infection can receive client-centered case management to coordinate medical and social services. Novel mobile health interventions could improve effective case management and retention in care, an important goal to help end the HIV epidemic. Using a hybrid type I effectiveness-implementation design, we assessed whether access to bidirectional, free-draft secure text messaging with a case manager and clinic pharmacist could improve client satisfaction and care retention in a Southern academic HIV clinic. Sixty-four clients enrolled between November 2019 and March 2020, had a median age of 39 years, and were mostly male, single, and African-American. Heavy app users texted over 100 times (n = 6) over the course of the 12-month intervention while others never texted (n = 12). App usage peaked during months of clinic closure due to COVID-19. Most participants reported high satisfaction with the app and planned continued usage after study completion. Changes in clinic retention and virologic suppression rates were not observed, a result confounded by practice changes due to COVID-19. High usage and satisfaction of free-draft text messaging in case-managed HIV clients supports inclusion of this communication option in routine HIV clinical care.


COVID-19 , Cell Phone , HIV Infections , Retention in Care , Text Messaging , Humans , Male , Adult , Female , HIV Infections/therapy
6.
Antiviral Res ; 221: 105779, 2024 01.
Article En | MEDLINE | ID: mdl-38070830

BACKGROUND: In the tolerogenic liver, inadequate or ineffective interferon signaling fails to clear chronic HBV infection. Lambda IFNs (IFNL) bind the interferon lambda receptor-1 (IFNLR1) which dimerizes with IL10RB to induce transcription of antiviral interferon-stimulated genes (ISG). IFNLR1 is expressed on hepatocytes, but low expression may limit the strength and antiviral efficacy of IFNL signaling. Three IFNLR1 transcriptional variants are detected in hepatocytes whose role in regulation of IFNL signaling is unclear: a full-length and signaling-capable form (isoform 1), a form that lacks a portion of the intracellular JAK1 binding domain (isoform 2), and a secreted form (isoform 3), the latter two predicted to be signaling defective. We hypothesized that altering expression of IFNLR1 isoforms would differentially impact the hepatocellular response to IFNLs and HBV replication. METHODS: Induced pluripotent stem-cell derived hepatocytes (iHeps) engineered to contain FLAG-tagged, doxycycline-inducible IFNLR1 isoform constructs were HBV-infected then treated with IFNL3 followed by assessment of gene expression, HBV replication, and cellular viability. RESULTS: Minimal overexpression of IFNLR1 isoform 1 markedly augmented ISG expression, induced de novo proinflammatory gene expression, and enhanced inhibition of HBV replication after IFNL treatment without adversely affecting cell viability. In contrast, overexpression of IFNLR1 isoform 2 or 3 partially augmented IFNL-induced ISG expression but did not support proinflammatory gene expression and minimally impacted HBV replication. CONCLUSIONS: IFNLR1 isoforms differentially influence IFNL-induced gene expression and HBV replication in hepatocytes. Regulated IFNLR1 expression in vivo could limit the capacity of this pathway to counteract HBV replication.


Hepatitis B virus , Interferon Lambda , Interferons/pharmacology , Hepatocytes , Virus Replication , Antiviral Agents/pharmacology , Antiviral Agents/metabolism , Protein Isoforms/genetics , Protein Isoforms/metabolism , Protein Isoforms/pharmacology , Gene Expression
8.
Article En | MEDLINE | ID: mdl-37160576

BACKGROUND: Underrepresented racial and ethnic groups (UREGs) with HIV have a higher risk of cardiovascular disease (CVD) compared with the general population. Referral to a cardiovascular specialist improves CVD risk factor management in high-risk individuals. However, patient and provider factors impacting the likelihood of UREGs with HIV to have an encounter with a cardiologist are unknown. METHODS: We evaluated a cohort of UREGs with HIV and borderline CVD risk (10-year risk ≥ 5% by the pooled cohort equations or ≥ 7.5% by Framingham risk score). Participants received HIV-related care from 2014-2020 at four academic medical centers in the United States (U.S.). Adjusted Cox proportional hazards regression was used to estimate the association of patient and provider characteristics with time to first ambulatory cardiology encounter. RESULTS: A total of 2,039 people with HIV (PWH) and borderline CVD risk were identified. The median age was 45 years (IQR: 36-50); 52% were female; and 94% were Black. Of these participants, 283 (14%) had an ambulatory visit with a cardiologist (17% of women vs. 11% of men, p < .001). In fully adjusted models, older age, higher body mass index (BMI), atrial fibrillation, multimorbidity, urban residence, and no recent insurance were associated with a greater likelihood of an encounter with a cardiologist. CONCLUSION: In UREGs with HIV and borderline CVD risk, the strongest determinants of a cardiology encounter were diagnosed CVD, insurance type, and urban residence. Future research is needed to determine the extent to which these encounters impact CVD care practices and outcomes in this population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04025125.

9.
Gen Hosp Psychiatry ; 82: 41-46, 2023.
Article En | MEDLINE | ID: mdl-36934530

OBJECTIVE: The purpose was to examine associations between HIV care engagement and mental health symptoms among persons living with HIV (PLWH) receiving ART. This study builds upon previous findings indicating a significant association between mental health and retention in HIV care,1 while also advancing the literature by examining the impact of substance use on this link, as well as potential bidirectional associations. METHOD: Participants of the current study were 493 patients who engaged in care and received antiviral therapy (ART) from Infectious Disease physicians between 2017 and 2019 in a large academic medical center. RESULTS: Results from hierarchical regression analyses revealed that patients who missed more days of ART medication had higher depressive symptoms, even when accounting for the effect of demographic variables and alcohol use. Further, depressive symptoms predicted significant variance in number of "no show" visits, but was not individually predictive of ""no show"" visits beyond the effect of other HIV care outcomes (e.g., number of days of medication missed). CONCLUSION: Findings reflect linkages among HIV treatment adherence, mental health, and substance use, and highlight the need to target mental health symptoms to improve outcomes among PLWH and prevent HIV transmission.


HIV Infections , Substance-Related Disorders , Humans , Mental Health , HIV Infections/drug therapy , HIV Infections/epidemiology , Medication Adherence , Antiviral Agents , Substance-Related Disorders/epidemiology , Substance-Related Disorders/therapy
10.
Viruses ; 15(3)2023 02 25.
Article En | MEDLINE | ID: mdl-36992341

Interferon lambdas (IFNLs) are innate immune cytokines that induce antiviral cellular responses by signaling through a heterodimer composed of IL10RB and the interferon lambda receptor 1 (IFNLR1). Multiple IFNLR1 transcriptional variants are expressed in vivo and are predicted to encode distinct protein isoforms whose function is not fully established. IFNLR1 isoform 1 has the highest relative transcriptional expression and encodes the full-length functional form that supports canonical IFNL signaling. IFNLR1 isoforms 2 and 3 have lower relative expression and are predicted to encode signaling-defective proteins. To gain insight into IFNLR1 function and regulation, we explored how altering relative expression of IFNLR1 isoforms influenced the cellular response to IFNLs. To achieve this, we generated and functionally characterized stable HEK293T clones expressing doxycycline-inducible FLAG-tagged IFNLR1 isoforms. Minimal FLAG-IFNLR1 isoform 1 overexpression markedly increased IFNL3-dependent expression of antiviral and pro-inflammatory genes, a phenotype that could not be further augmented by expressing higher levels of FLAG-IFNLR1 isoform 1. Expression of low levels of FLAG-IFNLR1 isoform 2 led to partial induction of antiviral genes, but not pro-inflammatory genes, after IFNL3 treatment, a phenotype that was largely abrogated at higher FLAG-IFNLR1 isoform 2 expression levels. Expression of FLAG-IFNLR1 isoform 3 partially augmented antiviral gene expression after IFNL3 treatment. In addition, FLAG-IFNLR1 isoform 1 significantly reduced cellular sensitivity to the type-I IFN IFNA2 when overexpressed. These results identify a unique influence of canonical and non-canonical IFNLR1 isoforms on mediating the cellular response to interferons and provide insight into possible pathway regulation in vivo.


Interferon Lambda , Receptors, Interferon , Humans , HEK293 Cells , Interferon Lambda/metabolism , Interferons , Protein Isoforms/genetics , Receptors, Interferon/genetics , Receptors, Interferon/metabolism , Antiviral Restriction Factors
11.
South Med J ; 115(6): 352-357, 2022 06.
Article En | MEDLINE | ID: mdl-35649518

OBJECTIVES: Therapeutic advances make the cure of chronic hepatitis C virus (HCV) infection achievable for individuals aware of their diagnosis who can access care. Identifying barriers to accessing care is critical to achieve population-level HCV elimination and improve the cascade of care from diagnosis to cure. METHODS: To identify barriers to HCV care, we performed a retrospective observational analysis of outcomes for patients with chronic HCV referred to an infectious diseases clinic at an academic medical center in Charleston, South Carolina between January 1, 2015 and January 1, 2020. We categorized outcomes in the cascade of care between "never presenting for evaluation" and "completed treatment with documented cure." Patient demographic factors, referral source, ZIP code of residence, insurance status, clinical characteristics, antiviral regimen, psychiatric and substance use history, and route of infection were assessed for associations with care outcomes. RESULTS: Of 407 referrals, 32% of patients never presented for an initial evaluation, an outcome that was associated with active substance use, mental health disease, and referral from an emergency department or obstetrics-gynecology provider. Of the patients who presented for an initial evaluation, 78% of patients initiated treatment. Active substance use was the only variable associated with lack of therapy initiation after presenting for an initial evaluation (odds ratio 2.5, 95% confidence interval 1.07-5.84). Once treatment had been initiated, no clinical or demographic variables were associated with odds of achieving documented or presumed HCV cure. CONCLUSIONS: Active substance use, mental health disease, and referral from an emergency department or obstetrics-gynecology provider were associated with a lower odds of presenting for evaluation and initiation of HCV treatment. Innovative models to improve access to care and increase outreach to vulnerable populations will be essential to eliminate HCV.


Hepatitis C, Chronic , Hepatitis C , Substance-Related Disorders , Academic Medical Centers , Hepacivirus , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C, Chronic/diagnosis , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Humans , Referral and Consultation , Retrospective Studies , Substance-Related Disorders/epidemiology , Substance-Related Disorders/therapy
12.
BMC Health Serv Res ; 22(1): 623, 2022 May 09.
Article En | MEDLINE | ID: mdl-35534889

BACKGROUND: Cardiology care may be beneficial for risk factor management in people living with HIV (PLWH), yet limited information is available about the referral process from the perspectives of HIV specialists and cardiologists. METHODS: We conducted 28 qualitative interviews at academic medical centers in the United States from December 2019 to February 2020 using components of the Specialty Referral Process Framework: referral decision, entry into referral care, and care integration. We analyzed the data using applied thematic analysis. RESULTS: Reasons for cardiology referral most commonly included secondary prevention, uncontrolled risk factors, cardiac symptoms, and medication management. Facilitators in the referral process included ease of referral, personal relationships between HIV specialists and cardiologists, and close proximity of the clinic to the patient's home. Barriers included lack of transportation, transportation costs, insurance coverage gaps, stigma, and patient reluctance. CONCLUSIONS: Our results will inform future studies on implementation strategies aimed at improving the specialty referral process for PLWH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04025125 .


Cardiologists , HIV Infections , HIV Infections/drug therapy , Humans , Qualitative Research , Referral and Consultation , Specialization , United States
13.
Am J Med Sci ; 364(3): 281-288, 2022 09.
Article En | MEDLINE | ID: mdl-35278364

BACKGROUND: Our objective was to safely and remotely assess longitudinal SARS-CoV-2 seroprevalence in at-risk health care workers at the onset of the epidemic. METHODS: Self-administered serologic testing was performed every 30 days up to 5 times using a point-of-care, lateral flow SARS-CoV-2 nucleocapsid IgG immunoassay in a cohort of at-risk health care workers (n = 339) and lower-risk controls (n = 100). RESULTS: Subjects were enrolled between 4/14/20-5/6/20 and most were clinicians (41%) or nurses (27%). Of 20 subjects who reported confirmed SARS-CoV-2 infection prior to (n = 5, 1%) or during the study (n = 15, 3%), half (10/20) were seropositive. Five additional subjects were seropositive and did not report documented infection. Estimated infection rates in health care workers did not differ from concurrent community rates. CONCLUSIONS: This remotely conducted, contact-free study did not identify serologic evidence of widespread occupational SARS-CoV-2 infection in health care workers.


COVID-19 , SARS-CoV-2 , Antibodies, Viral , COVID-19/epidemiology , Health Personnel , Humans , Immunoglobulin G , Seroepidemiologic Studies
14.
J Viral Hepat ; 28(11): 1614-1623, 2021 11.
Article En | MEDLINE | ID: mdl-34379872

Treatment of chronic hepatitis C virus with direct-acting antivirals usually eradicates infection, but liver fibrosis does not resolve concurrently. In patients who develop cirrhosis prior to hepatitis C virus treatment, hepatic decompensation and hepatocellular carcinoma can still occur after viral elimination due to residual fibrosis. We hypothesized the liver proteome would exhibit meaningful changes in inflammatory and fibrinogenic pathways change upon hepatitis C virus eradication, which could impact subsequent fibrosis regression. We analysed the liver proteome and phosphoproteome of paired liver biopsies obtained from 8 hepatitis C virus-infected patients before or immediately after treatment with direct-acting antivirals. Proteins in interferon signalling and antiviral pathways decreased concurrent with hepatitis C virus treatment, consistent with prior transcriptomic analyses. Expression of extracellular matrix proteins associated with liver fibrosis did not change with treatment, but the phosphorylation pattern of proteins present within signalling pathways implicated in hepatic fibrinogenesis, including the ERK1/2 pathway, was altered concurrent with hepatitis C virus treatment. Hepatitis C virus treatment leads to reduced expression of hepatic proteins involved in interferon and antiviral signalling. Additionally, changes in fibrosis signalling pathways are detectable before alteration in extracellular matrix proteins, identifying a putative chronology for the dynamic processes involved in fibrosis reversal.


Antiviral Agents , Hepatitis C, Chronic , Liver Cirrhosis , Liver/drug effects , Proteome , Antiviral Agents/therapeutic use , Hepacivirus , Hepatitis C, Chronic/drug therapy , Humans , Liver/metabolism , Liver Cirrhosis/drug therapy , Liver Cirrhosis/virology
15.
Viruses ; 13(6)2021 06 09.
Article En | MEDLINE | ID: mdl-34207487

Hepatitis B virus (HBV) chronically infects over 250 million people worldwide and causes nearly 1 million deaths per year due to cirrhosis and liver cancer. Approved treatments for chronic infection include injectable type-I interferons and nucleos(t)ide reverse transcriptase inhibitors. A small minority of patients achieve seroclearance after treatment with type-I interferons, defined as sustained absence of detectable HBV DNA and surface antigen (HBsAg) antigenemia. However, type-I interferons cause significant side effects, are costly, must be administered for months, and most patients have viral rebound or non-response. Nucleos(t)ide reverse transcriptase inhibitors reduce HBV viral load and improve liver-related outcomes, but do not lower HBsAg levels or impart seroclearance. Thus, new therapeutics are urgently needed. Lambda interferons (IFNLs) have been tested as an alternative strategy to stimulate host antiviral pathways to treat HBV infection. IFNLs comprise an evolutionarily conserved innate immune pathway and have cell-type specific activity on hepatocytes, other epithelial cells found at mucosal surfaces, and some immune cells due to restricted cellular expression of the IFNL receptor. This article will review work that examined expression of IFNLs during acute and chronic HBV infection, the impact of IFNLs on HBV replication in vitro and in vivo, the association of polymorphisms in IFNL genes with clinical outcomes, and the therapeutic evaluation of IFNLs for the treatment of chronic HBV infection.


Antiviral Agents/therapeutic use , Hepatitis B virus/immunology , Hepatitis B, Chronic/immunology , Hepatitis B/drug therapy , Hepatitis B/genetics , Interferons/genetics , Interferons/therapeutic use , Antiviral Agents/immunology , Hepatitis B/immunology , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/genetics , Hepatocytes/drug effects , Hepatocytes/virology , Humans , Immunity, Innate/genetics , Interferons/classification , Liver/virology
16.
JMIR Form Res ; 5(5): e22513, 2021 May 27.
Article En | MEDLINE | ID: mdl-34042596

BACKGROUND: Patient-provider communication is critical for engaging and retaining people living with HIV in care, especially among medically case-managed patients in need of service coordination and adherence support. Expanding patient-provider communication channels to include mobile health modalities, such as text messaging and video calling, has the potential to facilitate communication and ultimately improve clinical outcomes. However, the implementation of these communication modalities in clinical settings has not been well characterized. OBJECTIVE: The purpose of this study is to understand patient and provider perspectives on the acceptability of and preferences for using text messaging and video calling as a means of communication; perceived factors relevant to adoption, appropriateness, and feasibility; and organizational perspectives on implementation within an HIV clinic in South Carolina. METHODS: We conducted 26 semistructured in-depth interviews among patients receiving case management services (n=12) and clinic providers (n=14) using interview guides and content analysis informed by the Proctor taxonomy of implementation outcomes and the Consolidated Framework for Implementation Research. Participants were purposefully sampled to obtain maximum variation in terms of age and gender for patients and clinic roles for providers. The data were analyzed using quantitative and qualitative content analyses. RESULTS: Most patients (11/12, 92%) and providers (12/14, 86%) agreed that they should have the capacity to text message and/or video call each other. Although consensus was not reached, most preferred using a secure messaging app rather than standard text messaging because of the enhanced security features. Perceived benefits to adoption included the added convenience of text messaging, and potential barriers included the cost and access of smartphone-based technology for patients. From an organizational perspective, some providers were concerned that offering text messaging could lead to unreasonable expectations of instant access and increased workload. CONCLUSIONS: Patients and providers perceived text messaging and video calling as acceptable, appropriate, and feasible and felt that these expanded modes of communication could help meet patients' needs while being safe and not excessively burdensome. Although patients and providers mostly agreed on implementation barriers and facilitators, several differences emerged. Taking both perspectives into account when using implementation frameworks is critical for expanding mobile health-based communication, especially as implementation requires active participation from providers and patients.

17.
Open Forum Infect Dis ; 8(4): ofab118, 2021 Apr.
Article En | MEDLINE | ID: mdl-33959672

To identify immunologic correlates of hepatitis C virus (HCV) relapse after direct-acting antiviral (DAA) therapy, we quantified select immune transcripts in whole blood from noncirrhotic HCV subjects treated with 4-6 weeks of DAAs. We identified specific markers of natural killer-cell and CD8+ T-cell function (GZMB, PRF1, NKp46) with higher expression in subjects who relapsed. These findings suggest a role for host immunity in HCV eradication with ultrashort DAA therapy. We quantified whole blood immune transcripts in noncirrhotic HCV subjects treated with shortcourse antiviral therapy. Markers of natural killer-cell and CD8+ T-cell function had higher expression in virologic relapsers, suggesting a role for host immunity in HCV eradication.

18.
AIDS Res Hum Retroviruses ; 37(3): 184-188, 2021 03.
Article En | MEDLINE | ID: mdl-33066718

Immune non-responders (INRs) are people with HIV infection who fail to restore their CD4 T-cell counts in spite of prolonged virologic suppression, a condition associated with higher rates of all-cause mortality. The mechanisms of immune non-response are not entirely clear. We used existing clinical and genetic data from AIDS Clinical Trials Group clinical trials to ask whether an IFNL4 single-nucleotide polymorphism, shown to be associated with outcomes for other infectious diseases, correlated with immune non-response for HIV. Analysis of data from 426 participants with clearly defined CD4 T-cell recovery phenotypes, including 88 INRs with CD4 < 200 cells/mm3 after 2 years of suppressive antiretroviral therapy, did not identify an association of IFNL4 genotype with immune non-response. Thus, the IFNL4 genotype is unlikely to influence immunologic recovery.


HIV Infections , Antiretroviral Therapy, Highly Active , CD4 Lymphocyte Count , CD4-Positive T-Lymphocytes , Genotype , HIV , HIV Infections/drug therapy , Humans , Interleukins/genetics , Polymorphism, Single Nucleotide , Viral Load
19.
BMC Infect Dis ; 20(1): 929, 2020 Dec 04.
Article En | MEDLINE | ID: mdl-33276734

BACKGROUND: Treatment of chronic hepatitis C virus infection with direct acting antiviral therapy results in viral elimination in over 90% of cases. The duration of treatment required to achieve cure differs between individuals and relapse can occur. We asked whether cellular and transcriptional profiling of peripheral blood collected during treatment could identify biomarkers predictive of treatment outcome. METHODS: We analyzed peripheral blood collected during treatment of genotype 1 HCV with 24 weeks of sofosbuvir and weight-based or low dose ribavirin in a trial in which 29% of patients relapsed. Changes in host immunity during treatment were assessed by flow cytometry and whole blood gene expression profiling. Differences in expression of immune-relevant transcripts based on treatment outcome were analyzed using the Nanostring Human Immunology V2 panel. RESULTS: Multiple cellular populations changed during treatment, but pre-treatment neutrophil counts were lower and natural post-treatment killer cell counts were higher in patients who relapsed. Pre-treatment expression of genes associated with interferon-signaling, T-cell dysfunction, and T-cell co-stimulation differed by treatment outcome. We identified a pre- and post-treatment gene expression signature with high predictive capacity for distinguishing treatment outcome, but neither signature was sufficiently robust to suggest viability for clinical use. CONCLUSIONS: Patients who relapse after hepatitis C virus therapy differ immunologically from non-relapsers based on expression of transcripts related to interferon signaling and T-cell dysfunction, as well as by peripheral neutrophil and NK-cell concentrations. These data provide insight into the host immunologic basis of relapse after DAA therapy for HCV and suggests mechanisms which may be relevant for understanding outcomes with currently approved regimens.


Antiviral Agents/therapeutic use , Genotype , Hepacivirus/genetics , Hepatitis C, Chronic/blood , Hepatitis C, Chronic/drug therapy , Ribavirin/therapeutic use , Sofosbuvir/therapeutic use , Drug Therapy, Combination , Female , Hepatitis C, Chronic/immunology , Hepatitis C, Chronic/virology , Humans , Interferons/metabolism , Killer Cells, Natural/immunology , Longitudinal Studies , Male , Neutrophils/immunology , Recurrence , T-Lymphocytes/immunology , Transcriptome , Treatment Outcome
20.
Open Forum Infect Dis ; 7(9): ofaa361, 2020 Sep.
Article En | MEDLINE | ID: mdl-32995348

BACKGROUND: The impact of clinician specialty on cardiovascular disease risk factor outcomes among persons with HIV (PWH) is unclear. METHODS: PWH receiving care at 3 Southeastern US academic HIV clinics between January 2014 and December 2016 were retrospectively stratified into 5 groups based on the specialty of the clinician managing their hypertension or hyperlipidemia. Patients were followed until first atherosclerotic cardiovascular disease event, death, or end of study. Outcomes of interest were meeting 8th Joint National Commission (JNC-8) blood pressure (BP) goals and National Lipid Association (NLA) non-high-density lipoprotein (HDL) goals for hypertension and hyperlipidemia, respectively. Point estimates for associated risk factors were generated using modified Poisson regression with robust error variance. RESULTS: Of 1667 PWH in the analysis, 965 had hypertension, 205 had hyperlipidemia, and 497 had both diagnoses. At study start, the median patient age was 52 years, 66% were Black, and 65% identified as male. Among persons with hypertension, 24% were managed by an infectious diseases (ID) clinician alone, and 5% were co-managed by an ID clinician and a primary care clinician (PCC). Persons managed by an ID clinician were less likely to meet JNC-8 hypertension targets at the end of observation than the rest of the cohort (relative risk [RR], 0.84; 95% CI, 0.75-0.95), but when mean study blood pressure was considered, there was no difference between persons managed by ID and the rest of the cohort (RR, 0.96; 95% CI, 0.88-1.05). There was no significant association between the ID clinician managing hyperlipidemia and meeting NLA non-HDL goals (RR, 0.89; 95% CI, 0.68-1.15). CONCLUSIONS: Clinician specialty may play a role in suboptimal hypertension outcomes in persons with HIV.

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