Susanna Naggie

• MD, MHS
• Managing Director at Duke University Medical Center

Introduction Hepatitis C virus (HCV) infection remains a leading cause of morbidity and mortality in people with human immunodeficiency virus (HIV). Liver fibrosis progression is more rapid in people with HIV/HCV coinfection compared to HCV monoinfection and the rate of resolution of liver fibrosis after HCV cure is unknown in people with HIV. Inva...

In low-resource settings, providers often manage lower respiratory tract infections (LRTIs) without diagnostic tests, which may cause antibacterial overuse. Electronic clinical decision support tools (eCDSTs) can support evidence-based decision-making and judicious use of antibacterials. This study aimed to explore the potential of an eCDST to help...

Importance: The effect of metformin on reducing symptom duration among outpatient adults with coronavirus disease 2019 (COVID-19) has not been studied. Objective: Assess metformin compared with placebo for symptom resolution during acute infection with SARS-CoV-2. Design, Setting, and Participants: The ACTIV-6 platform evaluated repurposed medicati...

Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in people with HIV (PWH) and increases the risk of hepatic fibrosis and hepatocellular carcinoma. We sent an online survey to providers of the American Academy of HIV Medicine. Of respondents ( n = 214, 8% response rate), 65% reported screening for NAFLD in PWH, with 28% routinely screeni...

Background Simplified approaches to hepatitis C virus (HCV) treatment delivery are needed to meet elimination goals. However, the impact of low-touch strategies on individuals at higher risk due to treatment failure or reinfection is unknown. We estimated HCV reinfection rates, and the impact of resistance associated substitutions (RASs) on respons...

Importance The effect of montelukast in reducing symptom duration among outpatients with mild to moderate COVID-19 is uncertain. Objective To assess the effectiveness of montelukast compared with placebo in treating outpatients with mild to moderate COVID-19. Design, Setting, and Participants This randomized clinical trial (Accelerating COVID-19...

This manuscript addresses a critical topic: navigating complexities of conducting clinical trials during a pandemic. Central to this discussion is engaging communities to ensure diverse participation. The manuscript elucidates deliberate strategies employed to recruit minority communities with poor social drivers of health for participation in COVI...

Lower respiratory tract infection (LRTI) is a common reason for hospitalization and antibacterial use globally. There is considerable overlap in the clinical presentation of bacterial and viral LRTIs. Low- or middle-income countries (LMICs) face the dual challenge of appropriately targeting antibacterials for bacterial LRTI while reducing inappropr...

A subset of patients with chronic hepatitis C virus (HCV) infection demonstrate liver enzyme elevation (LEE) after achieving sustained virologic response (SVR). Risk factors for LEE are not well characterised. We conducted a single‐centre retrospective cohort study of adults with HCV infection in the Duke University Health System who received direc...

Background Metabolic dysfunction‐associated steatotic liver disease (MASLD) is common in people with HIV (PWH). The morphological spectrum of MASLD compared to matched controls and of the correlation between the NAFLD activity score (NAS) and fibrosis stage in PWH remains unknown. Methods Overall, 107 liver biopsies from PWH with MASLD (MASLD‐PWH)...

Importance: The effect of montelukast in reducing symptom duration among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) is uncertain. Objective: To assess the effectiveness of montelukast compared with placebo, in treating outpatients with mild to moderate COVID-19. Design, Setting, and Participants: The ACTIV-6 platform rand...

This case-control study explored cumulative tenofovir exposure among patients with HIV/HBV co-infection with HIV viral suppression. Among patients taking tenofovir disoproxil fumarate, median TFV-DP levels in dried blood spots were ∼3-fold lower among patients with incomplete HBV viral suppression (n=4) compared to those with complete suppression (...

Background and Aims Steatotic liver disease is common in people with human immunodeficiency virus (HIV)(PWH). Identifying those with advanced fibrosis (AF, bridging fibrosis or cirrhosis), F3-4, is important. We aimed to examine the performance of FIB-4 and nonalcoholic fatty liver disease (NAFLD) fibrosis score (NFS) in PWH to identify those with...

Background Metabolic dysfunction‐associated steatotic liver disease (MASLD) has recently been proposed as a replacement term for NAFLD. Aims To assess the effects of this new nomenclature on the prevalence and distribution of different SLD categories in people with HIV (PWH) and identified factors associated with MASLD and clinically significant f...

Background Women with HIV (WWH) are at higher and earlier risk of developing aging-related non-AIDS comorbidities (NACM) compared to those without HIV; however, the impact on health-related quality of life (QoL) is largely unknown. Methods We analyzed data from the Women’s Interagency HIV Study to evaluate the effect of comorbidity burden (total N...

Importance The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain. Objective To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19. Design, Setting, and Participants The ACTIV-6 platform randomized...

The goal of this review is to summarize the recent literature linking HIV to metabolic dysfunction-associated steatotic liver disease (MASLD). This is a pressing issue due to the scale of the MASLD epidemic and the urgent need for preventive and therapeutic strategies for MASLD in PWH. The prevalence of MASLD in PWH is higher than previously apprec...

Background: The effectiveness of inhaled glucocorticoids in shortening the time to symptom resolution or preventing hospitalization or death among outpatients with mild-to-moderate coronavirus disease 2019 (Covid-19) is unclear. Methods: We conducted a decentralized, double-blind, randomized, placebo-controlled platform trial in the United State...

Following the discovery of hepatitis C virus (HCV) in 1989, 3 decades of basic, translational, and clinical research culminated in the development of direct-acting antiviral (DAA) therapy-curative oral treatment for HCV infection. The availability of DAA therapy revolutionized HCV clinical management, including acute (duration of infection <6 mo) a...

Importance Despite aging-related comorbidities representing a growing threat to quality-of-life and mortality among persons with HIV (PWH), clinical guidance for comorbidity screening and prevention is lacking. Understanding comorbidity distribution and severity by sex and gender is essential to informing guidelines for promoting healthy aging in a...

While the Coronavirus Disease 2019 (COVID-19) pandemic continues to present global challenges, sufficient time has passed to reflect on lessons learned and use those insights to inform policy and approaches to prepare for the next pandemic. In May 2022, the Duke Clinical Research Institute (DCRI) convened a Think Tank with thought-leaders from acad...

Objective We studied the safety and efficacy of hydroxychloroquine (HCQ) as pre-exposure prophylaxis for COVID-19 in healthcare workers (HCWs), using a meta-analysis of randomised controlled trials (RCTs). Data sources PubMed and EMBASE databases were searched to identify randomised trials studying HCQ. Study selection Ten RCTs were identified (n...

Livers from donors with positive hepatitis B surface antigen (HBsAg+) have been used to expand the donor pool, but outcome data are limited. We aim to evaluate survival following liver transplant (LT) from HBsAg+ donors. Using the United Network for Organ Sharing registry, we identified HBsAg+ donors utilized for LT from 2009 to 2020. We used Kapla...

Importance It is unknown whether ivermectin, with a maximum targeted dose of 600 μg/kg, shortens symptom duration or prevents hospitalization among outpatients with mild to moderate COVID-19. Objective To evaluate the effectiveness of ivermectin at a maximum targeted dose of 600 μg/kg daily for 6 days, compared with placebo, for the treatment of e...

Objective: To determine whether hydroxychloroquine (HCQ) is safe and effective at preventing COVID-19 infections among health care workers (HCW). Methods: IN A 1: :1 randomized, placebo-controlled, double-blind, parallel-group, superiority trial at 34 US clinical centers, 1360 HCW at risk for COVID-19 infection were enrolled between April and No...

Importance: The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild to moderate symptomatic COVID-19 is unclear. Objective: To evaluate the efficacy of low-dose fluvoxamine (50 mg twice daily) for 10 days compared with placebo for the treatment of mild to moderate COVID-19 in the US. D...

Background To evaluate the effect of cumulative HIV-1 viremia on aging-related multimorbidity among women living with HIV (WLWH), we analyzed data collected prospectively among women who achieved viral suppression after antiretroviral therapy (ART) initiation (1997—2019). Methods We included WLWH with ≥2 plasma HIV-1 viral loads (VL) < 200 copies/...

Background: Whether ivermectin, with a maximum targeted dose of 600 mcg/kg, shortens symptom duration or prevents hospitalization among outpatients with mild to moderate coronavirus disease 2019 (COVID-19) remains unknown. Our objective was to evaluate the effectiveness of ivermectin, dosed at 600 mcg/kg, daily for 6 days compared with placebo for...

Background: We sought to characterize in people with HIV (PWH) the potential etiologies of elevated alanine aminotransferase (ALT) levels, which are common and often unexplained. Methods: Participants from the longitudinal observational AIDS Clinical Trials Group HAILO cohort without a history of hepatitis C virus (HCV) or hepatitis B virus (HBV...

Menopause may impact the earlier onset of aging-related comorbidities among women with versus without HIV. We found that menopausal status, age, and HIV were independently associated with higher comorbidity burden; and that HIV impacted burden most in the pre-/peri-menopausal phases.

Objectives: The coronavirus disease 2019 (COVID-19) pandemic has disproportionately afflicted vulnerable populations. Older adults, particularly residents of nursing facilities, represent a small percentage of the population but account for 40% of mortality from COVID-19 in the United States. Racial and ethnic minority individuals, particularly Bl...

Background Despite widespread availability of direct-acting antivirals including generic formulations, limited progress has been made in the global adoption of hepatitis C virus (HCV) treatment. Barriers to treatment scale-up include availability and access to diagnostic and monitoring tests, health-care infrastructure, and requirement for frequent...

Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published an...

Chronic hepatitis B virus (HBV) infection impacts an estimated 257–291 million people globally. The current approach to treatment for chronic HBV infection is complex, reflecting a risk:benefit approach driven by the lack of an effective curative regimen. This complexity and the lack of a durable treatment response, necessitating indefinite treatme...

Background HIV infection may accelerate development of aging-related non-AIDS comorbidities (NACM). The incidence of NACM is poorly characterized among women living with HIV (WLWH). Methods WLWH and HIV-seronegative participants followed in the Women’s Interagency HIV Study (WIHS) through ≥2009 (when >80% of WLWH used antiretroviral therapy) were...

Background Previous studies have reported an association of proton pump inhibitor (PPI) use and decreased sustained viral response rate (SVR) in patients taking ledipasvir/sofosbuvir (LDV/SOF). The relationship between PPI usage and SVR is less clear in patients with HIV/HCV coinfection, where concomitant antiretrovirals may result in more complex...

Background: To achieve global hepatitis C virus (HCV) elimination by 2030, 80% of the ~71 million people with chronic HCV infection will need to be treated, necessitating simplification of treatment delivery and associated laboratory monitoring without compromising efficacy or safety. The COVID-19 pandemic has further highlighted the need for innov...

Non-alcoholic fatty liver disease (NAFLD) affects 25% of adults in the general population and is a disease spectrum ranging from steatosis to non-alcoholic steatohepatitis (NASH) to end-stage liver disease. NAFLD is an independent risk factor for cardiovascular disease, diabetes mellitus and all-cause mortality, and NASH cirrhosis is a frequent ind...

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 five groups based on specialty of clinician managing their hypertension...

Exposure to hepatitis viruses is a recognized occupational risk for health care personnel (HCP). This report establishes new CDC guidance that includes recommendations for a testing algorithm and clinical management for HCP with potential occupational exposure to hepatitis C virus (HCV). Baseline testing of the source patient and HCP should be perf...

Background: Advanced liver disease due to HCV is a leading cause of HIV-related morbidity and mortality. There remains a need to develop noninvasive predictors of clinical outcomes in persons living with HIV/HCV co-infection. Methods: We conducted a nested case-control study in 126 patients with HIV/HCV and utilized multiple quantitative metabol...

Background: Response-guided hepatitis C therapy was standard with interferon-based regimens but is not used for direct-acting antivirals (DAAs). Week 4 viral kinetics may predict sustained virological response (SVR) with DAAs, but it is unclear whether extending therapy in slow responders affects outcomes. Objectives: The primary objective was t...

Introduction: The prevalence and burden of age-related non-AIDS comorbidities (NACM) is poorly characterized among women living with HIV (WLWH). Methods: Virologically-suppressed WLWH and HIV-seronegative participants followed in the Women's Interagency HIV Study (WIHS) through ≥2009 (when >80% WLWH used antiretroviral therapy) were included, wi...

Background and aims: Hepatitis C virus (HCV) and alcohol use are patient risk factors for accelerated fibrosis progression, yet few randomized controlled trials have tested clinic-based alcohol interventions. Approach and results: A total of 181 patients with HCV and qualifying alcohol screener scores at three liver center settings were randomly...

Purpose of Review Liver disease is a leading cause of non-AIDS-related death in the HIV population since the introduction of highly active antiretroviral treatment (HAART). Recent studies suggest that patients with HIV are at high risk for nonalcoholic fatty liver disease (NAFLD) and progressive liver fibrosis. Evidence for the prevalence, risk fac...

Background and aims: Nonalcoholic steatohepatitis (NASH) occurs in the context of aberrant metabolism. Glutaminolysis is required for metabolic reprograming of hepatic stellate cells (HSC) and liver fibrogenesis in mice. However, it is unclear how changes in HSC glutamine metabolism contribute to net changes in hepatic glutaminolytic activity duri...

Prisoners in the United States are disproportionately affected by hepatitis C. Addressing the disease behind bars is crucial for curtailing the epidemic in the greater population. Effective strategies for testing and treatment are elucidated here. Recommendations for changes in hepatitis C health care policy in North Carolina prisons are also descr...

Background Clinicians often encounter patients requiring simultaneous treatment for both HIV and HCV. Although several resources help clinicians identify potential drug interactions, these resources do not account for other factors that should be considered when selecting HIV and HCV regimens, such as renal function, HLA-B*5701 status, and HCV geno...

Background Direct-acting antivirals (DAA) and antiretroviral (ARV) medications pose treatment challenges in HIV/HCV co-infection. Management of contraindicated combinations varies across practices. ARV switches may increase the risk of HIV virologic and treatment failure, and has been reported to increase the risk of DAA treatment failure. This ana...

Improvement in survival in patients living with human immunodeficiency virus (PLHIV) has led to increased prevalence of cardiovascular disease. Whether HIV-associated immune dysfunction is associated with preclinical left ventricular (LV) dysfunction despite normal LV ejection fraction (LVEF) is unclear. Accordingly, we investigated the relation of...

Editorial in response to “Effectiveness of Ledipasvir/Sofosbuvir and Sofosbuvir/Velpatasvir in People Who Inject Drugs and/or Those in Opioid Agonist Therapy”

Background: Current guidelines for the management of hepatitis C virus (HCV) infections provide varying recommendations for the optimal treatment of acute HCV infections. There are limited data from small cohort studies to provide guidance on the best approach to treatment of this important patient population. Methods: Sofosbuvir-Containing Regi...

Background Concomitant dosing of ledipasvir (LDV) and tenofovir disoproxil fumarate (TDF) results in an increased tenofovir (TFV) area under the curve (AUC). The aim of this study was to examine whether there was a correlation between the renal biomarkers retinol binding protein–4 (RBP-4) and β2 microglobulin (β2M) and tenofovir AUC. Methods The I...

Introduction: Among patients with hepatitis C virus (HCV) infection, alcohol synergistically increases the risk of cirrhosis, hepatocellular carcinoma, and death. Randomized controlled trials of integrated models of HCV-alcohol treatment have been recommended but only performed in patients with severe alcohol use disorders. Objectives: This prag...

Purpose : In the interferon era of hepatitis C virus (HCV) therapies, genotype/subtype, cirrhosis, prior treatment failure, sex, and race predicted relapse. Our objective was to validate a targeted proteomics platform of 17 peptides to predict sustained virologic response (SVR). Experimental design : Stored plasma from three, open‐label, trials of...

Objective: To investigate determinants of structural myocardial abnormalities in persons living with HIV (PLWH). Methods: We reviewed archived transthoracic echocardiograms (TTE) performed on PLWH at Duke University Medical Center between 2001 and 2012. The primary outcomes were presence of left ventricular hypertrophy (LVH) or diastolic dysfunc...

Background: The nucleotide analogues tenofovir and sofosbuvir are considered to have low potential for drug interactions. Objectives: To determine the effect of sofosbuvir-based HCV treatment on plasma concentrations of tenofovir and cellular concentrations of tenofovir diphosphate. Methods: HIV-infected participants with acute HCV were treate...

In the ION-4 trial, hepatitis C virus relapse was rare, occurring only in African American patients, 80% receiving efavirenz for human immunodeficiency virus infection. We observed no indication that CYP2B6 polymorphisms associated with increased plasma efavirenz exposure explained the relapses.

Introduction Persons living with HIV (PLWH) are at higher risk for cardiovascular disease (CVD) events than uninfected persons. Current risk-stratification methods to define PLWH at highest risk for CVD events are lacking. Methods Using tandem flow injection mass spectrometry, we quantified plasma levels of 60 metabolites in 24 matched pairs of PL...

Cardiovascular disease (CVD) is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected adults; however, this population may be less likely to receive interventions during hospitalization for acute coronary syndrome (ACS). The degree to which this disparity can be attributed to poorly controlled HIV infection i...

Background Direct-acting antivirals (DAA) as curative therapy for hepatitis C virus (HCV) infection offer >95% sustained virologic response (SVR), including in patients with human immunodeficiency virus (HIV) infection. Despite improved safety and efficacy of HCV treatment, challenges remain, including drug-drug interactions between DAA and antiret...

Background Direct acting antiviral HCV therapies are highly effective but costly. Wider adoption of an 8-week ledipasvir/sofosbuvir treatment regimen could result in significant savings, but may be less efficacious compared to a 12-week regimen. We evaluated outcomes under a constrained budget and cost-effectiveness of 8 versus 12 weeks of therapy...

Opinion Statement Despite the excellent efficacy of direct-acting antivirals (DAA) for hepatitis C virus (HCV), treatment failures do occur. Until recently, retreatment decisions after DAA failure were influenced by the number of available agents, concerns about HCV drug resistance, and lack of data regarding retreatment. Recommended treatment appr...

Interferon (IFN)-free direct-acting antiviral agents (DAAs) have revolutionized chronic hepatitis C virus (HCV) treatment; early studies suggest excellent efficacy in acute HCV. However, changes in innate immune responses during DAA therapy for acute HCV are unknown. We studied interferon-stimulated gene (ISG) expression and related cytokines/chemo...

Background: A safe, simple, effective, and pan-genotypic regimen to treat hepatitis C virus (HCV) infection in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains a medical need. We assessed the efficacy and safety of the NS5B polymerase inhibitor sofosbuvir and the NS5A inhibitor velpatasvir for HCV in patients coinfected...

Background.: Historically, acute hepatitis C virus (HCV) infection was treated with shorter durations of interferon-containing therapies. In the era of direct-acting antivirals (DAAs), it is unclear whether the efficacy of treatment achieved in chronic infection can be maintained with abbreviated courses of therapy during the acute phase. Methods...

The current standard of care for the treatment of hepatitis C virus (HCV) consists of interferon-free direct-acting antiviral (DAA) regimens, including combinations of DAAs and fixed-dose combination pills. DAAs for HCV are likely to be heralded as one of medicine’s greatest advancements. Viral eradication rates are pushing 100% for many HCV-infect...

There is evidence that hepatitis C virus (HCV) infection, like HIV infection, may be associated with chronic inflam-mation, immune activation, and immune senescence, which contribute to increased risks for cardiometabolic or other diseases outside the liver, as well as to ongoing damage in the liver. These effects may persist after a sustained viro...

Hepatitis C virus (HCV) represents a significant global disease burden, with an estimated 130-150 million people worldwide living with chronic HCV infection. Within the six major clinical HCV genotypes, genotype 3 represents 22-30% of all infection and is described as a unique entity with higher rates of steatosis, faster progression to cirrhosis,...

Background The Simeprevir ObservatioNal Effectiveness across practice seTtings (SONET) study evaluated the real-world effectiveness of simeprevir-based treatment for hepatitis C virus (HCV) infection. Methods The SONET study was a phase 4, prospective, observational, United States–based study enrolling patients ≥18 years of age with chronic genoty...

Currently, 380,000-400,000 occupational exposures to blood borne pathogens occur annually in the United States. The management for occupational HIV or HBV exposures includes post-exposure prophylaxis (PEP) when necessary; however, PEP is not recommended for HCV exposures. Recent approval of HCV direct acting antivirals (DAAs) has renewed discussion...