Medicine and Health Sciences Commons^™

Effectiveness And Safety Of Bictegravir/Emtricitabine/Tenofovir Alafenamide In Patients With Hiv-1 Infection And Ongoing Substance Use Disorder: The Base Study, Joshua P. Havens, Sara Bares, Elizabeth Lyden, Anthony T. Podany, Kimberly Scarsi, Nada A. Fadul, Susan Swindells

Journal Articles: Infectious Diseases

BACKGROUND: People with human immunodeficiency virus (HIV) and substance use disorder (PWH/SUD) are at higher risk of nonadherence to antiretroviral therapy. Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) exhibits high rates of efficacy with a favorable adverse event profile. The BASE study (NCT03998176) is a phase 4, single-arm study evaluating the effectiveness and safety of B/F/TAF among PWH/SUD.

METHODS: Viremic (HIV RNA >1000 copies/mL) PWH/SUD initiated B/F/TAF once daily for 48 weeks (W). The primary endpoint was proportion of participants with HIV RNA/mL at W24. Secondary endpoints were proportion of participants with HIV-1 RNA/mL at W48, safety, B/F/TAF adherence (dried blood spot [DBS] concentrations …

Factors Associated With Prevalent Mycobacterium Tuberculosis Infection And Disease Among Adolescents And Adults Exposed To Rifampin-Resistant Tuberculosis In The Household, Soyeon Kim, Anneke C. Hesseling, Xingye Wu, Michael D. Hughes, N. Sarita Shah, Sanjay Gaikwad, Nishi Kumarasamy, Erika Mitchell, Mey Leon, Pedro Gonzales, Sharlaa Badal-Faesen, Madeleine Lourens, Sandy Nerette, Justin Shenje, Petra De Koker, Supalert Nedsuwan, Lerato Mohapi, Unoda A. Chakalisa, Rosie Mngqbisa, Rodrigo Otávio Da Silva Escada, Samuel Ouma, Barbara Heckman, Linda Naini, Amita Gupta, Susan Swindells, Gavin Churchyard, Actg A5300/Impaact 2003 Phoenix Feasibility Study Team

Journal Articles: Infectious Diseases

BACKGROUND: Understanding factors associated with prevalent Mycobacterium tuberculosis infection and prevalent TB disease in household contacts of patients with drug-resistant tuberculosis (TB) may be useful for TB program staff conducting contact investigations.

METHODS: Using data from a cross-sectional study that enrolled index participants with rifampin-resistant pulmonary TB and their household contacts (HHCs), we evaluated HHCs age ≥15 years for factors associated with two outcomes: Mycobacterium tuberculosis infection and TB disease. Among HHCs who were not already diagnosed with current active TB disease by the TB program, Mycobacterium tuberculosis infection was determined by interferon-gamma release assay (IGRA). TB disease was adjudicated …

Mitochondrial Redox Environments Predict Sensorimotor Brain-Behavior Dynamics In Adults With Hiv., Rachel K. Spooner, Brittany K. Taylor, Iman M. Ahmad, Kelsey Dyball, Katy Emanuel, Jennifer O'Neill, Maureen Kubat, Susan Swindells, Howard S. Fox, Sara Bares, Kelly L. Stauch, Matthew C. Zimmerman, Tony W. Wilson

Journal Articles: Infectious Diseases

Despite virologic suppression, people living with HIV (PLWH) remain at risk for developing cognitive impairment, with aberrations in motor control being a predominant symptom leading to functional dependencies in later life. While the neuroanatomical bases of motor dysfunction have recently been illuminated, the underlying molecular processes remain poorly understood. Herein, we evaluate the predictive capacity of the mitochondrial redox environment on sensorimotor brain-behavior dynamics in 40 virally-suppressed PLWH and 40 demographically-matched controls using structural equation modeling. We used state-of-the-art approaches, including Seahorse Analyzer of mitochondrial function, electron paramagnetic resonance spectroscopy to measure superoxide levels, antioxidant activity assays and dynamic magnetoencephalographic …

Caregiver Willingness To Give Tpt To Children Living With Drug-Resistant Tb Patients, V. Rouzier, M. Murrill, S. Kim, L. Naini, J. Shenje, E. Mitchell, M. Raesi, M. Lourens, A. Mendoza, F. Conradie, N. Suryavanshi, M. Hughes, S. Shah, G. Churchyard, Susan Swindells, A. Hesseling, A. Gupta

Journal Articles: Infectious Diseases

Pediatric household contacts (HHCs) of patients with multidrug-resistant TB (MDR-TB) are at high risk of infection and active disease. Evidence of caregiver willingness to give MDR-TB preventive therapy (TPT) to children is limited.METHODS This was a cross-sectional study of HHCs of patients with MDR-TB to assess caregiver willingness to give TPT to children aged <13 years.RESULTS Of 743 adult and adolescent HHCs, 299 reported caring for children aged <13 years of age. The median caregiver age was 35 years (IQR 27-48); 75% were women. Among caregivers, 89% were willing to give children MDR TPT. In unadjusted analyses, increased willingness was associated with TB-related knowledge (OR 5.1, 95% CI 2.3-11.3), belief that one can die of MDR-TB (OR 5.2, 95% CI 1.2-23.4), concern for MDR-TB transmission to child (OR 4.5, 95% CI 1.6-12.4), confidence in properly taking TPT (OR 4.5, 95% CI 1.6-12.6), comfort telling family about TPT (OR 5.5, 95% CI 2.1-14.3), and willingness to take TPT oneself (OR 35.1, 95% CI 11.0-112.8).CONCLUSIONS A high percentage of caregivers living with MDR- or rifampicin-resistant TB patients were willing to give children a hypothetical MDR TPT. These results provide important evidence for the potential uptake of …

Week 96 Extension Results Of A Phase 3 Study Evaluating Long-Acting Cabotegravir With Rilpivirine For Hiv-1 Treatment, Susan Swindells, Thomas Lutz, Lelanie Van Zyl, Norma Porteiro, Matthias Stoll, Essack Mitha, Alyssa Shon, Paul Benn, Jenny O. Huang, Conn M. Harrington, Kai Hove, Susan L. Ford, Christine L. Talarico, Vasiliki Chounta, Herta Crauwels, Rodica Van Solingen-Ristea, Simon Vanveggel, David A. Margolis, Kimberly Y. Smith, Kati Vandermeulen, William R. Spreen

Journal Articles: Infectious Diseases

BACKGROUND: ATLAS (NCT02951052), a phase 3, multicenter, open-label study, demonstrated that switching to injectable cabotegravir (CAB) with rilpivirine (RPV) long-acting dosed every 4 weeks was noninferior at week (W) 48 to continuing three-drug daily oral current antiretroviral therapy (CAR). Results from the W 96 analysis are presented.

METHODS AND DESIGN: Participants completing W 52 of ATLAS were given the option to withdraw, transition to ATLAS-2M (NCT03299049), or enter an Extension Phase to continue long-acting therapy (Long-acting arm) or switch from CAR to long-acting therapy (Switch arm). Endpoints assessed at W 96 included proportion of participants with plasma HIV-1 RNA less …

The Value Of A Longitudinal Human Immunodeficiency Virus Track For Medical Students: 10-Year Program Evaluation, Jasmine R. Marcelin, Paul Brosnihan, Susan Swindells, Nada A. Fadul, Sara Bares

Journal Articles: Infectious Diseases

We surveyed graduates of a longitudinal medical school human immunodeficiency virus curriculum to evaluate its impact. Respondents felt comfortable caring for people with human immunodeficiency virus (PWH) and found value from the curriculum regardless of ultimate career path. Programs like this contribute to the development of culturally sensitive clinicians comfortable caring for PWH.

Gray Matter Volumes Discriminate Cognitively Impaired And Unimpaired People With Hiv, Mikki Schantell, Brittany K. Taylor, Brandon Lew, Jennifer O'Neill, Pamela E. May, Susan Swindells, Tony W. Wilson

Journal Articles: Infectious Diseases

BACKGROUND: Current diagnostic criteria of HIV-associated neurocognitive disorders (HAND) rely on neuropsychological assessments. The aim of this study was to evaluate if gray matter volumes (GMV) can distinguish people with HAND, neurocognitively unimpaired people with HIV (unimpaired PWH), and uninfected controls using linear discriminant analyses.

METHODS: A total of 231 participants, including 110 PWH and 121 uninfected controls, completed a neuropsychological assessment and an MRI protocol. Among PWH, HAND (n = 48) and unimpaired PWH (n = 62) designations were determined using the widely accepted Frascati criteria. We then assessed the extent to which GMV, corrected for intracranial volume, could …

Patient-Reported Outcomes Through 1 Year Of An Hiv-1 Clinical Trial Evaluating Long-Acting Cabotegravir And Rilpivirine Administered Every 4 Or 8 Weeks (Atlas-2m), Vasiliki Chounta, Edgar T. Overton, Anthony Mills, Susan Swindells, Paul D. Benn, Simon Vanveggel, Rodica Van Solingen-Ristea, Yuanyuan Wang, Krischan J. Hudson, Mark S. Shaefer, David A. Margolis, Kimberly Y. Smith, William R. Spreen

Journal Articles: Infectious Diseases

BACKGROUND: Advances in HIV-1 therapeutics have led to the development of a range of daily oral treatment regimens, which share similar high efficacy rates. Consequently, more emphasis is being placed upon the individual's experience of treatment and impact on quality of life. The first long-acting injectable antiretroviral therapy for HIV-1 (long-acting cabotegravir + rilpivirine [CAB + RPV LA]) may address challenges associated with oral treatment for HIV-1, such as stigma, pill burden/fatigue, drug-food interactions, and adherence. Patient-reported outcomes (PROs) collected in an HIV-1 clinical trial (ATLAS-2M; NCT03299049) comparing participants' experience with two dosing regimens (every 4 weeks [Q4W] vs. every …

Multi-Level Considerations For Optimal Implementation Of Long-Acting Injectable Antiretroviral Therapy To Treat People Living With Hiv: Perspectives Of Health Care Providers Participating In Phase 3 Trials, Andrea Mantsios, Miranda Murray, Tahilin S. Karver, Wendy Davis, Noya Galai, Princy Kumar, Susan Swindells, U. Fritz Bredeek, Rafael Rubio García, Antonio Antela, Santiago Cenoz Gomis, Miguel Pascual Bernáldez, Maggie Czarnogorski, Krischan Hudson, Nicki Walters, Deanna Kerrigan

Journal Articles: Infectious Diseases

BACKGROUND: Long-acting injectable antiretroviral therapy (LA ART) has been shown to be non-inferior to daily oral ART, with high patient satisfaction and preference to oral standard of care in research to date, and has recently been approved for use in the United States and Europe. This study examined the perspectives of health care providers participating in LA ART clinical trials on potential barriers and solutions to LA ART roll-out into real world settings.

METHODS: This analysis draws on two data sources: (1) open-ended questions embedded in a structured online survey of 329 health care providers participating in the ATLAS-2 M …

The Promise Of Improved Adherence With Long-Acting Antiretroviral Therapy: What Are The Data?, Kimberly Scarsi, Susan Swindells

Journal Articles: Infectious Diseases

As with other chronic conditions, adherence to daily medications remains a challenge for many individuals living with HIV due to structural, behavioral, and social barriers. Unfortunately, high levels of adherence to antiretroviral therapy are required to maintain virologic suppression. Alternative approaches are being explored to decrease the burden of daily pill administration, including long-acting injectable, oral, and implantable products. Phase 3 data support the efficacy of nanoformulated injectable cabotegravir and rilpivirine for HIV treatment in patients with undetectable viremia, but we have yet to learn how this strategy may benefit those with medication adherence challenges. Despite this, the affected community …

A Midwestern Academic Hiv Clinic Operation During The Covid-19 Pandemic: Implementation Strategy And Preliminary Outcomes, Nada Fadul, Nichole Regan, Layan Kaddoura, Susan Swindells

Journal Articles: Infectious Diseases

During the COVID-19 pandemic, HIV clinics had to transform care delivery for people with HIV (PWH). We developed a multifaceted telehealth implementation strategy and monitored number of out of care patients (OOC), medical visit frequency (MVF), gap in care (GiC) and viral suppression (VS), and compared measures to baseline data. Between April and October 2020, 1559 visits were scheduled; 328 (21%) were missed, and 63 (4%) were new to care. Of the remaining 1168 follow-up visits, 412 (35%) were telehealth visits. As of October 2020, there were 53 patients OOC, MVF was 55% and GiC was 24% compared to 34, …

Surprisingly Low Levels Of Measles Immunity In Persons With Hiv: A Seroprevalence Survey In A United States Hiv Clinic, Lindsey Rearigh, Jennifer O'Neill, Maureen Kubat, Harlan Sayles, Susan Swindells, Sara Bares

Journal Articles: Infectious Diseases

Background: Measles outbreaks have become increasingly common due to deteriorating vaccination rates, fluctuating herd immunity, and varying antibody decline. Limited knowledge exists regarding prevalence and risk factors associated with measles seronegativity among persons with HIV (PWH).

Methods: This was a cross-sectional study conducted at an academic HIV clinic in Omaha, Nebraska. Participants were screened for the presence of measles IgG antibody. Demographic and clinical information was obtained through electronic medical record review. Simple and multivariable logistic regressions were performed to identify risk factors for measles seronegativity.

Results: Three hundred fifty-one participants were enrolled, with a measles seroprevalence rate of 70.3%. …

Controlling Latent Tb Tuberculosis Infection In High-Burden Countries: A Neglected Strategy To End Tb, Gavin J. Churchyard, Susan Swindells

Journal Articles: Infectious Diseases

In a Perspective, Gavin Churchyard and Sue Swindells discuss the importance of strategies to target latent tuberculosis infection in high risk populations and thus disrupt a reservoir for new infections in high burden countries.

Acceptability And Feasibility Of A Pharmacist-Led Hiv Pre-Exposure Prophylaxis (Prep) Program In The Midwestern United States, Joshua P. Havens, Kimberly Scarsi, Harlan Sayles, Donald G. Klepser, Susan Swindells, Sara H. Bares

Journal Articles: Infectious Diseases

BACKGROUND: HIV pre-exposure prophylaxis (PrEP) substantially reduces the risk of HIV acquisition, yet significant barriers exist to its prescription and use. Incorporating pharmacists in the PrEP care process may help increase access to PrEP services.

METHODS: Our pharmacist-led PrEP program (P-PrEP) included pharmacists from a university-based HIV clinic, a community pharmacy, and two community-based clinics. Through a collaborative practice agreement, pharmacists conducted PrEP visits with potential candidates for PrEP, according to the recommended CDC guidelines, and authorized emtricitabine-tenofovir disoproxil fumarate prescriptions. Demographics and retention in care over 12 months were summarized and participant satisfaction and pharmacist acceptability with the P-PrEP …

A Pharmacist-Led Medication Switch Protocol In An Academic Hiv Clinic: Patient Knowledge And Satisfaction, Sarah S. Lee, Joshua P. Havens, Harlan R. Sayles, Jennifer L. O'Neill, Anthony T. Podany, Susan Swindells, Kimberly K. Scarsi, Sara H. Bares

Journal Articles: Infectious Diseases

BACKGROUND: Tenofovir alafenamide (TAF) is associated with less renal and bone toxicity compared with tenofovir disoproxil (TDF). TAF's recent FDA approval has spurred HIV providers to consider switching antiretroviral therapy (ART) regimens containing TDF to TAF to minimize long term risks. Patient views on the process of such medication switches have not been explored.

METHODS: Patients taking elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) following the Food and Drug Administration's (FDA) approval of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) received medication education from an HIV pharmacist prior to switching to the tenofovir alafenamide (TAF) formulation. Patients were asked to complete a cross-sectional survey assessing satisfaction with …

Determinants Of Facilitated Health Insurance Enrollment For Patients With Hiv Disease, And Impact Of Insurance Enrollment On Targeted Health Outcomes., Renae Furl, Shinobu Watanabe-Galloway, Elizabeth Lyden, Susan Swindells

Journal Articles: Infectious Diseases

BACKGROUND: The introduction of the Affordable Care Act (ACA) has provided unprecedented opportunities for uninsured people with HIV infection to access health insurance, and to examine the impact of this change in access. AIDS Drug Assistance Programs (ADAPs) have been directed to pursue uninsured individuals to enroll in the ACA as both a cost-saving strategy and to increase patient access to care. We evaluated the impact of ADAP-facilitated health insurance enrollment on health outcomes, and demographic and clinical factors that influenced whether or not eligible patients enrolled.

METHODS: During the inaugural open enrollment period for the ACA, 284 Nebraska ADAP …

Aberrant Neuronal Dynamics During Working Memory Operations In The Aging Hiv-Infected Brain., Tony W. Wilson, Amy L. Proskovec, Elizabeth Heinrichs-Graham, Jennifer O'Neill, Kevin R. Robertson, Howard S. Fox, Susan Swindells

Journal Articles: Infectious Diseases

Impairments in working memory are among the most prevalent features of HIV-associated neurocognitive disorders (HAND), yet their origins are unknown, with some studies arguing that encoding operations are disturbed and others supporting deficits in memory maintenance. The current investigation directly addresses this issue by using a dynamic mapping approach to identify when and where processing in working memory circuits degrades. HIV-infected older adults and a demographically-matched group of uninfected controls performed a verbal working memory task during magnetoencephalography (MEG). Significant oscillatory neural responses were imaged using a beamforming approach to illuminate the spatiotemporal dynamics of neuronal activity. HIV-infected patients were …

A Survey Of Tuberculosis Infection Control Practices At The Nih/Niaid/Daids-Supported Clinical Trial Sites In Low And Middle Income Countries., Catherine Godfrey, Gail Tauscher, Sally Hunsberger, Melissa Austin, Lesley Scott, Jeffrey T. Schouten, Anne F. Luetkemeyer, Constance Benson, Robert Coombs, Susan Swindells

Journal Articles: Infectious Diseases

BACKGROUND: Health care associated transmission of Mycobacterium tuberculosis (TB) is well described. A previous survey of infection control (IC) practices at clinical research sites in low and middle income countries (LMIC) funded by the National Institute of Allergy and Infectious Diseases (NIAID) conducting HIV research identified issues with respiratory IC practices. A guideline for TB IC based on international recommendations was developed and promulgated. This paper reports on adherence to the guideline at sites conducting or planning to conduct TB studies with the intention of supporting improvement.

METHODS: A survey was developed that assessed IC activities in three domains: facility …

Predictors And Outcomes Of Mycobacterium Tuberculosis Bacteremia Among Patients With Hiv And Tuberculosis Co-Infection Enrolled In The Actg A5221 Stride Study., John A. Crump, Xingye Wu, Michelle A. Kendall, Prudence D. Ive, Johnstone J. Kumwenda, Beatriz Grinsztejn, Ute Jentsch, Susan Swindells

Journal Articles: Infectious Diseases

BACKGROUND: We evaluated predictors and outcomes of Mycobacterium tuberculosis bacteremia among participants undergoing baseline mycobacterial blood culture in the ACTG A5221 STRIDE study, a randomized clinical trial comparing earlier with later ART among HIV-infected patients suspected of having tuberculosis with CD4-positive T-lymphocyte counts (CD4 counts)/mm(3). We conducted a secondary analysis comparing participants with respect to presence or absence of M. tuberculosis bacteremia.

METHODS: Participants with a baseline mycobacterial blood culture were compared with respect to the presence or absence of M. tuberculosis bacteremia. Baseline predictors of M. tuberculosis bacteremia were identified and participant outcomes were compared by mycobacteremia status.

RESULTS: …