Netanya S. Utay

The University of Texas Southwestern Medical Center

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Anoma Somasunderam

The University of Texas Health Science Center at Houston

Jordan E. Lake

The University of Texas Health Science Center at Houston

David M. Asmuth

University of California, Davis

Roberto C. Arduino

The University of Texas Health Science Center at Houston

Heather L. Stevenson

The University of Texas Medical Branch at Galveston

Alan Landay

The University of Texas Medical Branch at Galveston

ÓA

Ómar A. Saldarriaga

The University of Texas Medical Branch at Galveston

Richard B. Pollard

University of California, Davis

Daniel C. Douek

National Institutes of Health

Surinder Mann

University of Southern California

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National Institutes of Health

National Institute of Allergy and Infectious Diseases

University of California, San Francisco

Harvard University

The University of Texas Health Science Center at Houston

The University of Texas Medical Branch at Galveston

University of California, San Diego

Johns Hopkins University

Baylor College of Medicine

Office of Infectious Diseases

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Ramipril for the Treatment of COVID-19: RAMIC, a Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Advances in Therapy (2023)

Daniel Q. Huang Veeral Ajmera Christian Tomaszewski Andrew Lafree Ricki Bettencourt

Ramipril

Clinical endpoint

10.1007/s12325-023-02618-7

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Citations (1)

Interferons and HIV Infection: The Good, the Bad, and the Ugly

Pathogens and Immunity (2016)

Netanya S. Utay Daniel C. Douek

Whether type I interferons (IFNs) hinder or facilitate HIV disease progression is controversial. Type I IFNs induce the production of restriction factors that protect against mucosal HIV/SIV acquisition and limit virus replication once systemic infection is established. However, type I IFNs also increase systemic immune activation, a predictor of poor CD4+ T-cell recovery and progression to AIDS, and facilitate production and recruitment of target CD4+ T cells. In addition, type I IFNs induce CD4+ T-cell apoptosis and limit antigen-specific CD4+ and CD8+ T-cell responses. The outcomes of type I IFN signaling may depend on the timing of IFN-stimulated gene upregulation relative to HIV exposure and infection, local versus systemic type I IFN-stimulated gene expression, and the subtype of type I IFN evaluated. To date, most interventional studies have evaluated IFNα2 administration largely in chronic HIV infection, and few have evaluated the effects on tissues or the HIV reservoir. Thus, whether the effect of type I IFN signaling on HIV disease is good, bad, or so complicated as to be ugly remains a topic of hot debate.

10.20411/pai.v1i1.125

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Citations (81)

Therapeutic microbiome modulation: new frontiers in HIV treatment

Current Opinion in HIV and AIDS (2024)

Rene Bulnes Netanya S. Utay

Purpose of review Dysbiosis may be a key driver of systemic inflammation, which increases the risk of non-AIDS events in people living with HIV (PLWH). Modulation of the microbiome to reverse this dysbiosis may be a novel approach to decrease inflammation and therefore morbidity and mortality in PLWH. Recent findings Fecal microbiota transplantation (FMT), probiotics, prebiotics, synbiotics, postbiotics, and dietary modifications have the potential to modulate the microbiome. These interventions have been well tolerated in clinical trials to date. However, these interventions have not resulted in consistent or lasting changes to the microbiome or consistent changes in biomarkers of intestinal permeability, microbial translocation, inflammation, immune activation, or CD4 + T cell counts. Sustained engraftment may require prebiotics and/or dietary modifications added to either probiotics or FMT. Summary Adequately powered randomized controlled trials are needed to elucidate whether microbiome modulation can be achieved and impact systemic inflammation in PLWH.

10.1097/coh.0000000000000864

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Potential use of serum‐derived bovine immunoglobulin/protein isolate for the management of COVID ‐19

Drug Development Research (2021)

Netanya S. Utay David M. Asmuth Shahin Gharakhanian Moises Contreras Christopher D. Warner

Abstract COVID‐19 manifests as a mild disease in most people but can progress to severe disease in nearly 20% of individuals. Disease progression is likely driven by a cytokine storm, either directly stimulated by SARS‐CoV‐2 or by increased systemic inflammation in which the gut might play an integral role. SARS‐CoV‐2 replication in the gut may cause increased intestinal permeability, alterations to the fecal microbiome, and increased inflammatory cytokines. Each effect may lead to increased systemic inflammation and the transport of cytokines and inflammatory antigens from the gut to the lung. Few interventions are being studied to treat people with mild disease and prevent the cytokine storm. Serumderived bovine immunoglobulin/protein isolate (SBI) may prevent progression by (1) binding and neutralizing inflammatory antigens, (2) decreasing gut permeability, (3) interfering with ACE2 binding by viral proteins, and (4) improving the fecal microbiome. SBI is therefore a promising intervention to prevent disease progression in COVID‐19 patients.

Cytokine Storm

Intestinal Permeability

Coronavirus

10.1002/ddr.21841

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Citations (7)

Initiation of antiretroviral therapy in early HIV infection reduces but does not abrogate chronic residual inflammation

Irini Sereti Shelly J. Krebs Nittaya Phanuphak James L. K. Fletcher Bonnie M. Slike

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Evaluation of Six Weekly Oral Fecal Microbiota Transplants in People with HIV

Pathogens and Immunity (2020)

Netanya S. Utay Ana Monczor Anoma Somasunderam Sofia Lupo Zhi‐Dong Jiang

Background: Reduced microbiota diversity (dysbiosis) in people with HIV (PWH) likely contributes to inflammation, a driver of morbidity and mortality. We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis.Methods: Six PWH on suppressive antiretroviral therapy (ART) received 6 weekly doses of lyophilized fecal microbiota product from healthy donors. Shotgun sequencing on stool before, after last FMT, and 20 weeks thereafter was performed. Inflammation and gut permeability biomarkers were measured.Results: Median age at week 0 was 39 years, CD4+ T cell count 496 cells/mm3, HIV RNA levels <20 copies/mL. FMT was safe and well-tolerated. Alpha diversity increased in 4 participants from weeks 0 to 6, including the 3 with the lowest alpha diversity at week 0. At week 26, alpha diversity more closely resembled week 0 than week 6 in these 4 participants. Metagenomic analysis showed no consistent changes across all participants. One participant had high gut permeability and inflammation biomarker levels and low alpha diversity that improved between weeks 0 and 6 with a shift in distribution.Conclusions: Weekly FMT was safe and well-tolerated. Alpha diversity increased in participants with the lowest baseline alpha diversity during the treatment period. Future randomized, controlled trials of FMT should consider evaluating PWH with greater inflammation, gut damage, or dysbiosis as this population may be most likely to show a significant response.ClinicalTrials.gov Identifier: NCT03329560

Dysbiosis

Tolerability

10.20411/pai.v5i1.388

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Citations (18)

Serum‐derived bovine immunoglobulin treatment in COVID‐19 is associated with faster resolution of symptoms: A randomized pilot clinical trial

Journal of Medical Virology (2024)

Netanya S. Utay Robert Güerri‐Fernández Shahin Gharakhanian David M. Asmuth Moises Contreras

Effective treatment to prevent hospitalization and death in people with COVID-19 exists, but people still need interventions that alleviate symptoms without drug interactions. Oral serum-derived bovine immunoglobulins (SBI) may reduce symptoms and time-to-improvement in people with mild-to-moderate COVID-19. In this randomized, open-label, single-site study, participants with mild-to-moderate COVID-19 received SBI 5.0 g bis in die (BID) + Standard of Care (SOC) or SOC alone (2:1) for 2 weeks. After 2 weeks, 78.8% of hospitalized participants on SBI + SOC improved by World Health Organization (WHO) scale of ≥3 compared to 61.1% on SOC alone (odds ratio: OR = 2.4; p = 0.0663), with older participants (>57 years) showing more significant differences between the arms (OR = 6.1; p = 0.0109). Further, more participants on SBI + SOC reported absence of COVID-19 symptoms at Week 2 (74.2%) compared to SOC alone (43.6%; OR = 3.7; p = 0.0031), most notably the absence of dyspnea on exertion (OR = 4.4; p = 0.0047), with women exhibiting the most significant eradication of all symptoms (OR = 5.8; p = 0.0080). No difference in change of IL-6 between arms was observed. Overall, participants with mild-to-moderate COVID-19 on SBI + SOC had a shorter time-to-recovery than on SOC alone, with a significantly higher rate of complete resolution of symptoms. Dyspnea on exertion was the symptom most significantly impacted. For people with mild-to-moderate COVID-19, oral SBI could be a safe and effective intervention, devoid of drug interactions.

10.1002/jmv.70005

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Stability of plasma indices of inflammation/coagulation and homeostasis after fatty and non-fatty meals in treated people with HIV

Journal of Virus Eradication (2019)

Dominic Dorazio Douglas Kitch Netanya S. Utay Bernard Macatangay Alan Landay

The relationship between lipid levels in plasma and inflammatory indices is complex and fatty meals alter plasma inflammatory markers in people with diabetes. There is interest in monitoring the effects of interventions on plasma inflammatory and coagulation elements in people with HIV, as they have been linked to risk for morbid outcomes and HIV persistence. Understanding the effects of feeding and time of specimen acquisition is important for the correct scheduling of clinical sampling.We examined the effects of feeding on plasma inflammatory, coagulation and homeostatic indices among 24 non-diabetic people with HIV, with controlled viraemia and on antiretroviral therapy after fasting and then 1, 3 and 6 hours after ingesting a fatty meal, and also approximately 1 week later after fasting and after an isocaloric non-fatty meal. Plasma levels of IL-6, IL-7, IP-10, sCD14, sCD163, sTNFrII and D-dimer were monitored by immunoassay.Fasting levels of all markers obtained approximately 1 week apart were significantly correlated (P<0.001). Mild alterations in plasma concentrations of inflammatory markers were observed after feeding but geometric means varied more than 10% from baseline for only IL-6 and IL-7. Meal type was differentially associated with changes in plasma levels for IL-7 only. Antiretroviral treatment regimen, body mass index and changes in plasma triglyceride levels were not linked to post-feeding changes in these biomarkers.These plasma inflammatory, coagulation and homeostatic indices are relatively stable at fasting and are only minimally affected by feeding or time of day. These findings will aid in the monitoring of inflammatory and homeostatic indices that may contribute to control of HIV expression and its persistence.

Homeostatic model assessment

Homeostasis

Regimen

Blood plasma

10.1016/s2055-6640(20)30274-0

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Hepatic steatosis in HCV-infected persons in the direct-acting antiviral era

Tropical Diseases Travel Medicine and Vaccines (2016)

Heather L. Stevenson Netanya S. Utay

Hepatitis C virus (HCV) infects 130–170 million people worldwide. Recently, direct-acting antivirals have been shown to eradicate HCV infection in 90–95 % of non-cirrhotic patients depending on genotype, treatment experience, and regimen used. Similar rates are achieved among compensated cirrhotics, although longer treatment duration and/or ribavirin may be required. HCV uses host lipid metabolism for its lifecycle and can cause hepatic steatosis and insulin resistance. Hepatic steatosis, defined as excessive triglyceride deposition in hepatocytes, affects approximately half of HCV-infected individuals. Genetic factors and co-morbidities can drive further steatosis, which in turn can instigate fibrosis and progression to cirrhosis and hepatocellular carcinoma. Polymorphisms in genes that modulate lipid deposition in hepatocytes such as patatin-like phospholipase domain-containing protein 3 (PNPLA3) and transmembrane six superfamily member 2 (TM6SF2) predispose people to steatosis. Metabolic syndrome, obesity, and insulin resistance are increasing worldwide and further contribute to hepatic steatosis, and alcohol has long been recognized as a cause of lipid deposition in the liver. HIV and antiretroviral drugs, but not HBV, may further drive hepatic steatosis. While many of these factors limit response to interferon-based regimens for treating HCV, responses to direct-acting antivirals appear not to be impaired. The effect of HCV eradication on hepatic steatosis and progression to fibrosis, cirrhosis, and hepatocellular carcinoma warrants further study in the era of direct-acting antivirals.

Steatosis

Hepatitis C

Lipid droplet

10.1186/s40794-016-0038-5

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Citations (24)

Raised Venous Lactate and Markers of Intestinal Translocation Are Associated With Mortality Among In-Patients With HIV-Associated TB in Rural South Africa

JAIDS Journal of Acquired Immune Deficiency Syndromes (2015)

Sathyavani Subbarao Katalin A. Wilkinson Clare L. van Halsema Suhasini Subba Rao Tom Boyles

Case fatality among in-patients with HIV-associated tuberculosis (HIV-TB) in Africa is high. We investigated the factors associated with mortality in a rural South African hospital.This was a prospective observational study of HIV-TB in-patients, with death by 8 weeks the endpoint.Of 99 patients (median CD4 count 72 cells/mm³), 32 (32%) died after median 8-day TB treatment. TB was diagnosed microbiologically in 75/99 and clinico-radiologically in 24, with no mortality difference between these groups [31% versus 38% (P = 0.53)]. Median venous lactate was 5.5 mmol/L (interquartile range 3.9-6.2) in those who died and 3.1 mmol/L (interquartile range 2.2-4.1) in survivors (P < 0.001). In multivariable analysis, lactate ≥4 mmol/L [adjusted odds ratio (aOR) 9.8, 95% confidence interval (CI): 3.0 to 32.2], Glasgow Coma Score <15 (aOR 6.6, 95% CI: 1.5 to 29.6), CD4 count <50 cells per cubic millimeter (aOR 5.5, 95% CI: 1.6 to 18.5), and age ≥50 (aOR 7.7, 95% CI: 1.2 to 46.9) independently predicted death. In a nested case-control study, comparing those who died versus CD4-matched survivors, median plasma lipopolysaccharide concentrations were 93 and 57 pg/mL (P = 0.026) and intestinal fatty acid-binding protein, 132 and 0 pg/mL (P = 0.002).Mortality was high and predicted by elevated lactate, likely reflecting a sepsis-syndrome secondary to TB or bacterial coinfection with intestinal barrier dysfunction appearing to contribute.

Interquartile range

Case fatality rate

10.1097/qai.0000000000000763

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Citations (19)