A randomized, placebo-controlled pilot trial of N-acetylcysteine on oxidative stress and endothelial function in HIV-infected older adults receiving antiretroviral treatment

Gupta, Samir K.; Kamendulis, Lisa M.; Clauss, Matthias; Liu, Ziyue

doi:10.1097/qad.0000000000001222

Cited by 10 publications

(6 citation statements)

References 7 publications

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“…Fasting banked serum samples were obtained from 66 adult HIV seropositive participants and 39 HIV seronegative participants who completed other local studies at Indiana University (ClinicalTrials.gov NCT00796822, NCT00864916, NCT00919724, NCT01270802, and NCT01962961) [ 20 , 21 ]. Seropositive participants were recruited from the HIV outpatient clinics associated with the Indiana University Health medical system.…”

Section: Methodsmentioning

confidence: 99%

“…Measurements of HIV RNA levels (‘viral loads’), CD4 counts, and glucose were measured by the IU Health Clinical Pathology lab using standard assays. High sensitivity C reactive protein (hsCRP), interleukin 6 (IL-6), C-peptide, and total proinsulin were assayed using commercially available ELISAs [ 20 , 21 , 23 , 24 ]. hsCRP was measured using a BNII Nephelometer (Siemens, Munich, Germany) with a minimum detection limit of 0.168 ng/mL with no upper bound and interassay CV of 1.56–5.43% [ 21 ].…”

Section: Methodsmentioning

confidence: 99%

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Immune reconstitution in ART treated, but not untreated HIV infection, is associated with abnormal beta cell function

et al. 2018

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HIV infection has been associated with increased diabetes risk, but prior work has mostly focused on insulin resistance, as opposed to beta cell effects, or included patients on antiretroviral therapies (ART) directly linked to metabolic toxicity. In this analysis, we measured markers of glucose homeostasis and beta cell function, stress, and death in fasting sera from a cross section of HIV+ individuals off ART (n = 43), HIV+ individuals on ART (n = 23), and HIV- controls (n = 39). Markers included glucose, HOMA%S, HOMA%B, proinsulin:C-peptide ratio (PI:C ratio), and circulating preproinsulin (INS) DNA. We performed multiple linear regressions with adjustments for age, sex, race, BMI, and smoking status. Compared to HIV- controls, HIV+ participants off ART exhibited similar beta cell function and insulin sensitivity, without increases in markers of beta cell stress or death. Specifically, in HIV+ participants with CD4 counts <350 cells/μL, PI:C ratios were lower than in HIV- controls (p<0.01), suggesting a reduction in intrinsic beta cell stress among this group. By contrast, HIV+ participants on ART had higher fasting glucose (p<0.0001) and lower HOMA%B (p<0.001) compared to HIV- controls. Among the entire HIV+ population, higher HIV RNA correlated with lower fasting glucose (r = -0.57, p<0.001), higher HOMA%B (r = 0.40, p = 0.001), and lower PI:C ratios (r = -0.42, p<0.001), whereas higher CD4 counts correlated with higher PI:C ratios (r = 0.2, p = 0.00499). Our results suggest that HIV seropositivity in the absence of ART does not worsen beta cell function or glucose homeostasis, but immune reconstitution with ART may be associated with worsened beta cell function.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Immune reconstitution in ART treated, but not untreated HIV infection, is associated with abnormal beta cell function

et al. 2018

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“…The blood specimens obtained during the trial were archived for later batch testing of biomarkers of interest, and FMD of the brachial artery was measured as a marker of physiologic endothelial function. Because we have observed a possible “regression to the mean” effect in FMD in our previous trials with high outlier values at baseline [ 16 , 17 ], we chose to perform 2 Entry visits, spaced between 1 and 15 days apart, for which biomarker and FMD measurements were averaged to obtain more stable baseline estimates. At the Second Entry Visit, participants were randomized 1:1, stratified by current use of antidepressant medications (yes/no), to either BtB or UC.…”

Section: Methodsmentioning

confidence: 99%

Effects of Internet Cognitive-Behavioral Therapy on Depressive Symptoms and Surrogates of Cardiovascular Risk in Human Immunodeficiency Virus: A Pilot, Randomized, Controlled Trial

Gupta

Slaven

Liu

et al. 2020

Open Forum Infectious Diseases

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Abstract Background Depression is associated with an increased risk of cardiovascular disease in HIV. We hypothesized that reducing depressive symptoms would improve HIV-related cardiovascular risk. Methods We conducted a single-center, randomized (1:1), controlled, parallel-group, assessor-blinded, pilot trial comparing Beating the Blues US™ (BtB) - an evidence-based, 8-session, internet cognitive behavioral therapy for depression - with usual care (UC) in HIV-positive participants receiving virologically-suppressive ART and with Patient Health Questionnaire (PHQ)-9 scores ≥10. The primary endpoint was change in brachial artery flow-mediated dilation (FMD) at 12 weeks. Secondary endpoints were FMD change at 24 weeks and inflammation, coagulation and metabolic biomarker changes at 12 and 24 weeks. Results 54 participants were randomized (27 in each arm). Mean reductions in PHQ-9 scores were significantly greater with BtB vs. UC at 12 weeks (-5.60 vs. -1.52; P=0.007) and 24 weeks (-6.00 vs. -1.38; P= 0.008); reductions in the Hopkins Symptom Checklist Depression Scale (SCL-20) scores were also significantly greater with BtB vs. UC at 24 weeks (-0.72 vs. -0.35; P=0.029). Changes in FMD between arms were not significantly different at 12 or 24 weeks. Significantly larger reductions in sCD14 and sCD163 with BtB vs. UC were found at 12 and 24 weeks, respectively. Conclusions Compared to usual care, internet cognitive behavioral therapy using BtB resulted in greater improvements in depressive symptoms and monocyte activation markers but did not improve FMD in this pilot trial. These data support performing larger studies to determine the potential salutatory effects of behavioral therapies for depression on HIV-related inflammation.

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“…A randomized, placebo-controlled pilot trial (NCT01962961) assessed the effect of PharmaNAC (at 900 mg twice daily for 8 weeks) on HIV-infected adults (above 50 years old) who were receiving antiretroviral treatment. They found that PharmaNAC effectively increased the levels of oxidized glutathione (GSH) but decreased the levels of reduced glutathione (GSSG) in red blood cells, thereby leading to non-significant increased ratios of GSH:GSSG compared to placebo (Gupta et al, 2016). More recently, another clinical trial (NCT02348775) reported that patients with HIV display premature aging and develop geriatric comorbidities; the authors hypothesized that these effects were derived from GSH deficiency in these patients.…”

Section: Thiol-based Agents: N-acetyl-l-cysteine (Nac) and Gshmentioning

confidence: 99%

Redox medicine in viral infections: focus on AIDS and COVID-19

Mas-Bargues

Borrás

Viña

2022

Redox Experimental Medicine

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Despite the great progress and advancements in scientific knowledge, technology, and medicine, viral infections continue to put human health in trouble. Both acquired immunodeficiency syndrome (AIDS) and coronavirus disease-2019 (COVID-19), caused by HIV and SARS-CoV-2, two RNA viruses responsible for global pandemics respectively, have poor outcomes associated with increased oxidative stress, systemic inflammation, and immunopathology. Here, we have collected the current knowledge linking both viral infections, focusing on the role of oxidative stress and the redox balance. Furthermore, we provide information on some redox-active compounds, such as vitamins, thiol-based agents, and polyphenols, and their possible beneficial effects on both diseases. Thus, in this review, we aim to highlight the importance and impact of nutritional strategies to strengthen our immune system, especially to increase the effectiveness of pharmacological treatments, or when there are no effective treatments.

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A randomized, placebo-controlled pilot trial of N-acetylcysteine on oxidative stress and endothelial function in HIV-infected older adults receiving antiretroviral treatment

Cited by 10 publications

References 7 publications

Immune reconstitution in ART treated, but not untreated HIV infection, is associated with abnormal beta cell function

Immune reconstitution in ART treated, but not untreated HIV infection, is associated with abnormal beta cell function

Effects of Internet Cognitive-Behavioral Therapy on Depressive Symptoms and Surrogates of Cardiovascular Risk in Human Immunodeficiency Virus: A Pilot, Randomized, Controlled Trial

Redox medicine in viral infections: focus on AIDS and COVID-19

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