Publications by authors named "Samir K Gupta"

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) is associated with increased cardiovascular disease (CVD) risk in persons with HIV (PWH). The lipidomic and metabolomic alterations contributing to this risk are poorly understood. We aimed to characterize the advanced lipoprotein and targeted metabolomic profiles in PWH and assess if the presence and severity of MASLD influence these profiles.

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  • REPRIEVE was a study that looked at how a medication called pitavastatin affects people with HIV and their risk of getting diabetes.
  • The study included over 7,700 participants aged 40 to 75 who didn't have diabetes at the start.
  • It found that people with more diabetes risk factors had a greater chance of developing diabetes, especially in places like South Asia.
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Background: Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk.

Methods: Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care.

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We assess associations of somatic and cognitive/affective depressive symptom clusters with monocyte activation (soluble (s)CD14, sCD163), systemic inflammation (interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP)), and coagulation (D-dimer, fibrinogen) in people with HIV (PWH) on suppressive antiretroviral therapy with depression. Utilizing baseline data from a randomized controlled trial, we found no significant associations in linear regression models examining individual depressive symptom clusters; however, models examining both clusters simultaneously showed that the somatic cluster was positively associated with inflammation biomarkers, while the cognitive/affective cluster was negatively associated with inflammation and coagulation biomarkers (suggesting a cooperative suppression effect). Our findings indicate a differential association with depressive symptom clusters and biological mechanisms underlying cardiovascular disease (CVD) in HIV, which may be driven by unique components of each depressive symptom cluster.

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We explored the impact of immune dysregulation on pancreatic beta cell injury in HIV patients. Analyzing 105 participant samples, we observed lower IL-21 levels and elevated immune checkpoint levels (e.g.

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Background: Remdesivir, an RNA-polymerase prodrug inhibitor approved for treatment of coronavirus disease 2019 (COVID-19), shortens recovery time and improves clinical outcomes. This prespecified analysis compared remdesivir plus standard of care (SOC) with SOC alone in adults hospitalized with COVID-19 requiring oxygen support in the early stage of the pandemic.

Methods: Data for 10-day remdesivir treatment plus SOC from the extension phase of an open-label study (NCT04292899) were compared with real-world, retrospective data on SOC alone (EUPAS34303).

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Background: Switching from non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens to dolutegravir (DTG) has been associated with greater weight gain.

Methods: We conducted our analysis using a longitudinal cohort of people with HIV (PWH) in Western Kenya. We evaluated changes in the rate of weight gain among treatment-experienced, virally suppressed PWH who switched from NNRTI to tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD).

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  • The INGENIOUS trial analyzed the impact of pharmacogenetic testing on ADE frequency among 2,612 patients prescribed certain medications, but found no significant difference in overall ADE occurrences.
  • However, specific groups, particularly those on aripiprazole and certain antidepressants, showed a reduction in serious ADEs, suggesting more research on proactive testing could be beneficial.
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  • Cryptococcal meningitis, typically affecting immunocompromised individuals, has been identified in a small number of young, healthy patients, raising concerns about under-recognition in this demographic.
  • A study at Indiana University Health found 4 local cases from 2015 to 2022 and a literature review revealed 51 additional worldwide cases, mostly linked to specific cryptococcal strains.
  • The condition can lead to complications such as postinfectious inflammatory response syndrome (PIIRS), with varied treatment regimens primarily involving antifungals like amphotericin, and only two reported deaths linked directly to cryptococcosis.
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Although depression is a risk and prognostic factor for cardiovascular disease (CVD), clinical trials treating depression in patients with CVD have not demonstrated cardiovascular benefits. We proposed a novel explanation for the null results for CVD-related outcomes: the late timing of depression treatment in the natural history of CVD. Our objective was to determine whether successful depression treatment before, versus after, clinical CVD onset reduces CVD risk in depression.

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Background Aims: The current prevalence of fatty liver disease (FLD) due to alcohol-associated (AFLD) and nonalcoholic (NAFLD) origins in US persons with HIV (PWH) is not well defined. We prospectively evaluated the burden of FLD and hepatic fibrosis in a diverse cohort of PWH.

Approach Results: Consenting participants in outpatient HIV clinics in 3 centers in the US underwent detailed phenotyping, including liver ultrasound and vibration-controlled transient elastography for controlled attenuation parameter and liver stiffness measurement.

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Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in persons with HIV (PWH) (HIV-NAFLD). It is unknown if HIV-NAFLD is associated with impairment in health-related quality of life (HRQOL). We examined HRQOL in PWH with and without NAFLD, compared HRQOL in HIV- versus primary NAFLD, and determined factors associated with HRQOL in these groups.

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Background: Antiretroviral agents with novel mechanisms and dosing intervals could expand treatment options for people with HIV. Lenacapavir, an inhibitor of capsid protein that makes use of a unique mechanism, can be administered orally or subcutaneously. We sought to explore the efficacy of lenacapavir in various combination regimens as initial and maintenance therapy for HIV.

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Background: Several recent studies have linked integrase strand transfer inhibitors (INSTI) with increased weight gain.

Setting: The effects of sex on weight gain with dolutegravir (DTG)-based antiretroviral therapy (ART) among treatment-naïve participants in a lower-income, sub-Saharan population with high rates of pre-ART underweight and tuberculosis (TB) coinfection are unknown.

Methods: Our analysis included treatment-naïve participants in Kenya and starting their first treatment regimen between January 1, 2015, and September 30, 2018.

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  • People with HIV have a heightened risk of cardiovascular disease (CVD) that isn't fully explained by existing risk factors, highlighting the need to explore new ones like depression.
  • A systematic review of 35 studies found that depression is linked to an increased risk of clinical CVD, although results for its association with subclinical CVD and biological mechanisms were mixed and varied.
  • The study suggests that depression could be an independent risk factor for CVD in people with HIV, and calls for more research to clarify its relationships with different aspects of CVD.
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Background: Persons with HIV (PWH) are at increasingly higher risk for metabolic complications, including diabetes mellitus (DM). Additionally, depression is highly prevalent among PWH and has been associated with increased risk for DM in the general population. However, the association of HIV and depression with incident DM has not been well established.

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Background: Older adults with HIV (OAH) experience more comorbidities and geriatric syndromes than their HIV-negative peers, perhaps because of chronic inflammation. Cell-free mitochondrial DNA (cfmtDNA) released from cells undergoing necrosis-mediated cell death potentially acts as both a mediator and marker of inflammatory dysregulation. We hypothesized that urinary cfmtDNA would be associated with frailty, body composition, and fall history in OAH.

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Background HIV infection and depression are each associated with increased ischemic stroke risk. Whether depression is a risk factor for stroke within the HIV population is unknown. Methods and Results We analyzed data on 106 333 (33 528 HIV-positive; 72 805 HIV-negative) people who were free of baseline cardiovascular disease from an observational cohort of HIV-positive people and matched uninfected veterans in care from April 1, 2003 through December 31, 2014.

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Background: Insomnia may be a risk factor for cardiovascular disease in HIV (HIV-CVD); however, mechanisms have yet to be elucidated.

Methods: We examined cross-sectional associations of insomnia symptoms with biological mechanisms of HIV-CVD (immune activation, systemic inflammation, and coagulation) among 1,542 people with HIV from the Veterans Aging Cohort Study (VACS) Biomarker Cohort. Past-month insomnia symptoms were assessed by the item, "Difficulty falling or staying asleep?," with the following response options: "I do not have this symptom" or "I have this symptom and…" "it doesn't bother me," "it bothers me a little," "it bothers me," "it bothers me a lot.

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  • The study evaluates outcomes between laparoscopic-assisted and traditional laparotomy methods for placing distal shunt catheters during ventriculoperitoneal shunt (VPS) surgeries in Medicare patients from 2004 to 2014.
  • Results indicated that laparoscopic-assisted VPS had lower odds of needing distal revision at both 6 and 12 months post-surgery compared to laparotomy, especially in patients with obesity and abdominal surgery history.
  • The findings suggest that the laparoscopic technique may help reduce complications for patients with certain risk factors, indicating its potential benefits in VPS procedures.
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  • Postmenopausal women experience increased disability and cardiovascular disease risks as they age, and while exercise can improve health, its benefits are often limited in this group.
  • This study investigates whether consuming dietary nitrate (from beetroot juice) before exercise can enhance physical mobility and cardiovascular health in postmenopausal women through a randomized trial.
  • The research will measure various health outcomes and assess the feasibility of implementing this intervention, aiming to support larger trials that might confirm the effectiveness of beetroot juice in promoting better fitness and reducing heart disease risks.
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Background: Depression is associated with an increased risk of cardiovascular disease in human immunodeficiency virus (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 antiretroviral therapy and with Patient Health Questionnaire (PHQ)-9 scores ≥10.

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  • In a study analyzing the effectiveness and safety of two HIV treatment regimens over 144 weeks, a combination of bictegravir, emtricitabine, and tenofovir alafenamide was found to be as effective as a dolutegravir-based regimen for treatment-naive patients.
  • *The studies included 1,274 participants who were randomly assigned to receive either the bictegravir regimen or various dolutegravir regimens, with the primary endpoint showing non-inferiority at week 48.
  • *By week 144, the efficacy results showed that a high percentage of participants in both treatment groups maintained low plasma HIV-1 RNA levels, indicating continued effectiveness of the bictegravir regimen.*
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Objective: We sought to determine the associations of total, cognitive/affective, and somatic depressive symptoms and antidepressant use with biomarkers of processes implicated in cardiovascular disease in HIV (HIV-CVD).

Methods: We examined data from 1546 HIV-positive and 843 HIV-negative veterans. Depressive symptoms were assessed using the Patient Health Questionnaire-9, and past-year antidepressant use was determined from Veterans Affair pharmacy records.

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