Inflammatory and Immune Mechanisms for Atherosclerotic Cardiovascular Disease in HIV.

Atherosclerotic vascular disease disproportionately affects persons living with HIV (PLWH) compared to those without. The reasons for the excess risk include dysregulated immune response and inflammation related to HIV infection itself, comorbid conditions, and co-infections. Here, we review an updated understanding of immune and inflammatory pathways underlying atherosclerosis in PLWH, including effects of viral products, soluble mediators and chemokines, innate and adaptive immune cells, and important co-infections.

Case Series of People With HIV on the Long-Acting Combination of Lenacapavir and Cabotegravir: Call for a Trial.

Background: Injectable cabotegravir (CAB)/rilpivirine (RPV) is the only combination long-acting (LA) antiretroviral regimen approved for HIV. RPV may not be effective among individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, which has >10% prevalence in many countries. Lenacapavir (LEN) is an LA capsid inhibitor given every 6 months, but has not been studied in combination with other LA agents.

Nurse-Led Strategy to Improve Blood Pressure and Cholesterol Level Among People With HIV: A Randomized Clinical Trial.

Importance: Despite higher atherosclerotic cardiovascular disease (ASCVD) risk, people with HIV (PWH) experience unique barriers to ASCVD prevention, such as changing models of HIV primary care.

Objective: To test whether a multicomponent nurse-led strategy would improve systolic blood pressure (SBP) and non-high-density lipoprotein (HDL) cholesterol level in a diverse population of PWH receiving antiretroviral therapy (ART).

Design, Setting, And Participants: This randomized clinical trial enrolled PWH at 3 academic HIV clinics in the US from September 2019 to January 2022 and conducted follow-up for 12 months until January 2023.

New-onset autoimmune disease after COVID-19.

Introduction: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may trigger autoimmune disease (AD) through initial innate immune activation with subsequent aberrations in adaptive immune cells leading to AD. While there are multiple reports of incident AD diagnosed after COVID-19, the risk in the context of key circulating strains is unknown.

Methods: TriNetX, a global, federated, health research network providing access to electronic medical records across 74 healthcare organizations, was utilized to define an adult cohort between January 1, 2020, and March 3, 2023.

Perceived Risks and Benefits and Frequency of Cannabis Use Among People with HIV in Different Legal Environments.

We sought to describe the prevalence of and motivation for cannabis use and whether legalization of cannabis impacts the frequency and perceived risks and benefits of use in people living with HIV (PWH). The study was based on two HIV clinics located in Cleveland, Ohio, and Aurora, Colorado. Participants responded to a 45-question survey, and responses were summarized in aggregate and stratified by the frequency of cannabis use and site.

The impact of COVID-19 on cardiovascular health behaviors in people living with HIV.

The COVID-19 pandemic's impact on cardiovascular health behaviors including diet, physical activity, medication adherence, and self-care among people living with HIV (PLWH) remains unknown. Using qualitative analyses, we examined the impact of the COVID-19 pandemic on cardiovascular health behaviors among PLWH. Twenty-four PLWH were enrolled in this multisite study from September to October 2020.

Heroin Use Is Associated With Vascular Inflammation in Human Immunodeficiency Virus.

Background: Heroin use may work synergistically with human immunodeficiency virus (HIV) infection to cause greater immune dysregulation than either factor alone. Unraveling how this affects end-organ disease is key as it may play a role in the excess mortality seen in people with HIV (PWH) who use heroin despite access to care and antiretroviral therapy.

Methods: This is a prospectively enrolled, cross-sectional study of adults with and without HIV who use and do not use heroin using (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to compare tissue-specific inflammation including aortic (target-to-background ratio [TBR]), splenic, and bone marrow (standardized uptake value [SUV]).

Impact of Heroin and HIV on Gut Integrity and Immune Activation.

Background: Altered gut integrity is central to HIV-related immune activation. Opioids may promote similar changes in gut permeability and/or increase systemic inflammation, potentially augmenting processes already occurring in people with HIV (PWH).

Setting: Urban hospital systems in Cleveland, Ohio, and surrounding communities.

Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study.

Background: With the highest rates of HIV/AIDS in the United States, Black Americans are still underrepresented in HIV medical research.

Setting: BRAAVE (NCT03631732) is a randomized, phase 3b, multicenter, open-label US study.

Methods: Adults identifying as Black or African American and virologically suppressed on 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus third agent were randomized (2:1) to switch to open-label bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) once daily or stay on baseline regimen (SBR) for 24 weeks, after which SBR had delayed switch to B/F/TAF.

Understanding constraints on integrated care for people with HIV and multimorbid cardiovascular conditions: an application of the Theoretical Domains Framework.

Background: People with HIV (PWH) experience increased cardiovascular disease (CVD) risk. Many PWH in the USA receive their primary medical care from infectious disease specialists in HIV clinics. HIV care teams may not be fully prepared to provide evidence-based CVD care.

Plasma Citrate and Succinate Are Associated With Neurocognitive Impairment in Older People With HIV.

Background: Neurocognitive impairment (NCI) is associated with monocyte activation in people with HIV (PWH). Activated monocytes increase glycolysis, reduce oxidative phosphorylation, and accumulate citrate and succinate, tricarboxylic acid (TCA) cycle metabolites that promote inflammation-this metabolic shift may contribute to NCI and slowed gait speed in PWH.

Methods: Plasma citrate and succinate were assayed by liquid chromatography-mass spectrometry from 957 participants upon entry to a multicenter, prospective cohort of older PWH.

The influence of healthcare financing on cardiovascular disease prevention in people living with HIV.

Background: People living with HIV are diagnosed with age-related chronic health conditions, including cardiovascular disease, at higher than expected rates. Medical management of these chronic health conditions frequently occur in HIV specialty clinics by providers trained in general internal medicine, family medicine, or infectious disease. In recent years, changes in the healthcare financing for people living with HIV in the U.

Use of a human-centered design approach to adapt a nurse-led cardiovascular disease prevention intervention in HIV clinics.

Stakeholder-informed strategies addressing cardiovascular disease (CVD) burden among people living with HIV (PWH) are needed within healthcare settings. This study provides an assessment of how human-centered design (HCD) guided the adaptation of a nurse-led intervention to reduce CVD risk among PWH. Using a HCD approach, research staff guided two multidisciplinary "design teams" in Ohio and North Carolina, with each having five HCD meetings.

The Opioid Epidemic: Impact on Inflammation and Cardiovascular Disease Risk in HIV.

Purpose Of Review: People infected with HIV through injection drug use are more likely to experience progression to AIDS, death due to AIDS, and all-cause mortality even when controlling for access to care and antiretroviral therapy. While high-risk behavior and concurrent infections most certainly are contributors, chronic immune activation, downstream metabolic comorbidities may play an important role.

Recent Findings: Altered intestinal integrity plays a major role in HIV-related immune activation and microbial translocation markers are heightened in active heroin users.

Rationale and design of a nurse-led intervention to extend the HIV treatment cascade for cardiovascular disease prevention trial (EXTRA-CVD).

Persons living with human immunodeficiency virus (PLHIV) are at increased risk of atherosclerotic cardiovascular disease (ASCVD). In spite of this, uptake of evidence-based clinical interventions for ASCVD risk reduction in the HIV clinic setting is sub-optimal. METHODS: EXTRA-CVD is a 12-month randomized clinical effectiveness trial that will assess the efficacy of a multi-component nurse-led intervention in reducing ASCVD risk among PLHIV.

Lower Pretreatment Gut Integrity Is Independently Associated With Fat Gain on Antiretroviral Therapy.

Background: Fat accumulation and insulin resistance remain a threat to the success of antiretroviral therapy (ART). The role of gut dysfunction in metabolic complications associated with ART initiation is unclear.

Methods: Human immunodeficiency virus (HIV)-infected ART-naive participants were randomized to tenofovir disoproxil fumarate/emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir (RAL).

Statin Therapy Does Not Reduce Liver Fat Scores in Patients Receiving Antiretroviral Therapy for HIV Infection.

Background & Aims: Therapies are needed to limit progression of fatty liver diseases in patients with human immunodeficiency virus (HIV) infection. We analyzed data from a prospective study of the effects of rosuvastatin (a statin) on hepatic steatosis in HIV-positive adults.

Methods: We performed a secondary analysis of data from a double-blind trial of adult patients with HIV infection (78% male; 68% African American; mean age, 46 y; body mass index, 29 kg/m; HIV1 RNA < 1000 copies/mL; low-density lipoprotein cholesterol, <130 mg/dL) receiving antiretroviral therapy.

The effects of HIV and smoking on aortic and splenic inflammation.

Objective: To determine the association of smoking and HIV status with tissue-specific inflammation measured by flurodeoxyglucose positron emission tomography (PET).

Design: A cross-sectional study.

Methods: We prospectively enrolled 55 HIV study participants on stable antiretroviral therapy and 19 age-matched HIV-uninfected controls without known cardiovascular disease.

Short Communication: The Effect of Rosuvastatin on Vascular Disease Differs by Smoking Status in Treated HIV Infection.

Smoking is an important contributor to cardiovascular disease risk and is highly prevalent in the HIV population. In the Stopping Atherosclerosis and Treating Unhealthy Bone with Rosuvastatin in HIV trial (SATURN-HIV), a 96-week, randomized placebo-controlled study testing the effect of rosuvastatin on subclinical vascular disease and immune activation in HIV-infected adults, rosuvastatin improved immune activation and arrested common carotid artery intima media thickness (CCA IMT) progression. In this exploratory analysis, ANOVA was used to test for effect modification by smoking.

Inflammation, Immune Activation, and Antiretroviral Therapy in HIV.

Purpose Of Review: This review focuses on the differential effects of contemporary antiretrovirals on systemic inflammation as heightened immune activation is linked to important co-morbidities and mortality with HIV infection.

Recent Findings: Antiretroviral therapy (ART) reduces dramatically systemic inflammation and immune activation, but not to levels synchronous with HIV-uninfected populations. In one ART initiation trial, integrase inhibitors appear to reduce inflammation to a greater degree than non-nucleoside reverse transcriptase inhibitors (NNRTIs); however, it is not clear that there are beneficial effects on inflammation resulting from treatment with integrase inhibitors compared to PIs, between PIs and NNRTIs, between specific nucleoside reverse transcriptase inhibitors, or with maraviroc in ART-naïve patients.

Baseline Vitamin D Deficiency Decreases the Effectiveness of Statins in HIV-Infected Adults on Antiretroviral Therapy.

Objective: Vitamin D deficiency is common in HIV. Statins may increase vitamin D, and it is unknown whether vitamin D modifies the effect of statins on cardiovascular disease.

Design: SATURN-HIV was a 96-week, randomized, placebo-controlled trial designed to evaluate the effect of rosuvastatin on immune activation and subclinical vascular disease in HIV-infected adults on antiretroviral therapy.

Incidental findings on chest computed tomography are common and linked to inflammation in HIV-infected adults.

Background: Chest imaging is performed for a variety of reasons in HIV-infected adults. There are limited data on the prevalence of incidental findings, progression of these findings over time and the relationship with inflammation in antiretroviral therapy (ART)-treated HIV-infected adults.

Methods: This study utilized data from a randomized clinical trial of rosuvastatin in HIV-infected adults on ART.