Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study.

Background: Semaglutide, a GLP-1 receptor agonist, is highly effective for decreasing weight. Concomitant loss of muscle mass often accompanies weight loss and may have consequences on muscle function.

Methods: This is a secondary analysis from the SLIM LIVER (ACTG A5371) study, a single-arm study of semaglutide in people with HIV (PWH) with metabolic dysfunction-associated steatotic liver disorder (MASLD).

Coronary Artery Plaque Composition and Severity Relate to the Inflammasome in People With Treated Human Immunodeficiency Virus.

Background: Inflammasome activation is increased in people with human immunodeficiency virus (PWH), but its relationship with coronary plaque is poorly understood in this setting.

Methods: In a large human immunodeficiency virus cardiovascular prevention cohort, relationships between caspase-1, interleukin (IL)-1β, and IL-18 and coronary plaque indices were assessed by multivariate logistic regression.

Results: Higher IL-18 and IL-1β were associated with Leaman score, an integrative measure of plaque burden and composition.

Pro-inflammatory and pro-resolving lipid mediators of inflammation in HIV: effect of aspirin intervention.

Background: Persons with HIV (PWH) have an increased risk of cardiovascular disease (CVD) compared to HIV-seronegative individuals (SN). Inflammation contributes to this risk but the role of lipid mediators, with central roles in inflammation, in HIV infection remain to be established; further aspirin reduces CVD risk in the general population through production of some of these anti-inflammatory lipid mediators, but they have not been studied in PWH.

Methods: We evaluated the relationship between plasma lipid mediators (i.

A Randomized, Placebo-Controlled Trial Assessing the Effect of VISBIOME ES Probiotic in People With HIV on Antiretroviral Therapy.

Background: A5350, a phase II, randomized, double-blind study, evaluated the safety and tolerability of the probiotic Visbiome Extra Strength (ES) over 24 weeks and measured effects on inflammation and intestinal barrier function.

Methods: The primary outcome was change in soluble CD14 (sCD14) levels; secondary outcomes included safety and tolerability, markers of inflammation and cellular activation, and microbiome. In a substudy, gut permeability was assessed by paired colonic biopsies measuring the area of lamina propria occupied by CD4+ cells, interleukin (IL)-17+ cells, and myeloperoxidase (MPO).

Short Communication: Impact of Fat Changes on the Effect of Protease Inhibitors on Lumbar Spine Bone Mineral Density Changes with Antiretroviral Therapy Initiation.

People living with HIV (PLWH) who are on protease inhibitor (PI)-containing regimens have been shown to have increases in visceral adipose tissue (VAT) and a greater decrease in spine bone mineral density (BMD) than those receiving non-PI regimens when initiating treatment. This increase in VAT has been hypothesized to falsely lower spine BMD measured via dual-energy X-ray absorptiometry, suggesting that the PI-associated BMD loss is an artefact rather than real. To test this, data collected from two completed 96-week clinical trials, AIDS Clinical Trial Group studies A5224s and A5260s, of antiretroviral therapy-naive PLWH initiating treatment with PI and non-PI-containing regimens were analyzed comparing VAT accumulation and spine BMD loss.

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

Objectives: 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.

Telmisartan Therapy Does Not Improve Lymph Node or Adipose Tissue Fibrosis More Than Continued Antiretroviral Therapy Alone.

Background: Fibrosis in lymph nodes may limit CD4+ T-cell recovery, and lymph node and adipose tissue fibrosis may contribute to inflammation and comorbidities despite antiretroviral therapy (ART). We hypothesized that the angiotensin receptor blocker and peroxisome proliferator-activated receptor γ agonist telmisartan would decrease lymph node or adipose tissue fibrosis in treated human immunodeficiency virus type 1 (HIV) infection.

Methods: In this 48-week, randomized, controlled trial, adults continued HIV-suppressive ART and received telmisartan or no drug.

The Impact of Statin and Angiotensin-Converting Enzyme Inhibitor/Angiotensin Receptor Blocker Therapy on Cognitive Function in Adults With Human Immunodeficiency Virus Infection.

Background: Although statins, angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) are generally well tolerated, the impact of these therapies individually or in combination on the change in neurocognitive function in persons with human immunodeficiency virus infection is unknown.

Methods: The study included participants in the AIDS Clinical Trials Group Longitudinal Linked Randomized Trials cohort participants not receiving a statin or ACEI/ARB within 30 days of first neurologic assessment (baseline), with assessments by NPZ-3 (z score of averaged Trailmaking A and B tests and digit symbol test [DST]) from ≥2 measurements. Marginal structural models estimated the causal effect of statin or ACEI/ARB initiation on neurocognitive function; initial constant slope was assumed during the first year of treatment and a second constant slope thereafter.

A Randomized Placebo Controlled Trial of Aspirin Effects on Immune Activation in Chronically Human Immunodeficiency Virus-Infected Adults on Virologically Suppressive Antiretroviral Therapy.

Background: Immune activation persists despite suppressive antiretroviral therapy (ART) in human immunodeficiency virus (HIV) infection and predicts non-Acquired Immune Deficiency Syndrome (AIDS) comorbidities including cardiovascular disease. Activated platelets play a key role in atherothrombosis and inflammation, and platelets are hyperactivated in chronic HIV infection. Aspirin is a potent inhibitor of platelet activation through the cyclooxygenase-1 (COX-1) pathway.

Bone mineral density reductions after tenofovir disoproxil fumarate initiation and changes in phosphaturia: a secondary analysis of ACTG A5224s.

Background: It is unknown if the greater reductions in bone mineral density (BMD) associated with initiation of tenofovir disoproxil fumarate compared with abacavir in previously untreated HIV-infected participants in the ACTG A5224s clinical trial were associated with potentially worsening tenofovir-related phosphaturia.

Methods: We correlated changes in BMD at the hip and spine with changes in phosphaturia [transtubular reabsorption of phosphorus (TRP) and tubular maximum phosphate reabsorption per glomerular filtration rate (TmP/GFR)] from entry through week 96 in those initiating tenofovir ( n  =   134) versus abacavir ( n  =   135) with efavirenz or atazanavir/ritonavir in A5224s. We also correlated changes in BMD with tenofovir AUC measured between weeks 4 and 24.

Long-term body composition changes in antiretroviral-treated HIV-infected individuals.

Objective: Body composition impacts physical function and mortality. We compared long-term body composition changes after antiretroviral therapy (ART) initiation in HIV-infected individuals to that in HIV-uninfected controls.

Design: Prospective observational study.

Long-term Bone Mineral Density Changes in Antiretroviral-Treated HIV-Infected Individuals.

We compared adjusted bone mineral density (BMD) changes between human immunodeficiency virus (HIV)-infected individuals during the first approximately 7.5 years after antiretroviral therapy (ART) initiation and HIV-uninfected controls. HIV-infected individuals (n = 97) had significantly greater adjusted BMD decline than controls (n = 614) during the first 96 weeks of ART.

Reductions in Plasma Cystatin C After Initiation of Antiretroviral Therapy Are Associated With Reductions in Inflammation: ACTG A5224s.

Background: Among patients with HIV infection, changes in the kidney filtration marker cystatin C after initiation of antiretroviral therapy (ART) may be related to changes in body composition or biomarkers of inflammation.

Methods: ACTG A5224s was a substudy of A5202, which randomly assigned ART-naive HIV-infected subjects to blinded abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or ritonavir-boosted atazanavir. This analysis explored changes in cystatin C from 0 to 96 weeks.

Differential skeletal impact of tenofovir disoproxil fumarate in young versus old HIV-infected adults.

Background: Lower peak bone mass in early adulthood predicts subsequent fragility fractures. Antiretroviral toxicity could contribute to young HIV-infected individuals not achieving adequate peak bone mass.

Objective: To determine if tenofovir disoproxil fumarate's (TDF) effect on bone mineral density (BMD) differs by age.

Cystatin C-based renal function changes after antiretroviral initiation: a substudy of a randomized trial.

Background: The effects of antiretrovirals on cystatin C-based renal function estimates are unknown.

Methods: We analyzed changes in renal function using creatinine and cystatin C-based estimating equations in 269 patients in A5224s, a substudy of study A5202, in which treatment-naive patients were randomized to abacavir/lamivudine or tenofovir/emtricitabine with open-label atazanavir/ritonavir or efavirenz.

Results: Changes in renal function significantly improved (or declined less) with abacavir/lamivudine treatment compared with tenofovir/emtricitabine using the Cockcroft-Gault formula (P = .

Changes in proteinuria and albuminuria with initiation of antiretroviral therapy: data from a randomized trial comparing tenofovir disoproxil fumarate/emtricitabine versus abacavir/lamivudine.

Background: Antiretroviral therapy (ART) is associated with improved kidney function; however, the nucleotide reverse transcriptase inhibitor (NRTI) tenofovir disoproxil fumarate (TDF) has been associated with decreased kidney function and proteinuria.

Methods: We examined changes in urine protein:creatinine (UPCR) and urine albumin:creatinine (UACR) ratios in 245 ART-naive participants in A5202 randomized in a substudy to blinded NRTI (abacavir/lamivudine, ABC/3TC, n = 124 or TDF/emtricitabine, TDF/FTC, n = 121) with open-label protease inhibitor (PI) atazanavir/ritonavir or nonnucleoside reverse transcriptase inhibitor (NNRTI) efavirenz.

Results: At baseline, 18% of participants had clinically significant proteinuria (UPCR ≥200 mg/g), and 11% had clinically significant albuminuria (UACR ≥30 mg/g).

Impact of randomized antiretroviral therapy initiation on glucose metabolism.

Objective: Prior studies have found that early HIV protease inhibitors contribute to glucose dysregulation. Few randomized trials have evaluated glucose indices in antiretroviral-naive individuals on newer antiretroviral therapy (ART).

Methods: A5224s was a substudy of A5202, a prospective trial of 1857 ART-naive participants randomized to blinded abacavir-lamivudine (ABC/3TC) or tenofovir DF-emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir-ritonavir (ATV/r).

Pilot study of pioglitazone before HCV retreatment in HIV/HCV genotype 1-infected subjects with insulin resistance and previous nonresponse to peginterferon and ribavirin therapy: A5239.

: Insulin resistance is associated with nonresponse to hepatitis C virus (HCV) treatment. In this multicenter, single-arm pilot study, adult, HIV/HCV genotype 1-coinfected previous nonresponders to peginterferon/ribavirin (PegIFN/RBV) with homeostatic model assessment of insulin resistance >2.5 were treated with pioglitazone (PIO) for 24 weeks followed by PegIFN/RBV/PIO.

Weight and lean body mass change with antiretroviral initiation and impact on bone mineral density.

Objective: To compare the effect that initiating different antiretroviral therapy (ART) regimens has on weight, BMI, and lean body mass (LBM) and explore how changes in body composition are associated with bone mineral density (BMD).

Methods: A5224s was a sub-study of A5202, a prospective trial of 1857 ART-naive participants randomized to blinded abacavir-lamivudine (ABC/3TC) or tenofovir DF-emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir-ritonavir (ATV/r). All participants underwent dual-energy absorptiometry (DXA) and abdominal computed tomography for body composition.

HIV transmission and 24-month survival in a randomized trial of HAART to prevent MTCT during pregnancy and breastfeeding in Botswana.

Objectives: HAART for prevention of mother-to-child HIV transmission (MTCT) may impact long-term survival of women and children.

Design: Randomized clinical trial.

Methods: HIV-infected pregnant women with CD4+ cell count at least 200 cells/µl were randomly assigned to abacavir, zidovudine, lamivudine (arm A) or lopinavir–ritonavir, zidovudine–lamivudine (arm B) from week 26 to 34 gestation through planned weaning by 6 months postpartum.

Associations of inflammatory markers with AIDS and non-AIDS clinical events after initiation of antiretroviral therapy: AIDS clinical trials group A5224s, a substudy of ACTG A5202.

Background: The association of inflammatory biomarkers with clinical events after antiretroviral therapy initiation is unclear.

Methods: A5202 randomized 1857 treatment-naive subjects to abacavir/lamivudine or tenofovir-DF/emtricitabine with efavirenz or atazanavir/ritonavir. Substudy A5224s measured inflammatory biomarkers on subjects with available plasma from baseline and week 24 or 96.

Low baseline CD4+ count is associated with greater bone mineral density loss after antiretroviral therapy initiation.

Background: Bone mineral density (BMD) decreases 2%-6% in the 2 years after antiretroviral therapy (ART) initiation. Pre-ART immune deficiency and early immune recovery may contribute to this loss.

Methods: We pooled data from 3 studies of ART initiation in treatment-naive patients in which serial whole-body dual-energy X-ray absorptiometry scans were performed.

Inflammation markers after randomization to abacavir/lamivudine or tenofovir/emtricitabine with efavirenz or atazanavir/ritonavir.

Background: The effect of specific antiretrovirals on inflammation is unclear.

Methods: A5224s was a substudy of A5202, which randomized HIV-infected treatment-naïve patients to blinded abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) with open-label efavirenz (EFV) or atazanavir/ritonavir (ATV/r) in a factorial design. Our analysis compared changes in inflammation markers from baseline to week 24 between ABC/3TC and TDF/FTC.

Increased risk of preterm delivery among HIV-infected women randomized to protease versus nucleoside reverse transcriptase inhibitor-based HAART during pregnancy.

Background: Protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) use in pregnancy has been associated with preterm deliveries in some observational studies.

Methods: HIV-infected, HAART-naive pregnant women with CD4+ counts ≥200 cells/mm(3) were randomized between 26 and 34 weeks gestation to lopinavir/ritonavir/zidovudine/lamivudine (PI group) or abacavir/zidovudine/lamivudine (NRTI group) in a clinical trial to prevent mother-to-child HIV transmission. Risk factors for preterm delivery (<37 weeks) and differences by randomization arm were evaluated for live infants by logistic regression.