Association of T-Cell Phenotypes With Peri-Coronary Inflammation in People With and Without HIV and Without Cardiovascular Disease.

Background: Persistent immune activation is linked to elevated cardiovascular diseases in people with HIV on antiretroviral therapy. The fat attenuation index (FAI) is a measure of peri-coronary inflammation that independently predicts cardiovascular disease risk in people without HIV. Whether FAI is associated with immune activation is unknown.

Deciphering the role of endothelial granulocyte macrophage-CSF in chronic inflammation associated with HIV.

People with HIV (PWH) experience endothelial dysfunction (ED) that is aggravated by chronic inflammation and microbial translocation across a damaged gut barrier. Although this paradigm is well-described, downstream pathways that terminate in endothelial dysfunction are only partially understood. This study found increased expression of granulocyte macrophage colony stimulating factor (GM-CSF), toll-like receptor-4 (TLR4), and myeloperoxidase in the aortic endothelium of PWH compared to those without HIV.

Sirolimus reduces T cell cycling, immune checkpoint marker expression, and HIV-1 DNA in people with HIV.

Key HIV cure strategies involve reversing immune dysfunction and limiting the proliferation of infected T cells. We evaluate the safety of sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, in people with HIV (PWH) and study the impact of sirolimus on HIV-1 reservoir size and HIV-1-specific immunity in a single-arm study of 20 weeks of treatment in PWH on antiretroviral therapy (ART). Sirolimus treatment does not impact HIV-1-specific CD8 T cell responses but leads to a significant decrease in CD4 T cell-associated HIV-1 DNA levels at 20 weeks of therapy in the primary efficacy population (n = 16; 31% decline, p = 0.

Brief Report: Low-Dose Methotrexate Does Not Affect Measures of HIV-1 Persistence in Individuals With Chronically Treated HIV-1 Infection.

Background: People with HIV-1 often have chronic inflammation leading to severe non-AIDS morbidity and mortality. The AIDS Clinical Trials Group Study A5314 sought to lower inflammation with low-dose methotrexate (LDMTX). The primary study outcomes were reported previously but here we present the impact of LDMTX on multiple measures of HIV-1 persistence.

Machine learning models based on fluid immunoproteins that predict non-AIDS adverse events in people with HIV.

Despite the success of antiretroviral therapy (ART), individuals with HIV remain at risk for experiencing non-AIDS adverse events (NAEs), including cardiovascular complications and malignancy. Several surrogate immune biomarkers in blood have shown predictive value in predicting NAEs; however, composite panels generated using machine learning may provide a more accurate advancement for monitoring and discriminating NAEs. In a nested case-control study, we aimed to develop machine learning models to discriminate cases (experienced an event) and matched controls using demographic and clinical characteristics alongside 49 plasma immunoproteins measured prior to and post-ART initiation.

Erratum to: Progress Note 2024: Curing HIV; Not in My Lifetime or Just Around the Corner?

[This corrects the article DOI: 10.20411/pai.v8i2.

Systemic inflammation in pregnant women with HIV: relationship with HIV treatment regimen and preterm delivery.

Objective: HIV treatment regimen during pregnancy was associated with preterm delivery (PTD) in the PROMISE 1077 BF trial. Systemic inflammation among pregnant women with HIV could help explain differences in PTD by treatment regimen. We assessed associations between inflammation, treatment regimen, and PTD.

Cytomegalovirus Infection Facilitates the Costimulation of CD57+CD28- CD8 T Cells in HIV Infection and Atherosclerosis via the CD2-LFA-3 Axis.

CD8 T cells are emerging as important mediators in atherosclerosis and cardiovascular disease (CVD). Immune activation may play a particular role in people with HIV (PWH) who are at an increased risk of CVD, even after controlling for known CVD risk factors. Latent CMV infection is associated with increased CVD risk for both PWH and people without HIV, and human CMV-specific CD4 and CD8 T cells are enriched for an immunosenescent phenotype.

Viral and host mediators of non-suppressible HIV-1 viremia.

Non-suppressible HIV-1 viremia (NSV) is defined as persistent low-level viremia on antiretroviral therapy (ART) without evidence of ART non-adherence or significant drug resistance. Unraveling the mechanisms behind NSV would broaden our understanding of HIV-1 persistence. Here we analyzed plasma virus sequences in eight ART-treated individuals with NSV (88% male) and show that they are composed of large clones without evidence of viral evolution over time in those with longitudinal samples.

Association of Soluble Markers of Inflammation With Peri-coronary Artery Inflammation in People With and Without HIV Infection and Without Cardiovascular Disease.

Background: Inflammation is linked to elevated cardiovascular disease (CVD) risk in people with HIV (PWH) on antiretroviral therapy (ART). Fat attenuation index (FAI) is a measure of peri-coronary inflammation that independently predicts CVD risk in HIV-uninfected persons. Whether FAI is associated with soluble inflammatory markers is unknown.

Platelet and Monocyte Activation After Transcatheter Aortic Valve Replacement (POTENT-TAVR): A Mechanistic Randomized Trial of Ticagrelor Versus Clopidogrel.

Background: Inflammation and thrombosis are often linked mechanistically and are associated with adverse events after transcatheter aortic valve replacement (TAVR). High residual platelet reactivity (HRPR) is especially common when clopidogrel is used in this setting, but its relevance to immune activation is unknown. We sought to determine whether residual activity at the purinergic receptor P2Y12 (P2Y12) promotes prothrombotic immune activation in the setting of TAVR.

Viral and Host Mediators of Non-Suppressible HIV-1 Viremia.

Non-suppressible HIV-1 viremia (NSV) can occur in persons with HIV despite adherence to combination antiretroviral therapy (ART) and in the absence of significant drug resistance. Here, we show that plasma NSV sequences are comprised primarily of large clones without evidence of viral evolution over time. We defined proviruses that contribute to plasma viremia as "producer", and those that did not as "non-producer".

Effect of Immune-Modulatory Interventions on Asymptomatic Cytomegalovirus Shedding During Suppressive Antiretroviral Therapy.

Long-term consequences of human immunodeficiency virus (HIV) are likely the result of persistent inflammation and immune dysfunction of which cytomegalovirus (CMV) is a known contributor. We leveraged 2 AIDS Clinical Trials Group clinical trials exploring the effects of immune modulators (ruxolitinib and sirolimus) on inflammation in people with HIV on antiretroviral therapy to determine whether these interventions affected CMV shedding at various mucosal sites. Analyzing 635 mucosal samples collected, we found no significant difference in CMV levels across study arms or time points.

HIV post-treatment controllers have distinct immunological and virological features.

HIV post-treatment controllers (PTCs) are rare individuals who maintain low levels of viremia after stopping antiretroviral therapy (ART). Understanding the mechanisms of HIV post-treatment control will inform development of strategies aiming at achieving HIV functional cure. In this study, we evaluated 22 PTCs from 8 AIDS Clinical Trials Group (ACTG) analytical treatment interruption (ATI) studies who maintained viral loads ≤400 copies/mL for ≥24 wk.

Association of Cytomegalovirus Serostatus With Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Responsiveness in Nursing Home Residents and Healthcare Workers.

Background: Latent cytomegalovirus (CMV) infection is immunomodulatory and could affect mRNA vaccine responsiveness. We sought to determine the association of CMV serostatus and prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with antibody (Ab) titers after primary and booster BNT162b2 mRNA vaccinations in healthcare workers (HCWs) and nursing home (NH) residents.

Methods: Nursing home residents ( = 143) and HCWs ( = 107) were vaccinated and serological responses monitored by serum neutralization activity against Wuhan and Omicron (BA.

Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy.

HIV-1 establishes a life-long reservoir of virally infected cells which cannot be eliminated by antiretroviral therapy (ART). Here, we demonstrate a markedly altered viral reservoir profile of long-term ART-treated individuals, characterized by large clones of intact proviruses preferentially integrated in heterochromatin locations, most prominently in centromeric satellite/micro-satellite DNA. Longitudinal evaluations suggested that this specific reservoir configuration results from selection processes that promote the persistence of intact proviruses in repressive chromatin positions, while proviruses in permissive chromosomal locations are more likely to be eliminated.

Limited impact of fingolimod treatment during the initial weeks of ART in SIV-infected rhesus macaques.

Antiretroviral therapy (ART) is not curative due to the persistence of a reservoir of HIV-infected cells, particularly in tissues such as lymph nodes, with the potential to cause viral rebound after treatment cessation. In this study, fingolimod (FTY720), a lysophospholipid sphingosine-1-phosphate receptor modulator is administered to SIV-infected rhesus macaques at initiation of ART to block the egress from lymphoid tissues of natural killer and T-cells, thereby promoting proximity between cytolytic cells and infected CD4+ T-cells. When compared with the ART-only controls, FTY720 treatment during the initial weeks of ART induces a profound lymphopenia and increases frequencies of CD8+ T-cells expressing perforin in lymph nodes, but not their killing capacity; FTY720 also increases frequencies of cytolytic NK cells in lymph nodes.