Effects of statins beyond lipid-lowering agents in ART-treated HIV infection.

Antiretroviral therapies (ART) have reduced human immunodeficiency virus (HIV) infection-associated morbidity and mortality improving the life of people with HIV (PWH). However, ART lead to residual HIV production, which in conjunction with microbial translocation and immune dysfunction contributes to chronic inflammation and immune activation. PWH on ART remain at an increased risk for cardiovascular diseases (CVDs) including myocardial infarction and stroke; which in part is explained by chronic inflammation and immune activation.

Perceptions of health care workers on maternal and child health services in Pakistan during COVID-19: A cross-sectional study.

Background: Maternal and child healthcare service delivery in vulnerable and fragile health systems has suffered a tremendous impact owing to the shift in focus to curtail the COVID-19 pandemic. We aimed to evaluate the impact of the COVID-19 pandemic on maternal and child healthcare services to inform policy advice for a more resilient maternal and child healthcare service delivery in Pakistan.

Methods: A descriptive cross-sectional study was conducted.

Barriers experienced by community midwives to provide basic emergency obstetric and newborn care in rural Pakistan.

Background: Considering the high maternal mortality rate, the government of Pakistan has deployed Community Midwives (CMWs) in rural areas of Pakistan. This relatively new cadre of community-based skilled birth attendants has previously reported to experience several challenges in providing maternal and child healthcare. However, what barriers they experience in providing basic emergency obstetric and newborn care needs to be further studied.

LILAC pilot study: Effects of metformin on mTOR activation and HIV reservoir persistence during antiretroviral therapy.

Background: Chronic inflammation and residual HIV transcription persist in people living with HIV (PLWH) receiving antiretroviral therapy (ART), thus increasing the risk of developing non-AIDS co-morbidities. The mechanistic target of rapamycin (mTOR) is a key regulator of cellular metabolism and HIV transcription, and therefore represents an interesting novel therapeutic target.

Methods: The LILAC pilot clinical trial, performed on non-diabetic ART-treated PLWH with CD4/CD8 T-cell ratios <0.

Cytomegalovirus Seropositivity Is Associated With Increased Microbial Translocation in People Living With Human Immunodeficiency Virus and Uninfected Controls.

Background: Cytomegalovirus (CMV) seropositivity and anti-CMV immunoglobulin G (IgG) levels are associated with adverse health outcomes in elderly populations. Among people living with human immunodeficiency virus (PLWH), CMV seropositivity has been associated with persistent CD8 T-cell elevation and increased risk of developing non-AIDS comorbidities despite long-term antiretroviral therapy (ART). Herein, we investigated whether CMV seropositivity and elevation of anti-CMV IgG levels were associated with increased epithelial gut damage, microbial translocation, and systemic inflammation.

HIV Diversity and Genetic Compartmentalization in Blood and Testes during Suppressive Antiretroviral Therapy.

HIV's ability to persist during suppressive antiretroviral therapy is the main barrier to cure. Immune-privileged tissues, such as the testes, may constitute distinctive sites of HIV persistence, but this has been challenging to study in humans. We analyzed the proviral burden and genetics in the blood and testes of 10 individuals on suppressive therapy who underwent elective gender-affirming surgery.

The anti-inflammatory IL-37/SIGIRR axis is functionally compromised in HIV infection.

Background: IL-37 is a member of the IL-1 family with potent anti-inflammatory effects. Little is known about regulation of the cytokine and of its signaling co-receptor SIGIRR in HIV infection.

Objectives: Our main objective was to investigate how production of the cytokine and expression of SIGIRR on immune cells is regulated in HIV infection.

Effect of metformin on the size of the HIV reservoir in non-diabetic ART-treated individuals: single-arm non-randomised Lilac pilot study protocol.

Introduction: People living with HIV (PLWH) on antiretroviral therapy (ART) do not progress to AIDS. However, they still suffer from an increased risk of inflammation-associated complications. HIV persists in long-lived CD4+ T cells, which form the major viral reservoir.

Circulating LPS and (1→3)-β-D-Glucan: A Folie à Deux Contributing to HIV-Associated Immune Activation.

Immune activation is the driving force behind the occurrence of AIDS and non-AIDS events, and is only partially reduced by antiretroviral therapy (ART). Soon after HIV infection, intestinal CD4+ T cells are depleted leading to epithelial gut damage and subsequent translocation of microbes and/or their products into systemic circulation. Bacteria and fungi are the two most abundant populations of the gut microbiome.

Circulating (1→3)-β-D-glucan Is Associated With Immune Activation During Human Immunodeficiency Virus Infection.

Background: Microbial translocation from the gut to systemic circulation contributes to immune activation during human immunodeficiency virus (HIV) infection and is usually assessed by measuring plasma levels of bacterial lipopolysaccharide (LPS). Fungal colonization in the gut increases during HIV-infection and people living with HIV (PLWH) have increased plasma levels of fungal polysaccharide (1→3)-β-D-Glucan (βDG). We assessed the contribution of circulating DG to systemic immune activation in PLWH.

Multiple remissions of extracavitary primary effusion lymphoma treated with a single cycle of liposomal doxorubicin in a patient infected with HIV.

Primary effusion lymphoma (pel) is a rare human herpesvirus 8 (hhv8)-related large B cell lymphoma with plasmablastic, immunoblastic, or anaplastic features that often carries a poor prognosis. This lymphoma occurs mainly in patients with hiv infection, most often with Epstein-Barr virus (ebv) co-infection, and usually presents as body cavity effusions or, less commonly, as extracavitary lesions without effusion (ec-pel). Chemotherapeutic treatment options are limited and require concurrent antiretroviral therapy (art).

Serum cryptococcal antigen titre as a diagnostic tool and a predictor of mortality in HIV-infected patients with cryptococcal meningitis.

Objectives: The aim was to determine the effectiveness of the serum cryptococcal antigen (CrAg) test in the diagnosis of concurrent cryptococcal meningitis (CM) and as a predictor of mortality in HIV-infected patients.

Methods: In this retrospective study, all HIV-infected patients admitted to Shanghai Public Health Clinical Center from 1 January 2014 to 31 August 2016 were screened for serum CrAg using the latex agglutination test. Serum CrAg-positive patients underwent lumbar puncture to confirm CM prior to the initiation of appropriate antifungal therapy and were followed up for at least 6 months.

Plasma Indoleamine 2,3-Dioxygenase Activity Is Associated With the Size of the Human Immunodeficiency Virus Reservoir in Patients Receiving Antiretroviral Therapy.

Background: Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that metabolizes tryptophan to immunosuppressive kynurenines. We investigated whether IDO activity is associated with the size of HIV reservoir.

Methods: Total human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells (PBMCs) from 127 HIV-infected patients receiving antiretroviral therapy (ART) was quantified.

The Control of HIV After Antiretroviral Medication Pause (CHAMP) Study: Posttreatment Controllers Identified From 14 Clinical Studies.

Background: HIV posttreatment controllers are rare individuals who start antiretroviral therapy (ART), but maintain HIV suppression after treatment interruption. The frequency of posttreatment control and posttreatment interruption viral dynamics have not been well characterized.

Methods: Posttreatment controllers were identified from 14 studies and defined as individuals who underwent treatment interruption with viral loads ≤400 copies/mL at two-thirds or more of time points for ≥24 weeks.

Use of (1→3)-β-d-glucan for diagnosis and management of invasive mycoses in HIV-infected patients.

People living with HIV (PLHIV) are highly vulnerable to invasive fungal infections (IFIs) due to their immune dysfunction. Diagnosis and treatment of IFIs remain challenging due to the requirement of deep tissue sampling to visualise and culture fungi before initiating treatment. Such techniques are less practical in resource-limited settings due to their cost and requirement of relatively invasive procedures.

HIV induces production of IL-18 from intestinal epithelial cells that increases intestinal permeability and microbial translocation.

Interleukin-18 (IL-18) is a pleiotropic cytokine of the IL-1 family with multiple context dependent functions. We and others have shown that HIV infection is accompanied by increased circulating levels of IL-18 along with decreased levels of its antagonist, Interleukin-18 Binding Protein (IL-18BP). The infection is also accompanied by intestinal inflammation and decreased intestinal integrity as measured by intestinal permeability, regeneration and repair.

Nasal Nitric Oxide Levels in HIV Infection: A Cross-Sectional Study.

Introduction: Low levels of nasal NO have been associated with increased propensity to rhinosinusitis and respiratory tract infections. Our objective was to describe nasal NO levels in HIV-infected individuals versus healthy controls and determine possible risk factors for reduced nasal NO levels.

Materials And Methods: HIV-infected individuals and healthy controls were recruited.

Socio-economic status and time trends associated with early ART initiation following primary HIV infection in Montreal, Canada: 1996 to 2015.

Introduction: Guidelines regarding antiretroviral therapy (ART) initiation in HIV infection have varied over time, with the 2015 World Health Organization recommendation suggesting ART initiation at the time of diagnosis regardless of CD4 T-cell counts. Herein, we investigated the influence of socio-demographic and clinical factors in addition to time trends on early ART initiation among participants of the Montreal Primary HIV Infection Study.

Methods: The Montreal Primary HIV Infection Study is a prospective cohort established in three community medical centres (CMCs) and two university medical centres (UMCs).

Characterization of myeloid cell populations in human testes collected after sex reassignment surgery.

The testis has been described in animal models as a site of immune privilege, which protects spermatids against tissue damage during inflammation. Myeloid cells, including macrophages and dendritic cells (DC), are defined as key players in the testicular immune privilege in animal models. However, their distribution and frequency in human testis remain poorly described.

The evaluation of risk-benefit ratio for gut tissue sampling in HIV cure research.

Introduction: Antiretroviral therapy (ART) does not cure HIV infection due to the persistence of HIV reservoirs in long-lived memory CD4 T cells present in the blood, lymph nodes, intestinal tract, and other tissues. Interest grows in obtaining gut-tissue samples for HIV persistence studies, which poses an ethical challenge to provide study volunteers with adequate information on risks and benefits. Herein we assess the risks and benefits of undergoing gut biopsy procedures for HIV pathogenesis and reservoir studies.

Potential contribution of gut microbiota and systemic inflammation on HIV vaccine effectiveness and vaccine design.

The quest for an effective HIV-1 vaccine began as soon as the virus causing AIDS was identified. After several disappointing attempts, results of the Phase-III RV144 trial in Thailand were a beacon of hope for the field demonstrating correlation between protection and immunological markers. In order to optimize vaccine response, we underline results from yellow fever and hepatitis B vaccines, where protective responses were predicted by the pre-vaccination level of immune activation in healthy individuals.