MAVMET trial: maraviroc and/or metformin for metabolic dysfunction associated fatty liver disease in adults with suppressed HIV.

Objective: Metabolic dysfunction associated fatty liver disease (MAFLD) is over-represented in people with HIV (PWH). Maraviroc (MVC) and/or metformin (MET) may reduce MAFLD by influencing inflammatory pathways and fatty acid metabolism.

Design: Open-label, 48-week randomized trial with a 2 x 2 factorial design.

Drug-induced liver injury secondary to increased levonorgestrel exposure in a patient taking ritonavir.

We report the first published case of a drug induced liver injury (DILI) presumed secondary to a drug-drug interaction between ritonavir and levonorgestrel progestogen-only emergency contraception (POEC). Our patient is a 25-year-old female living with human immunodeficiency virus (HIV), taking antiretroviral therapy (ART) containing tenofovir alafenamide/emtricitabine and darunavir/ritonavir. She was found to have elevated transaminases at a routine clinic appointment consistent with hepatocellular DILI.

Prognostic value of non-invasive scores based on liver stiffness measurement, spleen diameter and platelets in HIV-infected patients.

Background And Aims: People living with HIV (PLWH) are at high risk for advanced chronic liver disease and related adverse outcomes. We aimed to validate the prognostic value of non-invasive scores based on liver stiffness measurement (LSM) and on markers of portal hypertension (PH), namely platelets and spleen diameter, in PLWH.

Methods: We combined data from eight international cohorts of PLWH with available non-invasive scores, including LSM and the composite biomarkers liver stiffness-spleen size-to-platelet ratio score (LSPS), LSM-to-Platelet ratio (LPR) and PH risk score.

Identification of hepatitis delta superinfection when investigating transaminitis in HIV/hepatitis B virus co-infection.

Hepatitis delta virus (HDV) is a highly pathogenic virus which can cause rapidly progressive liver disease in individuals with chronic hepatitis B virus and for which treatment options are limited. The incidence of sexually transmitted HDV infection is unknown. Here we report the case of a HDV seronegative man with pre-existent HIV/hepatitis B virus, taking effective tenofovir-containing antiretroviral therapy, who experienced a significant acute transaminitis with HDV antibody seroconversion and viraemia and no other identifiable cause.

Increased Body Mass Index and Type 2 Diabetes Are the Main Predictors of Nonalcoholic Fatty Liver Disease and Advanced Fibrosis in Liver Biopsies of Patients With Human Immunodeficiency Virus Monoinfection.

Background: Liver disease is an important cause of morbidity and mortality in people living with human immunodeficiency virus (PLWH), of which nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause. There are limited data investigating NAFLD in HIV monoinfection and histologically defined disease. We aimed to identify who is at risk of fibrosis, NAFLD, and nonalcoholic steatohepatitis (NASH) among PLWH and explore the diagnostic accuracy of noninvasive markers of fibrosis.

Decline in Hepatitis C Virus (HCV) Incidence in Men Who Have Sex With Men Living With Human Immunodeficiency Virus: Progress to HCV Microelimination in the United Kingdom?

Background: Modeling of the London hepatitis C virus (HCV) epidemic in men who have sex with men (MSM) and are living with human immunodeficiency virus (HIV) suggested that early access to direct-acting antiviral (DAA) treatment may reduce incidence. With high rates of linkage to care, microelimination of HCV within MSM living with HIV may be realistic ahead of 2030 World Health Organization targets. We examined trends in HCV incidence in the pre- and post-DAA eras for MSM living with HIV in London and Brighton, United Kingdom.

Interventions to reduce acute hepatitis C virus in HIV-positive MSM.

Purpose Of Review: The WHO has set ambitious targets for hepatitis C virus (HCV) elimination by 2030. In this review, we explore the possibility of HCV micro-elimination in HIV-positive (+) MSM, discussing strategies for reducing acute HCV incidence and the likely interventions required to meet these targets.

Recent Findings: With wider availability of directly acting antivirals (DAAs) in recent years, reductions in acute HCV incidence have been reported in some cohorts of HIV+ MSM.

Spleen stiffness measurements using point shear wave elastography detects noncirrhotic portal hypertension in human immunodeficiency virus.

To assess the utility of spleen stiffness as a diagnostic tool in individuals with human immunodeficiency virus (HIV) and non-cirrhotic portal hypertension (NCPH).The Philips EPIQ7, a new point shearwave elastography (pSWE) technique, was used to assess liver and spleen stiffness in 3 patient groups. Group 1: HIV and NCPH (n = 11); Group 2: HIV with past didanosine (ddI) exposure without known liver disease or NCPH (n = 5); Group 3: HIV without known liver disease or ddI exposure (n = 9).

Monocyte-macrophage activation is associated with nonalcoholic fatty liver disease and liver fibrosis in HIV monoinfection independently of the gut microbiome and bacterial translocation.

Background: Nonalcoholic fatty liver disease (NAFLD) is common among people living with HIV. There are limited data available on the pathophysiology of NAFLD and the development of fibrosis in this population.

Objectives: The aim of this study was to investigate the association of bacterial translocation, adipose tissue dysfunction, monocyte activation and gut dysbiosis in patients with HIV monoinfection and NAFLD.

A comparison of two post-processing analysis methods to quantify cerebral metabolites measured via proton magnetic resonance spectroscopy in HIV disease.

Objective: Non-invasive biomarkers to monitor cerebral function in treated human immunodeficiency virus (HIV) disease are required. Cerebral metabolite ratios (CMRs) measured by proton-MR spectroscopy ((1)H-MRS) are a potential biomarker. Here, we compare two post-processing software packages to quantify CMRs.

Differences in the variability of cerebral proton magnetic resonance spectroscopy (1H-MRS) measurements within three HIV-infected cohorts.

Introduction: Cerebral functional impairment remains prevalent in effectively treated HIV-infected subjects. As the results of formal cognitive testing are highly variable, surrogate markers to accurately measure cerebral function parameters are needed. Such markers include measurement of cerebral metabolite ratios (CMR) using proton magnetic resonance spectroscopy (1H-MRS).

HIV-1 CNS in vitro infectivity models based on clinical CSF samples.

Background: The concentration of antiretrovirals in CSF is often utilized as a surrogate for CNS drug exposure. This measurement does not consider pharmacodynamic or combinative effects of ART. We have developed a novel endpoint measurement to assess antiretroviral activity of CSF from subjects on ART.

Cerebral function in perinatally HIV-infected young adults and their HIV-uninfected sibling controls.

Background: Perinatally acquired HIV-infected (PaHIV) young adults undergo neurodevelopment in the presence of HIV infection and antiretroviral therapy, which may lead to neurocognitive (NC) impairment. Knowledge of NC function in this group is sparse and control data lacking. We compared cerebral function in young adults with PaHIV infection to aged matched HIV negative family controls.

The impact of HIV-1 reverse transcriptase polymorphisms on responses to first-line nonnucleoside reverse transcriptase inhibitor-based therapy in HIV-1-infected adults.

Objective: HIV-1 genetic variability may influence antiretroviral therapy (ART) outcomes. The study aim was to determine the impact of polymorphisms in regions known to harbor major nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations (codons 90-108, 135-138, 179-190, 225-348) on virologic responses to first-line NNRTI-based ART.

Methods: Reverse transcriptase sequences from ART-naive individuals who commenced efavirenz (EFV) or nevirapine (NVP) with at least two nucleos(t)ide reverse transcriptase inhibitors (NRTIs) without major drug resistance mutations were analyzed.

Increased microglia activation in neurologically asymptomatic HIV-infected patients receiving effective ART.

Background: Neuroinflammation plays an important role in HIV-associated neurological disorders; however, its role prior to the onset of symptomatic disease is unclear. We imaged microglial activation, the hallmark of neuroinflammation, in asymptomatic HIV-infected patients on effective combination ART.

Methods: Seven neurologically and cognitively asymptomatic adults with chronic HIV-infection and nine healthy volunteers were investigated with [11C]-PK11195 PET, a marker of translocator protein (TSPO) expressed by activated microglia.

Alterations in cerebrospinal fluid chemokines are associated with maraviroc exposure and in vivo metabolites measurable by magnetic resonance spectroscopy.

Background: Cerebrospinal (CSF) fluid biomarkers may be a useful tool for assessing the cerebral effects of antiretroviral therapy.

Objective: The aim of the study was to investigate the relationship between 4 CSF chemokines with maraviroc exposure and cerebral metabolite ratios (CMR) measured by magnetic resonance spectroscopy (1H-MRS) in HIV-infected individuals following maraviroc intensification.

Methods: CSF concentration of maraviroc and 4 chemokines (MCP-1, IP-10, MCP-4, and MIP-1β), plasma concentration of maraviroc pre-CSF assessment, and right basal ganglia CMR were assessed in 12 male HIV-infected, neuro-asymptomatic adults after 14 days of antiretroviral therapy intensification with maraviroc 150 mg twice daily.

Acute HCV/HIV coinfection is associated with cognitive dysfunction and cerebral metabolite disturbance, but not increased microglial cell activation.

Background: Microglial cell activation and cerebral function impairment are described in both chronic hepatitis C viral (HCV) and Human-Immune-Deficiency viral (HIV) infections. The aim of this study was to investigate the effect of acute HCV infection upon cerebral function and microglial cell activation in HIV-infected individuals.

Methods: A case-control study was conducted.

Factors associated with cerebrospinal fluid HIV RNA in HIV infected subjects undergoing lumbar puncture examination in a clinical setting.

Background: Cerebrospinal fluid (CSF) HIV RNA load may be associated with central nervous system (CNS) disease in HIV infected subjects. We investigated parameters associated with CSF HIV RNA within a large clinical cohort.

Methods: All HIV infected subjects undergoing CSF examination including assessment of CSF HIV RNA at St.

Low rates of neurocognitive impairment are observed in neuro-asymptomatic HIV-infected subjects on effective antiretroviral therapy.

Background: Few studies investigating the rate of neurocognitive (NC) impairment in effectively treated neuro-asymptomatic HIV-infected subjects have been performed.

Methods: We assessed NC function via a computerized cognitive test in HIV-infected subjects on stable combination antiretroviral therapy (cART) with plasma HIV RNA<50 copies/mL for at least 3 months. Neurologically symptomatic subjects were excluded.

CNS effects of a CCR5 inhibitor in HIV-infected subjects: a pharmacokinetic and cerebral metabolite study.

Background: We conducted a pharmacokinetic and in vivo cerebral (1)H magnetic resonance spectroscopy ((1)H-MRS) study to assess CSF exposure and cerebral metabolite ratios (CMRs) following maraviroc intensification.

Methods: HIV-infected neurologically asymptomatic adults receiving tenofovir, emtricitabine and lopinavir/ritonavir with plasma HIV RNA <50 copies/mL were eligible and received intensified therapy with 150 mg of maraviroc twice daily. (1)H-MRS was performed in several cerebral locations, including the right basal ganglia (RBG), to assess CMRs, including N-acetyl aspartate/creatine (NAA/Cr), at baseline and after 14 days.