First-in-human immunoPET imaging of HIV-1 infection using 89Zr-labeled VRC01 broadly neutralizing antibody.

A major obstacle to achieving long-term antiretroviral (ART) free remission or functional cure of HIV infection is the presence of persistently infected cells that establish a long-lived viral reservoir. HIV largely resides in anatomical regions that are inaccessible to routine sampling, however, and non-invasive methods to understand the longitudinal tissue-wide burden of HIV persistence are urgently needed. Positron emission tomography (PET) imaging is a promising strategy to identify and characterize the tissue-wide burden of HIV. Here, we assess the efficacy of using immunoPET imaging to characterize HIV reservoirs and identify anatomical foci of persistent viral transcriptional activity using a radiolabeled HIV Env-specific broadly neutralizing antibody, 89Zr-VRC01, in HIV-infected individuals with detectable viremia and on suppressive ART compared to uninfected controls (NCT03729752). We also assess the relationship between PET tracer uptake in tissues and timing of ART initiation and direct HIV protein expression in CD4 T cells obtained from lymph node biopsies. We observe significant increases in 89Zr-VRC01 uptake in various tissues (including lymph nodes and gut) in HIV-infected individuals with detectable viremia (N = 5) and on suppressive ART (N = 5) compared to uninfected controls (N = 5). Importantly, PET tracer uptake in inguinal lymph nodes in viremic and ART-suppressed participants significantly and positively correlates with HIV protein expression measured directly in tissue. Our strategy may allow non-invasive longitudinal characterization of residual HIV infection and lays the framework for the development of immunoPET imaging in a variety of other infectious diseases.

Acquisition of human immunodeficiency virus infection in a patient with multiple sclerosis: could these conditions positively influence each other's course?

Patients with human immunodeficiency virus (HIV) infection have a decreased risk of developing multiple sclerosis (MS) and MS patients very rarely contract HIV infection. We report on a 35-year-old woman with relapsing-remitting MS, who acquired HIV infection 8 years after MS onset. During 7 years of follow-up without combined antiretroviral therapy (cART), CD4+ counts decreased and HIV viremia increased progressively, but slightly. These trends reverted after starting cART, with optimal viro-immunological control. While the patient had many MS relapses before acquiring HIV infection, she had then only one relapse, shortly after HIV infection, despite irregular or no MS therapy. This case contributes to the discussion about MS and HIV potential interactions and describes for the first time the effects of the MS-targeting drug natalizumab in an HIV-positive patient.

Progressive Multifocal Leukoencephalopathy after Treatment with Nivolumab.

Progressive multifocal leukoencephalopathy (PML) is increasingly being reported in patients undergoing immunotherapy. We report a case of progressive multifocal leukoencephalopathy after treatment with nivolumab, a PD-1 blocker that is used to restore impaired T-cell responses in patients with cancer and infections. Data for 4 other cases were obtained from pharmacovigilance databases.

Ultrasound evaluation of perihepatic lymph nodes during antiviral therapy with the protease inhibitor telaprevir (VX-950) in patients with chronic hepatitis C infection.

Previous studies have shown that the total perihepatic lymph node (PLN) volume is (1) associated with the extent of inflammatory activity in the liver and (2) changes according to the antiviral response in patients receiving interferon-based therapy for chronic hepatitis C (HCV) infection. The aim of this prospective pilot study was to examine whether the total PLN volume similarly changes in patients receiving antiviral monotherapy with the protease inhibitor telaprevir (VX-950). The present study was conducted in a subgroup of 19 patients with chronic hepatitis C genotype-1 infection treated with the protease inhibitor telaprevir (VX-950) or placebo in a phase Ib clinical trial. The total perihepatic lymph node volume was assessed using sonography before the initiation of antiviral therapy, at the end of 14 d of treatment, and at follow-up. Treatment with telaprevir resulted in a significant reduction of plasma HCV-RNA in all patients at the end of 14 d of treatment. In patients receiving telaprevir, the total PLN volume decreased significantly at the end of 14 d of treatment compared with pretreatment volume (1.26 mL to 0.76 mL, p=0.01). In contrast, no significant difference was seen in patients receiving placebo (1.00 mL to 1.06 mL, p=0.26). These results suggest that the perihepatic lymph node volume can be used as an indicator for viral and histologic response not only as previously reported in patients receiving interferon-based therapy, but also in patients receiving therapy with direct antivirals.

Anatomical loci of HIV-associated immune activation and association with viraemia.

BACKGROUND: Lymphocyte activation, associated with vaccination or infection, can be measured by positron emission tomography (PET). We investigated the ability of PET to detect and measure magnitude of lymph-node activation among asymptomatic HIV-1-infected individuals. METHODS: Initially we assessed PET response in eight HIV-1-uninfected individuals who had received licensed killed influenza vaccine. In an urban teaching hospital, we recruited 12 patients recently infected with HIV-1 (<18 months since seroconversion) and 11 chronic long-term HIV-1 patients who had stable viraemia by RT-PCR (non-progressors). After injection with fluorine-18-labelled fluorodeoxyglucose, patients underwent PET. We correlated summed PET signal from nodes with viral load by linear regression on log-transformed values. FINDINGS: Node activation was more localised after vaccination than after HIV-1 infection. In early and chronic HIV-1 disease, node activation was greater in cervical and axillary than in inguinal and iliac chains (p<0.0001), and summed PET signal correlated with viraemia across a 4 log range (r2=0.98, p<0.0001). Non-progressors had small numbers of persistently active nodes, most of which were surgically accessible. INTERPRETATION: The anatomical restriction we noted may reflect microenvironmental niche selection, and tight correlation of PET signal with viraemia suggests target-cell activation determines steady-state viral replication.