BACKGROUND: The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biological therapies.
OBJECTIVE: To review, from an infectious diseases perspective, the safety profile of immune checkpoint inhibitors, LFA-3-targeted agents, cell adhesion inhibitors, sphingosine-1-phosphate receptor modulators and proteasome inhibitors, and to suggest preventive recommendations.
METHODS: Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family.
BACKGROUND: T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death (PD)-1/PD-1 ligand 1 (PD-L1)-targeted agents do not appear to intrinsically increase the risk of infection but can induce immune-related adverse effects requiring additional immunosuppression. Although CD4+ T-cell lymphopenia is associated with alefacept, no opportunistic infections have been observed. Progressive multifocal leukoencephalopathy (PML) may occur during therapy with natalizumab (anti-α4-integrin monoclonal antibody (mAb)) and efalizumab (anti-CD11a mAb), but no cases have been reported to date with vedolizumab (anti-α4β7 mAb). In patients at high risk for PML (positive anti-JC polyomavirus serology with serum antibody index >1.5 and duration of therapy ≥48 months), the benefit-risk ratio of continuing natalizumab should be carefully considered. Fingolimod induces profound peripheral blood lymphopenia and increases the risk of varicella zoster virus (VZV) infection. Prophylaxis with (val)acyclovir and VZV vaccination should be considered. Proteasome inhibitors also increase the risk of VZV infection, and antiviral prophylaxis with (val)acyclovir is recommended. Anti-Pneumocystis prophylaxis may be considered in myeloma multiple patients with additional risk factors (i.e. high-dose corticosteroids).
CONCLUSIONS: Clinicians should be aware of the risk of immune-related adverse effects and PML in patients receiving immune checkpoint and cell adhesion inhibitors respectively.

Notably absent from current practice guidelines for common neurologic diseases as stroke and seizure is the revised Centers for Disease Control (CDC) recommendation for human immunodeficiency virus (HIV) testing of all clinical encounters. During a 9-month period 2 patients with treatable stroke mimics related to HIV type 1 infection were misdiagnosed resulting in delay in beginning antiretroviral therapy and increased cost and morbidity. This study was conducted to determine the frequency of HIV-1 screening in our stroke center population and consider the implications of such testing on neurologic disease. We surveyed our stroke center database to determine the frequency of HIV screening in ischemic strokes from January 2005 through May 2011. Of 2806 ischemic strokes, 27 (0.96%) patients were HIV-tested during the 6.5-year study period. We suggest that incorporating the CDC recommendations for HIV screening into neurology practice guidelines can impact diagnosis and treatment of unsuspected HIV-related neurologic disease with reduction in cost of care and morbidity.