Girish N. Vyas

Most individuals infected with human immunodeficiency virus-1, in the absence of antiretroviral therapy, exhibit persistent virus replication and declining CD4+ cell numbers, and progress to acquired immunodeficiency syndrome within 10 years of infection. Elite controllers are rare individuals with human immunodeficiency virus-1 infection who can maintain undetectable plasma virus levels and remain asymptomatic without antiretroviral therapy. It has been proposed that elite controllers benefit from being infected with attenuated human immunodeficiency virus-1 variants. A 31-year-old African woman presented with human immunodeficiency virus-1 infection during pregnancy and was diagnosed with acquired immunodeficiency syndrome. Subsequently, her husband, a 31-year-old African man, was tested and found to be seropositive for human immunodeficiency virus-1. His plasma human immunodeficiency virus-1 ribonucleic acid level was found to be below the limit of detection of the clinical assay. This report provides evidence for the first described case of human immunodeficiency virus-1 infection possibly transmitted from an elite controller to a patient who progressed to acquired immunodeficiency syndrome. This observation strengthens the case against avirulence as a mechanism that protects elite controllers.

Plasma utilization has increased over the past two decades, and there is a growing concern that many plasma transfusions are inappropriate. Plasma transfusion is not without risk, and certain complications are more likely with plasma than other blood components. Clinical and laboratory investigations of the patients suffering reactions after infusion of fresh‐frozen plasma (FFP) define the etiology and pathogenesis of the panoply of adverse effects. We review here the pathogenesis, diagnosis, and management of the risks associated with plasma transfusion. Risks commonly associated with FFP include: 1) transfusion‐related acute lung injury, 2) transfusion‐associated circulatory overload, and 3) allergic and/or anaphylactic reactions. Other less common risks include 1) transmission of infections, 2) febrile nonhemolytic transfusion reactions, 3) red blood cell alloimmunization, and 4) hemolytic transfusion reactions. The effects of pathogen inactivation or reduction methods on these risks are also discussed. Fortunately, a majority of the adverse effects are not lethal and are adequately treated in clinical practice.

Cellular substrate (CS) composed of phytohemagglutinin (PHA)-stimulated PBMNCs is required for isolating primary human immunodeficiency virus Type 1 from plasma (PHIV) during early acute infection. The transmitted founder PHIV is neutralization-sensitive and uses chemokine-receptor 5 to infect CD4-positive PBMNCs. Therefore, PHIV cocultured with optimized CS would enable efficient virologic diagnosis, vaccine development, and tests for broadly neutralizing antibodies (bnAb). Fifteen leukapheresis donations were used to isolate CD4-enriched PBMNCs. Individual or three or four donors' pooled cells were stimulated with PHA, and both CSs were evaluated in parallel cocultures using five different PHIV isolates from nucleic acid testing-positive anti-HIV-negative donations. Feasibility of coculturing PHIV with pooled PBMNC-CS after dimethyl sulfoxide cryopreservation was investigated. The cell-free supernatants from individual CSs contained mean HIV-p24 antigen varying between 20.35 and 85.54 ng/mL, while that from pooled CSs ranged between 57.54 and 88.10 ng/mL. Thus, PBMNCs pooled from multiple donors provide an optimal CS for coculturing PHIV. Cryopreserved PBMNC-CS for PHIV cocultures is promising for systematic biosynthesis of PHIV. Pooled CSs after cryopreservation were functional for PHIV replication and enable on-demand diagnostic cocultures, preparing panels of PHIV stocks for bnAb testing and developing an envelope-subunit vaccine candidate analogous to hepatitis B surface antigen, proven successful in preventing hepatitis B virus infection.