Update on Managing the Risks of Exposure to Lentiviral and Retroviral Vectors.

OBJECTIVE: This paper aims to review the risks associated with using lentiviral and retroviral vectors in research and clinical settings and to propose an update to an effective treatment plan. METHODS: Risks of exposure were evaluated based on vector design, safety features, viral tropism, transgene, and means and modes of transmission. These risks were weighed against the potential risks and benefits of current HIV medications. RESULTS: We recommend the following post-exposure prophylactic treatment for significant lentiviral vector exposures: 1) dolutegravir 50 mg. taken once a day for 7 days; and 2) tenofovir disoproxil fumarate 300 mg. taken once a day for 7 days (28 days of both medications for replication-competent vectors). CONCLUSIONS: Due to the highly efficient delivery of transgenes by modern lentiviral and retroviral vectors, post-exposure prophylaxis is indicated to prevent vector integration and oncogenic risks.

Risks Associated With Lentiviral Vector Exposures and Prevention Strategies.

Lentiviral vectors (LVVs) are powerful genetic tools that are being used with greater frequency in biomedical laboratories and clinical trials. Adverse events reported from initial clinical studies provide a basis for risk assessment of occupational exposures, yet many questions remain about the potential harm that LVVs may cause. We review those risks and provide a framework for principal investigators, Institutional Biosafety Committees, and occupational health professionals to assess and communicate the risks of exposure to staff. We also provide recommendations to federal research and regulatory agencies for tracking LVV exposures to evaluate long-term outcomes. U.S. Food and Drug Administration approved antiviral drugs for HIV have theoretical benefits in LVV exposures, although evidence to support their use is currently limited. If treatment is appropriate, we recommend a 7-day treatment with an integrase inhibitor with or without a reverse transcriptase inhibitor within 72 hours of exposure.

Empathy and the failure to treat pain.

We set out to discuss the psychological barriers that exist in the treatment of pain. Specifically, we argue that clinicians have several innate mechanisms at play that can hinder their judgment and lead to erroneous assumptions about their patients. Issues are discussed from social psychological and psychodynamic perspectives. A focus is placed on the issue of empathy and how this, too, can act as a barrier to rational judgment when evaluating patients. In the face of growing scrutiny on pain management in the United States, it is important to understand the barriers to providing care that already exist on an intrinsic level. Through the exploration of these barriers, clinicians might be better able to reflect on their own practice. Ultimately, we hope to push forward an agenda of rational therapy in pain management that utilizes safeguards against abuse and addiction while also preserving treatment modalities for patients in need of services.

General guidelines for experimenting with HIV.

Performing experiments using human immunodeficiency virus (HIV)-infected materials represents a potential biological hazard for the investigator. An intensive training program for laboratory personnel must always precede the actual execution of research involving manipulation of HIV. In addition, appropriate sterile tissue culture techniques are absolute prerequisites for producing meaningful experiments and for achieving safe working conditions. In most circumstances more than one investigator uses the same HIV research facility; therefore, careful training in biosafety is mandatory not only for self-protection, but for the safety of other investigators as well. The first protocol in this unit establishes a general framework for working safely with HIV and the second describes the proper storage of HIV stocks and test supernatants.