Identification, management, and prevention of adverse effects associated with highly active antiretroviral therapy.

PURPOSE: The adverse effects associated with highly active antiretroviral therapy (HAART), as well as potential options available for management of these complications, are summarized. SUMMARY: Effective treatment of human immunodeficiency virus (HIV) infection requires three or four drug regimens that are complicated and commonly associated with adverse effects. This makes compliance difficult and can result in treatment failures, development of resistance, and loss of future treatment options. In addition, some adverse effects may lead to an increase in morbidity and represent additional risk factors for future complications. Serious adverse events after the initiation of HAART are related to both patient and treatment characteristics. Most organ systems can be affected, depending on the drug or class of drugs being used; therefore, proper identification of adverse effects can be difficult. The most common adverse effects are gastrointestinal, neurologic, metabolic, and cardiovascular, although renal, dermatological, and hematologic events may also be encountered. Adverse-effect management has included treatment interruptions and therapeutic drug monitoring but most commonly involves switching to another drug or class of drugs. This requires a complete understanding of HAART regimens and their associated complications. HIV clinics that have employed clinical pharmacists have been able to successfully prevent or identify adverse effects through suggestions for effective treatment alternatives, medication counseling, and compliance education. CONCLUSION: The identification, management, and prevention of adverse events associated with HAART can be difficult but are integral components of effective treatment. Proper interventions are cost-effective and have resulted in improved quality of life for patients infected with HIV.     

Phagocytosis and cytokine response to rough and smooth colony variants of Mycobacterium abscessus by human peripheral blood mononuclear cells

Mycobacterium abscessus is a non‐tuberculous mycobacteria able to cause opportunistic infections in selected patient groups. During the last decades it has emerged as a cause of chronic pulmonary infection in patients with cystic fibrosis (CF). M. abscessus strains exhibit either smooth or rough colony morphology. Strains exhibiting the rough phenotype more often cause pulmonary infections in CF patients than did the smooth ones. Here, we examined phagocytosis and production of cytokines by human peripheral blood mononuclear cells, in response to M. abscessus strains with smooth and rough colony phenotype. The rough isolates all formed multicellular cords, similar to what is observed in Mycobacterium tuberculosis. Monocytes were generally unable to internalize these rough cord isolates, in contrast with the smooth ones. Furthermore, the rough M. abscessus strains induced a distinct cytokine profile differing from that induced by the smooth ones. Rough isolates induced significantly less IL‐10 and tumour necrosis factor compared to smooth strains, but more IL‐1β. Both varieties induced equal amounts of IFN‐γ, IL‐17, IL‐23, IL‐6, IL‐8 and equally little IL‐12. The ability to withstand phagocytosis might be a virulence factor contributing to the capacity of rough M. abscessus strains to give persistent pulmonary infections.     

Introducing a combinatorial DNA-toolbox platform constituting defined protein-based biohybrid-materials

The access to defined protein-based material systems is a major challenge in bionanotechnology and regenerative medicine. Exact control over sequence composition and modification is an important requirement for the intentional design of structure and function. Herein structural- and matrix proteins provide a great potential, but their large repetitive sequences pose a major challenge in their assembly. Here we introduce an integrative “one-vector-toolbox-platform” (OVTP) approach which is fast, efficient and reliable. The OVTP allows for the assembly, multimerization, intentional arrangement and direct translation of defined molecular DNA-tecton libraries, in combination with the selective functionalization of the yielded protein-tecton libraries. The diversity of the generated tectons ranges from elastine-, resilin, silk- to epitope sequence elements. OVTP comprises the expandability of modular biohybrid-materials via the assembly of defined multi-block domain genes and genetically encoded unnatural amino acids (UAA) for site-selective chemical modification. Thus, allowing for the modular combination of the protein-tecton library components and their functional expansion with chemical libraries via UAA functional groups with bioorthogonal reactivity. OVTP enables access to multitudes of defined protein-based biohybrid-materials for self-assembled superstructures such as nanoreactors and nanobiomaterials, e.g. for approaches in biotechnology and individualized regenerative medicine.     

Closing the gap: Novel therapies in treating acute lymphoblastic leukemia in adolescents and young adults

Acute lymphoblastic leukemia (ALL) is one of the most common cancer diagnoses identified in adolescents and young adults (AYAs). Although most children with ALL are cured of their disease, AYAs have experienced much worse outcomes over time, with event-free survival ranging from 30 to 45%. This survival disparity is likely due to differences in tumor biology, treatment-related toxicities, and nonmedical issues. This review summarizes these differences as well as focusing on the various trials that have demonstrated superior outcomes with pediatric protocols in AYAs with ALL. Even with the widespread use of these protocols, a treatment gap remains, and novel therapies are one way to address this problem. Still, these therapies also have significant toxicities and unique issues that need to be tested further, especially in the AYA population. The development of more AYA-specific trials will be an important way to examine novel therapies and interventions designed to reduce treatment-related toxicities and improve long-term outcomes.