The Role of Glutathione in the Management of Cell-Mediated Immune Responses in Individuals with HIV.

Human immunodeficiency virus (HIV) is a major cause of death worldwide. Without appropriate antiretroviral therapy, the infection can develop into acquired immunodeficiency syndrome (AIDS). AIDS leads to the dysregulation of cell-mediated immunity resulting in increased susceptibility to opportunistic infections and excessive amounts of inflammatory cytokines. HIV-positive individuals also demonstrate diminished glutathione (GSH) levels which allows for increased viral replication and increased pro-inflammatory cytokine release, further contributing to the high rates of mortality seen in patients with HIV. Adequate GSH supplementation has reduced inflammation and slowed the decline of CD4+ T cell counts in HIV-positive individuals. We aim to review the current literature regarding the role of GSH in cell-mediated immune responses in individuals with HIV- and AIDS-defining illnesses.

Engagement in decision-making and patient satisfaction: a qualitative study of older patients' perceptions of dialysis initiation and modality decisions.

BACKGROUND: Although shared decision-making (SDM) can better align patient preferences with treatment, barriers remain incompletely understood and the impact on patient satisfaction is unknown. METHODS: This is a qualitative study with semistructured interviews. A purposive sample of prevalent dialysis patients ≥65 years of age at two facilities in Greater Boston were selected for diversity in time from initiation, race, modality and vintage. A codebook was developed and interrater reliability was 89%. Codes were discussed and organized into themes. RESULTS: A total of 31 interviews with 23 in-center hemodialysis patients, 1 home hemodialysis patient and 7 peritoneal dialysis patients were completed. The mean age was 76 ± 9 years. Two dominant themes (with related subthemes) emerged: decision-making experiences and satisfaction, and barriers to SDM. Subthemes included negative versus positive decision-making experiences, struggling for autonomy, being a 'good patient' and lack of choice. In spite of believing that dialysis initiation should be the patient's choice, no patients perceived that they had made a choice. Patients explained that this is due to the perception of imminent death or that the decision to start dialysis belonged to physicians. Clinicians and family frequently overrode patient preferences, with patient autonomy honored mostly to select dialysis modality. Poor decision-making experiences were associated with low treatment satisfaction. CONCLUSIONS: Despite recommendations for SDM, many older patients were unaware that dialysis initiation was voluntary, held mistaken beliefs about their prognosis and were not engaged in decision-making, resulting in poor satisfaction. Patients desired greater information, specifically focusing on the acuity of their choice, prognosis and goals of care.

Effect of different detoxification procedures on the residual pertussis toxin activities in vaccines.

Pertussis toxin (PTx) is a major virulence factor produced by Bordetella pertussis and its detoxified form is one of the major protective antigens in vaccines against whooping cough. Ideally, PTx in the vaccine should be completely detoxified while still preserving immunogenicity. However, this may not always be the case. Due to multilevel reaction mechanisms of chemical detoxification that act on different molecular sites and with different production processes, it is difficult to define a molecular characteristic of a pertussis toxoid. PTx has two functional distinctive domains: the ADP-ribosyltransferase enzymatic subunit S1 (A-protomer) and the host cell binding carbohydrate-binding subunits S2-5 (B-oligomer); and in this study, we investigated the effect of different detoxification processes on these two functional activities of the residual PTx in toxoids and vaccines currently marketed worldwide using a recently developed in vitro biochemical assay system. The patho-physiological activities in these samples were also estimated using the in vivo official histamine sensitisation tests. Different types of vaccines, detoxified by formaldehyde, glutaraldehyde or by both, have different residual functional and individual baseline activities. Of the vaccines tested, PT toxoid detoxified by formaldehyde had the lowest residual PTx ADP-ribosyltransferase activity. The carbohydrate binding results detected by anti-PTx polyclonal (pAb) and anti-PTx subunits monoclonal antibodies (mAb) showed specific binding profiles for toxoids and vaccines produced from different detoxification methods. In addition, we also demonstrated that using pAb or mAb S2/3 as detection antibodies would give a better differential difference between these vaccine lots than using mAbs S1 or S4. In summary, we showed for the first time that by measuring the activities of the two functional domains of PTx, we could characterise pertussis toxoids prepared from different chemical detoxification methods and this study also highlights the potential use of this in vitro biochemical assay system for in-process control.

Five years' real-life experience with raltegravir in a large HIV centre.

Raltegravir was the first licensed integrase inhibitor. Real-life experience is informative and complements trial data. We therefore evaluated raltegravir use in adults in a large HIV treatment centre. From pharmacy and departmental HIV database records, we identified all adults taking ≥1 dose of raltegravir from first availability to the end of November 2012. Data were collected using a standardised case report form. Two hundred and fifteen individuals provided 502 patient-years (median 2.6 years/person) of raltegravir use. Of 215 individuals, 166 (77%) were male, median age 43 years; 189 (88%) were antiretroviral therapy (ART)-experienced and 26 (12%) ART-naive, with median baseline CD4 counts of 324 and 54 cells/µL, respectively. Of ten individuals using once-daily raltegravir, four, with good adherence remained virologically suppressed after a median 28 months, four stopped against medical advice, one stopped to simplify and one failed virologically. In hepatitis co-infection, 35 individuals (92 patient-years) took raltegravir without evidence of hepatotoxicity. Six women started raltegravir during pregnancy for intensification (5/6) or switch for tolerability without complications. Of ten individuals stopping raltegravir after virological failure, 2/4 with successful sequencing showed resistance. Raltegravir appears safe and effective, without evidence of toxicity above that in published trials, including in pregnancy and co-infections. Once-daily dosing seems effective where adherence is good.