The decision to forgo antiretroviral therapy in people living with HIV compliance as paternalism or partnership?

OBJECTIVE: The purpose of this study was to examine the self-reported reasons that people living with HIV (PLWH) provide to support their autonomous (i.e., against medical advice) decisions not to take, or to stop taking, highly active antiretroviral therapy (HAART). A further purpose of this study was to examine physicians' reactions to their patients' autonomous decisions and to examine physicians' conceptualization of compliance. DESIGN/METHODS: Semi structured interviews were conducted with 11 PLWH (5 male, 6 female) and their 8 HIV-care providers (4 male, 4 female). Interviews were analysed qualitatively using thematic coding. Patients also completed sociodemographic and medical information questionnaires. Interrater reliability was also calculated on patients' reasons supporting their decisions with coefficients ranging from .84 to 1.00 (all ps <.01). RESULTS: For all 11 patients, preservation of quality of life and critical attitudes toward allopathic medicine were identified as reasons supporting autonomous decisions to refuse HAART. In addition, 10 patients cited the prior experience of, or the anticipated fear of, side-effects as central to their decision. Nine patients articulated their preference for alternative medicine and five patients expressed moral objections as significant reasons underlying their decisions. Gender differences emerged in care providers' conceptualization of compliance. Female care providers tended to view compliance as a collaboration between patient and care provider whereas male physicians tended to view compliance more as the patients' capacity to adhere to the prescribed HAART-regimen. Physician response strategies to patients' autonomous decision to refuse HAART were characterized as coercive or not. Neither the physicians' conceptualization of compliance nor their response strategies were consistent with the patients' perspective. In contrast, the central component of the patients' decision making was the patients' subjective view of the benefit they would derive from HAART. CONCLUSIONS: The results of this study provide some initial evidence that health care providers integrate recommendations for HAART with patients concerns for their own quality of life and make these recommendations within the context of the patients' worldview. In addition, these results suggest that traditional views of compliance, that emphasize obedience to physician prescriptions, may be inadequate in this regard. Rather, these results suggest that a theory of compliance that is based upon collaboration between physician and patient will allow for a consideration of patients' subjective views, their worldview, and their health care beliefs.

A neuroprotective phase precedes striatal degeneration upon nucleolar stress.

The nucleolus is implicated in sensing and responding to cellular stress by stabilizing p53. The pro-apoptotic effect of p53 is associated with several neurodegenerative disorders, including Huntington's disease (HD), which is characterized by the progressive loss of medium spiny neurons (MSNs) in the striatum. Here we show that disruption of nucleolar integrity and function causes nucleolar stress and is an early event in MSNs of R6/2 mice, a transgenic model of HD. Targeted perturbation of nucleolar function in MSNs by conditional knockout of the RNA polymerase I-specific transcription initiation factor IA (TIF-IA) leads to late progressive striatal degeneration, HD-like motor abnormalities and molecular signatures. Significantly, p53 prolongs neuronal survival in TIF-IA-deficient MSNs by transient upregulation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumor suppressor that inhibits mammalian target of rapamycin signaling and induces autophagy. The results emphasize the initial role of nucleolar stress in neurodegeneration and uncover a p53/PTEN-dependent neuroprotective response.

Noncoding transcripts in sense and antisense orientation regulate the epigenetic state of ribosomal RNA genes.

Alternative transcription of the same gene in sense and antisense orientation regulates expression of protein-coding genes. Here we show that noncoding RNA (ncRNA) in sense and antisense orientation also controls transcription of rRNA genes (rDNA). rDNA exists in two types of chromatin--a euchromatic conformation that is permissive to transcription and a heterochromatic conformation that is transcriptionally silent. Silencing of rDNA is mediated by NoRC, a chromatin-remodeling complex that triggers heterochromatin formation. NoRC function requires RNA that is complementary to the rDNA promoter (pRNA). pRNA forms a DNA:RNA triplex with a regulatory element in the rDNA promoter, and this triplex structure is recognized by DNMT3b. The results imply that triplex-mediated targeting of DNMT3b to specific sequences may be a common pathway in epigenetic regulation. We also show that rDNA is transcribed in antisense orientation. The level of antisense RNA (asRNA) is down-regulated in cancer cells and up-regulated in senescent cells. Ectopic asRNA triggers trimethylation of histone H4 at lysine 20 (H4K20me3), suggesting that antisense transcripts guide the histone methyltransferase Suv4-20 to rDNA. The results reveal that noncoding RNAs in sense and antisense orientation are important determinants of the epigenetic state of rDNA.