Doctor-patient concordance during HIV treatment switching decision-making.

OBJECTIVES: The aim of the study was to explore levels of doctor-patient concordance during the making of decisions regarding HIV treatment switching and stopping in relation to patient health-related outcomes. METHODS: Adult patients attending five HIV clinics in the United Kingdom were requested to complete the study questionnaire, which included a Concordance Scale, and measures of symptoms [Memorial Symptom Assessment Short Form (MSAS) index], quality of life (EuroQol), satisfaction, adherence and sexual risk behaviour. Clinical health measures (HIV viral load and CD4 cell count) were also obtained. A total of 779 patients completed the questionnaire, giving a response rate of 86%; of these 779 patients, 430 had switched or stopped their HIV treatment and were thus eligible for inclusion. Of these patients, 217 (50.5%) fully completed the Concordance Scale. RESULTS: Concordance levels were high (88% scored between 30 and 40 on the scale; score range 10-40). Higher concordance was related to several patient outcomes, including: better quality of life (P=0.003), less severe and burdensome symptom experience (lower MSAS-physical score, P=0.001; lower MSAS-psychological score, P=0.008; lower MSAS-global distress index score, P=0.011; fewer symptoms reported, P=0.007), higher CD4 cell count (at baseline, P=0.019, and 6-12 months later, P=0.043) and greater adherence (P=0.029). CONCLUSIONS: High levels of doctor-patient concordance in HIV treatment decision-making are associated with greater adherence and better physical and psychological functioning. More research is needed to establish a causal relationship between concordance and these outcomes.

Self-reported non-adherence to ART and virological outcome in a multiclinic UK study.

Adherence is of fundamental importance to ART success. We examined the association of self-reported non-adherence with demographic factors, health and behaviour issues, and virological outcome, in a multi-clinic study. Seven hundred and seventy-eight HIV patients in five clinics in London and Brighton completed a questionnaire on adherence and HIV/health issues at baseline in 2005/6. For 486 subjects taking ART, non-adherence in the past week was defined as: (A)>or=1 dose missed or taken incorrectly (wrong time/circumstances); (B)>or=1 dose missed; (C)>or=2 doses missed. Questionnaire data were matched with routine treatment and virology data for consenting subjects (61.4%). We assessed four virological outcomes in 307 of 486 patients: (i) VL>50c/mL using latest VL at the questionnaire and excluding patients starting HAART<24 weeks ago; (ii) VL>50c/mL using the first VL from 6 to 12 months post-questionnaire; (iii) any VL>50c/mL from 6 to 12 months post-questionnaire; (iv) among patients with VL<50c/mL at questionnaire, time to first subsequent VL>50c/mL over two years follow up. Non-adherence was reported by 278 (57.2%), 102 (21.0%) and 49 (10.1%) of 486 patients, for definitions A, B and C, respectively. Non-adherence declined markedly with older age, and tended to be more commonly reported by Black patients, those born outside the UK, those with greater psychological symptoms and those with suicidal thoughts. There was a weaker association with physical symptoms and no association with gender/sexuality, education, unemployment, or risk behaviour (p>0.1). In logistic regression analyses, younger age, non-UK birth and psychological variables were independent predictors of non-adherence [e.g., for non-adherence B: odds ratios (95% CI) were 0.95 (0.92, 0.98) for every year older age; 1.6 (1.0, 2.5) for non-UK born; 2.3 (1.5, 3.7) for suicidal thoughts]. Non-adherence was associated with poorer virological outcome; the most consistent association was for definition C. Among 255 patients with VL<50c/mL at baseline, non-adherence definition C was independently associated with subsequent VL>50c/mL [adjusted hazard ratio (95% CI) 3.2 (1.5, 7.2)]. Non-UK birth and psychological symptoms predicted non-adherence, but the most striking association was with younger age. Age should be an important consideration in clinical strategies to minimise non-adherence and in decisions regarding ART initiation. A simple measure of non-adherence can identify patients at risk of poorer virological outcome.

Expression of Haemonchus contortus pepsinogen in Caenorhabditis elegans.

A genomic copy of a gut-expressed Haemonchus contortus candidate vaccine antigen, pepsinogen, was isolated using the polymerase chain reaction (PCR). The isolated sequence was 4 kb in length and contained eight introns ranging in size from 54 to 1475 base pairs. This sequence, together with its 3' non-coding DNA region containing a polyadenylation signal sequence, was cloned into the Bluescript SK(+) vector immediately downstream of the Caenorhabditis elegans cpr-5 gene promoter. This promoter has been shown previously to direct protein expression to the gut of C. elegans. The construct was micro-injected into DR96 unc-76(e911) mutant C. elegans together with a rescue plasmid and transgenic worms identified by reversion back to wild-type phenotype. Two transgenic lines of C. elegans were established. The presence of the injected construct and of the Haemonchus pepsinogen transcript in transgenic worms was confirmed by PCR analysis. Correct splicing of intronic sequences was observed. Immunohistochemistry showed expression of the Haemonchus pepsinogen protein in the gut of transgenic C. elegans, with reactivity evident in the larval and adult stages. Expression of the Haemonchus pepsinogen in C. elegans affirms the role of C. elegans as a model for parasitic nematodes and demonstrates its potential as a vector for expression of candidate vaccine antigens from parasitic nematodes.