Second-line antiretroviral therapy in a workplace and community-based treatment programme in South Africa: determinants of virological outcome.

: Background: As antiretroviral treatment (ART) programmes in resource-limited settings mature, more patients are experiencing virological failure. Without resistance testing, deciding who should switch to second-line ART can be difficult. The consequences for second-line outcomes are unclear. In a workplace- and community-based multi-site programme, with 6-monthly virological monitoring, we describe outcomes and predictors of viral suppression on second-line, protease inhibitor-based ART.Methods: We used prospectively collected clinic data from patients commencing first-line ART between 1/1/03 and 31/12/08 to construct a study cohort of patients switched to second-line ART in the presence of a viral load (VL) ?400 copies/ml. Predictors of VL<400 copies/ml within 15 months of switch were assessed using modified Poisson regression to estimate risk ratios.Results: 205 workplace patients (91.7% male; median age 43 yrs) and 212 community patients (38.7% male; median age 36 yrs) switched regimens. At switch compared to community patients, workplace patients had a longer duration of viraemia, higher VL, lower CD4 count, and higher reported non-adherence on first-line ART. Non-adherence was the reported reason for switching in a higher proportion of workplace patients. Following switch, 48.3% (workplace) and 72.0% (community) achieved VL<400, with non-adherence (17.9% vs. 1.4%) and virological rebound (35.6% vs. 13.2% with available measures) reported more commonly in the workplace programme. In adjusted analysis of the workplace programme, lower switch VL and younger age were associated with VL<400. In the community programme, shorter duration of viraemia, higher CD4 count and transfers into programme on ART were associated with VL<400.Conclusion: High levels of viral suppression on second-line ART can be, but are not always, achieved in multi-site treatment programmes with both individual- and programme-level factors influencing outcomes. Strategies to support both healthcare workers and patients during this switch period need to be evaluated; sub-optimal adherence, particularly in the workplace programme must be addressed

Attendance versus compliance with tuberculosis treatment in an occupational setting a pilot study

Aim. To determine the prevalence of non-compliance with tuberculosis treatment at Freegold Mines.Objectives. 1. To establish the rates of attendance and collection of anti-tuberculosis drugs. 2. To detennine prevalence of non-compliance by means of urine tests.Design. A cross-sectional study conducted over 2 weeks at mine medical stations.Method. Urine samples were collected from tuberculosis patients 3 hours after drug ingestion. Non-compliance was established by testing these samples for rifampicin and/or isoniazid (INH) metabolites. Non-compliance was defined as a negative urine test result for these drugs in participants whose treatment regimens included one or both. Daily attendance and collection of drugs statistics are recorded in the medical station tuberculosis register. The patient rate of adherence was calculated as the observed number of days on which medication had been collected over the expected treatment days in a given period.Results. Urine test results showed an overall prevalence of non-compliance of 14.6 ± 3.3%, The study showed that non-compliance with tuberculosis treatment was underestimated by the surveillance data, The rate of nonadherence with treatment established from the formal surveillance procedure was 0.2%. The poor response rate of patients was found to be a major problem and fewer than 40% per day returned to bring urine specimens. The mean prevalences of non-compliance established by rifampicin and INH tests were 19.5 ± 5.3% and 9.8 ± 3.9%, respectively, and these were significantly different (x2 = 7.44; P < 0.05). The proportion of false-positive results for INH and rifampicin urine tests were 21% (11/53) and 35%   (17/48), respectively, showing that some patients were taking the wrong treatment.Conclusions. It is clear that attendance at the clinics does not accurately reflect compliance. 80th programme compliance (dispensing of the correct treatment) and patient compliance need to be improved. This has important implications for the new national tuberculosis control policy adopted by the South African government that stresses the importance of directly observed therapy, short-course (DOTS) and a patient-centred approach

Emotion perception and electrophysiological correlates in Huntington\u27s disease

Objective This study aimed to characterise, emotion perception deficits in symptomatic Huntington\u27s disease (HD) via the use of event-related potentials (ERPs). Methods ERP data were recorded during a computerised facial expression task in 11 HD participants and 11 matched controls. Expression (scrambled, neutral, happy, angry, disgust) classification accuracy and intensity were assessed. Relationships between ERP indices and clinical disease characteristics were also examined. Results Accuracy was significantly lower for HD relative to controls, due to reduced performance for neutral, angry and disgust (but not happy) faces. Intensity ratings did not differ between groups. HD participants displayed significantly reduced visual processing amplitudes extending across pre-face (P100) and face-specific (N170) processing periods, whereas subsequent emotion processing amplitudes (N250) were similar across groups. Face-specific and emotion-specific derivations of the N170 and N250 (\u27neutral minus scrambled\u27 and \u27each emotion minus neutral\u27, respectively) did not differ between groups. Conclusions Our data suggest that the facial emotion recognition performance deficits in HD are primarily related to neural degeneration underlying \u27generalised\u27 visual processing, rather than face or emotional specific processing. Significance ERPs are a useful tool to separate functionally discreet impairments in HD, and provide an important avenue for biomarker application that could more-selectively track disease progression

Food Sovereignty and Agricultural Land Use Planning: The Need to Integrate Public Priorities Across Jurisdictions

Recent calls for national food policies that promote greater food sovereignty represent an emerging concern of public policy. Such a shift in food policy toward greater citizen control over domestic food supplies would have significant implications for all aspects of the agri-food system. One area of concern is the conservation and use of agricultural land because, in the end, every act of producing and consuming food has direct or indirect impacts on the land base. Yet no research has considered the potential interactions and implications between food sovereignty and agricultural land use planning. This gap in research presents an opportunity to critically examine the effects of the changing roles and values on agricultural land use planning within and across jurisdictions. We believe that a better understanding of the dominant policy regimes within the agri-food system, including global competitiveness, farmland preservation, and food sovereignty, can lead to land use planning practices that are most beneficial for integrating not only multiple interests across jurisdictions, but also multiple perspectives

The type of concurrent task affects dual-task performance in Huntington's disease

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Effects of task difficulty during dual-task circle tracing in Huntington's disease

YesHuntington’s disease (HD) is associated with impairments in dual-task performance. Despite that, only a few studies have investigated dual-tasking in HD. We examined dual-task performance in 15 participants in the early stages of HD and 15 healthy controls. Participants performed direct circle tracing (able to view arm) and indirect circle tracing (arm obscured) either on their own (single tasks) or paired with serial subtraction by twos or threes (dual tasks). Overall, our results suggested that HD participants were significantly slower and less accurate than controls. Both groups were slower and less accurate when performing indirect circle tracing compared with direct circle tracing. HD participants experienced greater dual-task interference in terms of accuracy when performing direct circle tracing compared with indirect circle tracing. Despite that, controls were more inclined to speed–accuracy trade-offs compared with HD participants. Importantly, unlike controls, HD participants were not disproportionately faster when performing direct circle tracing as a single task compared with the dual-task conditions. Our results suggest that simple tasks place greater attentional demands on HD participants compared with controls. These findings support that impaired automaticity may be responsible for some of the attentional deficits manifested in HD.Supported by the School of Psychological Sciences, Monash University

Plasma host protein biomarkers correlating with increasing Mycobacterium tuberculosis infection activity prior to tuberculosis diagnosis in people living with HIV

BACKGROUND: Biomarkers correlating with Mycobacterium tuberculosis infection activity/burden in asymptomatic individuals are urgently needed to identify and treat those at highest risk for developing active tuberculosis (TB). Our main objective was to identify plasma host protein biomarkers that change over time prior to developing TB in people living with HIV (PLHIV). METHODS: Using multiplex MRM-MS, we investigated host protein expressions from 2 years before until time of TB diagnosis in longitudinally collected (every 3-6 months) and stored plasma from PLHIV with incident TB, identified within a South African (SA) and US cohort. We performed temporal trend and discriminant analyses for proteins, and, to assure clinical relevance, we further compared protein levels at TB diagnosis to interferon-gamma release assay (IGRA; SA) or tuberculin-skin test (TST; US) positive and negative cohort subjects without TB. SA and US exploratory data were analyzed separately. FINDINGS: We identified 15 proteins in the SA (n=30) and 10 in the US (n=24) incident TB subjects which both changed from 2 years prior until time of TB diagnosis after controlling for 10% false discovery rate, and were significantly different at time of TB diagnosis compared to non-TB subjects (p<0.01). Five proteins, CD14, A2GL, NID1, SCTM1, and A1AG1, overlapped between both cohorts. Furthermore, after cross-validation, panels of 5 – 12 proteins were able to predict TB up to two years before diagnosis. INTERPRETATION: Host proteins can be biomarkers for increasing Mycobacterium tuberculosis infection activity/burden, incipient TB, and predict TB development in PLHIV. FUNDING: NIH/NIAID AI117927, AI146329, and AI127173 to JMA

Safety and immunogenicity of H1/IC31®, an adjuvanted TB subunit vaccine, in HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm3: a phase II, multi-centre, double-blind, randomized, placebo-controlled trial.

BACKGROUND: Novel tuberculosis vaccines should be safe, immunogenic, and effective in various population groups, including HIV-infected individuals. In this phase II multi-centre, double-blind, placebo-controlled trial, the safety and immunogenicity of the novel H1/IC31 vaccine, a fusion protein of Ag85B-ESAT-6 (H1) formulated with the adjuvant IC31, was evaluated in HIV-infected adults. METHODS: HIV-infected adults with CD4+ T cell counts >350/mm3 and without evidence of active tuberculosis were enrolled and followed until day 182. H1/IC31 vaccine or placebo was randomly allocated in a 5:1 ratio. The vaccine was administered intramuscularly at day 0 and 56. Safety assessment was based on medical history, clinical examinations, and blood and urine testing. Immunogenicity was determined by a short-term whole blood intracellular cytokine staining assay. RESULTS: 47 of the 48 randomised participants completed both vaccinations. In total, 459 mild or moderate and 2 severe adverse events were reported. There were three serious adverse events in two vaccinees classified as not related to the investigational product. Local injection site reactions were more common in H1/IC31 versus placebo recipients (65.0% vs. 12.5%, p = 0.015). Solicited systemic and unsolicited adverse events were similar by study arm. The baseline CD4+ T cell count and HIV viral load were similar by study arm and remained constant over time. The H1/IC31 vaccine induced a persistent Th1-immune response with predominately TNF-α and IL-2 co-expressing CD4+ T cells, as well as polyfunctional IFN-γ, TNF-α and IL-2 expressing CD4+ T cells. CONCLUSION: H1/IC31 was well tolerated and safe in HIV-infected adults with a CD4+ Lymphocyte count greater than 350 cells/mm3. The vaccine did not have an effect on CD4+ T cell count or HIV-1 viral load. H1/IC31 induced a specific and durable Th1 immune response. TRIAL REGISTRATION: Pan African Clinical Trials Registry (PACTR) PACTR201105000289276

Mortality associated with delays between clinic entry and ART initiation in resource-limited settings: results of a transition-state model.

OBJECTIVE: To estimate the mortality impact of delay in antiretroviral therapy (ART) initiation from the time of entry into care. DESIGN: A state-transition Markov process model. This technique allows for assessing mortality before and after ART initiation associated with delays in ART initiation among a general population of ART-eligible patients without conducting a randomized trial. METHODS: We used patient-level data from 3 South African cohorts to determine transition probabilities for pre-ART CD4 count changes and pre-ART and on-ART mortality. For each parameter, we generated probabilities and distributions for Monte Carlo simulations with 1-week cycles to estimate mortality 52 weeks from clinic entry. RESULTS: We estimated an increase in mortality from 11.0% to 14.7% (relative increase of 34%) with a 10-week delay in ART for patients entering care with our pre-ART cohort CD4 distribution. When we examined low CD4 ranges, the relative increase in mortality delays remained similar; however, the absolute increase in mortality rose. For example, among patients entering with CD4 count 50-99 cells per cubic millimeter, 12-month mortality increased from 13.3% with no delay compared with 17.0% with a 10-week delay and 22.9% with a 6-month delay. CONCLUSIONS: Delays in ART initiation, common in routine HIV programs, can lead to important increases in mortality. Prompt ART initiation for patients entering clinical care and eligible for ART, especially those with lower CD4 counts, could be a relatively low-cost approach with a potential marked impact on mortality

Rationing tests for drug-resistant tuberculosis - who are we prepared to miss?

BACKGROUND: Early identification of patients with drug-resistant tuberculosis (DR-TB) increases the likelihood of treatment success and interrupts transmission. Resource-constrained settings use risk profiling to ration the use of drug susceptibility testing (DST). Nevertheless, no studies have yet quantified how many patients with DR-TB this strategy will miss. METHODS: A total of 1,545 subjects, who presented to Lima health centres with possible TB symptoms, completed a clinic-epidemiological questionnaire and provided sputum samples for TB culture and DST. The proportion of drug resistance in this population was calculated and the data was analysed to demonstrate the effect of rationing tests to patients with multidrug-resistant TB (MDR-TB) risk factors on the number of tests needed and corresponding proportion of missed patients with DR-TB. RESULTS: Overall, 147/1,545 (9.5%) subjects had culture-positive TB, of which 32 (21.8%) had DR-TB (MDR, 13.6%; isoniazid mono-resistant, 7.5%; rifampicin mono-resistant, 0.7%). A total of 553 subjects (35.8%) reported one or more MDR-TB risk factors; of these, 506 (91.5%; 95% CI, 88.9-93.7%) did not have TB, 32/553 (5.8%; 95% CI, 3.4-8.1%) had drug-susceptible TB, and only 15/553 (2.7%; 95% CI, 1.5-4.4%) had DR-TB. Rationing DST to those with an MDR-TB risk factor would have missed more than half of the DR-TB population (17/32, 53.2%; 95% CI, 34.7-70.9). CONCLUSIONS: Rationing DST based on known MDR-TB risk factors misses an unacceptable proportion of patients with drug-resistance in settings with ongoing DR-TB transmission. Investment in diagnostic services to allow universal DST for people with presumptive TB should be a high priority