Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring

BACKGROUND: In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia. DESIGN AND METHODS: Multicohort study of 17 ART programmes. All sites monitored CD4 cell count and had access to second-line ART and 10 sites monitored viral load. We compared times to switching, CD4 cell counts at switching and obtained adjusted hazard ratios for switching (aHRs) with 95% confidence intervals (CIs) from random-effects Weibull models. RESULTS: A total of 20 113 patients, including 6369 (31.7%) patients from 10 programmes with access to viral load monitoring, were analysed; 576 patients (2.9%) switched. Low CD4 cell counts at ART initiation were associated with switching in all programmes. Median time to switching was 16.3 months [interquartile range (IQR) 10.1-26.6] in programmes with viral load monitoring and 21.8 months (IQR 14.0-21.8) in programmes without viral load monitoring (P < 0.001). Median CD4 cell counts at switching were 161 cells/microl (IQR 77-265) in programmes with viral load monitoring and 102 cells/microl (44-181) in programmes without viral load monitoring (P < 0.001). Switching was more common in programmes with viral load monitoring during months 7-18 after starting ART (aHR 1.38; 95% CI 0.97-1.98), similar during months 19-30 (aHR 0.97; 95% CI 0.58-1.60) and less common during months 31-42 (aHR 0.29; 95% CI 0.11-0.79). CONCLUSION: In resource-limited settings, switching to second-line regimens tends to occur earlier and at higher CD4 cell counts in ART programmes with viral load monitoring compared with programmes without viral load monitoring.

Predicting the population impact of chlamydia screening programmes: comparative mathematical modelling study

BACKGROUND: Published individual-based, dynamic sexual network modelling studies reach different conclusions about the population impact of screening for Chlamydia trachomatis. The objective of this study was to conduct a direct comparison of the effect of organised chlamydia screening in different models. METHODS: Three models simulating population-level sexual behaviour, chlamydia transmission, screening and partner notification were used. Parameters describing a hypothetical annual opportunistic screening program in 16-24 year olds were standardised, whereas other parameters from the three original studies were retained. Model predictions of the change in chlamydia prevalence were compared under a range of scenarios. RESULTS: Initial overall chlamydia prevalence rates were similar in women but not men and there were age and sex-specific differences between models. The number of screening tests carried out was comparable in all models but there were large differences in the predicted impact of screening. After 10 years of screening, the predicted reduction in chlamydia prevalence in women aged 16-44 years ranged from 4% to 85%. Screening men and women had a greater impact than screening women alone in all models. There were marked differences between models in assumptions about treatment seeking and sexual behaviour before the start of the screening intervention. CONCLUSIONS: Future models of chlamydia transmission should be fitted to both incidence and prevalence data. This meta-modelling study provides essential information for explaining differences between published studies and increasing the utility of individual-based chlamydia transmission models for policy making.

Paediatric antiretroviral treatment programmes in sub-Saharan Africa: a review of published clinical studies

Knowledge of the experience and outcomes of current paediatric antiretroviral treatment (ART) programmes in sub-Saharan Africa can inform new programmes in the region as well as enhance existing ones. This is urgently needed to facilitate the scale-up of treatment, which is needed to address the burden of paediatric HIV cases on the continent. We reviewed the characteristics and outcomes of programmes with clinical paediatric ART studies published prior to 1 January 2008. The outcomes of the studies were comparable to similar ones from developed countries; however, the duration of follow-up was relatively limited in almost all the studies reviewed. One-year survival probability was between 84% and 91%, and considerable improvement in the clinical, immunologic and iral status of the paediatric patients was generally recorded. Loss to follow-up was less than 10% in all but two studies. Adherence to treatment was good and few adverse events were reported. This is despite the fact that many programmes were subject to enormous constraints in terms of health services, and despite widespread use of adult fixed-dose combinations for paediatric patients, including young infants. While the majority of children commencing ART were severely ill, most children were old (median age >5 years for almost all studies) with relatively few infants and young children (age <2 years) receiving treatment. This is in contrast to knowledge of rapid disease progression in the majority of HIV-infected infants and despite the World Health Organization’s recent recommendations to commence ART in all HIV-infected infants less than one year old. There is an urgent need to address barriers to ART for infants. Studies of the outcomes of programmes treating infants as well as those with longer-term follow-up are also needed.

Tracing of patients lost to follow-up and HIV transmission: Mathematical modelling study based on two large ART programmes in Malawi

OBJECTIVES: Treatment as prevention depends on retaining HIV-infected patients in care. We investigated the effect on HIV transmission of bringing patients lost to follow up (LTFU) back into care. DESIGN: Mathematical model. METHODS: Stochastic mathematical model of cohorts of 1000 HIV-infected patients on antiretroviral therapy (ART), based on data from two clinics in Lilongwe, Malawi. We calculated cohort viral load (CVL; sum of individual mean viral loads each year) and used a mathematical relationship between viral load and transmission probability to estimate the number of new HIV infections. We simulated four scenarios: 'no LTFU' (all patients stay in care); 'no tracing' (patients LTFU are not traced); 'immediate tracing' (after missed clinic appointment); and, 'delayed tracing' (after six months). RESULTS: About 440 of 1000 patients were LTFU over five years. CVL (million copies/ml per 1000 patients) were 3.7 (95% prediction interval [PrI] 2.9-4.9) for no LTFU, 8.6 (95% PrI 7.3-10.0) for no tracing, 7.7 (95% PrI 6.2-9.1) for immediate, and 8.0 (95% PrI 6.7-9.5) for delayed tracing. Comparing no LTFU with no tracing the number of new infections increased from 33 (95% PrI 29-38) to 54 (95% PrI 47-60) per 1000 patients. Immediate tracing prevented 3.6 (95% PrI -3.3-12.8) and delayed tracing 2.5 (95% PrI -5.8-11.1) new infections per 1000. Immediate tracing was more efficient than delayed tracing: 116 and to 142 tracing efforts, respectively, were needed to prevent one new infection. CONCLUSION: Tracing of patients LTFU enhances the preventive effect of ART, but the number of transmissions prevented is small.

Monitoring of antiretroviral therapy and mortality in HIV programmes in Malawi, South Africa and Zambia: mathematical modelling study

OBJECTIVES Mortality in patients starting antiretroviral therapy (ART) is higher in Malawi and Zambia than in South Africa. We examined whether different monitoring of ART (viral load [VL] in South Africa and CD4 count in Malawi and Zambia) could explain this mortality difference. DESIGN Mathematical modelling study based on data from ART programmes. METHODS We used a stochastic simulation model to study the effect of VL monitoring on mortality over 5 years. In baseline scenario A all parameters were identical between strategies except for more timely and complete detection of treatment failure with VL monitoring. Additional scenarios introduced delays in switching to second-line ART (scenario B) or higher virologic failure rates (due to worse adherence) when monitoring was based on CD4 counts only (scenario C). Results are presented as relative risks (RR) with 95% prediction intervals and percent of observed mortality difference explained. RESULTS RRs comparing VL with CD4 cell count monitoring were 0.94 (0.74-1.03) in scenario A, 0.94 (0.77-1.02) with delayed switching (scenario B) and 0.80 (0.44-1.07) when assuming a 3-times higher rate of failure (scenario C). The observed mortality at 3 years was 10.9% in Malawi and Zambia and 8.6% in South Africa (absolute difference 2.3%). The percentage of the mortality difference explained by VL monitoring ranged from 4% (scenario A) to 32% (scenarios B and C combined, assuming a 3-times higher failure rate). Eleven percent was explained by non-HIV related mortality. CONCLUSIONS VL monitoring reduces mortality moderately when assuming improved adherence and decreased failure rates.

Outcomes of antiretroviral treatment programmes in rural Lesotho: health centres and hospitals compared

Introduction: Lesotho was among the first countries to adopt decentralization of care from hospitals to nurse-led health centres (HCs) to scale up the provision of antiretroviral therapy (ART). We compared outcomes between patients who started ART at HCs and hospitals in two rural catchment areas in Lesotho. Methods: The two catchment areas comprise two hospitals and 12 HCs. Patients ≥16 years starting ART at a hospital or HC between 2008 and 2011 were included. Loss to follow-up (LTFU) was defined as not returning to the facility for ≥180 days after the last visit, no follow-up (no FUP) as not returning after starting ART, and retention in care as alive and on ART at the facility. The data were analysed using logistic regression, competing risk regression and Kaplan-Meier methods. Multivariable analyses were adjusted for sex, age, CD4 cell count, World Health Organization stage, catchment area and type of ART. All analyses were stratified by gender. Results: Of 3747 patients, 2042 (54.5%) started ART at HCs. Both women and men at hospitals had more advanced clinical and immunological stages of disease than those at HCs. Over 5445 patient-years, 420 died and 475 were LTFU. Kaplan-Meier estimates for three-year retention were 68.7 and 69.7% at HCs and hospitals, respectively, among women (p=0.81) and 68.8% at HCs versus 54.7% at hospitals among men (p<0.001). These findings persisted in adjusted analyses, with similar retention at HCs and hospitals among women (odds ratio (OR): 0.89, 95% confidence interval (CI): 0.73-1.09) and higher retention at HCs among men (OR: 1.53, 95% CI: 1.20-1.96). The latter result was mainly driven by a lower proportion of patients LTFU at HCs (OR: 0.68, 95% CI: 0.51-0.93). Conclusions: In rural Lesotho, overall retention in care did not differ significantly between nurse-led HCs and hospitals. However, men seemed to benefit most from starting ART at HCs, as they were more likely to remain in care in these facilities compared to hospitals.

Monitoring Programmes, Multiple Stress Analysis and Decision Support for River Basin Management

The identification of plausible causes for water body status deterioration will be much easier if it can build on available, reliable, extensive and comprehensive biogeochemical monitoring data (preferably aggregated in a database). A plausible identification of such causes is a prerequisite for well-informed decisions on which mitigation or remediation measures to take. In this chapter, first a rationale for an extended monitoring programme is provided; it is then compared to the one required by the Water Framework Directive (WFD). This proposal includes a list of relevant parameters that are needed for an integrated, a priori status assessment. Secondly, a few sophisticated statistical tools are described that subsequently allow for the estiation of the magnitude of impairment as well as the likely relative importance of different stressors in a multiple stressed environment. The advantages and restrictions of these rather complicated analytical methods are discussed. Finally, the use of Decision Support Systems (DSS) is advocated with regard to the specific WFD implementation requirements.

Schulpraktika in der Lehrerbildung. Theoretische Grundlagen, Konzeptionen, Prozesse und Effekte = Pedagogical field experiences in teacher education. Theoretical foundations, programmes, processes, and effects

Seit mehr als zwanzig Jahren werden in der tertiären Lehramtsausbildung Schulpraktika reformiert und neuerdings in ihrem zeitlichen Umfang relativ zur Studienzeit vergrößert. Zum Gegenstand reger Forschungsaktivitäten avancierten Schulpraktika jedoch erst im letzten Jahrzehnt. Hiermit werden ein Überblick über das Forschungsfeld (Grundlagen der schulpraktischen Komponenten der Lehrerbildung; Forschungsmethodik) vorgelegt und aktuelle Forschungsergebnisse zu zentralen Aspekten der Wirksamkeit von Praktika und Effekten von Mentoring präsentiert. In englischsprachigen bzw. deutschsprachigen Beiträgen wird der Forschungsstand in Deutschland, den Niederlanden, Österreich und der Schweiz sowie den USA aufgezeigt. Der Band richtet sich an Personen, die in der Lehrerbildung tätig sind, also an Dozent/inn/en in Hochschulen und Seminaren, an Lehrerbildungsforscher/innen sowie an Fachpersonen in der Bildungsadministration und interessierte Studierende.

Integrated care programmes for adults with chronic conditions: a meta-review.

OBJECTIVE To review systematic reviews and meta-analyses of integrated care programmes in chronically ill patients, with a focus on methodological quality, elements of integration assessed and effects reported. DESIGN Meta-review of systematic reviews and meta-analyses identified in Medline (1946-March 2012), Embase (1980-March 2012), CINHAL (1981-March 2012) and the Cochrane Library of Systematic Reviews (issue 1, 2012). MAIN OUTCOME MEASURES Methodological quality assessed by the 11-item Assessment of Multiple Systematic Reviews (AMSTAR) checklist; elements of integration assessed using a published list of 10 key principles of integration; effects on patient-centred outcomes, process quality, use of healthcare and costs. RESULTS Twenty-seven systematic reviews were identified; conditions included chronic heart failure (CHF; 12 reviews), diabetes mellitus (DM; seven reviews), chronic obstructive pulmonary disease (COPD; seven reviews) and asthma (five reviews). The median number of AMSTAR checklist items met was five: few reviewers searched for unpublished literature or described the primary studies and interventions in detail. Most reviews covered comprehensive services across the care continuum or standardization of care through inter-professional teams, but organizational culture, governance structure or financial management were rarely assessed. A majority of reviews found beneficial effects of integration, including reduced hospital admissions and re-admissions (in CHF and DM), improved adherence to treatment guidelines (DM, COPD and asthma) or quality of life (DM). Few reviews showed reductions in costs. CONCLUSIONS Systematic reviews of integrated care programmes were of mixed quality, assessed only some components of integration of care, and showed consistent benefits for some outcomes but not others.