bluuebunny/crossref_metadata_2025 huggingface dataset:
Éviter les guerres tout en imitant le « modèle militaire » : la pédagogie pacifiste esquissée par Alain
Authors: Jacomino Baptiste
Published: November 2012

Résumé Alain veut mettre l’école au service de la paix. Les guerres, écrit-il, n’ont qu’une cause : les passions. Or, l’éducation peut beaucoup contre les passions. Grâce aux Humanités, à la géométrie et à des exercices mécaniques, on peut délivrer l’enfant du fanatisme et des tensions qui conduisent aux guerres. Tout en défendant cette ligne pacifiste, Alain invite le maître à s’inspirer du « modèle militaire ». Il semble considérer qu’une discipline parfois brutale permet de donner à l’enfant la confiance en soi grâce à laquelle il va pouvoir apprendre à douter et à se méfier de lui-même, se libérant ainsi de tout fanatisme. Il y a donc chez Alain des pistes pour bâtir une pédagogie pacifiste en partie inspirée du « modèle militaire », mais il s’agit seulement de pistes et non d’une doctrine parfaitement articulée et claire.
Enfants du viol : questions, silence et transmission
Authors: Godard Marie-Odile , Ukeye Marie-Josée
Published: November 2012

Résumé Bientôt dix-huit ans que le génocide des Tutsi a bouleversé le Rwanda. Il a été perpétré en cent jours et a fait plus d’un million de morts. Les survivants tentent de reconstruire un pays, une culture, une vie qui est entachée par le génocide. Si la société rwandaise post-génocidaire s’est attachée à interdire la mention de l’ethnie, à rendre la scolarité obligatoire, à juger les génocidaires par l’instauration des Gacaca, à créer le Fond d’aide aux rescapés du génocide (FARG), certains enfants portent en eux la marque du génocide. Nous voulons parler ici des enfants nés du viol de leurs jeunes (ou moins jeunes) mères. Ils ont entre 16 et 17 ans, et c’est parce que leur parole devient de plus en plus claire que nous les entendons. Que savent-ils de leur histoire ? Qui la leur a racontée ? Que peuvent-ils faire du poids de leurs ascendants ? Nous étudierons le cheminement de ces enfants et de ces mères à partir de l’élaboration menée dans deux groupes thérapeutiques, l’un de ces femmes violées et l’autre de ces enfants issus du viol.
Justicia conciliatoria durante el liberalismo hispano en el Perú: el caso de Huamanga
Authors: Sala i Vila Nuria
Published: November 2012

La Constitución de 1812 estableció la división de poderes, excepto en el ámbito local. Los alcaldes tenían competencias en el gobierno interior de los pueblos y, al mismo tiempo, eran los jueces legos en las conciliaciones, un trámite preceptivo para los litigantes y para dirimir cualquier conflicto ante la justicia letrada —jueces de partido o audiencias. A partir del estudio de caso de Huamanga, se analizan los actores y la tipología de las causas dirimidas durante las dos etapas en que el virreinato del Perú ensayó la política liberal hispana —1812-1814 y 1820-1824. La cultura jurídica municipal estuvo dominada por una serie de cambios y reivindicaciones, que aportan nuevas perspectivas para comprender los convulsos tiempos de las guerras por la independencia en los Andes y que en ocasiones trascendieron a la temprana república.
«Los naturales son ciudadanos de la gran familia boliviana». La participación indígena en la construcción del departamento del Beni, siglo XIX
Authors: Guiteras Mombiola Anna
Published: November 2012

En 1842, la creación del departamento del Beni implicó la extensión de la ciudadanía a sus habitantes, en su gran mayoría indígenas. A través de la legislación sancionada a lo largo del sigo XIX, se analizan las estrategias, actividades e instituciones de esta población en relación al ejercicio de las garantías constitucionales en el ámbito sociopolítico —gobierno local— y en el socioeconómico —propiedad de la tierra.
«La revolución está vencida, pero el gobierno está muerto». Crisis política, discursos periodísticos y demostraciones callejeras en Buenos Aires, 1890
Authors: Rojkind Inés
Published: November 2012

Este trabajo aborda la crisis que atravesó en 1890 el régimen conservador, en el contexto de una fallida rebelión armada y de la renuncia del presidente Miguel Juárez Celman. La intención es explicar el modo en que la ampliación y la diversificación de la participación política contribuyeron a profundizar los cuestionamientos que corroían la legitimidad del orden vigente. Se analizan las demostraciones callejeras que, alimentadas por los discursos de la prensa y por los debates parlamentarios, se sucedieron en la ciudad de Buenos Aires durante varios días.
«Aquí yace Sebastián de Ocampo, que Dios perdona» (Perfil biográfico de un mercader indiano †1514)
Authors: Mena García Carmen
Published: November 2012

El gallego Sebastián de Ocampo ha pasado a la historia como marino y explorador, sobre todo a raíz de su expedición para averiguar la insularidad de la isla de Cuba en 1506. Se le reconoce también por su relación con Vasco Núñez de Balboa, quien lo nombró por apoderado en defensa de sus intereses ante la Corte. El análisis de su testamento nos revela otras facetas, desconocidas hasta la fecha, de este curioso personaje de la época de la conquista de América: además de su círculo familiar más inmediato, sus vínculos con la isla de la Gomera, donde estuvo avecindado por algún tiempo, y su actuación en Santo Domingo, en donde transcurrieron sus últimos años, y en Sevilla, donde falleció, como cambista y mercader del comercio atlántico con socios y protectores convenientemente instalados en las altas esferas del poder.
Aforismos militares y guerra del Arauco: las Memorias de los sucesos de la guerra de Chile de Jerónimo de Quiroga
Authors: Espino López Antonio
Published: November 2012

En el presente trabajo hemos pretendido recuperar el pensamiento militar del maestre de campo del ejército de Chile, Jerónimo de Quiroga, autor de unas Memorias de los sucesos de la guerra de Chile escritas a finales del siglo XVII y que permanecieron inéditas, donde éste analizaba no sólo las causas de la prolongación de tan sangriento conflicto, criticando la labor política de muchos gobernadores, sino que también representa un buen ejemplo de cómo trascendieron ciertas ideas en torno a la problemática de la guerra.
Matched filter separation of magnetic anomalies caused by scattered surface debris at archaeological sites
Authors: Sheriff Steven D.
Published: November 2012

Randomly scattered debris, some of it ferromagnetic, on or near the ground surface regularly degrades magnetic data acquired for archaeological purposes. These sources create short‐wavelength high‐amplitude dipolar anomalies in total field magnetic intensity maps and they can dominate maps of the vertical magnetic gradient. Thus, we generally wish to separate longer wavelength anomalies created by features of interest, such as foundations or building perimeters, from the shorter wavelength anomalies created by debris on or near the ground surface. Matched bandpass filtering, employed extensively in the aeromagnetic industry, is an effective way to separate magnetic anomalies arising from different depths. It entails fitting the radially averaged power spectrum of the total field magnetic data with a series of power spectra corresponding to simple equivalent layers at the archaeological site. We show that applying matched bandpass filtering to a set of total field magnetic intensity data yields two equivalent layers with excellent separation of near‐surface sources from deeper sources of interest. The benefit of this approach over enhancing surface features using magnetic gradiometry, analysis by upward continuation, or the analytic signal is that we isolate the source layers without losing information.
Socially responsible ethnobotanical surveys in the Cape Floristic Region: ethical principles, methodology and quantification of data
Authors: Van Wyk Ben-Erik , De Beer Josef J.
Published: November 2012

A broad overview of published and unpublished ethnobotanical surveys in the Cape Floristic Region (the traditional home of the San and Khoi communities) shows that the data is incomplete. There is an urgent need to record the rich indigenous knowledge about plants in a systematic and social responsible manner in order to preserve this cultural and scientific heritage for future generations. Improved methods for quantifying data are introduced, with special reference to the simplicity and benefits of the new Matrix Method. This methodology prevents or reduces the number of false negatives, and also ensures the participation of elderly people who might be immobile. It also makes it possible to compare plant uses in different local communities. This method enables the researcher to quantify the knowledge on plant use that was preserved in a community, and to determine the relative importance of a specific plant in a more objective way. Ethical considerations for such ethnobotanical surveys are discussed, through the lens of current ethical codes and international conventions. This is an accessible approach, which can also be used in the life sciences classroom.
Multi-Destination Trips and Tourism Statistics: Empirical Evidences in Sicily
Authors: Parroco Anna Maria , Vaccina Franco , De Cantis Stefano , Ferrante Mauro
Published: November 2012

The knowledge of the actual magnitude and main features of tourism flows in a given destination is an essential prerequisite for the evaluation of tourism impacts and externalities. Indeed, many pleasure trips are often characterized by the visit to more than a single destination. Although the topic is well-documented in literature, the empirical results are limited to a few pioneering studies. The lack may be attributable to the failure of tourism organizations to collect data on multi-destination trip behaviour. This can be seen, for example, in the system of European statistics on tourism (according to the Council Directive 95/57 EC), where information on the average number of visited destinations within a single trip is not provided. This paper aims at discussing the main implications of multi-destination trips, both on tourism statistics and on destination management. It also proposes to describe the research design and main preliminary results of a survey on incoming tourism in Sicily. Some remarks dealing with the positive and negative impacts of unobserved tourism and of multi-destination trips are reported at the end.
Assessment of COSMIC radio occultation retrieval product using global radiosonde data
Authors: Wang B.-R. , Liu X.-Y. , Wang J.-K.
Published: November 2012

Abstract. The radio occultation retrieval product of the Constellation Observing System for Meteorology, Ionosphere, and Climate (COSMIC) radio occultation sounding system was verified using the global radiosonde from 2007 to 2010. 4 yr of samples were used to collect quantities of data using much stricter matching criteria than previous studies to obtain more accurate results. The horizontal distance between the radiosonde station and the occultation event is within 100 km, and the time window is 1 h. The comparison was performed from 925 hPa to 10 hPa. The results indicated that the COSMIC's temperature data agreed well with the radiosonde data. The global mean temperature bias was −0.09 K, with a standard deviation (SD) of 1.72 K. The water vapor pressure of COSMIC showed a systematic bias in relation to radiosonde in higher layers. The mean specific humidity bias of 925–200 hPa is about −0.011 g kg−1, with a SD of about 0.662 g kg−1. The COSMIC quality control process could not detect some abnormal extremely small humidity data which occured frequently in subtropical zone. Despite the large relative error of water vapor pressure, the relative error of refractivity is small. This paper also provides a comparison of eight radiosonde types with COSMIC product. Because the retrieval product is affected by the background error which differed between different regions, the COSMIC retrieval product could be used as a benchmark if the precision requirement is not strict.
Organic carbon stocks in Mediterranean soil types under different land uses (Southern Spain)
Authors: Muñoz-Rojas M. , Jordán A. , Zavala L. M. , De la Rosa D. , Abd-Elmabod S. K. , Anaya-Romero M.
Published: November 2012

Abstract. Soil C sequestration through changes in land use and management is one of the sustainable and long-term strategies to mitigate climate change. This research explores and quantifies the role of soil and land use as determinants of the ability of soils to store C along Mediterranean systems. Detailed studies of soil organic C (SOC) dynamics are necessary in order to identify factors determining fluctuations and intensity of changes. In this study, SOC contents from different soil and land use types have been investigated in Andalusia (Southern Spain). We have used soil information from different databases, as well as land use digital maps, climate databases and digital elevation models. The average SOC content for each soil control section (0–25, 25–50 and 50–75 cm) was determined and SOC stocks were calculated for each combination of soil and land use type, using soil and land cover maps. The total organic C stocks in soils of Andalusia is 415 Tg for the upper 75 cm, with average values ranging from 15.9 Mg C ha−1 (Solonchaks under "arable land") to 107.6 Mg C ha−1 (Fluvisols from "wetlands"). Up to 55% of SOC accumulates in the top 25 cm of soil (229.7 Tg). This research constitutes a preliminary assessment for modelling SOC stock under scenarios of land use and climate change.
Insight into collision zone dynamics from topography: numerical modelling results and observations
Authors: Bottrill A. D. , van Hunen J. , Allen M. B.
Published: November 2012

Abstract. Dynamic models of subduction and continental collision are used to predict dynamic topography changes on the overriding plate. The modelling results show a distinct evolution of topography on the overriding plate, during subduction, continental collision and slab break-off. A prominent topographic feature is a temporary (few Myrs) basin on the overriding plate after initial collision. This "collisional mantle dynamic basin" (CMDB) is caused by slab steepening drawing, material away from the base of the overriding plate. Also, during this initial collision phase, surface uplift is predicted on the overriding plate between the suture zone and the CMDB, due to the subduction of buoyant continental material and its isostatic compensation. After slab detachment, redistribution of stresses and underplating of the overriding plate cause the uplift to spread further into the overriding plate. This topographic evolution fits the stratigraphy found on the overriding plate of the Arabia-Eurasia collision zone in Iran and south east Turkey. The sedimentary record from the overriding plate contains Upper Oligocene-Lower Miocene marine carbonates deposited between terrestrial clastic sedimentary rocks, in units such as the Qom Formation and its lateral equivalents. This stratigraphy shows that during the Late Oligocene–Early Miocene the surface of the overriding plate sank below sea level before rising back above sea level, without major compressional deformation recorded in the same area. Our modelled topography changes fit well with this observed uplift and subsidence.
Predictive factors of therapeutic success of a HAART regimen including atazanavir with or without ritonavir in HIV‐infected patients
Authors: Giacomelli A , Franzetti M , Vergani B , Oreni L , Morosi M , Di Cristo V , Colella E , Vigano O , Galli M , Rusconi S
Published: November 2012

To evaluate the factors that may influence the persistence and the virological failure of an atazanavir (ATV)‐containing antiretroviral regimen. We conducted a retrospective cohort study in HIV‐positive patients (pts) who were being followed at the Infectious Diseases Division, University of Milan. Data regarding viral load, CD4 lymphocytes and the blood chemistry parameters were collected at 1st, 3rd, 6th months from the beginning of therapy and then every six months. Factors related to persistence of therapy with ATV and virological failure (HIV‐RNA>50cp/mL after six months) were evaluated with Kaplan‐Meier curve, Cox model and logistic regression. 574 pts were evaluated: 480 experienced therapy with ATV with ritonavir (ATV/r) (80 naïve), 218 with unboosted ATV (5 naïve) and 124 with both regimens. At baseline: median age of 43 years (IQR 39–48), CD4+median count 418 cell/mm3 (IQR 277–606), VL<50cp/mL in 370 pts (54.4%), and median duration of infection 12 years (IQR 6–18). The median duration of therapy was 21 months (IQR 7–49) in pts treated with ATV/r and 22 months (IQR 8–44) with unboosted ATV. We observed a borderline significant difference for the persistence of the regimen between the two groups (p=0.05) that disappears after removing the suspensions for simplification. Pts treated with ritonavir (OR=1.563; 95% CI 1.058–2.308, p=0.025) and with a backbone containing AZT‐ddI‐d4T (OR=3.34; 95% CI 1.873–5.956, p<0.001) had an increased risk of therapy suspension, whereas starting therapy with ATV in recent years resulted protective (OR=0.741; 95% CI 0.678–0.809, p<0.001). The suspension for toxicity was not significantly different between pts treated with ATV/r and unboosted ATV. No significant difference between the two therapies was observed regarding virological failure. Of note, pts with an elevated VL at baseline (OR 1.234; 95% CI 1.065–1.429, p=0.005) and male gender (OR 1.667; 95% CI 1.06–2.621, p=0.027) were at elevated risk of failure, whereas a backbone containing AZT‐ddI‐d4T (OR 0.356; 95% CI 0.196–0.638, p=0.001) and a recent year of starting ATV (OR 0.64; 95% CI 0.579–0.71, p<0.001) are protective factors. No significant difference between pts treated with ATV/r or unboosted was observed regarding the induction of hyperbilirubinemia of ACTG grade III and IV. Treatment with unboosted ATV can last longer than that with ATV/r without an increased risk of therapeutic failure. A comparable safety profile was seen for pts who received ATV/r or unboosted ATV.
Etravirine with 2 NRTIs: an effective switch option for ARV simplification and side effect management
Authors: Smith G , Brunetta J , Loutfy M , Crouzat F , Hedgecock M , Merkley B , Chang B , Tilley D , Kovacs C , Fletcher D
Published: November 2012

Etravirine (ETV) has been approved for use in treatment‐experienced patients based on results of the Duet clinical trials [1]. Less experience exists with ETV in earlier stages of treatment. ETV has a favorable genetic barrier, lipid profile, and little associated CNS toxicity. These characteristics make ETV attractive as a switch strategy for simplification and/or management of side effects. A retrospective chart review was conducted at a large urban HIV clinic in Toronto. All patients who were switched to ETV plus 2 nucleosides and whose viral load (VL) was <200 copies/ml at the time of switch were included. Maintenance of viral suppression, CD4 and lipid changes at 24 weeks and reason for switch to ETV are reported. Seventy‐three patients (67 male) were identified. Mean age was 46±10 and mean duration of HIV infection was 11.7±7.4 years. Switches were from efavirenz=29, atazanavir=23, lopinavir=16, other=5. Duration of prior regimen was long; median 195 weeks. CNS and GI intolerance were the most common reasons for switches. At the time of analysis, 63 patients had reached week 24. Three patients had discontinued ETV prior to week 24, 3 LTF/U, 4 had <24 weeks follow‐up. 92% (67/73) maintained VL suppression (ITT); failures were 6 patients who stopped/lost‐to‐follow‐up prior to week 24. On treatment, CD4 increased and lipid decreased changes as seen below. All patients who switched due to CNS side effects had subjective improvement.

Baseline
Change from baseline to week 24 (OT, n=63)
P value

CD4 (cells/mm3)
632±269
+49±137
<0.01

Total cholesterol (mmol/L)
4.76±1.11
−0.57±0.77
<0.01

HDL (mmol/L)
1.20±0.36
−0.05±0.21
0.06

LDL (mmol/L)
2.71±1086
−0.40±0.73
<0.01

Triglycerides (mmol/L)
2.06±1.86
−0.55±1.76
0.02

Switch to ETV plus 2 nucleosides maintained viral suppression, improved lipid profiles and improved side effect profile in this selected group of patients. 48 week f/u will be presented.
Persistence of antiretroviral treatment in emtricitabine/tenofovir (FTC/TDF) users vs other NRTI in ART‐naïve patients>50 years: TRIP study
Authors: Pedrol E , Castaño M , Olalla J , Domingo P , Arazo P , Gómez‐Sirvent J , Riera M , Pulido F , Vera F , Vergara A , Aguirrebengoa K , Portilla J , Blanco J
Published: November 2012

The major antiretroviral guidelines recommend starting ART in patients>50 y of age, regardless of CD4 cell count. However, no references to the preferred cART for these patients have been described. The combination FTC/TDF is one of the cornerstones of combined antiretroviral therapy (cART) in naïve patients. We studied the persistence of coformulated FTC/TDF in this scenario. National, retrospective cohort analysis of HIV‐infected patients>50 y at the time they began the first cART regimen (January 1, 2006 – December 31, 2009). Patients were selected in a proportion 2:1 to FTC/TDF vs. other NRTI regimens (no‐TDF). We compared the persistence of treatment in FTC/TDF users vs. no‐TDF (main groups). Among TDF users, we compared the persistence in PI vs. NNRTI users and in lopinavir/r vs. efavirenz users. Persistence was defined as the duration of the initial treatment; we analyzed time to any change or discontinuation according to initial regimen. We included 161 patients: median age: 54.6 y, 83% males, median CD4 count 191 cells/μl, median viral load 4.7 log, follow up: median 19 months, max 48 months. Of them, 112 started with FTC/TDF (53 with PIs, 57 with NNRTIs); and 49 with other NRTIs (no‐TDF) (22 with PI, 23 NNRTI). During the follow‐up period 79 patients (49%) modified their treatment, with statistically significant differences among groups, as shown in Table 1.

*Adjusted by age, sex, transmission category and baseline CD4 count and viral load.

In our study (antiretroviral‐naïve patients>50 y), the persistence of FTC/TDF regimens was significantly higher than other NRTI regimens. According to the third agent, there was a trend to a higher persistence with NNRTI vs. PI. This reaches statistical significance when we compare EFV vs. LPV/r. In the absence of randomized clinical trials, our data may contribute to a better understanding on how cART works in this ageing population, which is progressively increasing.

Proportion and hazard ratio of non‐persistence (any change or discontinuation of any component of initial cART), aOR adjusted by age, sex, transmission category and baseline CD4 count and viral load

Initial cART
Non‐persistence, N (%)
Log rank
Crude HR (95% CI)
Adjusted HR* (95% CI)

No‐TDF vs. TDF
35/49 (71.4) vs. 44/112 (38.6)
0.001
2.04 (1.31, 3.18)
2.10 (1.34, 3.29)

Among TDF users:

PI vs. NNRTI
26/53 (49.1) vs. 18/57 (31.6)
0.108
1.63 (0.89, 2.97)
1.63 (0.87, 3.06)

Lopinavir/r vs. efavirenz
19/35 (54.3) vs. 16/52 (30.8)
0.033
2.03 (1.04, 3.96)
2.05 (1.05, 3.99)
Activation and inflammation markers in HIV‐1‐infected patients in dependency of treatment strategies
Authors: Ehret R , Wienbreyer A , Obermeier M , Baumgarten A , Krznaric I , Ingiliz P , Carganico A , Dupke S , Cordes C , Schulbin H , Claus J , Berg T
Published: November 2012

Purpose of the study

HIV‐1‐infected patients have elevated levels of immune activation and systemic inflammatory markers which are partially strong predictors of disease progression or are associated with increased cardiovascular risk. The dependency of anti‐retroviral treatment (ART), the usage of NNRTI or PI‐based and the application of non‐nuc regimens is analysed here on the basis of a dataset (Chronic Inflammation Dependency on TREatment: CIDRE cohort) from 1500 patients in Berlin.

Methods

In a retrospective analysis we compared relative CD4+ cell counts, viral load, relative CD8+CD38+DR‐and CD3+DR+cells, concentration of high‐sensitivity C‐reactive protein (hsCRP) and interleukin‐6 (IL‐6) in therapy‐naïve or treated patients dependent on usage or non‐usage of NUCs, PI or NNRTI. Statistics were performed with R (R Core Team; 2012; R: A language and environment for statistical computing) using Wilcoxon rank sum test in two‐sided analysis.

Summary of results

As to expect, ART‐naïve patients (n=190) had significantly higher viral loads and lower CD4+cell counts (p: both<0.05) and showed higher activation levels than treated patient (CD8+CD38+DR‐ and CD3+DR+both<0.05). But no significant difference was calculated for hsCRP or IL‐6. Nuc‐sparing regimen (n=46) did not show any distinction compared to nuc‐containing therapies (n=1249) for the analysed parameters. Significant differences were detected for PI‐regimen (n=711) with lower CD4+ cell counts and higher activation (CD8+38+DR‐, CD3+DR+) and IL‐6 (p: all<0.05) but not for hsCRP (p=0.39). The opposite was true for NNRTI‐based therapies (n=445) with higher CD4+ cell percentages and lower activation and inflammation markers (p: all<0.05) and as well no difference in hsCRP (p=0.97) compared with all other treated patients.

Conclusions

The lack of differences between therapy‐naïve patients and patients on ART for inflammation markers may be due to the relative good immunological state of the first group, which could be one of the reasons why they are not treated so far. The number of nuc‐sparing regimen is perhaps too low and too undifferentiated to find diverse inflammation states. Although the differences in activation status can be attributed to different treatment strata, there is no clear explanation for this outcome. A possible reason could be a pre‐selection bias either for NNRTI‐based or PI‐based regimens. Additional data is acquired to perform longitudinal analysis to gain further insight.
Pregnant … pause? Is there a difference in the long‐term outcome of women starting ART for the first time in pregnancy?
Authors: Farne H , Russell J , Kegg S
Published: November 2012

Purpose of the study

The guidelines on the initial choice of antiretroviral therapy (ART) in women starting ART for the first time in pregnancy have changed considerably over the past 13 years [1,2]. We sought to determine whether these different ART strategies have influenced subsequent clinical, immunological or virological outcomes in our population. Women in our cohort received either zidovudine (AZT) monotherapy, short course antiretroviral therapy (SCART) or continued ART post‐partum. AZT monotherapy in pregnancy was common a decade ago, but its use declined amidst concerns about efficacy and the potential development of resistance with monotherapy. SCART more effectively suppresses viral load (VL) but avoids unnecessary treatment post‐partum in those considered at low risk of disease progression. This is used less now the benefits of starting ART at better‐conserved CD4 counts and the risks of treatment interruption are known.

Method

30 women who commenced ART during a pregnancy which resulted in a live birth between 1999 and 2004 were identified from a departmental database. Women already on ART or who had previously received AZT monotherapy or SCART were excluded, as were women with less than 2 years follow up post‐partum. Outcomes included time to starting ART, CD4 count and VL on starting ART and at last follow up.

Summary of results

12 women received AZT monotherapy, 7 SCART and 11 continued ART post‐partum. In total there were 269 years of patient follow up (mean 9, range 2–13).

(mean)
AZT monotherapy
SCART
Continued ART

Baseline CD4
409
359
190

Baseline VL
1,950
6,799
59,566

Time to starting ART
5.2 years*
4.6 years**

CD4 on starting ART
254
178

CD4 <350 on starting ART
3/12
3/7

CD4 at last follow up
519
451
543

1 still not on ART at last follow up; **2 not on ART at last follow up.

None of the women who received AZT monotherapy or SCART experienced clinical disease progression during their time off therapy, which was considerable (mean 4–5 years). All achieved virological suppression and good CD4 recovery on commencing ART. None of the available genotypes in these patients showed resistance mutations. Of the women who continued ART, more than half modified their regimen and a significant number experienced transient VL rebounds.

Conclusions

The clinical choices made a decade ago do not appear to have been detrimental to the longer‐term treatment responses in this group of women. However, the effects of treatment interruption remain unclear and we suggest a cautious approach.
Efficacy and safety of switching double‐boosted protease inhibitors to boosted darunavir in HIV‐infected patients with virologic suppression
Authors: Curran A , Villar J , Burgos J , González A , van den Eynde E , Guelar A , Falcó V , Crespo M , Knobel H , Ribera E
Published: November 2012

Purpose of the study

Switching to ritonavir‐boosted darunavir (DRV/r) in patients treated with double ritonavir‐boosted protease inhibitors (PI/r) may result in better tolerability, less pill burden, better lipid profile and a lower cost, while maintaining virologic efficacy.

Methods

Multicentre, concurrent cohort observational study. HIV‐infected adults with HIV RNA <50 copies/mL for at least the previous 12 months on a double PI/r‐based therapy were offered to switch to DRV/r (DRV group) or to continue on the same regimen (control group). Visits (including blood tests, adherence and side effects assessment) were performed every 3 months, with a follow‐up of at least one year. Descriptive values are described as n (%) or median (interquartile range). Changes from baseline in quantitative variables have been calculated with the Wilcoxon Signed Ranks Test and comparisons between groups have been performed with the Mann‐Whitney test, using SPSS 20.0 statistical package.

Summary of results

65 patients were included (35 DRV group and 30 control group); median age was 46 (40–49) years, 76% were male. At baseline, double‐boosted PI regimens were lopinavir‐atazanavir/r 24%, lopinavir‐saquinavir/r 46%, lopinavir‐fosamprenavir/r 8%, atazanavir‐saquinavir/r 18% and others 4%. There were no significant differences between groups in baseline characteristics, except for patients who switched to DRV had a higher number of prior antiretroviral regimens [6 (3–8) vs 2 (1–4), p=.002]. Of the patients who switched to DRV/r, 46% received DRV/r once‐daily and 54% twice‐daily. After 48 weeks, one patient in each arm had virologic failure and one patient in the DRV arm stopped treatment due to side effects (depressive syndrome); there were no episodes of rash or clinical hepatitis. Efficacy (HIV RNA <50 copies/mL) was similar in the DRV and control groups by intention‐to‐treat analysis (94 vs. 97%, p=NS). There were no significant differences in laboratory parameters between treatment groups except for a decrease in total bilirrubin in patients who switched to DRV/r (−0.69 vs +0.28 mg/dL, p=.028). Treatment switch represented a median saving of 157 (32–264) euros per patient per month.

Conclusions

Switching from a double‐boosted PI regimen to DRV maintains virologic efficacy, with good tolerability and a lower cost.
Safety and efficacy of a raltegravir‐based dual antiretroviral therapy in clinical practice
Authors: Cenderello G , Penco G , Pontali E , Feasi M , Cassola G
Published: November 2012

Background

HAART has revolutionized HIV disease management and increased life expectancy for most HIV‐infected individuals on treatment. A nucleoside/tide reverse transcriptase (NRTI) inhibitor backbone is a recommended component of standard first‐line HAART. Nevertheless, NRTI‐sparing alternatives are warranted in order to reduce long‐term toxicities in many patients (pts). Aim of the study was to evaluate safety of raltegravir‐based dual antiretroviral therapy (DUAL) in a clinical practice setting.

Methods

All pts on DUAL regimen followed at our outpatient HIV service on May 31st 2012 were recruited. Their clinical files were retrospectively studied. Collected data included: demographics, CDC staging, reason to DUAL switching, cholesterol (total and HDL), creatinine, CK, CD4+ count and HIV RNA were recorded at switch and every six months after for the first year. Change in CD4 count after the switch was evaluated by Student t‐test.

Results

The cohort included 55 pts (27 M); mean age was 54 years (38–72). HIV infection was acquired through: injective drug abuse (25), unprotected homosexual (24) and heterosexual (16) intercourse. CDC staging was: A=16, B=26, C=13. Mean previous treatment regimens were 4. At time of study pts had been on DUAL regimen for 23 months. They had been switched to DUAL therapy for: drug resistance (14; 25.5%) (DRR) or drug toxicity (41; 74.5%). The most frequently associated drug was darunavir/rtv (19; 34.5%), followed by atazanavir (13; 23.6%; 5 were unboosted); lopinavir/rtv (12; 21.8%), and NVP (11; 20%). DRR pts presented at baseline a mean viral load of 40,153 copies of HIV‐RNA/ml; after at 12 months all but 3 showed undetectable (<40 copies) viral load and a mean CD4 gain of 142 cells/ml. Pts switched to DUAL for toxicity presented persistent undetectable viral load and a mean CD4+gain of 94 cells/ml. The observed CD4+ increase in both groups (DRR and toxicity) presented a statistical significance (p<0.01). Total and HDL cholesterol, and creatinine did not present significant variations. CK remained stable and no toxicity episode was observed.

Conclusion

DUAL approach showed good safety and also remarkable results in terms of viral suppression and immunological recovery. Notwithstanding the potential low genetic barrier of some combinations (e.g. NVP+RAL) this strategy demonstrated to be effective. The long term reliability of DUAL should be confirmed by studies with a longer follow up and a wider sample.
Predictors of long‐term HIV RNA suppression on darunavir/ritonavir monotherapy in the MONET trial
Authors: Arribas J , Pulido F , Hill A , van Delft Y , Moecklinghoff C
Published: November 2012

Background

In previous studies of protease inhibitor (PI) monotherapy, patients with higher nadir CD4 counts, baseline HIV RNA<1 copy/mL and high adherence to treatment have been most likely to show sustained HIV RNA suppression<50 copies/mL.

Methods

In the MONET trial, 256 patients with HIV RNA <50 copies/mL at screening switched to DRV/r 800/100 mg once daily, either as monotherapy (n=127) or with 2 NRTIs (n=129). HIV RNA results were classified as either<5 (no detection), 5–49 (virus detected under quantification limit) or >50 copies/mL. Treatment failure was defined as two consecutive HIV RNA levels >50 copies/mL (TLOVR) by Week 144, or discontinuation of study drugs. Additional analyses were conducted (i) excluding discontinuations for adverse events or other reasons (ii) including patients who intensified with NRTIs. Multivariate logistic regression was used to identify factors predictive of treatment failure by Week 144.

Results

By Week 144, the percentage of patients with HIV RNA <50 copies/mL (ITT, TLOVR, Switch=Failure) was 69% versus 75% in the DRV/r monotherapy and triple therapy arms respectively. In the Switch Included analysis, HIV RNA <50 copies/mL was 84.0% versus 83.5% in the DRV/r monotherapy and triple therapy arms respectively. In the multivariate analysis for the TLOVR endpoint, positive HCV serology correlated with treatment failure (odds ratio [OR]=2.44, 95% CI 1.20–5.00). In the analysis including only virological endpoints, both positive HCV serology (OR=2.77, 95% CI 1.18‐6.67) and baseline HIV RNA >5 copies/mL (OR=2.71, 95% CI 1.21‐6.08) predicted treatment failure. In the Switch Included analysis, only HIV RNA >5 copies/mL was predictive of treatment failure (OR=2.78, 95% CI 1.28–6.01). Nadir CD4 count and prior PI use were not predictive of treatment failure in any analysis. In the ITT TLOVR analysis, the response rates in the DRV/r monotherapy arm at Week 144 were 79% (66/84) for HCV‐ve patients with baseline HIV RNA <5 copies/mL, 63% (12/19) for HCV‐ve patients with baseline HIV RNA >5 copies/mL, 47% (9/19) for HCV+ve patients with baseline HIV RNA<5 copies/mL and 20% (1/5) for HCV+ve patients with baseline HIV RNA>5 copies/mL.

Conclusions

In the MONET trial, patients without HCV co‐infection (based on serology), and with baseline HIV RNA <5 copies/mL by the Roche Amplicor assay (i.e. no virus detected) were most likely to show sustained HIV RNA suppression<50 copies/mL on DRV/r monotherapy.
A clinical trial to compare the quality of life of HIV+ patients who start monotherapy with LPV/r versus continuing triple therapy with a boosted PI
Authors: Pasquau J , Hidalgo C , Vergara A , Montes M , Vergas J , Sanjoaquín I , Hernández‐Quero J , Aguirrebengoa K , Orihuela F , Rodríguez‐Baño J , Imaz A , García‐Vallecillos C
Published: November 2012

Purpose of the study

Efficacy, toxicity and complexity of antiretroviral (ARV) regimens may impact the quality of life (QoL). Since over the past years the simplification approach of lopinavir/ritonavir (LPV/r) as monotherapy (MT) has been shown to be non‐inferior to triple therapy (TT) in virological and immunological efficacy, the objective of this study was to compare several health‐ and treatment‐related outcomes between both ARV strategies with LPV/r.

Methods

A phase IV national, multicenter, controlled, randomized (2:1), open label, parallel‐group clinical trial to compare the QoL in patients on ARV TT containing any boosted protease inhibitor (PI), undetectable viral load (VL< 50 cop/mL) in the past 6 months and a CD4 nadir > 100 cells/µL, versus those who were simplified to LPV/r MT, for 24 weeks. QoL and health outcomes were evaluated by the Medical Outcomes Study HIV Health Survey (MOS‐HIV) and the five‐dimensional EuroQol questionnaire (EQ‐5D). Treatment satisfaction was assessed by the Spanish Questionnaire of Satisfaction with ARV Treatment (CESTA). Treatment adherence was assessed by the Spanish Multifactorial Adherence questionnaire (GEEMA) and a visual analog scale (VAS). Tolerability, safety and virological and immunological efficacy at week 24 were also analyzed.

Summary of results

225 patients from 29 sites were enrolled (MT: 146, 64.5%; TT: 79, 35.1%). Mean age (years) was 44.5 in MT and 45.2 in TT (p=0.745); mean duration (years) from HIV infection was 13.4 in MT and 12.8 in TT (p=0.587) and 71% were male in both arms. 87.6% of patients completed correctly the study (MT: 88.4%; TT: 86.1%; p=0.674). Health and treatment outcomes evaluated at final study visit are shown in figure 1 1. At study end, 84.1% in MT and 89.6% in TT had undetectable VL (p=0.313) and mean CD4 count were 742.8 cells/µL in MT and 646.5 cells/µL in TT (p=0.060). There were no significant differences in the percentage of patients with virological failure at week 24 as VL >50 cop/mL (MT: 8.2%; TT: 3.9%; p=0.271) and as VL >200 cop/mL (MT: 3.4%; TT: 0%; p=0.167).

‘Quality of life’ impact: monotherapy vs triple therapy.

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Conclusions

The MT simplification strategy with LPV/r maintains comparable virological and immunological efficacy, as well as the tolerability profile, than the TT. The saving resulting from NRTIs withdrawal from the ARV regimen and the good results on QoL and patients treatment satisfaction make MT strategy with LPV/r be taken into account in clinical practice.
STRike ‐ characteristics of HIV‐1‐infected patients treated with a single‐tablet regimen in daily clinical practice
Authors: Esser S , Heiken H , Gallo L , Schellberg S , Schlag M , Moll A , Pauli R , Stoehr A , Degen O , Jaeger H , Stephan C , Fätkenheuer G
Published: November 2012

The life‐long antiretroviral treatment of HIV‐1 infection requires effective and well tolerated medications complemented by high rates of adherence in order to achieve viral suppression, immunologic reconstitution and to prevent the development of resistance. Single‐tablet regimens (STRs), combining a full antiretroviral regimen in one tablet taken once daily, have been designed to achieve high adherence and better long‐term outcomes. “STRike” is the first cohort study, describing the use of various STRs in routine clinical practice in Germany. In this observational cohort study 800 participants will be included in 4 treatment arms, treated with the STRs of TDF/FTC/EFV (a retrospective and prospective arm), TDF/FTC/RPV or TDF/FTC/COBI/EVG after regulatory approval. Patients are followed for at least two years, and reasons for choice of medications and treatment satisfaction will be collected, in addition to safety, demographic, effectiveness data. To date 344 patients on TDF/FTC/EFV and 123 patients on TDF/FTC/RPV are being followed. In general, the spectrum of patients in the study reflects the German HIV‐1 infected population with regards to gender (88%/89% male), age (median 40/38 years of age) and mode of infection (71%/63% MSM). However, patients starting TDF/FTC/RPV are less progressed in their disease according to their CDC stage compared with patients on TDF/FTC/EFV (74.5% stage “A” vs. 53.2%). Patients starting TDF/FTC/RPV show less comorbidities (54% vs. 82%) with a spectrum different from patients on TDF/FTC/EFV. Pre‐existing neuropsychiatric comorbidities are relatively more common (10% more) among patients starting TDF/FTC/RPV than TDF/FTC/EFV. The decision to use an STR is mostly driven by patient preference to start with a more convenient ART regimen (56%) or to simplify their current ART regimen (75%). STRs aim to make treatment of HIV more convenient, more efficacious and more durable and by that allowing for earlier initiation of treatment. Different STRs may meet the requirements of distinct patient populations. TDF/FTC/RPV in this early review of our data, is utilized by younger patients with fewer overall comorbidities, but is selected more frequently for patients with pre‐existing neuropsychiatric comorbidities presumably to avoid the known neuropsychiatric complications of TDF/FTC/EFV. TDF/FTC/RPV appears to fit into the concept of early HIV treatment initiation as recommended by national and international guidelines.

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Monotherapy with boosted protease inhibitors as antiretroviral treatment simplification strategy in the clinical setting
Authors: Santos J , Berrio D , Miranda C , Bravo I , Pérez S , Llibre J , Paredes R , Clotet B , Moltó J
Published: November 2012

Antiretroviral treatment simplification with darunavir/ritonavir or lopinavir/ritonavir monotherapy maintains sustained HIV viremia suppression in clinical trials. However, data about the efficacy of this strategy in routine clinical practice is still limited, and no direct comparison between darunavir/ritonavir and lopinavir/ritonavir has been performed to date. We retrospectively studied all HIV‐1‐infected subjects who initiated monotherapy with darunavir/ritonavir or lopinavir/ritonavir while having plasma VL<50 c/mL, and had at least 1 subsequent follow‐up visit in our clinic. When two consecutive PI‐monotherapy regimens were used, each regimen was considered separately. The primary endpoint was the percentage of patients who maintained virological suppression (HIV‐1 VL <50 c/mL) through follow‐up. Virological failure was defined as at least two consecutive HIV‐1 VL >50 c/mL. We also evaluated other reasons for treatment discontinuation. Analyses were performed considering all regimens (full dataset analysis) either as “on treatment” or as “treatment switch equals failure”. Five hundred and seventy‐three PI‐monotherapy regimens corresponding to 520 subjects were included, 262 with darunavir/ritonavir and 311 with lopinavir/ritonavir. Medians (IQR) follow‐up were 50 (26.3–107.6) and 85.6 (36.9–179.1) weeks for subjects on darunavir/ritonavir and lopinavir/ritonavir, respectively (p<0.001). Overall, 67 (11.7%) subjects experienced virological failure, 23 (8.7%) were on darunavir/ritonavir and 42 (13.5%) were on lopinavir/ritonavir (p=0.796). Two hundred and three (77.5%) patients on darunavir/ritonavir and 154 (49.5%) on lopinavir/ritonavir maintained virological suppression in the “treatment switch equals failure” (p=0.002). Other reasons for treatment discontinuation were gastrointestinal toxicity and dyslipidemia in 7.2% and 5.9% of cases, respectively. Gastrointestinal toxicities and dyslipidemia leading to treatment discontinuation were more frequent in patients on lopinavir/ritonavir (10.6% and 10.3%, respectively) than in patients on darunavir/ritonavir (3.1% and 0.8%, respectively). Monotherapy with darunavir/ritonavir or lopinavir/ritonavir as simplification strategy appears to be effective and safe in subjects with virological suppression in clinical practice. Virological efficacy seems to be similar between regimens. However, rates of discontinuation due to toxicities were higher in subjects on lopinavir/ritonavir than darunavir/ritonavir.
Switching to an etravirine regimen in virologically suppressed patients with previous virological failures and presence of resistance mutations
Authors: Blanco J , Casado J , González‐Cordón A , Martinez E , del Palacio M , Domingo P , Mallolas J , Mateo M , Pérez Elías M , Pérez I , Gutiérrez M , Gatell J
Published: November 2012

Background

Simplification of antiretroviral therapy (ART) may be an option for virologically suppressed patients for a variety of reasons. Etravirine (ETV) 400 mg qd has a good safety profile and retains activity against viruses resistant to nevirapine or efavirenz. Our objective was to evaluate the efficacy of ETV plus two nucleoside reverse transcriptase inhibitors (NRTIs) as a simplification strategy in treatment‐experienced virologically suppressed individuals with prior episodes of virological failure (VF) and presence of genotypic resistance mutations (GRM).

Methods

Eligible subjects were followed for ≥6 mo. Primary endpoint was proportion of patients remaining virologically suppressed using an ITT analysis. Genotypic sensitivity score (GSS) to new regimen was calculated according to Stanford resistance database.

Results

Fourteen (10%) of 145 subjects switching to ETV+2NRTIs while virologically suppressed had a documented prior VF and presence of GRM and were included in the analysis. Median (range) number of previous episodes of VF to ART, NRTI‐containing regimen, to a NNRTI‐containing regimen and to a PI‐containing regimen were 4 (1–6), 2 (1–5), 1 (0–2) and 1 (0–2) respectively. Median duration of virological suppression before switching therapy was 22.5 months (1‐65). All patients switched from an effective PI‐containing regimen (8 LPV/r, 5 ATV/r and 1 DRV/r) to a qd regimen with ETV 400 mg plus Truvada® (n=12) or Kivexa® (2). 11/14 patients (79%) remained virologically suppressed at ≥6 mo. All of them had a GSS >1.5 to the new regimen and none had resistance to etravirine. Conversely 3/14 (21%) developed a VF at 1, 3 and 6 months respectively. All these 3 patients had a GSS ≤1.5 to the new regimen and 2 of them intermediate resistance to ETV (Y181C). No side effects were reported.

Conclusions

Our results suggest that ETV plus 2NRTI could be a good strategy for simplification in virologically suppressed patients despite previous episodes of VF if the GSS to the new regimen is ≥1.5 and ETV remains active.