bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unlinked Memory Helper Responses Promote Long-Lasting Humoral Alloimmunity
Authors: Conlon Thomas M. , Cole Jennifer L. , Motallebzadeh Reza , Harper Inês , Callaghan Chris J. , Bolton Eleanor M. , Bradley J. Andrew , Saeb-Parsy Kourosh , Pettigrew Gavin J. 
Published: November 2012

Abstract
Essential help for long-lived alloantibody responses is theoretically provided only by CD4 T cells that recognize target alloantigen, processed and presented by the allospecific B cell. We demonstrate that in an alloresponse to multiple MHC disparities, cognate help for class-switched alloantibody may also be provided by CD4 T cells specific for a second “helper” alloantigen. This response was much shorter-lived than when help was provided conventionally, by Th cell recognition of target alloantigen. Nevertheless, long-lasting humoral alloimmunity developed when T cell memory against the helper alloantigen was first generated. Costimulatory blockade abrogated alloantibody produced through naive Th cell recognition of target alloantigen but, crucially, blockade was ineffective when help was provided by memory responses to the accessory helper alloantigen. These results suggest that memory Th cell responses against previously encountered graft alloantigen may be the dominant mechanism for providing help to generate new specificities of alloantibody in transplant patients receiving immunosuppression.
Overview of recent developments in chronic lymphocytic leukemia
Authors: Jain Preetesh , Rai Kanti R. 
Published: November 2012

AbstractMultiple advances have been made in our understanding of pathobiology of chronic lymphocytic leukemia (CLL). These developments in the laboratory include new prognostic markers, risk stratification of the disease and newer therapeutic agents in CLL. These advances in CLL have come a long way in the past three decades since the development of Rai and Binet clinical staging systems. Important strides in the pathobiology, from defining mutational status of IGHV, to B-cell receptor (BCR) signaling pathways and CLL microenvironment have made a major difference in our understanding of this disease. Mutational status of immunoglobulin heavy chain genes (IGHV), CD38 and Zap-70, chromosomal aberrations and newer mutations, are the most clinically relevant prognostic markers. Chemoimmunotherapy (CIT) has become the treatment of choice for young and fit CLL patients. Various inhibitors of BCR signaling pathways and immunomodulatory drugs have shown efficacy in clinical trials. The most recent advance is the use of chimeric antigen receptor therapy (CAR) based on autologous T-lymphocytes. Nevertheless, CLL remains an incurable disease today. Coordinated developments between laboratory and clinic will hopefully translate into a cure for CLL. This short review focuses on advances in prognostication and therapy in CLL.
Adherence in HIV‐positive patients treated with single‐tablet regimens and multi‐pill regimens: findings from the COMPACT study
Authors: Antinori A , Angeletti C , Ammassari A , Sangiorgi D , Giannetti A , Buda S , Girardi E , Degli Esposti L 
Published: November 2012

The use of Combination AntiRetroviral Therapy (cART) has decreased the morbidity and mortality of patients infected with HIV. However, adherence to cART remains crucial to prevent virological failure and disease progression. The aim of this study was to assess adherence to treatment among patients treated with Single Tablet Regimen (STR) or with multi‐pill regimens based on Protease Inhibitors (PI), Non‐Nucleoside Reverse‐Transcriptase Inhibitors (NNRTI), or raltegravir (RAL). An observational retrospective cohort analysis based on administrative and clinical databases was conducted at the National Institute for Infectious Diseases (Rome, Italy). HIV‐positive patients treated with a cART between Jan 1st, 2008–Dec 31st, 2010 were included. Patients were followed‐up for one year since the first prescription during the inclusion period or up to death or switch of at least one drug of the regimen. Adherence and selective non‐adherence (days without backbone or 3rd drug) were calculated using pharmacy refill compliance [1]. cART regimens were classified based on number of daily pills (STR vs multi‐pill regimen) and on type of third drug. Viral Load (VL) and CD4 cell counts at the end of the follow‐up were evaluated. A total of 1,604 patients were analyzed, 70.0% male, age 45.0±8.7, 14.3% newly treated. Patients on STR were 159 (9.9%), PI 878 (54.7%), NNRTI 523 (32.6%), RAL 44 (2.7%). Presence of at least one AIDS‐defining conditions (according to Centers for Disease Control classification) was 30% in the STR group, 34% PI, 26% NNRTI, 34% RAL (p=n.s.). Adherence was 80.4±14.7% for STR, 71.8±21.8% PI, 77.1±20.3% NNRTI, 74.0±22.4% RAL. Selective non‐adherence was 5.5% (18 days) PI, 2.8% (8 days) NNRTI, 12.5% (43 days) RAL (Figure 1). At the end of the follow‐up, VL/CD4 values were available among 709 patients (44%); CD4 count >500 cell/mm3 was observed among 61% of patients on STR, 44% PI, 48% NNRTI, 42% RAL and VL < 50 copies/ml was observed among 96% of patients on STR, 78% PI, 88% NNRTI, 87% RAL. Interruptions in cART refill remain a relevant problem across all cART regimens. Patients on STR displayed a higher adherence rate compared to multi‐pill regimes (PI, NNRTI, and RAL), primarily due to lack of selective non‐adherence. Patients on STR experienced also higher rates of VL < 50 and CD4 > 500. The use of an STR regimen appears an effective therapeutic option to avoid selective non‐adherence and, consequently, to prevent virological failure and disease progression.Non‐adherence to cART regimens.image
CD4 count evolution of HIV‐infected patients in follow‐up as an indicator of quality of care
Authors: Sasse A , Van Beckhoven D ,   for the Belgian Research AIDS and HIV Consortium (BREACH)
Published: November 2012

ObjectiveTo study the evolution of CD4 count of HIV‐infected patients in follow‐up as an indicator of quality of care.MethodsAdult patients newly diagnosed with HIV in 2007 who entered in care in the AIDS Reference Centres (ARC) and remained in care for at least one year were studied until end 2009. Optimal CD4 evolution was defined as having a CD4 count above 350 cells/mm3 after 1 year in HIV care, or an increasing rate exceeding 50 cells/mm3 per year, and this regardless of antiviral therapy. The proportion of patients with optimal CD4 evolution was measured and factors associated with outcome were identified by logistic regression.Results482 patients were included. Median age was 37 years, 31.1% were females, 51.7% Belgians, 32.2% from Sub‐Saharan Africa, 50.5% heterosexual, 48.7% MSM. 59.5% had a CD4 count above 350 at entry in care, 11.2% did not have a regular retention in care (at least 1 consultation/6‐month period). 401 (83.2%) patients had an optimal CD4 evolution after 1 year in care. 60.5% of patients with non‐optimal evolution had a CD4 count below 350 at entry in care. Although the proportion of female sex, heterosexual transmission, Sub‐Saharan nationality and low retention in care was higher in the non‐optimal CD4 evolution group compared to the optimal group, none of these characteristics showed a significant association with non‐optimal CD4 count evolution.Conclusion83.2% of patients had an optimal CD4 evolution after at least 1 year in HIV care. This indicator, analysed together with indicators of entry and retention in care, could contribute to a better monitoring of the HIV epidemic and to identify more precisely the steps in care system that could be improved. These indicators should be fully integrated in HIV surveillance.
Characteristics associated with non optimal CD4 evolution among patients in care

Optimal CD4 evolution
Non‐optimal CD4 evolution
OR (95% CI)
Adjusted OR (95% CI)

Gender (N, %)

Male
281 (70.1)
51 (63.0)
1
1

Female
120 (29.9)
30 (37.0)
1.38 (0.84–2.27)
0.89 (0.41–1.91)

Age at diagnosis (N, %)

<40 yrs
252 (62.8)
51 (63.0)
1
1

≥40 yrs
149 (37.2)
30 (37.0)
0.99 (0.61–1.63)
1.06 (0.60–1.98)

Way of transmission (N, %)

Heterosexual
162 (49.4)
37 (56.1)
1
1

MSM
163 (49.7)
29 (43.9)
0.78 (0.46–1.33)
0.85 (0.40–1.80)

IDU
3 (0.9)
0 (0.0)
/

Nationality (N, %)

Belgian
177 (52.8)
32 (46.4)
1
1

SSA
103 (30.8)
27 (39.1)
1.45 (0.82–2.56)
1.37 (0.62–3.01)

European
39 (11.6)
4 (5.8)
0.57 (0.19–1.70)
0.57 (0.19–1.73)

Other
16 (4.8)
6 (8.7)
2.07 (0.75–1.70)
1.74 (0.57–5.30)

Retention in care (N, %)

≥1 consult./period
359 (89.5)
69 (85.2)
1
1

<1 consult./period
42 (10.5)
12 (14.8)
1.49 (0.74–2.97)
1.45 (0.68–3.12)
Single‐tablet regimens (STRs) enhance patients’ acceptability of HAART
Authors: Maggiolo F , Fregosi S , Bortolussi P , Marcotullio S , Murri R 
Published: November 2012

Patients’ acceptability of HAART is a subjective variable that may deeply influence therapeutic outcome. The feeling of the patient may alter adherence and lead to virologic failure. Acceptability may depend on various variables often difficulty evaluated by the care‐giver. In a clinical setting the evaluation of acceptability is difficult, too, as patients may feel a judgement and be less sincere. Aim of this study was to asses adherence and acceptability of HAART. To limit reporting biases, the study was performed in five different non‐clinic settings covering North and Central Italy. A total of 230 patients on stable HAART were asked to complete a semi‐structured, anonymous questionnaire reporting their attitude toward HAART, their adherence and the acceptability of their regimen. In these notes we focus on this last patient‐oriented outcome. Most of the subjects were males (66%) with a mean age of 46 years, with higher education level (72%) and a long history of HIV infection (mean 13.6 years). Consequently only 17% of patients were on a first‐line regimen. Patients reporting a high or very high acceptability of HAART were 60% compared to a 31% reporting a fair grade of satisfaction and a 9% indicating low or null acceptability. However the type of the regimen significantly influenced patients’ acceptability. Single‐tablet regimens (STRs), OD regimens with more than one tablet/day or BID regimens were scored as highly acceptable in 84%; 61%; and 53% of cases, respectively (P < 0.0001) (Figure). Statistical significance was retained when the dosing schedule was entered in a multivariate logistic model. When the analysis was restricted to experienced patients 62% of them were currently on a regimen based on a reduced number of pills compared to the previous one. Patients scored the previous regimen as more difficult to comply with in 72% of cases; as difficult in 22% and less difficult in 6%. The eventuality of AEs (40%); respect of timing of pill intake (39%) and number of pills (27%) were the major reasons of patients’ low acceptability of HAART. High acceptability is one of the winning characteristics of a regimen, favoring long‐term adherence, durability and efficacy. Although highly subjective, acceptability may be positively influenced by characteristics of the HAART regimen such as simplicity. According to our results, STRs show a higher acceptability compared to more complex regimens.Patient reported acceptability for thier current HAART regimen.image
Self‐reported adherence supports patient preference for the single tablet regimen (STR) in the current cART era
Authors: Sterrantino G , Santoro L , Trotta M , Antinori A , Bartolozzi D , Zaccarelli M 
Published: November 2012

ObjectiveTo analyze self‐reported adherence to antiretroviral regimens containing ritonavir‐boosted protease inhibitors, non‐nucleoside reverse transcriptase inhibitors (NNRTI), raltegravir, and maraviroc.MethodsOverall, 372 consecutive subjects attending a reference center for HIV treatment in Florence, Italy, were enrolled in the study, from December 2010 to January 2012 (mean age 48 years). A self‐report questionnaire was filled in. Patients were defined as “non‐adherent” if reporting one of the following criteria:<90% of pills taken in the last month, ≥1 missed dose in the last week, spontaneous treatment interruptions reported, or refill problems in the last 3 months. Gender, age, CD4, HIV‐RNA, years of therapy, and type of antiretroviral regimen were analyzed with respect to adherence.ResultsAt the time of the questionnaire, 89.8% of patients had <50 copies/mL HIV‐RNA and 14.2% were on their first combined antiretroviral therapy. 57% of patients were prescribed a regimen containing ritonavir boosted protease inhibitors (boosted PI), 41.7% NNRTI, 17.2% raltegravir, and 4.8% maraviroc; 49.5% of the subjects were on bis‐in‐die regimens, while 50.5% were on once‐daily regimens, with 23.1% of these on the single tablet regimen (STR): tenofovir/emtricitabine/efavirenz. The non‐adherence proportion was lower in NNRTI than in boosted‐PI treatments (19.4% vs 30.2%), and even lower in STR patients (17.4%). In multivariable logistic regression, patients with the NNRTI regimen (OR: 0.56, 95% CI: 0.34–0.94) and the STR (OR: 0.45, 95% CI: 0.22–0.92) reported lower non‐adherence. Efavirenz regimens were also associated with lower non‐adherence (OR: 0.42, 95% CI: 0.21–0.83), while atazanavir/ritonavir regimens were associated with higher non‐adherence. No other relation to specific antiretroviral drugs was found. A higher CD4 count, lower HIV‐RNA, and older age were also found to be associated with lower non‐adherence, while a longer time on combined antiretroviral therapy was related to higher non‐adherence.ConclusionIn conclusion, older age, higher CD4 cell counts, lower HIV‐RNA viral loads, and the use of STR are all related to lower non‐adherence. In particular, the use of STR maintains an advantage in improving adherence with respect to other cARTs, even with the availability of new, well‐tolerated antiretroviral drugs and drug classes in recent years.
Adherence and neurocognitive screening in Romanian HIV patients
Authors: Arbune M 
Published: November 2012

BackgroundAdherence is critical for the effectiveness of antiretroviral HIV therapy (ART), accordingly decreasing the opportunistic diseases and increasing the quality of life. Neurocognitive disorders (NCD) are still frequent in ART era and could impair the adherence, but how ethical is to refer ART in patients with NCD?ObjectiveTo assess the relation between NCD and adherence in HIV Romanian patients.Material and methodsCross‐sectional screening study on 151 patients under ART, no drug users, from HIV Clinic ‐ Galati, assessed by HIV‐Associated Dementia Scale (HDS), Hospital Anxiety and Depression Scale (HADS) [1], ART CNS‐effectiveness Letendre scores [2] and adherence assessment questionnaire CNLAS‐ Romania. Normal values: HDS >10; anxiety/ depression <8. Statistical analysis performed: Chi‐square test and Mann‐Whitney test, with 5% significance level.ResultsCharacteristics of the patients: median age 22 [20; 56] years old; sex ratio F/M 1.17; median educational level 8 [0; >12] years; HBV co‐infection 27.8%; AIDS stage 85.3%; current median CD4 526/mm3 [8; 1605] and 65% undetectable HIV‐RNA levels. 49.6% (75/151) patients attain HDS scores <10 and imply probable NCD. Scores below 8 for anxiety are more frequent than for depression: 24% vs 13%. The median ART CNS penetration score is 8 [5; 12]. Adherence is considered for 66% patients and is correlating with CD4 number (p=0.001), educational level >4 years (p=0.001; OR=4.2), HDS >10 (p=0.01; OR=2.4) and ART‐CNS penetration score >7 (p=0.023; OR=2.4). Low HDS are influenced by old age (p=0.003), depression (p=0.02) and ART‐CNS penetration scores <7 (p=0.01). Anxiety is related neither with adherence nor with NCD by HDS, but females are obvious anxious than males (p<0.001).ConclusionsBasic educational level is sufficient for developing ART adherence. High scores of HDS screening should be predictors for ART adherence. Referring ART as well to patients with low HDS scores is rational and ethical, if joint actions of effective ART‐CNS regimens and depression improvement strategy are considered.
Efficacy assessment of the implemented strategies to improve loss to follow‐up in recently diagnosed HIV patients
Authors: Fridman V , Bello N , Lasala M 
Published: November 2012

Purpose of the studyThe aim of the present study is to evaluate the strategies performed to decrease the loss to follow up in recently diagnosed HIV patients.MethodWe reviewed the clinical charts of the recently diagnosed adult (>18 y/o) HIV patients who presented for the first time in our HIV clinic between 1/Jan/2009 and 30/Nov/2010. Among the patients who were newly diagnosed with HIV infection, we identified those who attended our clinic only once. Since January 2009, we implemented new strategies: those patients who were diagnosed with HIV infection were assigned an early appointment with an attending; those patients who did not attend the appointment were called to reassign another appointment; clinic hours were increased, another attending joined the team and the matters the patients had to deal with were reduced. The results obtained with regard to loss to follow up in these patients were compared with previous results, before January 2009, to assess the effectiveness of these measures.Summary of the results247 patients attended the clinic for the first time, 43 (17.4%) of them attended the clinic only once. Comparing with the 45‐month period before the implementation of these strategies in which 256 patients attend the clinic and 135 (52.7%) attended the clinic only once, loss to follow up was improved (P=0.0000 [OR 0.19, 95% CI 0.12–0.29]). No statistically significant differences were found between both groups regarding age, gender, nationality, employment status, presence of family/partner at home or access to health insurance.

Patients who attended the clinic for the first time between Jan 2005–Sept 2008, n=256
Patients who attended the clinic for the first time between Jan 2009–Nov 2010, n=247

Male/female
186/70
182/65
P=0.79, OR 1.05 (95% CI 0.70–1.59)

Argentinian
218
199
P=0.17, OR 0.13 (95% CI 0.84–2.26)

Health insurance
107
94
P=0.39, OR 0.86 (95% CI 0.59–1.24)

Tertiary/university degree
74
71
P=0.96, OR 1.01 (95% CI 0.67–1.15)

Employed
182
192
P=0.08, OR 1.42 (95% CI 0.93–2.17)

Living alone
52
63
P=0.16, OR 1.34 (95% CI 0.87–2.08)

Loss to follow up
135/(52.7%)
43/(17.4%)
P=0.0000, OR 0.19 (95% CI 0.12–0.29)

ConclusionsAlthough the small sample size, the implemented measures decreased the lost to follow up in our clinic. This study emphasises the need to continue reinforcing engagement with clinical care in the newly diagnosed HIV patients.
A dynamic assessment of medication‐taking behavior during pregnancy and postpartum: should cART adherence be reinforced during postpartum?
Authors: Michel O , Gertsch A , Locatelli I , Cavassini M , Rickenbach M , Bugnon O , Schneider M 
Published: November 2012

This study compared adherence (persistence and execution) during pregnancy and postpartum in HIV‐positive women having taken part in the adherence‐enhancing program of the Community Pharmacy of the Department of Ambulatory Care and Community Medicine in Lausanne between 2004 and 2012. This interdisciplinary program combined electronic drug monitoring and semi‐structured, repeated motivational interviews. This was a retrospective, observational study. Observation period spread over from first adherence visit after last menstruation until 6 months after childbirth. Medication‐taking was recorded by electronic drug monitoring. Socio‐demographic and delivery data were collected from Swiss HIV Cohort database. Adherence data, barriers and facilitators were collected from pharmacy database. Electronic data were reconciled with pill‐count and interview notes in order to include reported pocket‐doses. Execution was analyzed over 3‐day periods by a mixed effect logistic model, separating time before and after childbirth. This model allowed us to estimate different time slopes for both periods and to show a sudden fall associated with childbirth. Twenty‐five pregnant women were included. Median age was 29 (IQR: 26.5, 32.0), women were in majority black (n = 17,68%) and took a cART combining protease and nucleoside reverse transcriptase inhibitors (n = 24,96%). Eleven women (44%) were ART‐naïve at the beginning of pregnancy. Twenty women (80%) were included in the program because of pregnancy. Women were included at all stages of pregnancy. Six women (24%) stopped the program during pregnancy, 3 (12%) at delivery, 4 (16%) during postpartum and 12 (48%) stayed in program at the end of observation time. Median number of visits was 4 (3.0, 6.3) during pregnancy and 3 (0.8, 6.0) during postpartum. Execution was continuously high during pregnancy, low at beginning of postpartum and increased gradually during the 6 months of postpartum.imageMajor barriers to adherence were medication adverse events and difficulties in daily routine. Facilitators were motivation for promoting child‐health and social support. The dramatic drop and very slow increase in cART adherence during postpartum might result in viral rebound and drug resistance. Although much attention is devoted to pregnant women, interdisciplinary care should also be provided to women in the community during first trimester of postpartum to support them in sustaining cART adherence.
Late gadolinium enhancement and subclinical cardiac dysfunction on cardiac MRI in asymptomatic HIV‐positive men
Authors: Loy A , Morgan R , O'Dea S , Takacs E , Daly C , Mulcahy F 
Published: November 2012

BackgroundHIV is associated with an increased risk of cardiovascular disease (CVD) and related clinical events. While traditional risk factors play an important role in the pathology of cardiovascular disease, HIV infection and its sequelae of immune activation and inflammation may have significant effects on the myocardium before becoming clinically evident. Cardiac MRI (CMR) can be used to detect the pattern of these subclinical changes. This will lead to a better understanding of risk factors contributing to cardiovascular disease prior to it becoming clinically significant in HIV‐positive patients.MethodsProspective cohort study of 127 asymptomatic HIV‐positive men on ART compared to 35 matched controls. Baseline demographics, HIV parameters, 12‐lead ECG, routine biochemistry, and traditional cardiovascular risk factors were recorded. Images were acquired on a 3T Achieva Philips MRI scanner with 5 channel phase array cardiac coil and weight‐based IV gadolinium was given at 0.15 mmol/kg dose with post‐contrast inversion recovery imaging after 10 minutes.Results6/127 (4.7%) of asymptomatic HIV‐positive men had late gadolinium enhancement (LGE) on MRI verses 1/35 (2.9%) in the control group. In 3/6 (50%) of cases this was in a classical infarction pattern with subendocardial involvement. 3/6 (50%) were consistent with prior myocarditis. There was no significant difference in mean LVEF (66.93% vs 65.18%), LVMI (60.05g/m2 vs 55.94g/m2) or posterolateral wall thickness (8.28 mm and 8.16 mm) between cases and controls respectively. There was significantly more diastolic dysfunction, E:A ratio < 1, found in the HIV‐positive group, 18% vs 7% of controls (p = 0.037). Framingham risk did not predict either of these outcomes.ConclusionsThere is an increased incidence of LGE detected on CMR in this asymptomatic HIV‐positive cohort. Two distinct pathological processes were identifed as causing these changes, myocardial infarction and myocarditis. These findings were independent of traditional cardiac risk factors, duration of HIV infection and ART therapy. Sub clinical cardiac dysfunction may be underreported in other cardiac evaluation studies. The true impact of other potential risk factors may also be underestimated, highlighting the need for the development of more complex prediction models.