bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of the Dielectric Constant as a Function of Temperature at Constant Electric Fields for the Smectic A-Smectic G Transition in A6
Authors: Yurtseven H. , Kilit E.
Published: November 2012

The temperature dependence of the dielectric constant is studied under some fixed electric fields for the smectic G- (tilted-) smectic A (orthogonal) transition of the ferroelectric liquid crystal of compound A6. For this study, a mean field model with the quadrupole-quadrupole interactions is introduced. By fitting the inverse dielectric susceptibility from the mean field model to the experimental data from the literature, the observed behaviour of the dielectric constant is described satisfactorily for the smectic AG transition in A6. The transition temperature induced by an external electric field is also discussed for this ferroelectric compound.
Lung cancer in HIV‐infected patients
Authors: Palacios R , Lebrón J , Guerrero‐León M , Del Arco A , Colmenero J , Márquez M , Santos J
Published: November 2012

Purpose

Several studies have shown that HIV patients are at higher risk of lung cancer. Our aim is to analyse the prevalence and features of lung cancer in HIV‐infected patients.

Methods

The clinical charts of 4,721 HIV‐infected patients seen in three hospitals of southeast Spain (study period 1992–2012) were reviewed, and all patients with a lung cancer were analysed.

Results

There were 61 lung cancers, giving a prevalence of 1.2%. There was a predominance of men (82.0%), and smokers (96.6%; mean pack‐years 35.2), with a median age of 48.0 (41.7–52.9) years, and their distribution according to risk group for HIV was: intravenous drug use 58.3%, homosexual 20.0%, and heterosexual 16.7%. Thirty‐four (56.7%) patients were Aids cases, and 29 (47.5%) had prior pulmonar events: tuberculosis 16, bacterial pneumonia 9, and P. jiroveci pneumonia 4. The median nadir CD4 count was 149/mm3 (42–232), the median CD4 count at the time of diagnosis of the lung cancer was 237/mm3 (85–397), and 66.1%<350/mm3. 66.7% were on ART, and 70% of them had undetectable HIV viral load. The most common histological types of lung cancer were adenocarcinoma and epidermoid, with 24 (40.0%) and 23 (38.3%) cases, respectively. There were 49 (80.3%) cases with advanced stages (III and IV) at diagnosis. The distribution of treatments was: only palliative 23 (39.7%), chemotherapy 14 (24.1%), surgery and chemotherapy 8 (13.8%), radiotherapy 7 (12.1%), surgery 4 (6.9%), and other combined treatments 2 (3.4%). Forty‐six (76.7%) patients died, with a median survival time of 3 months. The Kaplan‐Meier survival rate at 6 months was 42.7% (at 12 months 28.5%).

Conclusions

The prevalence of lung cancer in this cohort of HIV‐patients is high. People affected are mainly men, smokers, with transmission of HIV by intravenous drug use, and around half of them with prior opportunistic pulmonary events. Most patients had low nadir CD4 count, and were immunosuppressed at the time of diagnosis. Adenocarcinoma is the most frequent histological type. The diagnosis is usually made at advanced stages of the neoplasm, and mortality is high.
Cost‐effectiveness of atazanavir+ritonavir (ATV+RTV) vs. lopinavir/ritonavir (LPV/r) in women of childbearing age in the United Kingdom
Authors: Simpson K , Kirbach S , Van de Steen O , Gooch K
Published: November 2012

Purpose of the study

In the UK, an increasing proportion of individuals with HIV are women of childbearing age (WOCBA). Literature on the potential effects of antiretroviral therapy (ART) on certain risk factors for coronary heart disease (CHD), such as total cholesterol (TC), has not differentiated the reported ART‐associated risk by other risk factors for CHD (e.g. age and gender). Given the different age‐specific CHD risk estimates for men and women, particularly the low risk of CHD in WOCBA, the cost‐effectiveness of LPV/r vs ATV+RTV specifically among WOCBA warrants examination. Therefore, the objective of this study was to perform a cost‐effectiveness and budget impact analysis of two first‐line protease inhibitor‐based regimens, LPV/r versus ATV+RTV, among HIV‐infected, ARV‐naïve WOCBA in the UK.

Methods

A modified version of a previously published Markov model was utilized [1]. CHD risk estimates were based on the Framingham risk score. Baseline assumptions were that 33% of women were smokers with a mean age of 25 years. Guidelines regarding therapeutic drug monitoring among pregnant women in the 3rd trimester who receive ATV+RTV were incorporated [2]. Age‐specific pregnancy rates were estimated in order to determine ARV utilization during gestation. The model employed a lifetime horizon under a NHS perspective and a discount rate of 3.5%. Costs were presented in 2011 GBP.

Summary of results

The model predicted no appreciable difference in quality‐adjusted survival (in terms of QALYs) between the two regimens over a lifetime (0.2 days in favor of ATV+RTV) and an increased cost of £3,003 per patient on the ATV+RTV regimen. Cost savings of £1,977 over 5 years and £2,916 over 10 years were predicted for patients who initiated LPV/r. Furthermore, for every 100 patients started on LPV/r, the savings accrued after one year allow for the treatment of 6 additional patients. After 10 years, the number of additional patients that can be treated accumulated to 42. The model predicted a mean of 1.4 pregnancies per woman, and an overall difference between the regimens of 0.3% in CHD events after 10 years.

Conclusions

Initiating HIV infected, ARV‐naïve WOCBA on a LPV/r‐based regimen compared to an ATV+RTV‐based regimen produces substantial short‐ and long‐term cost savings with similar life expectancy. These results warrant consideration, as selecting LPV/r over ATV+RTV may provide an opportunity for improving access to ART for WOCBA living with HIV in the UK.
A MultiFactorial Risk Score to weigh toxicities and co‐morbidities relative to costs of antiretrovirals in a cohort of HIV‐infected patients
Authors: Tontodonati M , Sozio F , Vadini F , Polilli E , Ursini T , Calella G , Di Stefano P , Mazzotta E , Costantini A , D'Amario C , Parruti G
Published: November 2012

Purpose of the study

Considering costs of antiretrovirals (ARVs) for HIV patients is increasingly needed. A simple and comprehensive tool weighing comorbidities and ARV‐related toxicities could be useful to judge the appropriateness of use of more expensive drugs. We conceived a MultiFactorial Risk Score (MFRS) to evaluate the appropriateness of ARVs prescription relative to their costs.

Methods

HIV patients were consecutively enrolled in 2010‐2011. We considered socio‐demographic characteristics, HIV history, cardiovascular risk factors, low energy fractures, bone density. Psychological factors were assessed by BDI, DS14 and TAS‐20. The MFRS was calculated as the sum of the following: age (<30y 1 point; 1 point increase every 5y, 10 for≥70); AIDS diagnosis (5); CD4 nadir (5 if <100; 1 point less every 100 CD4 increase); ART line (0 first, up to 5 for≥6 lines); lipodistrophy (5); HCV coinfection (7); education (1 degree, 2 secondary, 3 primary); alcohol (3) and drug abuse (5); working activity (3 if unemployed); hypertension (3); cholesterol≥200 mg/dl (3); diabetes (3); Framingham score (7 if>7%); creatinine (0 if <1 mg/dl, 1 if<1.2; 2 if<1.5>1.2, 5 if<2> 1.5, 7 if≥2); bone fractures (7); bone status at DEXA (0 normal, 3 osteopenic, 5 osteoporotic); cancer (5); depression (3 if BDI>17); other psychiatric illness (5). Annual costs of individual ART regimens were calculated. MFRS was correlated in univariate and multivariate models with all variables. All statistical analyses were carried out using Stata 10.1.

Summary of results

We enrolled 241 HIV patients, 74.3% males, aged 44.5±9.9y; 19 patients (7.8%) were untreated, 74.8% of treated had undetectable HIV RNA. Mean Nadir CD4 counts were 218±168, 38.5% of patients had an AIDS diagnosis. Mean individual ARV annual cost was 10,976±5,360. Mean MFRS was 28.5±13.9 (4–64). MFRS was significantly higher (p<0.001) in patients with older age, longer duration of HIV infection, lower CD4 nadirs, AIDS diagnosis, lipodistrophy, HCV, smoking, lower education, alcohol/drug abuse, hypertension, carotid plaques, higher Framingham score, diabetes, bone fractures or disorders, depression, alexithymia, and higher ARV costs. In multivariate models, ARV costs were significantly higher in patients with older age, previous AIDS diagnosis, lower CD4 nadir and higher MFRS.

Conclusions

MFRS may be a simple and reliable tool to match patients’ complexity and ARV costs, deserving further validation on larger samples.
Prescription patterns and costs of antiretroviral therapy in HIV‐infected naïve patients: theoretical impact of a regional therapeutic protocol
Authors: Ammassari A , Angeletti C , Murachelli S , Girardi E , Antinori A
Published: November 2012

In the Lazio region, about 10.000 HIV+subjects receive combination antiretroviral therapy (cART) with a medication expense of 78.177.632,28. In 2011, in order to standardize prescriptions, to monitor appropriateness, and to decrease drug costs, the Protocol for Regional Therapeutics (PTR) for cART was developed. Aim was to describe prescription patterns and costs of first‐line cART in 2010 and to estimate the theoretical impact of PTR application on medication costs. A cross‐sectional evaluation of first‐line cART prescribed during 2010 at the National Institute for Infectious Diseases was carried out. Data collected: age, date of HIV diagnosis, CD4, HIV‐RNA, antiretroviral drugs. cART were classified based on the PTR ranks as follows: a) recommended regimen (rank A1/A1); b) alternative regimens (ranks A1/B1; B1/A1; B1/B1); c) not recommended regimens. A descriptive analysis of prescription patterns together with their economic impact was carried out. A multivariate analysis was performed to identify predictive factors of higher regimen costs. The hypothetical transition of not recommended regimens to recommended or alternative regimens was assessed. 370 naïve patients were evaluated: mean age 42 y (range, 1–84), mean duration of HIV 41 months (range, 1–84); median CD4 269/mmc (135–349), log10HIV RNA 4.91 (4.4–5.4). A1/A1 regimens were prescribed in 62.2% (€163.789,28); A1/B1‐B1/A1‐B1/B1 in 22.8% (€73.831,75); not recommended cART in 15% (€54.929,95). Among A1/A1 regimes the most frequent were: TDF/FTC+EFV/(TDF+ FTC+EFV) in 39.4% and TDF+FTC+atazanavir/ritonavir in 22.7%. Up to 30 different cART (79% of all prescribed regimens) were used, each with a prescription prevalence lower than 1%. Mean patient‐month cART expense was €790,68. At multivariate analysis, higher plasma HIV RNA was associated with significantly higher first‐line regimen costs (coeff. B 48.64; 95% CI 22.78–74.50; P<0.0001). When applying the simulation model with the transition of all patients treated with not recommended regimens to recommended or alternative regimens, a total of €18.036,41 and €10.078,35 may have been achieved, respectively. A high prescription variability of cART has emerged. This finding is unlikely to be determined by clinical needs, especially because of the high frequency of not recommended regimens. Our findings highlight the need of standardized prescription strategies and that the introduction of PTR may allow a saving of up 10.4% of total cART expenses.
Comprehensive care with antiretroviral therapy for injecting‐drug users associates to low community viral load and restriction of HIV outbreak
Authors: Kivelä P , Liitsola K , Aho I , Simola S , Tuomola P , Salminen M , Ristola M
Published: November 2012

An outbreak of HIV was detected amongst Finnish injecting‐drug users (IDUs) in 1998. The outbreak was caused by CRF01‐AE virus [1]. A comprehensive care programme including infectious diseases, addiction medicine, low threshold methadone program, needle exchange, accommodation and other social services started in December 2000. Funding was provided by municipalities. We have described earlier how the outbreak became geographically and socially restricted [2]. The data of newly diagnosed HIV infections in the hospital district of Helsinki and Uusimaa (Helsinki region) amongst IDUs and HIV‐1 subtypes were obtained from the Finnish national HIV registry. The Helsinki University Central Hospital (HUCH) registry was used to obtain the number of IDUs in HIV care, on antiretroviral therapy (ART), and plasma HIV‐1 RNA (VL) amongst IDUs. The HUCH registry also includes IDUs diagnosed with HIV infection in other Finnish regions, but currently living in Helsinki region. The highest number (n=65) of newly diagnosed HIV infections among IDUs in Helsinki region was observed in 1999 (Figure 1). Between 1998 and 2011, 249 IDUs were diagnosed with HIV infection. From 1998 to 2004 the subtype was CRF01‐AE in 187 (92%) cases, other subtypes in 5 (2%) cases and not subtyped in 11 (5%) cases. From 2005 to 2011 the subtype was CRF01‐AE in 25 (54%) cases, other subtypes in 15 (33%) cases and not subtyped in 6 (13%) cases. In 2011 there were 4 IDUs diagnosed with HIV, one of them with CRF01‐AE. In the Helsinki region out of 183 HIV‐infected IDUs in 2005, 100 (55%) had VL<50 copies/ml and out of 167 HIV‐infected IDUs in 2011, 133 (80%) had VL<50 copies/ml in 2011. We propose that from 2005 the low HIV‐1 RNA in plasma of IDUs has contributed to the low incidence of HIV among IDUs in Helsinki region. However, the incidence of HIV started to decline before the decline of VL in the cohort (Figure 1). This suggests that other factors besides ART may have decreased the risk of HIV infection among IDUs before ART coverage of the cohort became considerable. Other subtypes of HIV circulated among IDUs in the Helsinki region during the observation period, which emphasises the necessity of health promoting services (e.g. needle exchange) to be available to all IDUs.

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Observational study on HIV‐1‐infected patients treated with an ARV combination therapy including raltegravir: the RACING cohort results at month 12
Authors: Pugliese P , Poizot‐Martin I , Billaud E , Spire B , Marcelin A , Julien V , Nait‐Ighil L
Published: November 2012

The French RACING cohort study is a 24‐month, observational, longitudinal, prospective, multicenter study on HIV‐1 infected patients being treated with an antiretroviral combination therapy containing raltegravir. The objectives of this study are to describe the viro‐immunological course, characterize and document adverse events (AEs), describe patient adherence at M6 (month 6) and examine clinical‐biological data for patients undergoing ARV therapy including raltegravir at M12 (month 12). Demographic, viro‐immunological, safety and clinical‐biological data were collected at M6 and M12 and self‐reported patient adherence to treatment regimen at M6. Data from 478 of 482 patients were available at M12. The median age was 45.9 years (IQR: 40.0–52.2), 64.1% were male and the median duration of infection was 13.2 years (IQR: 5.5–21). At the baseline, 64.1% of patients had a cardiovascular risk factor or a history of cardiovascular events and 65.2% had received concomitant treatment (psychotropic drugs: 33.5%, lipid‐lowering drugs: 30% and antihypertensive agents: 24.8%). The virological response, viral load and CD4 cell count are shown in Table 1 (based on data available at M6 and M12). Of the 134 reported and treatment‐related AEs, the symptoms most frequently described (>5%) were myalgia (6.7%) and nausea (5.2%). A total of 34 serious adverse events were reported, of which 5 were possibly or probably related to raltegravir. Self‐reported patient adherence at M6 is described as follows: ‘high’ for 56% of patients, ‘average’ for 36% of patients and ‘low’ for 8% of patients (205 questionnaires). To conclude, in a real‐life setting concerning patients with a strong proportion of co‐morbidity and variation in adherence, the efficacy and safety data observed after 12 months are comparable to the data observed (not shown) in clinical studies.

Viro‐immunological data

Naïve No previous treatment n=65
Switch Previous treatment with a viral load<50 copies/mL n=258
Failure Previous treatment with a viral load>50 copies/Ml n=151

Median Viral Load (copies/mL) at baseline
64,513
–
1,891

Median CD4 (cells/mm3) at baseline
308
556
365

M6
M12
M6
M12
M6
M12

Virological Response% (HIV‐RNA<50 copies/mL)
77% n=56
87% n=62
92% n=191
94% n=211
70% n=112
73% n=125

Immunological Response Median CD4 count (cells/mm3)
461 n=58
514 n=63
592 n=205
591 n=209
451 n=124
490 n=126
The impact of introducing a satellite dispensary service at an outpatient HIV clinic
Authors: Vekeria S , Jalali F , Sonecha S , Bates I
Published: November 2012

Background

Studies have demonstrated the potential impact of pharmaceutical services in HIV care [1]. We sought to extend HIV pharmacy services at the Dean Street outpatient HIV/GUM clinic to improve efficiency and enhance client satisfaction. The pharmacy team was expanded and a satellite dispensary was opened in the clinic. This project compares the new dispensary service with the previous one offered.

Method

Comparisons were made between the pre‐ and post‐change period across a range of pharmaceutical services provided and patient satisfaction feedback. Medicine‐related interventions, repeat prescription requests, waiting and dispensing times were recorded. Service satisfaction questionnaires were designed for patients to quantify aspects of service provision.

Results

Types of interventions remain broadly similar (p=0.353), with an increase in the daily number of interventions (p=0.0038) and a decrease in time spent per intervention (p=0.006) in the new service delivery model. A greater dispensing time (p=0.035, p=0.001) and time per item (p=0.043, p=0.002) for prescriptions with related queries was seen across both periods. However, the time taken to dispense prescriptions remained similar pre‐ and post change (p=0.8). The patient satisfaction survey had a series of statements relating to pharmacy services; there was a stronger association with patient satisfaction seen for the provided services during the post‐change period. The number and types of repeat prescription requests remain unchanged (p=0.342); however, patient prescription requests were completed more efficiently post‐change (mean time 5.4 minutes) as compared to pre‐change (mean 12.6 minutes; p = 0.001). There was also a significantly lower rate of FP10 prescriptions issued in the post‐change period due to a greater choice of available medications.

Conclusion

The care contributions of HIV pharmacists to a multidisciplinary HIV clinic providing patient‐centred care were measured before and after the introduction of a satellite dispensary service. The expanded pharmacy service has increased efficiency by completing more tasks in less time and increased access to medications for patients. Its focus is dealing with patient‐related queries and providing support for the patients seen at the clinic.
Reasons of hospitalization for HIV‐positive patients in the Infectology Center of Latvia in the period from 2009 to 2011
Authors: Sture G , Rozentale B , Zeltina I , Januskevica I , Sangirejeva A
Published: November 2012

Introduction

In Latvia, HIV‐positive patient count increases every year. 5189 HIV patients were registered in Latvia until January 2012. 1047 of them were in the AIDS stage. For the moment, healthcare of HIV patients is realized in two inpatient departments and one outpatient department; only patients with dual infection ‐ HIV and TB ‐ are observed in the TB center.

Aim of study

To identify problems, which are related to hospitalization of HIV‐positive patients, by improving patient care standards and if necessary change it.

Materials

1205 patient cards of hospitalization were analyzed in the period from January 2009 till December 2011 (year 2009 ‐ 351 patients, 2010 ‐ 391 patients, 2011 ‐ 463 patients). Statistical data analysis made by software ‐ SPSS and Microsoft Excel and described methods.

Results

Within three years 1205 patients were hospitalized. In late AIDS stage, 714 patients were hospitalized. For the treatment of these patients ART, OI prophylactic treatment and OI therapy had to be included. Most common cause of hospitalization was opportunistic infection: 2009 ‐ 168 patients (47.8%); 2010 ‐ 201 patients (51.4%); 2011 ‐ 193 patients (41.9%). Second most common cause of hospitalization was liver disease: 2009 ‐ 37 patients (10.5%); 2010 ‐ 55 patients (14%); 2011 ‐ 47 patients (10.1%). Other reasons of hospitalization were lower respiratory tract infections‐pneumonia, bronchitis. Only in 5.9% cause of hospitalization was acute retroviral syndrome. In 4.4% hospitalizations outcome was death, only in 0.2% cases cause of death was associated with non‐AIDS disease. Average time of hospitalization was 12.8 days.

Patients' distribution by HIV/AIDS stage

Clinical categories/CD4
A
B
C

>500 c/mm3

79
22
41

499–200 c/mm3

141
55
115

<200 c/mm3

75
119
558

Conclusions

1. HIV‐positive patient hospitalization count increases every year. 2. More often hospitalized patients are in late stage of HIV infection and reason of hospitalization is opportunistic infection, which extends time of hospitalization and costs. 3. Recommended immunization against VHB and S. pneumoniae, which would protect against non‐AIDS diseases. 4. Medical staff education needs to be updated, which would help to diagnose HIV infection in early stage of disease.
Impact of pharmacogenetic markers of CYP2B6 and clinical factors on plasma efavirenz level in HIV/tuberculosis co‐infected Thai patients
Authors: Manosuthi W , Sukasem C , Lueangniyomkul A , Mankatitham W , Thongyen S , Nilkamhang S , Manosuthi S , Sungkanuparph S
Published: November 2012

Purpose of study

Polymorphisms of CYP2B6 are associated with altered activity of cytochrome P450 2B6 which has an effect on plasma efavirenz level. The data of these polymorphisms and their effect, particularly in HIV/TB co‐infected patients, is still limited.

Methods

A total of 150 HIV‐infected Thai adults with active tuberculosis (TB) and receiving rifampicin‐containing anti‐TB regimen were prospectively enrolled to receive a once‐daily regimen of efavirenz 600 mg/tenofovir/lamivudine. Nine single nucleotide polymorphisms (SNPs) within CYP2B6 were genotyped using real‐time PCR‐based allelic discrimination. At 12 weeks after ART, plasma efavirenz levels at 12 hours after dosing were measured by HPLC assay.

Summary of results

Of all, the median (IQR) CD4 count was 44 (17–113) cells/mm3 and median (IQR) plasma HIV‐1 RNA was 5.8 (5.4–6.3) log copies/mL. Eight (5.3%) patients discontinued efavirenz due to adverse events prior to measuring efavirenz level. Of 142 patients, the frequencies of wild type, heterozygous mutant, and homozygous mutant of each SNP were 64C>T (89%, 10%, 1%), 499C>G (99%, 1%, 0%), 516G>T (45%, 47%, 8%), 785A>G (36%, 54%, 10%), 1375A>G (100%, 0%, 0%), 1459C>T (97%, 3%, 0%), 3003C>T (29%, 44%, 27%), 18492T>C (55, 39%, 6%), and 21563C>T (38%, 57%, 5%). Median (IQR) plasma efavirenz level of 102 patients who were concurrently receiving efavirenz and rifampicin was 2.08 (1.33–3.51) mg/dL and those of 40 patients who did not received rifampicin was 2.72 (1.80–5.21) mg/dL. Of 102 patients, heterozygous/homozygous mutant vs. wild type of 5 SNPs associated with high mean efavirenz level were 516G>T (3.6 vs. 1.9 mg/dL, P<0.001), 785A>G (3.2 vs. 2.0 mg/dL, P=0.001), 3003C>T (4.0 vs. 2.4 mg/dL, P=0.012), 18492T>C (3.5 vs. 2.0, P<0.001), 21563C;>T (3.4 vs. 1.9 mg/dL, P<0.001). Three of 9 haplotypes identified, including *6/*6, *1/*6, and *4/*6, were associated with high efavirenz level. By multivariate analysis, factors associated with high efavirenz level included specific haplotype (P<0.001), low body weight (P=0.003), and receiving rifampicin (P=0.058).

Conclusions

Particular SNPs and haplotype of CYP2B6, especially *6/*6, has the greatest impact on efavirenz level in HIV/TB co‐infected Thai patients whereas low body weight and concurrent receiving rifampicin have lesser effects.
Mortality among HIV/AIDS patients with/without Mycobacterium tuberculosis infection in southern region of Thailand
Authors: Chaimay B , Woradet S , Chantutanon S , Phuntara S , Suwanna K
Published: November 2012

Object

The purpose of this study was to gain knowledge of tuberculosis infection in HIV/AIDS‐infected patients, the purpose of this study was to investigate an association between tuberculosis infection and mortality in HIV/AIDS‐infected patients.

Methods

A prospective, hospital‐based cohort study was conducted in HIV/AIDS patients registered in hospitals between January 1993 and April 2010. In total, 52,459 patients with HIV/AIDS infection were routinely observed and followed up, covering 14 provinces in southern region of Thailand.

Results

The main results found that one‐third of the HIV/AIDS patients were infected with Mycobacterium tuberculosis (27.94%) during the follow‐up period. However, the risk of Mycobacterium tuberculosis infection was not statistically significant in terms of association with mortality among HIV/AIDS patients (HR: 1.01; 95% CI: 0.96 to 1.05). In contrary, HIV/AIDS patients with pulmonary tuberculosis were more likely to have a longer life by about 19% (HR: 0.81, 95% CI: 0.73 to 0.91). As well, HIV/AIDS patients with extrapulmonary tuberculosis were more likely to have a longer life by about 31% (HR: 0.69; 95% CI: 0.57 to 0.83).

Conclusion

In conclusion, tuberculosis infection was associated with mortality among HIV/AIDS patients. Early treatment of tuberculosis is needed for HIV/AIDS patients, in order to decrease morbidity and mortality among HIV/AIDS patients with tuberculosis.
Characteristics of tuberculous meningitis in HIV‐infected patients
Authors: Hristea A , Manciuc C , Zaharia‐Kezdi E , Dorobat C , Arbune M , Olaru I , Jipa R , Niculescu I , Streinu‐Cercel A
Published: November 2012

Background

Tuberculous meningitis (TBM) has a substantial mortality even with anti‐tuberculous treatment, in HIV‐non‐infected patients. Purpose of the study. The objectives were to describe clinical and laboratory differences of TBM in HIV‐infected versus HIV non‐infected patients and to assess risk factors of death in HIV‐infected patients.

Methods

We retrospectively analyzed patients admitted to four infectious diseases hospitals in Romania, between 2001 and 2011, with TBM. Patients were defined as having TBM according to a consensus definition published by Marais et al. [1] and further divided into three categories of TBM (definite, probable and possible).

Results

We identified 162 patients with TBM of which 47 (29%) tested positive for HIV infection. Sixty‐six patients had definite, 53 probable and 43 possible TBM. Out of the 47 HIV‐infected patients 25 had definite, 17 probable and 5 possible TBM. TBM in HIV‐infected patients vs. HIV non‐infected patients was significantly associated in multivariable analysis with younger age (p=0.01), in‐hospital mortality (p<0.001), absence of meningean syndrome (p=0.021), and absence of cranial nerve palsy (p=0.036). HIV‐infected patients who died had a median CD4 count of 61 cells/mm3 (IQR 21‐132) vs. 135 cells/mm3 (IQR 61–255) in patients who survived (p=0.014). HIV infection was diagnosed before TBM episode in 35 (75%) patients. Twenty‐four (51%) HIV‐infected patients had concomitant extra‐central nervous system tuberculosis.

Conclusions

HIV infection is associated with increased mortality in patients with TBM. Most of our patients with TBM were late presenters. Death in HIV infected patients was associated with a lower median CD4 count.

HIV‐infected
HIV‐non‐infected
p‐value

Male N (%)
32 (68)
68 (59)
0.287

Age (years) (median, IQR)
22 (18–34)
34 (20–51)
0.005

Duration of symptoms before admission (days) (median, IQR)
10 (7–14)
10 (7–14)
0.878

Cranial nerve palsy N (%)
6 (13)
31 (27)
0.051

Meningean syndrome N (%)
34 (72)
102 (89)
0.010

Glasgow Coma Scale<7 N (%)
11 (23)
18 (16)
0.243

Cell number in CSF (cells/mm3) (median, IQR)
180 (91–457)
200 (86–400)
0.799

Protein CSF level (mg/dl) (median, IQR)
175 (120–542)
198 (129–279)
0.701

CSF/serum glucose<0.5 N (%)
32 (71)
96 (84)
0.079

In‐hospital mortality N (%)
18 (38)
13 (11)
<0.001
Optimizing ribavirin dose in HIV/hepatitis C (HCV) co‐infected individuals treated for HCV
Authors: Farley J , Truong A , Horvath G , Nguyen T , Shum W
Published: November 2012

Hepatitis C (HCV) and HIV share common transmission pathways and the acquisition of both viruses are relatively common. Concurrent treatment for HCV with highly active anti‐retroviral therapy (HAART) should be considered in HIV co‐infected individuals to decrease the progression of liver damage. Adverse effects and less satisfactory treatment outcomes are often concerns when treating co‐infected individuals. Although, direct acting antivirals (DAAs) may increase SVR, they may not be possible because of drug‐drug interactions. he objective of this study is to investigate the difference in response rates of HCV treatment in HIV co‐infected inmates with varying doses of ribavirin. Retrospective medical chart reviews of 52 HCV/HIV co‐infected inmates who underwent HCV therapy between 2003 and 2010. All received standard doses of pegylated interferon alpha 2a or 2b and 800–1600 mg of ribavirin depending on weight. The recommended dosage for genotypes 2 and 3 is 800 mg/day. For other genotypes, if weight is<75 kg, the recommended ribavirin dose is 1000 mg/day or 1200 mg/day if>75 kg. Efficacy was defined as attaining sustained virological response (SVR) six months post treatment. Univariate analyses was performed using SPSS‐18; Chi‐square test with p‐value<0.05 was defined significant. 52 co‐infected (3 females & 49 males) were identified. Mean age was 40±7 years. Caucasians accounted for 84.6%; First Nations for 13.5% and Asians 1.9%. 36 were concurrently on HAART. The genotype distribution was: geno 1, 66.0%; geno 2, 7.5%; geno 3, 26.4%. SVR by ribavirin dosage ratio (actual dosage/recommended dosage):=1.0; 41.2% (14/34),>1.0; 58.8% (20/34). Doses greater than 1.5 times were associated with higher adverse events and lower SVR. Suboptimal doses of weight‐based ribavirin may be contributing to a lower treatment response in HCV/HIV co‐infectants. In our experience, the optimal dose of ribavirin is between 1 and 1.2 times the current recommended dose. We recommend that ribavirin dose be individualized in co‐infected in order to enhance the likelihood of achieving SVR. Dual therapy is more practical in many of our population because of chaotic lifestyle. Therefore optimizing the ribavirin dose should be initially undertaken.
Telaprevir‐based triple‐therapy in patients with chronic hepatitis C in Germany: a 12‐week interim analysis of real‐life data
Authors: Berg T , Buggisch P , Hueppe D , Mauss S , Wedemeyer H , Decker‐Burgard S
Published: November 2012

Telaprevir (TVR)‐based triple therapy in patients (pts) with chronic hepatitis C (HCV) in daily practice in Germany is investigated in this non‐interventional study. Aims are the evaluation of the implementation of futility rules, as well as safety and efficacy of TVR‐based therapy. This prospective, multi‐center study investigates TVR‐based therapy in therapy‐naïve and pretreated pts with genotype 1 chronic HCV in Germany, including pts with HIV co‐infection. Patients are treated with a combination of TVR, ribavirin and peg‐interferon. This interim analysis includes data from the first 100 pts (12.5% of the planned total) at 32 sites completing 12 weeks (W) of treatment. 66% of pts were pretreated for HCV. 36.4% of pts with pre‐treatment were prior relapsers and 30.3% null or partial responders. Cirrhosis was present in 11% of all pts at baseline. HCV RNA levels below 800.000 IU/ml at baseline were present in 50% of pts. 67% of pts showed rapid virological response (RVR, undetectable HCV RNA at W4). Adherence to the futility rule (treatment stop if HCV‐RNA>1000 IU/ml at W4) was 100% (N=9). At W12, 91.4% of pts had undetectable HCV RNA. 57.7% of therapy‐naïve pts and 86.4% of previous relapsers were HCV‐RNA negative at both W4 and 12 (70.8% in total). Only one patient achieving RVR at W4 suffered a virologic breakthrough. Nearly all pts (99%) had adverse events (AE) during the first 12W, 6% reported serious adverse events (SAE). AEs were mostly mild (63.9%) or moderate (34.6%) and frequently mentioned dry skin/pruritus (54%), gastrointestinal disorders (48%), anorectal discomfort (30%), rash (29%) and anemia (23%). Rash was mostly rated as mild or moderate (97.1%). An Hb decrease<12 g/dl (female) or<13 g/dl (male) was reported in 87% of pts. Mean Hb levels decreased from 14.8 g/dl at baseline to 10.6 g/dl at W12; Hb levels<8.5 g/dl at any time within the first 12W of treatment were present in 11% of anemia cases and 6.6% required transfusion. Only one patient received erythropoietin treatment. 2 cases each of anemia and rash were considered as SAE. These interim results suggest that TVR‐based triple‐therapy is efficient against GT1 chronic hepatitis C in a real life setting. Adherence to futility rules was confirmed in all patients. As observed in clinical trials, adverse events were reported frequently, including anemia and rash. As more data become available, results will be updated.
Depressive disorders in HIV‐HCV patients undergoing interferon‐α treatment for hepatitis C
Authors: Fialho R , Eccles J , Keller M , Pereira M , Haq I , Tibble J , Whale R
Published: November 2012

Effective clearance rates of HCV with interferon alpha plus ribavirin treatment are reported to be reduced in the co‐infected HIV/HCV population when compared to the HCV monoinfected population [1]. Neuropsychiatric adverse events are associated with hepatitis C treatment and interferon alpha‐induced major depressive disorder is commonly reported [2]. This study examined the rate and predictors of depression during interferon alpha plus ribavirin treatment in a Brighton, UK cohort of HCV‐infected patients including a subsample with HIV coinfection. Depressive disorder was explored at baseline and monthly up to 6 months using the Structured Clinical Interview for DSMIV and the Hamilton Rating Scale for depression. Six month treatment response was determined using viral load assay (clearance achieved if HCV RNA<400 IU/mL). A cohort of 237 HCV patients consented to participate in the study, including 38 coinfected with HIV. The HCV monoinfected group had a mean age of 45.60 years (SD=8.93) and 64.3% were male. The HIV/HCV coinfected group had a mean age of 41.34 (SD=9.8) and 94.7% were male. The most common mode of HCV transmission was intravenous drug use in both groups. Notably, clearance rates at 6 months were equivalent in both groups: 88.3% in the HCV group vs 86.5% in the coinfected group. Baseline DSMIV depressive disorder rates and mean HAMD scores were not significantly different between groups. For Hamilton depression scores over time, a significant multivariate effect was found with the co‐infected group having lower scores. For the whole sample, post‐hoc comparisons revealed that all depression scores after week 8 were significantly different from baseline scores and scores at week 4. Multiple regression analysis revealed DSMIV depressive disorder at week 4 was significantly predicted by baseline DSMIV depression (β=.30), past psychiatric history (β=.25), and not being coinfected (β=−.16). Age and gender had no significant effect. Only baseline depression predicted depression at later time points. Lower rates of depression in this coinfected group may relate to antiretroviral treatment effects. Limitations of our study include a small coinfected sample size and the absence of immunological data over the time course.
Insights on treatment of a Portuguese cohort of HCV/HIV coinfected patients
Authors: Silva C , Doroana M , Afonso C , Fernandes J , Antunes F
Published: November 2012

Purpose of the study

This study intends to characterize a Portuguese patient population with chronic HCV and HIV coinfection, followed at our Research Unit, underline the importance of early treatment and incorporate the importance of DDA for retreatment of HCV infection.

Methods

Retrospective, observational analysis of medical records of 348 HCV/HIV coinfected patients from 2001 to 2011. Demographic, epidemiological, clinical and laboratory data and virologic response were collected.

Summary of results

Review of 348 HCV/HIV coinfected patients, 121 of those (34.7%) under treatment, predominantly male (77.0%) and Caucasians (94.8%) with a median age of 44 yrs old (min 25; max 77 yrs). Intravenous drug use was the main route of HCV infection, in 71.3% of patients, and 8.3% were related with MSM. Frequent morbidities were alcohol abuse (46.8%), illicit drug use (70.1%), methadone (25.6%) and mental disturbances (12.3%) of patients. Regarding HIV infection, six were HIV‐2 and 342 HIV‐1; 36.1% were stage A and 29.6% were stage C (CDC Atlanta), 94.8% on antiretroviral treatment and only 21.9% of them with more than 350 TCD4 cell count. Genotype 1 was the most prevalent (58.1%–117 genotype 1a, 26 genotype 1b); 1.6% were genotype 2, 22.8% genotype 3 and 17.5% genotype 4. Previous to treatment initiation, HCV ARN was above 600.000 IU/mL in 56.9% patients. Fibrosis was evaluated by fibroelastography in 41.1% and hepatic biopsy in 26.3% of patients; in those, 44.0% had a score above F2 (METAVIR) and ALT was elevated 2 times the limit in 38.0%, with an average value of 94 UI/L. IL 28B testing was performed in only 35 patients at the time, with 45.7% CC and 17.1% CT genotype. Treatment was started in 34.8% of patients, with 1.7 treatments per individual, and regimen was based on peguilated interferon with ribavirin in 93.6% of cases (72.1% with peginterferon alfa 2a). The SVR rate was 51.2%, with 28.9% non responders, 3 relapsers and 9 treatment interruptions due to major toxicities.

Conclusions

Our data presents a low HCV treatment initiation, illustrated by 65.2% patients who did not begin any treatment. The majority completed treatment and the SVR rate was similar to literature. Individualized approach is essential to determine the optimal time to initiate HCV treatment, to assess patient adherence and adverse events management, in order to optimize treatment and reserve DDA drugs to experienced patients with worse predictive factors.
Sexually transmitted infection with an immune‐escape mutant hepatitis B virus (HBV) in an HBV‐vaccinated individual with acute HIV‐HCV infection
Authors: Ingiliz P , Krznaric I , Behrendt D , Baumgarten A , Berg T , Obermeier M
Published: November 2012

Immune pressure exerted on HBV by anti‐HBV antibodies and long‐term therapy with drugs that mutagenize the viral polymerase gene can select for mutations in its surface gene, leading to vaccine escape and evasion from serological detection. In general, these mutations are considered to be poorly transmissible. However, cases of HBV infection with vaccine‐escape mutant viruses have been reported in vaccinated individuals, mainly from high‐prevalence regions of the world. The possibility of an infection with HBV despite an effective vaccination may pose a major health issue, requiring a change in routine diagnostic and screening programmes. Here, we report a case of a HBV vaccine escape mutant infection in an effectively vaccinated individual. The patient was a 27‐year old man who has sex with men (MSM) who presented in September 2011 for the first time in a Berlin outpatient HIV clinic due to a newly diagnosed HIV infection. He was aware of several sexual high‐risk contacts within the past, but had a negative HIV and HCV antibody test (ELISA) in April 2011. He complained about slight fever, swollen cervical and axillary lymph nodes and general muscle pain. The Western blot confirmed an HIV infection. The HIV viral load was 24,000 copies/mL, the CD4 count was 550/mm3. His ALT levels were elevated to 10×the upper limit of normal (ULN) and he was additionally found to have acute HCV infection: The HCV viral load was 2 million IU/mL, the HCV genotype was 2c. Furthermore, he was anti‐HBc negative, HBsAG negative, and his anti‐HBs level was 121 IU/L. He reported to have been vaccinated for HBV in the past. Three months later, the patient was routinely retested. At this time point, his HBsAg turned out to be positive and anti‐HBs antibodies had vanished. His HBV viral load was 600 million IU/mL, and ALT had decreased to 2×ULN. Population sequencing revealed a genotype F and a S143L mutation in the surface gene consistent with a vaccine escape mutant HBV. A retrospective analysis of the initial blood sample showed a HBV DNA of 90 IU/mL.

Conclusion

To our knowledge, this is the first report of a sexually transmitted HBV virus with vaccine‐escape mutation in a vaccinated individual. Despite a fairly high CD4 count, the transmission may have been promoted by a loss of immunity through an acute HIV infection. Clinicians need to be aware of the possibility of HBV infections with mutant viruses.
Serum cotinine as a biomarker of tobacco exposure and the association with treatment response in early rheumatoid arthritis
Authors: Maska Leann B. , Sayles Harlan R. , O'Dell James R. , Curtis Jeffrey R. , Bridges S. Louis , Moreland Larry W. , Cofield Stacey S. , Mikuls Ted R.
Published: November 2012

Objective

Cigarette smoking has emerged as a risk factor for the development of rheumatoid arthritis (RA). Recent studies have suggested that cigarette smoking may lead to lower treatment response rates with methotrexate (MTX) and some biologic agents in RA. Knowledge of whether tobacco exposure reduces treatment efficacy is important, since smoking could represent a modifiable factor in optimizing RA treatment.

Methods

The study participants included patients with early RA (<3 years in duration) enrolled in the Treatment of Early Aggressive Rheumatoid Arthritis study, a randomized, blinded, placebo‐controlled clinical trial comparing early intensive therapy (MTX + etanercept or MTX + hydroxychloroquine + sulfasalazine triple therapy) versus initial treatment with MTX with step‐up to MTX + etanercept or to triple therapy if the disease was still active at 24 weeks. Serum cotinine was measured using a commercially available enzyme‐linked immunosorbent assay at baseline and at 48 weeks, with detectable concentrations at both visits serving as an indicator of smoking status. The mean Disease Activity Score in 28 joints (DAS28) was compared by smoking status, adjusting for baseline disease activity.

Results

Of the 412 subjects included in the analysis, 293 (71%) were categorized as nonsmokers and 119 (29%) as current smokers. There were no differences in the mean DAS28 score between 48 and 102 weeks based on smoking status for the overall group (P = 0.881) or by specific treatment assignment.

Conclusion

Among patients enrolled in a large randomized controlled trial of early RA with poor prognostic factors, smoking status did not impact treatment responses for those receiving early combination or initial MTX with step‐up therapy at 24 weeks if the disease was still active.
Comparative study of environmental factors influencing motor task learning and memory retention in sighted and blind crayfish
Authors: Bierbower Sonya M. , Shuranova Zhanna P. , Viele Kert , Cooper Robin L.
Published: November 2012

In classical conditioning, an alteration in response occurs when two stimuli are regularly paired in close succession. An area of particular research interest is classical conditioning with a chemical signal and visual and/or tactile stimuli as the unconditional stimuli, to test manipulative and motor behaviors in a learning paradigm. A classical learning task chamber was developed to examine learning trends in a sighted surface‐dwelling crayfish, Procambarus clarkii, and in a blind cave‐dwelling crayfish, Orconectes australis packardi. We examined whether learning is influenced by environmental factors and/or reliance on different primary sensory modalities. Crayfish were trained to manipulate a large, cumbersome cheliped through a small access point to obtain a food reward. In both species, acquisition of the learning task was rapid when they were in nonstressed conditions. The blind crayfish tested in low white light did not successfully complete the task, suggesting a stress response.
A Series of 1D, 2D, and 3D Coordination Polymers Based on Flexible 3‐Carboxy‐1‐Carboxymethyl‐2‐Oxidopyridinium and Different N‐Donor Ligands – Syntheses, Structures, and Luminescent Properties
Authors: Yang Ying‐Qi , Yang Jin , Kan Wei‐Qiu , Yang Yan , Guo Jiao , Ma Jian‐Fang
Published: November 2012

Twelve new coordination polymers, namely, [Pb(L)] (1), [Mn2(L)2(H2O)] (2), [Mn(L)(H2O)] (3), [Zn3(L)2(H2O)4] (4), [Zn(L)(pbib)0.5]·1.5H2O (5), [Cd(L)(pbib)0.5]·2H2O (6), [Zn(L)(bbtz)0.5]·H2O (7), [Zn(L)(bbmb)0.5] (8), [Co(L)(bbmb)0.5(H2O)] (9), [Zn(L)(biim‐6)0.5]·2H2O (10), [Cd(L)(biim‐6)0.5]·2H2O (11), and [Cd(L)(biim‐4)0.5]·2H2O (12) have been synthesized under hydrothermal conditions [H2L = 3‐carboxy‐1‐carboxymethyl‐2‐oxidopyridinium, pbib = 1,4‐bis(imidazol‐1‐ylmethyl)benzene, bbtz = 1,4‐bis(1H‐1,2,4‐triazol‐1‐ylmethyl)benzene, bbmb = 1,1′‐(1,4‐butanediyl)bis(2‐methylbenzimidazole), biim‐6 = 1,1′‐(1,6‐hexanediyl)bis(imidazole), and biim‐4 = 1,1′‐(1,4‐butanediyl)bis(imidazole)]. Compound 1 features 1D double‐chain structures, which are further linked by C–H···O hydrogen‐bonding interactions to form a 3D supramolecular architecture. Compounds 2–11 have 2D layer structures. Compound 2 possesses a 2D (42·64) layer. Compound 3 exhibits a 2D undulated 44‐squar lattice (sql) sheet. The 2D layers of 2 and 3 are further connected by intermolecular hydrogen‐bonding interactions, which lead to 3D supramolecular architectures. The structure of 4 is a 2D (3,4)‐connected net with the (42·62·82)(42·6) topology. Compounds 5–7 have similar structures and show 2D networks with 4‐connected 44‐sql topologies. Compounds 8 and 9 have similar structures and display (3,4)‐connected networks with the (42·6)(42·63·8) topology. Compounds 10 and 11 reveal similar 4‐connected 44‐sql nets. The 2D layers of 5–11 are further extended into 3D supramolecular architectures through π–π interactions. Compound 12 has a 3D (65·8) CdSO4‐type framework. The thermal stabilities of 1–12 have been studied by thermogravimetric analysis. The luminescent properties for 4–8 and 10–12 have also been investigated in detail.
Synthesis and Configuration of the Phenolic Nonadecanediol Isolated from the Resinous Exudates of Heliotropium sinuatum
Authors: Chen Chao‐Yuan , Zhang Shao‐Min , Wu Yikang , Gao Po
Published: November 2012

The (3S,5R) and (3R,5R) isomers of the title compound were synthesized from enantiopure epoxide chiral building blocks readily accessible from D‐gluconolactone. The former (a syn‐1,3‐diol) gave 1H and 13C NMR spectroscopic data and optical rotation in good agreement with those reported for the natural product, whereas distinct differences were found with the data for the latter (an anti‐1,3‐diol). These results unambiguously showed that the absolute configuration of the natural product must be (3S,5R).
Forty years of USAID health cooperation in Bolivia. A lose–lose game?
Authors: Tejerina Herland , Closon Marie‐Christine , Paepe Pierre De , Darras Christian , Dessel Patrick Van , Unger Jean‐Pierre
Published: November 2012

The present article proposes an analysis of the USA–Bolivia relationships in the health sector between 1971 and 2010 based on a grey and scientific literature review and on interviews. We examined United States Agency for International Development (USAID) interventions, objectives, consistency with Bolivian needs, and impact on health system integration. USAID operational objectives—decentralization, fertility and disease control, and maternal and child health—may have worked against each other while competing for limited Ministry of Health resources. They largely contributed to the segmentation and fragmentation of the Bolivian health system. US cooperation in health did not significantly improve health status while the USAID failed to properly tackle anti‐drugs, political, and economic US interests in Bolivia. Copyright © 2012 John Wiley & Sons, Ltd.