bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted destruction of HIV‐positive cells
Authors: Sharma Jyoti R , Dodgen Cleo , Skepu Amanda , Meyer Mervin 
Published: November 2014

IntroductionHIV/AIDS is now a global epidemic that has become the leading infectious killer of adults worldwide. Although antiretroviral (ARV) therapy has dramatically improved the quality of life and increased the life expectancy of those infected with HIV but frequency of dosing and drug toxicity as well as the development of viral resistance pose additional limitations. The rapidly expanding field of nanotechnology has vast potential to radically advance the treatment and prevention of HIV/AIDS. Nanoparticles can provide improved drug delivery, by virtue of their small size, robustness, safety, multimodality or multifunctionality.Aims and objectivesSince HIV primarily infects CD4+ cells; we aim to use CD4 as a selectable target to deliver a pro‐apoptotic protein to HIV‐infected cells using nanoparticles as carriers. The aim of study was to develop a nanotechnology‐based death inducing delivery system for the destruction of CD4+HIV infected cells through the activation of caspase‐3.MethodologyA modified caspase‐3 protein (Mut‐3) was engineered, which is cleavable only by HIV‐1 protease. Mut‐3 can activate apoptosis in the presence of HIV‐1 protease, consequently killing HIV‐positive cells. Mut‐3 protein was conjugated to gold nanoparticles together with a CD4‐targeting peptide. The efficacy of the gold nanoparticles was tested on CHO cells that were genetically engineered to express GFP labelled CD4 and HIV‐1 protease.ResultsMut‐3 was expressed in bacterial cells and purified. CHO cells that stably over express CD4‐GFP and HIV‐1 protease were selected using Fluorescence Activated Cell Sorting. Dose response cell culture experiments showed that gold nanoparticles without Mut‐3 and CD4‐targeting peptide did not induce cell death in CHO cells, while gold nanoparticles that was conjugated with Mut‐3 and the CD4‐targeting peptide rapidly induced cell death in CHO cells.ConclusionsOur results suggest that gold nanoparticles conjugated with Mut‐3 and a CD4‐targeting peptide could potentially induce apoptosis in HIV‐infected cells.
Viro‐immunological characterization of naïve patients with high cerebrospinal fluid (CSF) HIV RNA
Authors: Iannuzzi Francesca , Bai Francesca , Merlini Esther , Trunfio Mattia , Borghi Lidia , Bini Teresa , d'Arminio Monforte Antonella , Marchetti Carla Giulia 
Published: November 2014

BackgroundHIV can spread into the central nervous system (CNS) early in the course of infection and this turns into intrathecal inflammation and neuronal damage. We aimed to investigate clinical and immunological parameters associated with elevated CSF VL in HIV‐infected ART‐naïve patients.Materials and MethodsHIV+ ART‐naïve patients underwent a comprehensive battery of neurocognitive (NC) tests and lumbar puncture (LP) for CSF HIV‐RNA detection. Plasma HIV‐RNA and peripheral T‐cell immune‐phenotypes (CD38/CD45RA/CD45R0/CD127 on CD4/CD8) were also assessed (flow cytometry). High‐CSF HIV RNA was defined as≥10000cp/mL (H‐CSF), while CSF HIV RNA<10000cp/mL characterized low VL patients (L‐CSF). Chi‐square and Mann‐Whitney tests were used. Parameters independently associated with CSF VL were explored by multivariate regression.ResultsA total of 131 patients were retrospectively enrolled. Forty‐two patients (32%) had CSF VL >10000 cp/mL.Table 1 shows the features of H‐ versus L‐CSF patients. Compared to L‐CSF patients, H‐CSF patients displayed lower current CD4+%, lower CD4/CD8 ratio and higher CD8%. No differences in NC tests performance were observed between groups (p=0.6). Regarding T‐cell immuno‐phenotypes, H‐CSF patients displayed a higher proportion of CD45R0+CD38+CD8+ (11 vs 7%, p=0.02) and lower expression of CD45RA+CD8+ % (16 vs 20%, p=0.007), in comparison to L‐CSF patients. In multivariate analysis CD45RA+CD8+ T‐cells % (OR 0.917, CI 95% 0.852–0.987, p=0.002) was associated with H‐CSF, even after adjustment for plasma VL, CD8 and CD4 count. Globally, in univariate CSF VL inversely correlated with CD45RA+CD8+ % (r=−0.223, p=0.0217) and CD127+CD4+ % (r= −0.204, p= 0.0225), while a positive association was found between CSF and plasma VL (r=0.303, p=0.0004) and CD8 % (r=0.211, p=0.016). In multivariate linear regression, in addition to positive association between plasma and CSF VL (β: 0.212, 95% CI 0.02–0.41, p=0.032), also CD45RA+CD8+ % were confirmed inversely associated to CSF VL (β: 0.21, 95% CI −0.5 to −0.002, p=0.036), adjusting for CD4/CD8 and CD4CD127 %.ConclusionsWe hereby describe a 32% prevalence of H‐CSF in a cohort of HIV+ ART‐naïve patients. Subjects with high‐CSF viral replication are mostly with higher systemic immune activation, in particular the percentage of naïve CD8 T‐cell is positively associated with CSF VL, irrespective of plasma VL. In HIV+ ART‐naïve patients, especially if featuring a hyperactivated T‐cell immune‐phenotype, lumbar puncture should be considered to further guide CNS‐targeted cART.
Factors associated with HPV‐DNA clearance in a cohort of HIV‐positive patients: role of cART and gender
Authors: Suardi Elisa , Bai Francesca , Comi Laura , Pandolfo Alessandro , Rovati Marco , Barco Ambra , Dalzero Serena , Cassani Barbara , Marchetti Giulia , D'Arminio Monforte Antonella 
Published: November 2014

IntroductionWe aimed to assess any factors associated with dysplasia regression and with HPV clearance in a cohort of HIV+ patients, with particular focus on cART and gender.MethodsAsymptomatic HIV+ patients of the San Paolo Infectious Disease (SPID) cohort who underwent anoscopy/gynaecological evaluation were enrolled. Anal/cervical brushing were analyzed for: HPV‐PCR detection/genotyping (HR‐HPV), cytologic abnormalities (Bethesda System 2001: LSIL‐HSIL). Demographics and HIV‐related parameters were evaluated at baseline. Activated CD8+/CD38+ lymphocytes were measured (flow citometry). Patients were examined at baseline (T0) and at 12–18 months visit (T1). HPV clearance was defined as negativisation of HPV at T1; SIL regression (SIL‐R) and progression (SIL‐P) were defined as change from HSIL/LSIL to a lower‐grade/absence of dysplasia and as change from absence of HSIL/LSIL to a higher‐grade dysplasia at T1, respectively. Mann Whitney test, Chi‐square test and multivariate logistic regression were used.ResultsA total of 189 patients were examined, 60 (32%) were women. One hundred fifty patients (79%) were HPV+, 113 (75%) harboured HR‐HPV; 103 (68%) showed LSIL/HSIL at T0 (32% of women and 65% of men) (all were HPV‐positive). No differences in demographics and HIV‐related markers were found between patients with SIL‐P (33, 41%) and patients with SIL‐R (47, 59%). HPV+ patients who cleared HPV (28, 18%) were found to be more frequently female, heterosexual infected, more frequently on cART and with lower Log10 HIV‐RNA and lower levels of CD8+/CD38+ % compared with HPV persistence group (Table 1).No differences in PI exposure were found between the two groups (p=.08). Interestingly, also when only HR‐HPV were considered, clearance was associated with exposure to cART (naïve 4%, vs cART 86%, p=.048). In multivariate analysis, heterosexuals (AOR 5.123, 95% CI 1.5–17.5 vs homosexuals) were independently associated to HPV clearance, whereas CD8+/CD38+% (AOR 0.44, 95% CI 0.65–1.01 for each % more) were predictive of HPV persistence.ConclusionsClose follow‐up of HPV and SIL should be promoted particularly in men and in untreated individuals. We cannot exclude behavioural variables linked to risky sex and reinfection.
Improvement of endothelial function after switching previously treated HIV‐infected patients to an NRTI‐sparing bitherapy with maraviroc
Authors: Bernal Enrique , Miguel Gomez Verdú Jose , Vera Francisco , Martinez Onofre , Bravo Joaquin , Galera Carlos , Muñoz Angeles , Garcia Eva , Serrano Jose , Perez Ana , Vera Carmen , Marín Irene , Cano Alfredo 
Published: November 2014

IntroductionNucleoside reverse transcriptase inhibitor (NRTI) is associated with endothelial dysfunction and proinflammatory effects. Maraviroc (MVC) is an antagonist of CCR5 receptor. CCR5 is the receptor of RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted), a mediator of chronic inflammation and endothelial function. Our aim was to evaluate the maintenance of viral suppression and improvement of endothelial function in virologically suppressed HIV‐infected patients switched to an NRTI‐sparing combined antiretroviral therapy (cART) with MVC.Materials and MethodsThis observational, non‐interventional, multicenter study was performed at the Infectious Diseases Service of Santa Lucia, Morales Meseguer, Virgen de la Arrixaca and Reina Sofía University Hospital (Murcia, Spain). The selection criteria were to be asymptomatic on a regimen with undetectable viral load (<50 HIV‐RNA copies/mL) for at least six months, no previous treatment with R5 antagonists, no evidence of previous protease inhibitor (PI) failure and available R5 tropism test. Twenty‐one HIV‐infected patients were selected after the treatment regimen was changed to Maraviroc 150 mg/once daily plus ritonavir‐boosted PI therapy. Endothelial function was prospectively evaluated through flow‐mediated dilatation (FMD) of the brachial artery at baseline and at weeks 24.ResultsWe included 21 patients on treatment with PI in combination with 2 NRTI. The mean cART exposition was 133±68.9 months. Fourteen (66.6%) were males, aged 49±9 years, 15 (71.4%) smokers, 4 (19.04%) family history of coronary heart disease, 1 (5.76%) type 2 diabetes and 3 (14.28%) hypertensive, mean total cholesterol was 185.5±35 mg/dL, c‐LDL 100.2±37 mg/dL, tryglicerides 170.42±92.03 mg/dL, cHDL 52.6±15.5 mg/dL, CD4 779,5±383.28 cells/mL, nadir CD4 187,96±96 cells/mL. After 24 weeks of follow‐up of a switch to an NRTI‐sparing regimen, 95.2% of HIV‐patients on viral suppressive cART maintained viral suppression and CD4+ T cell count. This cART switch improve endothelial function in patients with lower baseline FMD levels after 24 weeks (baseline FMD −1.19±4.84 % to 24 weeks FMD 11.32±7.27%; p=0.002).ConclusionsThe results of our study show that a switch to an NRTI‐sparing bi‐therapy with MVC improves endothelial function and maintained the immune‐virologic efficacy. This regimen emphasizes the needs for further clinical studies to associate these achievements with the incidence of non‐AIDS‐defining illnesses.
Mediterranean diet: the impact on cardiovascular risk and metabolic syndrome in HIV patients, in Lisbon, Portugal
Authors: Policarpo Sara , Valadas Emilia , Rodrigues Teresa , Catarina Moreira Ana 
Published: November 2014

IntroductionMetabolic syndrome (MS) is common in HIV‐infected individuals and it is associated with higher cardiovascular risk (CVR). Mediterranean diet has been associated with a better metabolic control and lower CVR.Materials and MethodsFrom December 2013 to May 2014, individuals between 18 and 65 years of age, who attended the outpatient HIV Clinic at the University Hospital Santa Maria, Lisbon, were selected. Adherence to Mediterranean diet was evaluated with MedDietScore, a scale from 0 to 55 that punctuates 11 food items according to the frequency of intake. Higher scores represent higher adherence. CVR was assessed using D.A.D tool (classified as low, moderate or high risk). We excluded individuals with opportunistic disease, hospitalized in the past three months or with renal disease diagnosis. All participants gave written informed consent.ResultsIn the 571 HIV patients included, 67.1% (n=383) were male, 91.6% (n=523) Caucasian, with a mean age of 46.5±8.9 years. Patients were divided in two groups: naïve (7.5%; n=43) or on antiretroviral treatment (ART) (92.5%; n=528). Mean length of HIV diagnosis was 6.7±6.5 years (naïve) and 13.3±6.1 years (ART); TCD4+ counts were above 500 cel/mm3 in 55.8% (n=24) and 67.6% (n=357) of the patients, respectively. MS was present in 33.9% (n=179) of patients in ART group and 16.3% (n=7) in naïve group. Presence of MS was associated with ART group (OR=2.7; p=0.018). MS was also associated with older age in this group (p=0.000). Overall, mean MedDietScore was 27.3±5.5. Higher score was associated with older age (r=0.319; p=0.000). Naïve patients presented a trend to higher adherence to Mediterranean diet (65.1% vs 51.7% in naïve group; p=0.090). No relation between MS and Mediterranean diet was found. Higher CVR was associated with the presence of MS in the ART group (p=0.001). In this group, individuals with moderate CVR presented higher rates of adherence to Mediterranean diet (p=0.036) when compared to low and high CVR score.ConclusionsIn this cross‐sectional study, naïve individuals presented a trend to higher adherence to Mediterranean diet. On the ART group, higher adherence to Mediterranean diet was found in individuals with moderate CVR score. We think that this might suggest that this group of patients adopt this diet only in the presence of metabolic alterations or perceived CVR. Prospective studies in HIV patients are required to determine the impact of adherence to Mediterranean diet on the reduction of CVR.
Research on demands and accessibility of health services for AIDS long‐surviving patients with AIDS‐nonrelated diseases: a survey in central China
Authors: He Na , Ye Yingfeng 
Published: November 2014

IntroductionCompared with western countries, China started to provide free medicine for AIDS patients years later, which leads to the late emergence of problems on health service demands of AIDS long‐surviving patients with non‐AIDS‐related diseases. Government hasn't laid enough stress on it.Materials and MethodsThe interviews and questionnaire surveys are conducted and analyzed to get information. The interviewees include 81 AIDS long‐surviving patients in three villages and several hospitals in Shangcai, Zhumadian, and 18 AIDS‐related decision makers and health service providers.ResultsThere are 79 long‐surviving patients out of 81. 58 patients have non‐AIDS‐related diseases. 21 patients get hypertension and 28 get HCV. 100% patients have been to the clinics with their real‐name IC cards for minor illness. 43 patients have been transferred to assigned hospitals at the county level. Seven have the experience utilizing health services in the municipal or provincial assigned hospitals. The problem is on accessibility. 40 patients hope to get more convenient and cheap health services. Among them, 37 say the kinds and the amount of medicine in village clinics are not adequate. Seven give up because of the expensive treatment expense. For 21 patients with hypertension, 3 buy medicine at the county‐level hospitals. The other 18 choose to buy at private pharmacy. For 28 patients with HCV, 3 are not aware they actually got HCV. Free hepatic protector medicine is provided at village clinics. Up to 11 patients have not taken any treatment for HCV.ConclusionsPatients with hypertension go to the private pharmacy for medicine instead of higher level hospital because of lack of medicine in clinics, far distance from hospitals, cumbersome procedures in hospitals, limited dosage of prescriptions and too little discount. The situation for patients with HCV is even worse. It is predicted 70% of AIDS long‐surviving patients have HCV. The treatment is expensive and out of pocket. And free liver‐protection medicine does not work sometimes. Some patients working outside their home town do not want to reveal their health situation to get free medicine. The elderly with multiple co‐morbidities need more caring. Government should expand the scale of free medicine. Hospitals need to improve medicine plans and assist on medicine purchase. For patients, attitude decides everything.
Smoking prevalence, readiness to quit and smoking cessation in HIV+ patients in Germany and Austria
Authors: Degen Olaf , Arbter Peter , Hartmann Peter , Mayr Christoph , Buhk Thomas , Schalk Horst , Brath Helmut , Ernst Dorner Thomas 
Published: November 2014

IntroductionDue to the interaction between smoking and the virus and the antiretroviral therapy, the excess health hazard due to smoking is higher in HIV+ patients than in the general population. International studies suggest a higher prevalence of smoking in HIV+ subjects compared to the general population. It was the aim of the study to assess prevalence of smoking, to analyze determinants of smoking, and to evaluate readiness to quit in HIV+ patients in Germany and Austria.Material and MethodsConsecutive patients with positive tested HIV status, smokers and non‐smokers, who are treated in seven different HIV care centres in Austria and Germany were included. Nicotine dependence was assessed with the Fagerström Test for Nicotine Dependency (FTND), and stages of change by a standardized readiness to quit questionnaire. Self‐reported smoking status was objectified by measuring exhaled carbon monoxide levels. Smokers who wanted to quit were offered a structured smoking cessation programme, and those who did not want to quit received a 1‐minute consultation. After six months, the smoking status of all included subjects was reassessed.ResultsA total of 447 patients were included; the response rate was 92%. Prevalence of smoking was 49.4%. According to a multivariate logistic regression analysis, lower age, male sex, lower educational level, and smoking of the partner were significantly associated with the smoking status. According to the FTND, 25.3% showed a low (0–2 points), 27.6 a moderate (3–4 points) and 47.1% a high (5–10 points) dependency. Regarding stages of change, 15.4% of the smokers were in the stadium precontemplation, 48.4 in contemplation, 15.4 in preparation and 10.0 in the stadium action. 11.0% were not assignable in any stadium. Higher education level and lower grade of dependency were significantly associated with the wish to quit smoking. Six months after the baseline examination, smoking cessation visits (at least one session) was performed in 28.5% of the smokers. 13% of the smokers have quit smoking, 23% have reduced smoking and 63% did not change smoking habits positively 6 months after the first visit.ConclusionsPrevalence rates for smoking in HIV+ subjects are higher than in the general population. Readiness to quit is, however, high, and 13% of smokers who have quit smoking after six months is a remarkable short‐term success. This observation underlines the importance and feasibility of addressing smoking habits in HIV care.
The suspected unexpected and serious adverse events of antiretroviral drugs used as HIV prophylaxis in HIV uninfected persons
Authors: Pietraszkiewicz Ewa , Firlag‐Burkacka Ewa , Horban Andrzej , Kowalska Justyna D 
Published: November 2014

IntroductionWith increased usage of antiretroviral drugs (ARVs) in HIV uninfected persons proper reporting on suspected unexpected serious adverse reactions (SUSARs) and continued insight into serious adverse events (SAEs) is needed for adequate information on ARVs safety in such populations.MethodsWe have evaluated medical documentation of persons receiving ARVs after non‐occupationally HIV exposure (nPEP) during five concomitant years (2009–2013). SAEs and SUSARs were evaluated by two HIV physicians and defined according to international standards. In statistical methods, Kaplan Meier survival analysis was used to estimate the probability of SAE and Cox proportional hazard models to identify independent predictors of developing SAE. Only the first SAE was included in these analyses.ResultsIn total, 375 persons received nPEP. The most common reason was needle stick (43%), followed by unprotected sexual intercourse (17%), rape (10%) and first aid (10%). In 84 (22%) cases, the source patient was either known to be HIV positive or within a high risk group (active injecting drug user). In total, 170 SAEs were reported, 139 persons had only one SAE and majority developed it within first two weeks. The most frequent first SAEs were gastrointestinal disorders (22%), followed by general symptoms (9%), hypersensitivity reactions (1.6%) and CNS symptoms (1.3%). The remaining events were laboratory abnormalities of liver and kidney function, haematological disorders, other and unknown, each contributing to less than 1% of all patients. 8 (2.1%) patients have developed a SUSAR (bradycardia, vivid dreams, lymphadenopathy of the neck, increased platelet count, swelling and pain of large joints, swelling of lower limbs, peripheral oedema and loss of concentration). 22 (5.9%) persons discontinued nPEP due to adverse event and 19 (5.1%) required a paid sick leave from work. In multivariate analyzes, only age was independent predictor of developing SAE (HR 1.17; [95% CI 1.03–1.34]; p=0.02).ConclusionsIn our observation, SAEs in reaction to nPEP were frequent yet usually mild events, mostly occurring in first two weeks and rarely causing discontinuation. The only significant factor increasing the risk of SAE was age. SUSARs were rare and moderately significant. More insight into this important area is required in order to ascertain proper pharmacovigilance of ARVs usage in HIV uninfected persons.
Rilpivirine versus etravirine validity in NNRTI‐based treatment failure in Thailand
Authors: Teeranaipong Phairote , Sirivichayakul Sunee , Mekprasan Suwanna , Ruxrungtham Kiat , Putcharoen Opass 
Published: November 2014

IntroductionEtravirine (ETR) and rilpivirine (RPV) are the second‐generation non‐nucleoside reverse transcriptase inhibitors (NNRTI) for treatment of HIV‐1 infection. Etravirine is recommended for patients with virologic failure from first generation NNRTI‐based regimen [1]. RPV has profile with similar properties to ETR but this agent is approved for treatment‐naïve patients [2]. In Thailand, ETR is approximately 45 times more expensive than RPV. We aimed to study the patterns of genotypic resistance and possibility of using RPV in patients with virologic failure from two common NNRTI‐based regimens: efavirenz (EFV)‐ or nevirapine (NVP)‐based regimen.Materials and MethodsData of clinical samples with confirmed virologic failure during 2003–2010 were reviewed. We selected the samples from patients who failed EFV‐ or NVP‐based regimen. Resistance‐associated mutations (RAMs) were determined by IAS‐USA Drug Resistance Mutations. DUET, Monogram scoring system and Stanford Genotypic Resistance Interpretation were applied to determine the susceptibility of ETR and RPV.ResultsA total of 2086 samples were analyzed. Samples from 1482 patients with virologic failure from NVP‐based regimen treatment failure (NVP group) and 604 patients with virologic failure from EFV‐based regimen treatment failure (EFV group) were included. 95% of samples were HIV‐1 CRF01_AE subtype. Approximately 80% of samples in each group had one to three NNRTI‐RAMs and 20% had four to seven NNRTI‐RAMs. 181C mutation was the most common NVP‐associated RAM (54.3% vs 14.7%, p<0.01). 103N mutation was the most common EFV‐associated RAM (56.5% vs 19.1%, p<0.01). The calculated scores from all three scoring systems were concordant. In NVP group, 165 (11.1%) and 161 (10.9%) patients were susceptible to ETR and RPV, respectively (p=0.81). In EFV group, 195 (32.2%) and 191 (31.6%) patients were susceptible to ETR and RPV, respectively (p=0.81). The proportions of viruses that remained susceptible to ETR and RPV in EFV group were significantly higher than NPV group (ETR susceptibility 32.2% vs 11.1%, p<0.01, RPV susceptibility 31.6% vs 10.9%, p<0.01), respectively.ConclusionsRPV might be a cost saving and reasonable second line NNRTI for patients who failed EFV‐ or NVP‐containing regimens, especially in resource‐limited setting because these two agents have comparable susceptibility identified by genotyping. From our study, approximately 30% of patients who failed EFV‐based regimens had viruses that remained susceptible to RPV.