bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of darunavir/ritonavir (DRV/r) in HIV‐1‐infected DRV/r‐experienced and ‐naïve patients: analysis of data in the real‐world setting in Italy
Authors: Antinori Andrea , Borderi Marco , Cauda Roberto , Bini Teresa , Chirianni Antonio , Squillace Nicola , Mancusi Daniela , Termini Roberta 
Published: November 2014

IntroductionThis descriptive, non‐interventional study on HIV‐1‐infected patients treated with DRV/r in the usual clinical setting, with a single‐arm prospective observational design, collected data on utilization of darunavir/ritonavir (DRV/r) under the conditions described in marketing authorization in usual clinical practice in Italy to evaluate efficacy and safety of DRV/r‐based antiretroviral (ARV) treatment. This analysis focussed on the safety profile of DRV/r in HIV‐1 infected patients.Materials and MethodsData were analyzed from four cohorts of HIV‐1‐infected patients treated with DRV/r in the real‐world setting, including an ARV‐naïve‐DRV/r‐naïve cohort (Cohort 1), an ARV‐experienced‐DRV/r‐naïve cohort (Cohort 2) and two ARV‐DRV/r‐experienced cohorts (Cohorts 3 and 4), one of which (Cohort 3) was from the DRV/r Early Access Program. The objective of this analysis was to examine the safety data obtained in these four cohorts in patients enrolled from June 2009 to November 2011 and observed until December 2012 or DRV/r discontinuation.ResultsSafety data from 875 patients were analyzed. DRV/r‐based treatment was well tolerated, with 36.2% of patients reporting ≥1 adverse event (AE) and very few discontinuations due to study drug‐related AEs (3.0% overall). The most frequent AEs were diarrhoea (2.7%), reduced bone density (2.6%) and hypercholesterolaemia (2.1%) (Table 1). Regarding metabolic parameters, levels of liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) remained stable from baseline to the last study visit (LSV) in DRV‐experienced patients and decreased in DRV‐naïve patients. Blood glucose concentrations remained stable in all cohorts. Serum triglyceride and cholesterol concentrations remained stable in DRV‐experienced patients but increased in naïve patients, yet were still within normal range.ConclusionsIn HIV‐1‐infected patients treated with DRV/r in these settings, the tolerability profile was favourable and similar to (or better than) that reported in controlled clinical trials. These data confirm DRV/r to be a safe treatment choice in DRV/r‐experienced and naïve patients.
Prevalence and risk factors of sleep disturbances in a large HIV‐infected adult population
Authors: Allavena Clotilde , Guimard Thomas , Billaud Eric , de la Tullaye Sylvie , Reliquet Véronique , Pineau Solène , Hüe Hervé , Supiot Christelle , Marie Chennebault Jean , Michau Christophe , Hitoto Hikombo , Vatan Rémi , Raffi François 
Published: November 2014

IntroductionSleep disturbances are frequently reported in HIV‐infected patients but there is a lack of large studies on prevalence and risk factors, particularly in the context of current improved immuno‐clinical status and use of the newest antiretrovirals (ARV).MethodCross‐sectional study to evaluate the prevalence and factors associated with sleep disturbance in adult HIV‐infected patients in six French centres of the region “Pays de la Loire”. Patients filled a self‐administered questionnaire on their health behaviour, sleep attitudes (Pittsburgh Sleep Quality Index PSQI), quality of life (WHO QOL HIV BREF questionnaire) and depression (Beck depression Inventory (BDI)‐II questionnaire). Socio‐demographic and immunovirologic data, medical history, ARVs were collected.ResultsFrom November 2012 to May 2013, 1354 consecutive non‐selected patients were enrolled. Patients’ characteristics were: 73.5% male, median age 47 years, active employment 56.7%, France‐native 83% and Africa‐native 14.7%, CDC stage C 21%, hepatitis co‐infection 13%, lipodystrophy 11.8%, dyslipidemia 20%, high BP 15.1%, diabetes 3%, tobacco smokers 39%, marijuana and cocaine users, 11.7% and 1.7% respectively, and excessive alcohol drinkers 9%. Median (med) duration of HIV infection was 12.4 years, med CD4 count was 604/mm3; 94% of Patients were on ARVs, 87% had undetectable viral load. Median sleeping time was 7 hours. Sleep disturbances (defined as PSQI score >5) were observed in 47% of the patients, more frequently in female (56.4%) than in male (43.9%) (p<0.05) and moderate to serious depressive symptoms (BDI score>19) in 19.7% of the patients. In multivariate analysis, factors associated with sleep disturbances (p<0.05) were depression (odds ratio [OR] 4.6; 95% confidence interval [CI] 3.2–6.8), male gender (OR 0.7; CI 0.5–0.9), active employment (OR 0.7; CI 0.5–0.9), living single (OR 1.5; CI 1.2–2.0), tobacco‐smoking (OR 1.3; CI 1.0–1.8), duration of HIV infection (>10 vs. <10 y.) (OR 1.5; CI 1.1–2.0), ARV regimen containing nevirapine (OR 0.7; CI 0.5–0.9) or efavirenz (OR 0.5; CI 0.3–0.7).ConclusionsPrevalence of sleep disturbances is high in this HIV population and roughly similar to the French population. Associated factors are rather related to social and psychological status than HIV infection. Depression is frequent and should be taken in care to improve sleep quality.
Should the dose of tenofovir be reduced to 200–250 mg/day, when combined with protease inhibitors?
Authors: Hill Andrew , Khoo Saye , Back David , Pozniak Anton , Boffito Marta 
Published: November 2014

IntroductionThe approved dose of tenofovir disproxil fumarate, 300 mg once daily, was established in clinical trials in combination with efavirenz, which does not significantly affect tenofovir concentrations. Combining tenofovir with lopinavir/r, darunavir/r or atazanavir/r increases tenofovir concentrations, which could raise the risk of renal adverse events. Newly approved tenofovir tablets are available at lower strength (200 or 250 mg) for use in paediatrics.MethodsA literature search was used to assess the effects of lopinavir/r, darunavir/r and atazanavir/r on tenofovir plasma Cmax, AUC and Cmin (Geometric Mean Ratio and 90% confidence intervals). Assuming linear dose‐proportional pharmacokinetics (as observed in dose‐ranging studies), the 250 mg tablet was predicted to achieve plasma concentrations 17% lower than the 300 mg dose, and the 200 mg tablet to achieve plasma levels 33% lower. Effects on tenofovir plasma Cmax, AUC and Cmin concentrations were assessed for combined dosing of each protease inhibitor with 250 or 200 mg daily doses of tenofovir, versus standard dose tenofovir (300 mg daily) without protease inhibitors.ResultsIn drug‐drug interaction studies, lopinavir/ritonavir significantly increased tenofovir Cmax, AUC and Cmin. Effects of each PI on tenofovir Cmin were greater than effects on Cmax or AUC. Using a 250 mg paediatric dose of tenofovir with lopinavir/ritonavir, tenofovir Cmin was predicted to remain higher than tenofovir 300 mg used with efavirenz (GMR=1.26, 95% CI 1.14–1.38). Similar results were observed for use of tenofovir 250 mg with atazanavir/ritonavir (GMR=1.07, 95% CI 1.01–1.13) and with darunavir/ritonavir (GMR=1.14, 95% CI 0.99–1.31). Predicted tenofovir AUC levels for the 250 mg dose with protease inhibitors were all within the bioequivalence range, relative to use with efavirenz. Using a 200 mg paediatric dose of tenofovir with lopinavir/ritonavir, the tenofovir Cmin was predicted to be bioequivalent to tenofovir 300 mg used with efavirenz (GMR=1.02, 95% CI 0.92–1.11). Similar results were observed for use of tenofovir 200 mg with atazanavir/ritonavir (GMR=0.86, 95% CI 0.82–0.91) and with darunavir/ritonavir (GMR=0.92, 95% CI 0.80–1.05). All three results were within the bioequivalence limits of 0.8–1.25.ConclusionsUse of approved paediatric doses of tenofovir (200–250 mg once daily) in combination with lopinavir/r,darunavir/r or atazanavir/r could compensate for known drug interactions. This dose modification could potentially improve renal safety.
Low isoniazid and rifampicin concentrations in TB/HIV co‐infected patients in Uganda
Authors: Sekaggya Wiltshire Christine , Lamorde Mohammed , Scherrer Alexandra , Musaazi Joseph , Corti Natascia , Allan Buzibye , Nakijoba Rita , Nalwanga Damalie , Henning Lars , Von Braun Amrei , Okware Solome , Castelnuovo Barbara , Kambugu Andrew , Fehr Jan 
Published: November 2014

IntroductionThere is limited data available on exposure to anti‐tuberculosis (TB) drugs in this region. Peloquin has described reference ranges [1] however some studies have demonstrated that patients actually achieve concentrations below these ranges [2]. There is limited data about exposure to anti‐TB drugs in the HIV/TB co‐infected population in Sub‐Saharan Africa. Our objective is to describe the concentration of anti‐TB drug levels in a well characterized prospective cohort of adult patients starting treatment for pulmonary TB.MethodsThis study is an ongoing study carried out in the TB/HIV integrated clinic at the Infectious Diseases Institute in Kampala, Uganda. Sputum culture and microscopy was done for all patients. We performed pharmacokinetic blood sampling of anti‐TB drugs for 1 hour, 2 hours and 4 hours post dose at 2 weeks, 8 weeks and 24 weeks after initiation of anti‐TB treatment using ultraviolet high‐performance liquid chromatography (UV‐HPLC). We described the maximum concentration (Cmax) of isoniazid (H), rifampicin (R), ethambutol (E) and pyrazinamide (Z) and compare them with the values observed by Peloquin et al. referenced in other studies.ResultsWe started 113 HIV infected adults on a fixed dose combination of HREZ. The median age of our population was 33 years, of which 52% were male with a median BMI of 19 kg/m2 and a median CD4 cell count of 142 cells/µL. In 90% of the participants, the diagnosis of TB was based on microscopy and or cultures. The boxplot graph shows the median Cmax and IQR of H and R.Levels of H were found to be below the reference ranges (3–6 µg/mL) in 54/77(70.1%), 38/59(64.4%) and 15/24(62.5%) participants at weeks 2, 8 and 24. Rif levels were also found to be below the reference ranges (8–24 µg/mL) in 41/66(62.1%), 26/48(54.2%) and 8/10(8%) participants at weeks 2, 8 and 24, respectively. The mean Cmax of E and Z were within the reference range at week 2 and 8; mean Cmax of 3.2±SD2.1 µg/mL and 4.0±SD3.1 µg/mL for E and 41.6±SD13.1 µg/mL and 42.6±SD16.4 µg/mL for Z.ConclusionWe observed lower concentrations of isoniazid and rifampicin in our study population of HIV/TB co‐infected patients. The implications of these findings are not yet clear. We therefore need to correlate our findings with the response to TB treatment.
HIV positive asylum seekers receiving the order to leave the Belgian territory
Authors: Demeester Remy , Legrand Jean‐Claude 
Published: November 2014

IntroductionIn a human rights based approach, the Parliamentary Assembly of the Council of Europe has recently released a resolution about migrants and refugees and the fight against HIV [1]. It states that “an HIV positive migrant should never be expelled when it is clear that he will not receive adequate health care and assistance in the country to which he is being sent back. To do otherwise would amount to a death sentence for that person.” Nevertheless, in Belgium, for the last 2 years, none of the HIV‐infected migrants in care in the AIDS Reference Centers (ARC) received the right to stay in Belgium for medical reasons.MethodsWe identified all HIV‐infected asylum seekers in care between 1 July 2012 and 1 July 2014 in the ARC of Charleroi, Belgium, and we analyzed their medical and social files.ResultsAmong the 302 patients in active follow up in our ARC, 45 HIV positive asylum seekers were in care during the last 2 years. Male/female ratio was 0/96. Mean age was 35 years. Countries of origin and reasons for migration are detailed in the Table 1. 18% (8/45) knew their seropositivity before arriving in Europe. All the patients introduced an asylum request, 29 (64%) have received a negative answer and an order to leave the territory, 4 (9%) were regularized for non‐medical reasons (see Table 1), 4 (9%) are waiting for an answer and for 8 (18%) outcome is unknown due to lost follow up (LFU). 31 (69%) patients have also introduced a request to stay for medical reasons: 18 (58%) have received a refusal, 7 (23%) are still waiting for an answer, and 6 (19%) are LFU. Only 23 (51%) patients are still in care in our ARC on 1 July 2014 (see Table 1). The immigration office bases its decisions on availability of the treatment in the country even if accessible only to a limited number of patients.ConclusionsDecisions taken by the Belgian authorities for the last two years concerning HIV‐infected asylum seekers do not guarantee the continuity of care of those patients and push them towards illegality. Such decisions ignore the international commitments of Belgium in the fight against HIV [2] and are contradictory with the recommendations of the recent resolution of the Council of Europe [1]. An approach more respectful of Human Rights in the decisions concerning the seropositive asylum seekers patients taken by the authorities is urgently needed in Belgium. We invite our European colleagues to describe the situation of the HIV asylum seekers in their countries.
EATG training academy STEP‐UP: skills training to empower patients
Authors: Martynenko Oleksandr , Kelly Damian , Say Vanessa 
Published: November 2014

IntroductionMost existing conventional capacity building and educational programs are currently executed on ad‐hoc basis. Such approach no longer responds to the needs and capabilities of patients, supporters and healthcare providers in their engagement with and contribution to response to HIV/AIDS. In contrast, long‐term, course‐like trainings have considerably broader thematic scope and are conducive to more effective and sustainable learning, exchange of experience and best practices.MethodOver the period of one year, the Academy trains a cohort of 20 activists (10 from East Europe and Central Asia and 10 from Western and Southern Europe). The Academy goes beyond “treatment only” paradigm. Conceptually, five training modules are grouped under three larger domains: treatment literacy, treatment advocacy and treatment activism, thus covering most of the topics pertinent to the current discourse of HIV and related co‐infections. To ensure cascade effect and sustainability of the learning, the trainees are offered participation in pan‐European HIV conferences (EACS and HIV Glasgow) and resources for follow‐up activities.ResultsThe trainees empirically applied the knowledge to the benefits of their communities. In Uzbekistan, a trainee introduced EACS treatment guidelines to fellow medical students and junior doctors. In Armenia and Albania a series of small‐scale trainings were held, outreaching to young homeless people who were traditionally excluded from HIV treatment and prevention discourse in the two countries. A trainee from Spain used the materials of the Academy in his work in Mozambique and the Spanish Ministry of Health. Five trainees engaged in a joint European cross‐countries project on treatment literacy for young people who are most at risk of infection.ConclusionsEATG Training Academy is a unique initiative in the WHO Europe region that both trains future treatment activists and addresses treatment literacy, advocacy and advocacy topics. This type of capacity building can respond to existing HIV‐related problems more effectively using less limited resources and reaching out to larger communities.
Hidden costs of HIV treatment in Spain: inefficiency of the antiretroviral drug packaging
Authors: Llibre‐Codina Josep M , Andreu‐Crespo Angels , Cardona‐Peitx Gloria , Sala‐Piñol Ferran , Clotet‐Sala Bonaventura , Bonafont‐Pujol Xavier 
Published: November 2014

IntroductionAntiretroviral drugs in Spain are delivered by law only in hospital pharmacies. Commercial packages meet variable quality standards when dispensed drugs are returned due to treatment changes or adherence problems Nearly 20–25% of the initial regimens will be changed at 48 weeks for different reasons. We evaluated the economic impact on public health system of the inability of using returned drugs due to inefficient packaging.Materials and MethodsWe defined socially efficient packaging as the best adapted one to being delivered in unit dose to outpatients and classified: Class A ‐ Drug packed in unit doses with complete info (name of drug, dosage in mg, lot, and expiring date) in each unit, maintaining complete information of the drug if returned when the external package is opened. Class B ‐ packed in blisters with complete info in the blister, but not in unit doses, without special conservation conditions (should be re‐packed in unit doses in the pharmacy before its dispensation to assure a class A excellence). Class C ‐ packed in plastic containers with complete info written only on a label over the container, would allow repackaging only before its initial delivery, but not when returned. Class D ‐ drug packed in plastic containers with manufacturer's warning that the product cannot be placed outside of the original package due to special conditions of conservation (fridge, humidity) that doesn't allow a unit dose repackaging or reusing an opened container. We analysed a 12‐month period (July 2011–June 2012) in a hospital‐based HIV outpatient pharmacy that serves 2413 treated individuals.ResultsPatients generated 23,574 visits to pharmacy, and received 48,325 drug packages, with 2.529.137 pills delivered. The patients suffered 1051 treatment changes for any reason. A total amount of 122.945€ in treatment were returned to pharmacy in opened packages during the study period. 47.139.91€ would be totally lost, mainly due to being packaged in class C and D boxes, the equivalent of treating 78 patients with rilpivirine/TDF/FTC during 1 month. Class A and B packages in bad condition represented only 1.1% of the cost. However, 75.805€ came from returned packages in good condition that could potentially be reused. Most of the treatment changes were not foreseeable.ConclusionsA significant economic budget is lost through socially inefficient antiretroviral packages. Newer treatments are packaged in C and D categories, therefore maintaining these hidden costs in the near future. Any improvement in the excellence of packaging by the manufacturer, and favouring the choice of drugs supplied through efficient packages (when efficacy, toxicity and convenience are similar) should minimize the treatment expenditures paid by national health budgets.
Early HIV diagnosis through use of rapid diagnosis test (RDT) in the community and direct link to HIV care: a pilot project for vulnerable populations in Athens, Greece
Authors: Kakalou Eleni , Papastamopoulos Vasileios , Ioannidis Panagiotis , Papanikolaou Kostas , Georgiou Ourania , Skoutelis Athanasios 
Published: November 2014

IntroductionAn increase in the incidence of HIV new infections among intravenous drug users (IDUs) by 1500%, was noted in the center of Athens in 2011. Increasing problematic drug use, homelessness, health cuts amidst the economic crisis, have contributed to the epidemic. New cases doubled within a year, challenging the HIV care delivery system [1].Materials and MethodsA pilot project funded by the National Strategic Reference Framework (NSRF) 2007–2013 of the European Union (EU), was launched from August 2012 to March 2014. It was a partnership between the HIV Clinic of Evangelismos Hospital and the NGO PRAKSIS. The project is aimed at offering early diagnosis and comprehensive care to hard to reach populations. RDT diagnosis through mobile units, direct linkage to care, elimination of waiting times, flexibility, psychosocial support and link to harm reduction services for active IDUs were offered to the beneficiaries.ResultsA total of 117 people enrolled in the program following HIV RDT offered by mobile units of the NGO PRAKSIS in community sites. Sixty‐eight percent were IDUs, 12% were men who have sex with men (MSM) and 19.5% were heterosexuals. Men were 74.3% and women were 25.6%. Country born patients were 43.5% and non‐country born patients were 56.4%. Nine people were HIV negative but needed post‐exposure prophylaxis (PEP), treatment for Hepatitis C and one test was false positive. Two deaths occurred and six people were deported. Of the remaining 100 patients, 84 enrolled in the care program. Of those 77% (65/84) remain in care for three months after the end of the project. Care retention was 73.5% (39/53) for IDUs, 91% (10/11) for MSM, 80% (16/20) for heterosexuals, 73% (25/35) for country born and 82% (40/49) for non‐country born individuals. Among those that remain in care, 77.7% (42/54) with <350 CD4 are on antiretroviral therapy (ART). Among those on ART >90% have undetectable viral load. Mean value of CD4 cells at enrollment was 298 cells/mm3. At follow up, three months after the end of the program, the mean value of CD4 cells was 464 cells/mm3.ConclusionsThe project has proven the feasibility of a novel approach of active case finding in the community with direct link to care. Retention to care was satisfactory as most of those patients would not have been able to access care through the normal ART delivery mode of the Public Health System. However, more obstacles to care remain. Being homeless, poor nutrition, complicated access to harm reduction services, lack of One Stop Shop services and police operations in the city center impede further progress [2,3].