bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety of rilpivirine plus nucleoside reverse‐transcriptase inhibitors in HIV‐infected Taiwanese with a higher prevalence of hepatitis virus infection
Authors: Wu Pei‐Ying , Cheng Chien‐Yu , Luo Yu‐Zhen , Zhang Jun‐Yu , Yang Shan‐Ping , Cheng Shu‐Hsing , Hung Chien‐Ching 
Published: November 2014

IntroductionCombination antiretroviral therapy (cART) containing rilpivirine plus 2 NRTIs are effective antiretroviral (ARV) regimens for ARV‐naive HIV‐infected patients who had baseline plasma HIV RNA load (PVL) <5 log10 copies/mL and as switch therapy for those with viral suppression. In this study, we aimed to assess the short‐term safety of rilpivirine‐containing regimens among HIV‐infected patients who initiated or switched to rilpivirine plus two NRTIs in Taiwan.Materials and MethodsBetween January and June 2014, medical records of all HIV‐infected patients who initiated or switched to rilpivirine plus two NRTIs, during the follow‐up were reviewed to assess the tolerance and adverse effects. Using a standardized data collection form, we recorded data of PVL and CD4 count, serologies for hepatitis B and C virus (HBV and HCV, respectively), haemogram, aminotransferases, bilirubin and serum creatinine before starting rilpivirine‐containing regimens at four weeks and every 12 weeks thereafter.ResultsDuring the study period, medical records of 246 patients initiated their first ARV therapy with rilpivirine‐containing regimens (n=90) or switched to rilpivirine‐containing regimen from other regimens (156). Of the 246 patients, 73.4% were men who have sex with men and 9.1% and 25.6% tested positive for HBsAg and anti‐HCV antibody, respectively. Baseline CD4 was 395 cells/mm3 (range, 2‐1581) and PVL, 2.76 log10 copies/mL (range, <1.3>7.0 log10 copies/mL). As of 10 July, 23 patients (9.3%) stopped rilpivirine‐containing regimens due to gastrointestinal upset (n=4), skin rash (2), depression (2), poor sleep (3), anaemia (4, all being with zidovudine/lamivudine), nail hyperpigmentation (1), presence of transmitted drug resistance (4), and elevated aminotransferase levels (1). The proportion of the patients with aminotransferases of fivefold or higher than the upper limit of normal (ULN) was 1.7% and 1.5% for AST and ALT, respectively, before starting rilpivirine‐containing regimens; the respective value was 1.4% and 2.4% after 12 weeks of cART.ConclusionsRilpivirine‐containing regimens were generally well tolerated and less than 10% of the patients had to stop rilpivirine due to various reasons. Despite a higher prevalence of chronic HBV or HCV infection, rilpivirine‐containing regimens did not cause significant changes of aminotransferases from baseline.
CSF LPV concentrations and viral load in viral suppressed patients on LPV/r monotherapy given once daily
Authors: Tiraboschi Juan , Imaz Arkaitz , Ferrer Elena , Saumoy Maria , Rozas Nerea , Maso Marga , Vila Antonia , Niubo Jordi , Podzamczer Daniel 
Published: November 2014

IntroductionPlasma trough concentrations of lopinavir (LPV) given as LPV/r 800/200 mg once daily (OD) are reduced in comparison with 400/100 mg twice daily (BID). While OD dosage of LPV/r is sufficient to achieve viral suppression in plasma, data about drug penetration and viral suppression in central nervous system (CNS) is needed, mainly if LPVr is used as maintenance monotherapy strategy in selected patients. The objective of this study was to evaluate CSF HIV‐1 RNA and CSF LPV concentrations in patients receiving LPV/r monotherapy OD (LPVrMOD).Material and MethodsThis is a cross‐sectional sub‐study within a prospective, open‐label pilot simplification study to evaluate the efficacy and safety of LPV/rMOD in virologically suppressed patients previously receiving a BID LPV/r monotherapy regimen (LPV/rMBID), the “Kmon study” (NCT01581853). To assess LPV concentrations and HIV‐1 RNA in CSF, a lumbar puncture (LP) was performed in a subgroup of patients after at least one month of LPVrMOD treatment. Plasma‐paired samples of all patients were also obtained. HIV‐1 RNA was determined by real‐time PCR (limit of detection 40 copies/mL). Liquid chromatography‐tandem mass spectrometry (Tandem labs, NJ) was used to determine CSF and blood plasma LPV concentrations.ResultsNine patients were included. Median (range) age was 48 (34–56) years, median CD4 cell count 672 (252–1,408) cells/mL, median nadir CD4 count 125 (35–537) cells/mL and 40% of subjects were HCV‐positive. Before starting LPV/rMOD median time on a LPV/r‐containing regimen and on LPV/rMBID were 9 (4–11) years and 15 (7–24) months respectively, median time with undetectable HIV viral load was 5 (3–12) years and 2 patients had a previous documented blip. LP was performed a median of 24 (8–36) weeks after starting LPV/rMOD and 24 (11–28) hours after the last LPV/rMOD dose CSF and plasma HIV RNA was 40 copies/mL in all patients. Median LPV CSF concentration was 9.78 (1.93–78.3) ng/mL, median LPV plasma concentration 1,103 (377–16,700) ng/mL and median LPV CSF/plasma ratio 0.3% (0.1–1.2).ConclusionsNo CSF viral escape was detected and LPV concentrations were above the IC50 for wtHIV‐1 (1.9 ng/mL). However, as concentrations were close to IC50 in some patients, a careful clinical follow up of patients receiving this regimen would be advisable. Larger longitudinal studies will be helpful for a better understanding of the CNS antiviral activity of LPVr monotherapy.
Should we offer routine hepatitis C antibody testing in men who have sex with men?
Authors: Ward Christopher , Lee Vincent 
Published: November 2014

IntroductionThere has been a significant rise in the number of HIV positive men who have sex with men (MSM) co‐infected with hepatitis C (HCV). Most infections are thought to occur through high risk sexual practices, exacerbated by drug use. Previous data has suggested no need for routine screening in HIV negative MSM. We looked at HCV antibody testing and HCV risk assessment in all MSM clinic attenders as part of a Public Health England initiative.Materials and MethodsRoutine HCV antibody testing was offered to all MSM attending a large inner city sexual health clinic from April to June 2014. Patients were asked to fill in a questionnaire assessing HCV risk. Demographic data, HIV status and STI results were collected and compared.ResultsWe collected 471 HCV risk assessment questionnaires during the eight‐week period. The median age was 34 (range 18–71) and 403 (85.6%) were White British. Ten (2.1%) patients were known to be HCV positive, of which 3 were on treatment and 5 (1.1%) had cleared HCV. One hundred and forty‐nine (31.6%) patients were HIV negative, 254 (53.9%) were HIV positive and 68 (14.5%) had unknown HIV status at time of clinic visit. In the last three months 151 (32.1%) reported unprotected receptive anal intercourse, 58 (12.3%) reported group sex, 11 (2.3%) reported receptive fisting and 32 (6.8%) reported more than 10 partners. Eighty‐seven (18.5%) patients had shared notes/straws to snort drugs and 29 (6.2%) reported injecting drugs or slamming. One hundred and forty‐two (30.0%) patients reported recreational drug use in the last 12 months, with cocaine, methadrone and ketamine most popular. One hundred and fifteen (24.4%) patients reported sex under the influence of recreational drugs. There were no statistical differences between HIV positive and HIV negative patients in their risk, sexual behaviour and drug use. STI screens were performed on 269 patients with nine (3.3%) new HIV diagnoses, four (1.5%) early syphilis, and 28 (10.4%) rectal gonorrhoea infections. There were three (1.1%) new HCV diagnoses, and one (33.3%) was in an HIV negative patient.ConclusionsOur results show increased risk behaviour for both HIV positive and HIV negative MSM. There are a high number of patients using party drugs, participating in group sex and not using condoms, leading to high rates of new STI diagnoses. With similar rates of risk we believe HCV testing and risk assessment should be considered in all MSM regardless of HIV status.
Transmission route and reasons for HIV testing among recently diagnosed HIV patients in HIV‐TR cohort, 2011–2012
Authors: Dokuzoguz Basak , Korten Volkan , Gökengin Deniz , Fincanci Muzaffer , Yildirmak Taner , Nuray Kes Uzun , Tasdelen Fisgin Nuriye , Inan Dilara , Eraksoy Haluk , Akalin Halis 
Published: November 2014

IntroductionRoutes of transmission and reasons for HIV testing are important epidemiologic data to analyze the epidemic and to tailor the response to AIDS. The aim of this study was to analyze reasons for testing and transmission ways of HIV among recently diagnosed HIV patients registered in the multicenter HIV‐TR cohort in Turkey.MethodsTransmission ways and reasons for testing of all patients diagnosed in 2011 and 2012 were recorded on a web‐based data collection system and were analyzed retrospectively.ResultsThe study included 693 patients (561 male, 132 female) from 24 sites. Reason for HIV testing was available in 640 patients (92%). The most common reason for HIV testing was diagnostic workout for other conditions or illness followed by patient‐initiated testing. The reasons for testing were listed in Table 1. The most common routes of HIV transmission were heterosexual intercourse (62.7%) and sex among men who have sex with men (MSM) (22.6%). At the time of HIV diagnosis, the mean CD4 lymphocyte cell count was 355/mm3 (3–1433/mm3). Primary HIV infection was determined in 42/693 (6%) patients and 9/693 (% 1, 2) cases were considered “probable primary HIV infection.” The majority of the cases presented to a clinic for follow‐up right after the diagnosis. On the other hand 32/616 (5.2%) patients delayed their presentation for more than 3 months. The longest delay was 11 months.ConclusionsThe results of the database suggest that targeted testing is lacking in the country. The shift toward homosexual transmission during the last 2 years emphasizes the need for targeted interventions. Patients present relatively late and HIV infection could only be diagnosed when immunosuppression related findings appeared. Patient‐initiated testing,an indicator of awareness, was very low suggesting a need to scale‐up awareness raising interventions.
Cost/efficacy analysis of preferred Spanish AIDS study group regimens and the dual therapy with LPV/r+3TC for initial ART in HIV infected adults
Authors: Gatell Josép M , Arribas José R , Lázaro Pablo , Blasco Antonio 
Published: November 2014

IntroductionThe National AIDS Plan and the Spanish AIDS study group (GESIDA) panel of experts propose “preferred regimens” of antiretroviral treatment (ART) as initial therapy in HIV‐infected patients for 2013 [1]. All these regimens are triple therapy regimens. The Gardel Study assessed the efficacy and safety of a dual therapy (DT) combination of lopinavir/ritonavir (LPV/r) 400/100 mg BID+ lamivudine (3TC) 150 mg BID [2]. The objective of this study is to evaluate the costs and efficiency of initiating treatment with the GESIDA “preferred regimens” and DT.Materials and MethodsEconomic assessment of costs and efficiency (cost/efficacy) through decision tree analysis models. Efficacy was defined as the probability of having viral load <50 copies/mL at week 48, in an intention‐to‐treat analysis. Cost of initiating treatment with an ART regime was defined as the costs of ART and its consequences (adverse effects, changes of ART regime and drug resistance tests) during the first 48 weeks. The payer perspective (Spanish National Health System) was applied considering only differential direct costs: ART (official prizes), management of adverse effects, resistance tests, and determination of HLA B*5701. The setting is Spain and the costs are those of 2013. A sensitivity deterministic analysis was conducted, building three scenarios for each regime: base, most favourable and most unfavourable cases.ResultsIn the base case scenario, the cost of initiating treatment ranges from 5138 euros for DT, to 12,059 euros for tenofovir DF/emtricitabine (TDF/FTC)+raltegravir (RAL). The efficacy ranges between 0.66 for abacavir (ABC)/3TC+LPV/r and ABC/3TC+atazanavir (ATV)/r, and 0.88 for DT. Efficiency, in terms of cost/efficacy, varies between 5817 and 13,930 euros per responder at 48 weeks, for DT and TDF/FTC+RAL respectively. DT is the most efficient regimen in the most favourable (5503 euros per responder) and most unfavourable (6169 euros per responder) scenarios.ConclusionsConsidering the ART official Spanish prizes, the most efficient regimen was DT, followed by the triple therapy with non‐nucleoside containing regimens. The sensitivity analysis confirms the robustness of these findings.
Prices of second‐line antiretroviral treatment for middle‐income countries inside versus outside sub‐Saharan Africa
Authors: Simmons Bryony , Hill Andrew , Ford Nathan , Ruxrungtham Kiat , Ananworanich Jintanat 
Published: November 2014

IntroductionAntiretrovirals are available at low prices in sub‐Saharan Africa, but these prices may not be consistently available for middle‐income countries in other regions with large HIV epidemics. Over 30% of HIV infected people live in countries outside sub‐Saharan Africa. Several key antiretrovirals are still on patent, with generic production restricted. We assessed price variations for key antiretroviral drugs inside versus outside sub‐Saharan Africa.MethodsHIV drug prices used in national programmes (2010–2014) were extracted from the WHO Global Price Reporting Mechanism database for all reporting middle‐income countries as classified by the World Bank. Treatment costs (branded and generic) were compared for countries inside sub‐Saharan Africa versus those outside. Five key second‐line antiretrovirals were analysed: abacavir, atazanavir, darunavir, lopinavir/ritonavir, raltegravir.ResultsPrices of branded antiretrovirals were significantly higher outside sub‐Saharan Africa (p<0.001, adjusted for year of purchase) (see Table 1). For example, the median (interquartile range) price of darunavir from Janssen was $732 (IQR $732‐806) per person‐year in sub‐Saharan Africa versus $4689 (IQR $4075‐5717) in non‐African middle‐income countries, an increase of 541%. However, when supplied by generic companies, most antiretrovirals were similarly priced between countries in sub‐Saharan Africa and other regions.ConclusionsPharmaceutical companies are selling antiretrovirals to non‐African middle‐income countries at prices 74–541% higher than African countries with similar gross national incomes. However, generic companies are selling most of these drugs at similar prices across regions. Mechanisms to ensure fair pricing for patented antiretrovirals across both African and non‐African middle‐income countries need to be improved, to ensure sustainable treatment access.
Acceptability and confidence in antiretroviral generics of physicians and HIV‐infected patients in France
Authors: Allavena Clotilde , Jacomet Christine , Pereira Bruno , Morand‐Joubert Laurence , Bagheri Haleh , Cotte Laurent , Garaffo Rodolphe , Gerbaud Laurent , Dellamonica Pierre 
Published: November 2014

IntroductionSwitching brand name medications to generics is recommended in France in the interest of cost effectiveness but patients and physicians are sometimes not convinced that switching is appropriate. Some antiretroviral (ARV) generics (ZDV, 3TC, NVP) have been marketed in France since 2013.Materials and MethodsA multicentric cross‐sectional survey was performed in September 2013 to evaluate the perception of generics overall and ARV generics in physicians and HIV‐infected patients and factors associated to their acceptability. Adult HIV outpatients were asked to complete a self‐questionnaire on their perception of generics. Physicians completed a questionnaire on the acceptability of generics and ARV generics. Socio‐demographic data, medical history and HIV history were collected.Results116 physicians in 33 clinics (68% in University Hospital) included 556 patients (France‐native 77%, active employment 59%, covered by social Insurance 100%, homosexual/bisexual contamination 47%, median HIV duration 13 years, hepatitis coinfection 16%, on ARV therapy 95%). Overall, patients accepted and had confidence in generics in 76% and 55% of the cases, respectively. Switching ARVs for generics was accepted by 44% of the patients but only by 17% if the pill burden was going to increase. 75% of the physicians would prescribe generics, but this decreased to only 26% if the combo had to be broken. The main reasons for non‐prescription of generics were previous brand name ARV‐induced side effects (35%), refusal of generics overall (37%), lack of understanding of generics (26%), risk of non‐observance of treatment (44%), anxiety (47%) and depressive symptoms (25%). In multivariate analysis, factors associated with the acceptability of ARV generics in patients were the use of generics overall (p<0.001) and in physicians, the absence of concern regarding the drug efficacy (p<0.001) and being aware that the patient would accept generics overall (p=0.03) and ARV generics (p=0.04). No factors related to sociodemographic conditions, HIV status or comorbidities had a constrictive influence on the use of ARV generics.ConclusionAcceptability of ARV generics in this French population is mostly dictated by the patient's and physician's knowledge and use of generics overall. Switching ARV brand name to a generic would be better accepted if the pill burden remained unchanged.
Results from a national treatment database – does it matter which ART combination is prescribed in the real world?
Authors: Scott Gordon , Wallace Lesley 
Published: November 2014

IntroductionClinical trials frequently show differences in viral load (VL) response between antiretroviral therapy (ART) regimes. Patterns of prescribing vary from country to country (Mocroft et al. Infection 2014 Jun 6 [epub ahead of print]), and are likely to vary between individual clinics. Scotland has a national database that records VL results and specific ART regimes for every patient under care, thus allowing different prescribing patterns between clinical centres to be monitored. Does this reveal any difference in achievement of undetectable VL?Materials and MethodsWe interrogated the database held by Health Protection Scotland (HPS) that contains a record of every VL result matched against prescribed ART. Results were censored at the end of December 2013 and are based on the latest attendance of patients who have been under monitoring for at least six months. For simplicity, we have broken the results into class of drug rather than individual drugs for example, nucleoside reverse transcriptase inhibitor (NRTI) rather than lamivudine, abacavir etc. The data were analyzed using univariate Poisson regression.ResultsThe anonymized records of 3302 individual patients who attended in 11 separate regions were scrutinized. Sixty‐eight different combinations of antiretroviral regimes were identified. The prescribing patterns for the five most frequently prescribed regimes in the four largest clinics are shown in Table 1, along with the overall percentage of patients with undetectable VL. A higher proportion of patients in Scotland who are prescribed regimes of NRTI×2 or NRTI/NtRTI plus PI have detectable VL but this is not statistically significant. Although the percentage of patients with VL<50 varies between regions 1 and 4 versus regions 2 and 3, this is also not statistically significant.ConclusionsOverall, a high proportion of Scottish patients on ART have undetectable VL. Patterns of ART prescribing in Scotland do vary by region but there are no significant differences in outcome with regard to undetectable VL. There is a non‐significant trend which may be accounted for by differing levels of PI prescribing.
Determinants of HIV‐1 drug resistance in treatment‐naïve patients and its clinical implications in an antiretroviral treatment program in Cameroon
Authors: Zoufaly Alexander , Jochum Johannes , Hammerl Raffaela , Nassimi Nilofar , Raymond Yurika , Burchard Gerd‐Dieter , Schmiedel Stefan , Drexler Jan‐Felix , Naomi Kay Campbell , Taka Nchang , Awasom Charles , Metzner Karin , Jan van Lunzen , Feldt Torsten 
Published: November 2014

IntroductionFacing the rapid scale‐up of antiretroviral treatment (ART) programs in resource‐limited settings, monitoring of treatment outcome is essential in order to timely detect and tackle drawbacks [1].MethodsIn a prospective cohort study, 300 consecutive patients starting first‐line ART were enrolled between 2009 and2010 in a large HIV treatment centre in rural Cameroon. Patients were followed up for 12 months. Virologic failure was defined as a VL >1000 cop/mL at month 12. Besides CD4 and viral load (VL) analysis, HIV‐1 drug resistance testing was performed in patients with VL>1000 copies (c)/mL plasma. In those patients and controls, minority HIV‐1 drug resistance mutations at baseline, and plasma drug levels were analyzed in order to identify the risk factors for virologic failure.ResultsMost enrolled patients (71%) were female. At baseline median CD4 cell count was 162/µL (IQR 59‐259), median log10 VL was 5.4 (IQR 5.0–5.8) c/mL, and one‐third of patients had World Health Organisation (WHO) stage 3 or 4; 30 patients died during follow‐up. Among all patients who completed follow‐up 38/238 had virologic failure. These patients were younger, had lower CD4 cell counts and more often had WHO stage 3 or 4 at baseline compared to patients with VL<1000c/mL. Sixty‐three percent of failing patients (24/38) had at least one mutation associated with high‐level drug resistance. The M184V mutation was the most frequently detected nucleoside reverse transcriptase inhibitor (NRTI) mutation (n=18) followed by TAMs (n=5) and multi‐NRTI resistance mutations (n=4). The most commonly observed non‐nucleoside reverse‐transcriptase inhibitor (NNRTI) resistance mutations were K103N (n=10), Y181C (n=7), and G190A (n=6). Drug resistance mutations at baseline were detected in 12/65 (18%) patients, in 6 patients with and 6 patients without virological failure (p=0.77). Subtherapeutic NNRTI levels (OR 6.67, 95% CI 1.98–22.43, p<0.002) and poorer adherence (OR 1.54, 95% CI 1.00–2.39, p=0.05) were each associated with higher risk of virologic failure in the matched pair analysis. Unavailability of ART at the treatment centre was the single most common cause (37%) for incomplete adherence in these patients.ConclusionsVirologic failure after one year of first‐line ART in rural Cameroon was not associated with transmitted drug resistance, but with reduced drug plasma levels and incomplete adherence. Strategies to assure adherence and uninterrupted drug supply are important factors for therapy success.