Distribution by Scientific Domains
Distribution within Humanities and Social Sciences

Kinds of Art

  • christian art
  • contemporary art
  • der art
  • expressive art
  • greek art
  • italian renaissance art
  • language art
  • modern art
  • performing art
  • renaissance art
  • rock art
  • verbal art

  • Terms modified by Art

  • art and literature
  • art collection
  • art curriculum
  • art education
  • art form
  • art gallery
  • art historian
  • art history
  • art market
  • art museum
  • art object
  • art practice
  • art production
  • art teacher
  • art therapy
  • art work
  • art world

  • Selected Abstracts

    Assisted reproductive technologies and birth defects

    Kohei Shiota
    ABSTRACT In vitro fertilization (IVF) and other assisted reproductive technologies (ART) are effective treatments for infertility and are widely provided at infertility clinics. Although IVF and related ART procedures are generally considered safe, some studies have suggested an excess occurrence of major malformations, low birth-weight and other perinatal complications in babies conceived by ART. Further, it was recently reported that IVF and intracytoplasmic sperm injection (ICSI) are associated with imprinting disorders in the offspring such as Beckwith-Wiedemann syndrome and Angelman syndrome. Here we review the human and animal studies investigating the potential risks of ART, and discuss the need for further investigation. [source]

    Infertility and assisted reproductive technologies: Bright and dark sides

    Kaoru Suzumori
    ABSTRACT, Infertility is defined as a couples failure to conceive following 2 years of unprotected sexual intercourse, affects 10% of reproductive age couples in Japan. There are 3 main causes: (1) ovarian failure-anovulation (29%); (2) tubal factor-anatomic defects of the female genital tract (36%); (3) male factor-abnormal spermatogenesis (31%). The goal of the infertility evaluation are to determine the probable cause of infertility regarding prognosis and to provide guidance regarding options for treatment In the event an obstruction of the fallopian tubes is discovered or spermatogenesis cannot be improved, assisted reproductive technologies (ART) such as gamete intrafallopian tube transfer (GIFT) and in vitro fertilization with embryo transfer (IVF-ET) are recommended. Since the successful birth of Louise Brown by this IVF-ET, an explosion of ART has occurred all over the world in the last decade. In this review we discuss the revolution brought about by ART focusing on results in Japan, and clarify ethical issues that must be resolved. [source]


    Johanna Jones Senior Associate
    First page of article [source]

    Close association of CD8+/CD38bright with HIV-1 replication and complex relationship with CD4+ T-cell count,

    CYTOMETRY, Issue 4 2009
    Edouard Tuaillon
    Abstract Background: Measuring lymphocyte activation provides information in addition to CD4+ T-cell count for immune monitoring of HIV-1 infected patients. CD38 is a well-established activation marker that is generally analyzed on the whole population of CD8+ T-cells. Focusing specifically on CD38 high expression (CD8+/CD38bright) may be an interesting surrogate gating strategy because CD38bright characterizes principally activated memory cells. Methods: CD8+/CD38bright was investigated in 1,353 HIV-1 infected patients over a one-year period to establish relevant cutoff values and clarify the relationships of this marker with HIV-1 RNA viral load (VL) and CD4+ T-cell count. Results: The CD8+/CD38bright (>8,500 CD38 binding site per cells) is well correlated with HIV-1 VL (r = 0.87, P < 0.001) in this longitudinal follow-up of nonimmunodepressed patients that initiated antiviral therapy (ART). In aviremic patients on ART, the marker was highly predictive of VL rebound (sensitivity 93%, specificity 64% for a VL level of detection >200 copies/ml). While the CD8+/CD38bright moderately correlated with CD4+ T-cell count independently of the VL (r = ,0.37, P < 0.001), it increased dramatically in aviremic patient groups that exhibited profound CD4+ T-cell depletion (median 39% for CD4+ T-cell counts <50/mm3). This result indicates that other additional immunological and/or viral factors than readily detectable HIV-1 replication appears to be involved in T-cell activation of immunodepressed individuals. Conclusions: CD8+/CD38bright is an effective marker for monitoring T-cell activation, which is a central factor of HIV-1 pathogenesis. This gating strategy requires only a single additional staining in conventional four color CD4 protocols. © 2008 Clinical Cytometry Society [source]

    A North American multilaboratory study of CD4 counts using flow cytometric panleukogating (PLG): A NIAID-DAIDS Immunology Quality Assessment Program Study,,§¶

    CYTOMETRY, Issue S1 2008
    Thomas N. Denny
    Abstract Background The global HIV/AIDS pandemic and guidelines for initiating anti-retroviral therapy (ART) and opportunistic infection prophylaxis demand affordable, reliable, and accurate CD4 testing. A simple innovative approach applicable to existing technology that has been successfully applied in resource-challenged settings, PanLeukogated CD4 (PLG), could offer solutions for cost saving and improved precision. Methods Day-old whole blood from 99 HIV+ donors was simultaneously studied in five North-American laboratories to compare the performance of their predicate methods with the dual-platform PLG method. The predicate technology included varying 4-color CD45/CD3/CD4/CD8 protocols on different flow cytometers. Each laboratory also assayed eight replicate specimens of day-old blood from 10 to 14 local donors. Bias and precision of predicate and PLG methods was studied between- and within-participating laboratories. Results Significantly (P < 0.0001) improved between-laboratory precision/coefficient of variation (CV%) was noted using the PLG method (overall median 9.3% vs. predicate median CV 13.1%). Within-laboratory precision was also significantly (P < 0.0001) better overall using PLG (median 4.6% vs. predicate median CV 6.2%) and in 3 of the 5 laboratories. PLG counts tended to be 11% smaller than predicate methods (P < 0.0001) for shipped (median of predicate,PLG = 31) and local specimens (median of predicate,PLG = 23), both overall and in 4 of 5 laboratories (median decreases of 4, 16, 20, and 21% in shipped specimens); the other laboratory had a median increase of 5%. Conclusion Laboratories using predicate CD4 methods similar to those in this study could improve their between-laboratory and their within-laboratory precision, and reduce costs, by switching to the PLG method after adequate training, if a change (usually, a decrease) in CD4 counts is acceptable to their health systems. © 2008 Clinical Cytometry Society [source]

    Surgical Monotherapy Versus Surgery Plus Adjuvant Radiotherapy in High-Risk Cutaneous Squamous Cell Carcinoma: A Systematic Review of Outcomes

    BACKGROUND Adjuvant radiotherapy (ART) has been recommended for squamous cell carcinoma (SCC) with a high risk of recurrence, particularly perineurally invasive disease. The utility of ART is unknown. This study compares reported outcomes of high-risk SCC treated with surgical monotherapy (SM) with those of surgery plus ART (S+ART). METHODS The Medline database was searched for reports of high-risk SCC treated with SM or S+ART that reported outcomes of interest: local recurrence, regional or distant metastasis, or disease-specific death. RESULTS There were no controlled trials. Of the 2,449 cases of high-risk SCC included, 91 were treated with S+ART. Tumor stage and surgical margin status before ART were generally unreported. In 74 cases of perineural invasion (PNI), outcomes were statistically similar between SM and S+ART. In 943 high-risk SCC cases in which clear surgical margins were explicitly documented, risks of local recurrence, regional metastasis, distant metastasis, and disease-specific death were 5%, 5%, 1%, and 1%, respectively. CONCLUSIONS High cure rates are achieved in high-risk cutaneous SCC when clear surgical margins are obtained. Current data are insufficient to identify high-risk features in which ART may be beneficial. In cases of PNI, the extent of nerve involvement appears to affect outcomes, with involvement of larger nerves imparting a worse prognosis. [source]

    Response to first-line antiretroviral treatment among human immunodeficiency virus-infected patients with and without a history of injecting drug use in Indonesia

    ADDICTION, Issue 6 2010
    Rudi Wisaksana
    ABSTRACT Background There is a common belief that injecting drug use (IDU) is associated with lower uptake, retention and success of antiretroviral treatment (ART) in human immunodeficiency virus (HIV)-infected patients. We examined this in an Indonesian setting, where IDU is the main risk factor for HIV infection. Methods Patient characteristics and response to ART were recorded for all patients diagnosed with HIV infection in the referral hospital for West Java (40 million people). Kaplan,Meier estimates and Cox's regression were used to compare mortality, loss to follow-up and virological failure between patients with and without a history of IDU. Result A total of 773 adult HIV patients (81.9% IDUs) presented between January 1996 and April 2008. IDUs had a median CD4 cell count of 33 [interquartile ratio (IQR), 12,111] cells/mm3 compared to 84 (IQR, 28,224) cells/mm3 in non-IDUs. Among patients with a history of IDU, 87.7% were coinfected with hepatitis C (HCV). Mortality was associated strongly with CD4 count; after 6 months of ART, 18.3, 20.3, 7.1 and 0.7% of patients with CD4 cell counts <25, 25,99, 100,199, respectively, ,200/mm3 had died (P < 0.0001). Mortality [adjusted for CD4; hazard ratio (HR) = 0.65; 95% confidence interval (CI) 0.35,1.23], loss to follow-up (HR = 0.85, 95% CI 0.51,1.41) and virological failure (HR = 0.47, 95% CI 0.19,1.13) were not significantly different in IDUs and non-IDUs. Conclusion Intravenous drug users (IDUs) in Indonesia with HIV/acquired immune deficiency syndrome tend to have more advanced disease but respond similarly to non-IDUs to antiretroviral therapy. [source]

    Methadone maintenance therapy promotes initiation of antiretroviral therapy among injection drug users

    ADDICTION, Issue 5 2010
    Sasha Uhlmann
    ABSTRACT Aims Despite proven benefits of antiretroviral therapy (ART), many human immunodeficiency virus (HIV)-infected injection drug users (IDU) do not access treatment even in settings with free health care. We examined whether methadone maintenance therapy (MMT) increased initiation and adherence to ART among an IDU population with free health care. Design We examined prospectively a cohort of opioid-using antiretroviral-naive HIV-infected IDU and investigated factors associated with initiation of antiretroviral therapy as well as subsequent adherence. Factors associated independently with time to first initiation of antiretroviral therapy were modelled using Cox proportional hazards regression. Findings Between May 1996 and April 2008, 231 antiretroviral-naive HIV-infected opioid-using IDU were enrolled, among whom 152 (65.8%) initiated ART, for an incidence density of 30.5 [95% confidence interval (CI): 25.9,35.6] per 100 person-years. After adjustment for time-updated clinical characteristics and other potential confounders, use of MMT was associated independently with more rapid uptake of antiretroviral therapy [relative hazard = 1.62 (95% CI: 1.15,2.28); P = 0.006]. Those prescribed methadone also had higher rates of ART adherence after first antiretroviral initiation [odds ratio = 1.49 (95% CI: 1.07,2.08); P = 0.019]. Conclusion These results demonstrate that MMT contributes to more rapid initiation and subsequent adherence to ART among opioid-using HIV-infected IDU. Addressing international barriers to the use and availability of methadone may increase dramatically uptake of HIV treatment among this population. [source]


    ECONOMIC AFFAIRS, Issue 2 2002
    Bunny Smedley
    Commentators from the ,Right' have contributed little to ,is-it-art' discussions. The Saatchi Sensation exhibition of 1997 offers the opportunity to explain what contribution anti-socialist, anti-collectivist writers might make. In particular, they should be honest in their response to contemporary art rather than treating it as a no-go area. [source]


    FAMILY COURT REVIEW, Issue 1 2008
    Monica Sharma
    In the midst of a genetic revolution in medicine, Assisted Reproductive Technology (ART) has become a well-established technique to help infertile women achieve pregnancy. But many women are now turning to ART not just to circumvent infertility, but consciously to shape their families by determining the sex of their children. Many patriarchal cultures have a gender preference for males and to date have used technological advances in reproductive medicine to predetermine the sex of the child being born. Women have sought sex-selective abortions, where the pregnancy was being terminated solely on the basis of the sex of the unborn fetus. The combination of ART advances and gender preference has led to the disappearance of at least 100 million girls from the world's population leading to a mass gendercide. This article examines the societal impact of unbalanced gender ratios and the need to regulate sex selection to avoid nations of bachelors. [source]

    Efficacy of acupuncture in patients with chronic low back pain , the Acupuncture Randomised Trials (ART)

    B Brinkhaus

    ,My biggest fear was that people would reject me once they knew my status,': stigma as experienced by patients in an HIV/AIDS clinic in Johannesburg, South Africa

    Leah Gilbert BA MPH PhD
    Abstract Stigma is not a new concept; however, it remains highly significant in the context of HIV/AIDS in South Africa. There is wide consensus that HIV/AIDS-related stigma compromises the well-being of people living with the disease. This paper is part of a larger study that seeks to understand the social and cultural complexity related to the provision and outcomes of antiretroviral therapy (ART) in South Africa. It explores and analyses how patients on ART perceived and experienced stigma and how it has shaped their behaviour towards, as well as their understanding of the epidemic. The data have been collected by means of in-depth face-to-face interviews, conducted between June and November 2007, with a sample of 44 patients in an HIV/AIDS clinic in a resource-limited setting in Johannesburg, South Africa. The findings reveal that the level of felt and anticipated stigma is intense and affects all dimensions of living with HIV/AIDS, particularly disclosure and treatment. Stigma permeates the experience of HIV-positive people on ART who participated in this study. The intensity of HIV/AIDS-related stigma can threaten to compromise the value of ART, thus impacting on the daily lives of people living with HIV/AIDS (PLWHA). This study suggests that three decades into the epidemic, stigmatisation remains a core feature of the patient experience of HIV/AIDS. In the clinic in which this research was conducted, HIV/AIDS was regarded as a chronic condition increasingly manageable by ongoing access to ART. However, this approach was not shared by many family members, neighbours and employers who held highly stigmatised views. [source]

    No significant effect of uridine or pravastatin treatment for HIV lipoatrophy in men who have ceased thymidine analogue nucleoside reverse transcriptase inhibitor therapy: a randomized trial,

    HIV MEDICINE, Issue 8 2010
    A Calmy
    Background Lipoatrophy can complicate thymidine analogue nucleoside reverse transcriptase inhibitor (tNRTI)-based antiretroviral therapy (ART). Lipoatrophy may be less likely with ART including ritonavir-boosted lopinavir (LPV/r). Small, placebo-controlled studies found that uridine (in tNRTI recipients) and pravastatin improved HIV lipoatrophy over 12 weeks. Today, most patients with lipoatrophy receive non-tNRTI-based ART; the effect of uridine in such patients is unknown. Methods We performed a prospective, randomized trial in lipoatrophic adults with plasma HIV RNA<50 HIV-1 RNA copies/mL on tNRTI-sparing ART including LPV/r. Patients received uridine [36 g three times a day (tid) on 10 consecutive days per month; n=10], pravastatin [40 mg every night (nocte); n=12], uridine plus pravastatin (n=11) or neither (n=12) for 24 weeks. The primary endpoint was mean change in limb fat mass as assessed by dual-energy X-ray absorptiometry (DEXA). With 20 patients per intervention, the study had 80% power to detect a mean difference between a treatment and the control of 0.5 kg, assuming a standard deviation of 0.9 and an alpha threshold equal to 5% (two-sided). Results Of 45 participants (all men, with median age 49.5 years and median limb fat 2.6 kg), two discontinued pravastatin and one participant stopped both pravastatin and uridine. The difference between the mean changes in limb fat mass for uridine vs. no uridine was 0.03 kg [95% confidence interval (CI) ,0.35, +0.28; P=0.79]. The respective difference for pravastatin was ,0.03 kg (95% CI ,0.29, +0.34; P=0.84). Pravastatin slightly decreased total cholesterol (0.44 mmol/L; P=0.099). Visceral adipose tissue measured by computed tomography did not change significantly. Conclusion In this population and at the doses used, neither uridine nor pravastatin for 24 weeks significantly increased limb fat mass. [source]

    HIV and the body: a review of multidisciplinary management

    HIV MEDICINE, Issue 2010
    J Rockstroh
    Abstract The increase in the life expectancy achieved following the introduction of more effective antiretroviral therapy (ART) in recent years now means that the HIV-infected population are for the first time being exposed to the age-related diseases that affect the general population. Nevertheless, the prevalence of these diseases (which include cardiovascular disease, dyslipidaemia, glucose intolerance and diabetes) is higher, and their onset earlier in the HIV population, probably due to the complex interplay between HIV infection, coinfection with hepatitis B and C, and ART. As a result, HIV physicians are now required to adopt a new approach to the management of HIV, which involves screening and regular monitoring of all HIV-infected individuals for the presence of comorbidities and prompt referral to other clinical specialties when required. If this challenge to patient management is to be overcome, it is clear that educating physicians in the diagnosis and treatment of age-associated comorbidities is essential, either through ongoing programmes such as the HIV and the Body initiative, an overarching independent medical education programme established in 2007 and overseen by an independent Steering Committee, organized and funded by Gilead, and/or through internal training. To assist in this process, this article provides an overview of common comorbidities affecting HIV-infected persons and provides practical guidance on their management. [source]

    Non-medically supervised treatment interruptions among participants in a universally accessible antiretroviral therapy programme

    HIV MEDICINE, Issue 5 2010
    DM Moore
    Background We examined clinical outcomes, patient characteristics and trends over time of non-medically supervised treatment interruptions (TIs) from a free-of-charge antiretroviral therapy (ART) programme in British Columbia (BC), Canada. Methods Data from ART-naïve individuals ,18 years old who initiated triple combination highly active antiretroviral therapy (HAART) between January 2000 and June 2006 were analysed. Participants having ,3 month gap in HAART coverage were defined as having a TI. Cox proportional hazards modelling was used to examine factors associated with TIs and to examine factors associated with resumption of treatment. Results A total of 1707 participants were study eligible and 643 (37.7%) experienced TIs. TIs within 1 year of ART initiation decreased from 29% of individuals in 2000 to 19% in 2006 (P<0.001). TIs were independently associated with a history of injection drug use (IDU) (P=0.02), higher baseline CD4 cell counts (P<0.001), hepatitis C co-infection (P<0.001) and the use of nelfinavir (NFV) (P=0.04) or zidovudine (ZDV)/lamivudine (3TC) (P=0.009) in the primary HAART regimen. Male gender (P<0.001), older age (P<0.001), AIDS at baseline (P=0.008) and having a physician who had prescribed HAART to fewer patients (P=0.03) were protective against TIs. Four hundred and eighty-eight (71.9%) participants eventually restarted ART with male patients and those who developed an AIDS-defining illness prior to their TI more likely to restart therapy. Higher CD4 cell counts at the time of TI and unknown hepatitis C status were associated with a reduced likelihood of restarting ART. Conclusion Treatment interruptions were associated with younger, less ill, female and IDU participants. Most participants with interruptions eventually restarted therapy. Interruptions occurred less frequently in recent years. [source]

    Insights into reasons for discontinuation according to year of starting first regimen of highly active antiretroviral therapy in a cohort of antiretroviral-naïve patients

    HIV MEDICINE, Issue 2 2010
    P Cicconi
    Objectives The aim of the study was to determine whether the incidence of first-line treatment discontinuations and their causes changed according to the time of starting highly active antiretroviral therapy (HAART) in an Italian cohort. Methods We included in the study patients from the Italian COhort Naïve Antiretrovirals (ICoNA) who initiated HAART when naïve to antiretroviral therapy (ART). The endpoints were discontinuation within the first year of ,1 drug in the first HAART regimen for any reason, intolerance/toxicity, poor adherence, immunovirological/clinical failure and simplification. We investigated whether the time of starting HAART (stratified as ,early', 1997,1999; ,intermediate', 2000,2002; ,recent', 2003,2007) was associated with the probability of reaching the endpoints by a survival analysis. Results Overall, the 1-year probability of discontinuation of ,1 drug in the first regimen was 36.1%. The main causes of discontinuation were intolerance/toxicity (696 of 1189 patients; 58.5%) and poor adherence (285 of 1189 patients; 24%). The hazards for all-reason change were comparable according to calendar period [2000,2002, adjusted relative hazard (ARH) 0.82, 95% confidence interval (CI) 0.69,0.98; 2003,2007, ARH 0.94, 95% CI 0.76,1.16, vs. 1997,1999; global P -value=0.08]. Patients who started HAART during the ,recent' period were less likely to change their initial regimen because of intolerance/toxicity (ARH 0.67, 95% CI 0.51,0.89 vs. ,early' period). Patients who started in the ,intermediate' and ,recent' periods had a higher risk of discontinuation because of simplification (ARH 15.26, 95% CI 3.21,72.45, and ARH 37.97, 95% CI 7.56,190.64, vs. ,early' period, respectively). Conclusions It seems important to evaluate reason-specific trends in the incidence of discontinuation in order to better understand the determinants of changes over time. The incidence of discontinuation because of intolerance/toxicity has declined over time while simplification strategies have become more frequent in recent years. Intolerance/toxicity remains the major cause of drug discontinuation. [source]

    PENTA 2009 guidelines for the use of antiretroviral therapy in paediatric HIV-1 infection

    HIV MEDICINE, Issue 10 2009
    PENTA Steering Committee
    PENTA Guidelines aim to provide practical recommendations for treating children with HIV infection in Europe. Changes to guidance since 2004 have been informed by new evidence and by expectations of better outcomes following the ongoing success of antiretroviral therapy (ART). Participation in PENTA trials of simplifying treatment is encouraged. The main changes are in the following sections: ,When to start ART': Treatment is recommended for all infants, and at higher CD4 cell counts and percentages in older children, in line with changes to adult guidelines. The number of age bands has been reduced to simplify and harmonize with other paediatric guidelines. Greater emphasis is placed on CD4 cell count in children over 5 years, and guidance is provided where CD4% and CD4 criteria differ. ,What to start with': A three-drug regimen of two nucleoside reverse transcriptase inhibitors (NRTIs) with either a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (PI) remains the first choice combination. Lamivudine and abacavir are the NRTI backbone of choice for most children, based on long-term follow-up in the PENTA 5 trial. Stavudine is no longer recommended. Whether to start with an NNRTI or PI remains unclear, but PENPACT 1 trial results in 2009 may help to inform this. All PIs should be ritonavir boosted. Recommendations on use of resistance testing, therapeutic drug monitoring and HLA testing draw from data in adults and from European paediatric cohort studies. Recently updated US and WHO paediatric guidelines provide more detailed review of the evidence base. Differences between guidelines are highlighted and explained. [source]

    How reliable is an undetectable viral load?

    HIV MEDICINE, Issue 8 2009
    C Combescure
    Objectives An article by the Swiss AIDS Commission states that patients with stably suppressed viraemia [i.e. several successive HIV-1 RNA plasma concentrations (viral loads, VL) below the limits of detection during 6 months or more of highly active antiretroviral therapy (HAART)] are unlikely to be infectious. Questions then arise: how reliable is the undetectability of the VL, given the history of measures? What factors determine reliability? Methods We assessed the probability (henceforth termed reliability) that the n+1 VL would exceed 50 or 1000 HIV-1 RNA copies/mL when the nth one had been <50 copies/mL in 6168 patients of the Swiss HIV Cohort Study who were continuing to take HAART between 2003 and 2007. General estimating equations were used to analyse potential factors of reliability. Results With a cut-off at 50 copies/mL, reliability was 84.5% (n=1), increasing to 94.5% (n=5). Compliance, the current type of HAART and the first antiretroviral therapy (ART) received (HAART or not) were predictive factors of reliability. With a cut-off at 1000 copies/mL, reliability was 97.5% (n=1), increasing to 99.1% (n=4). Chart review revealed that patients had stopped their treatment, admitted to major problems with compliance or were taking non-HAART ART in 72.2% of these cases. Viral escape caused by resistance was found in 5.6%. No explanation was found in the charts of 22.2% of cases. Conclusions After several successive VLs at <50 copies/mL, reliability reaches approximately 94% with a cut-off of 50 copies/mL and approximately 99% with a cut-off at 1000 copies/mL. Compliance is the most important factor predicting reliability. [source]

    British HIV Association (BHIVA) national cohort outcomes audit of patients commencing antiretrovirals from naïve

    HIV MEDICINE, Issue 6 2009
    E Street
    Objectives The aim of this work was to audit the extent to which routine HIV care in the UK conforms with British HIV Association (BHIVA) guidelines and specifically the proportion of patients starting highly active antiretroviral therapy (HAART) who achieve the outcome of virological suppression below 50 HIV-1 RNA copies/mL within 6 months. Methods A prospective cohort review of adults with HIV infection who started antiretroviral therapy (ART) for the first time between April and September 2006 was carried out using structured questionnaire forms. Results A total of 1170 adults from 122 clinical sites participated in the review. Of these patients, 699 (59.7%) started ART at CD4 counts <200 cells/,L and 193 (16.5%) had not been tested for HIV drug resistance. Excluding patients with valid reasons for stopping short-term ART, 795 (73.5%) of 1081 patients had an undetectable viral load (VL) at follow-up. Detectable VL was strongly associated with pretreatment CD4 count below 50 cells/,L and pretreatment VL above 100 000 copies/mL, and was not associated with clinic location or case load. About a quarter of patients did not have a VL measurement during the first 6 weeks after starting ART. Conclusions The majority of patients who initiated ART at sites participating in this UK national audit were managed within the BHIVA guidelines and achieved virological suppression below 50 copies/mL around 6 months after commencing treatment. Poor VL outcomes were associated with very low CD4 cell count and/or high VL at baseline but not with clinic case load or location. There is an urgent need to diagnose patients at an earlier stage of their HIV disease. [source]

    Lipoprotein(a) in patients initiating antiretroviral therapy

    HIV MEDICINE, Issue 6 2008
    S Mauss
    Objectives The interaction between lipoprotein(a), an emerging cardiovascular risk factor, and antiretrovirals (ARVs) has been less well studied than the interaction between either cholesterol or triglycerides and these drugs. In this study we assessed the effect of initiating antiretroviral therapy (ART) on lipoprotein(a) levels. Methods Fasting samples from 95 patients initiating ART with nucleoside/nucleotide reverse transcriptase inhibitors plus nonnucleoside reverse transcriptase inhibitors or protease inhibitors were obtained. Lipids and lipoproteins were determined until week 48. Results As in the general population, the study population showed a highly skewed lipoprotein(a) distribution (median 9.9 mg/dL, range 0.1,110 mg/dL). The study population was divided into individuals with lipoprotein(a) ,30 mg/dL at baseline (n=28) and those with <30 mg/dL (n=67). Almost exclusively, patients with high lipoprotein(a) at baseline (median 51.6 mg/dL) showed a profound increase of median 26.7 mg/dL (week 24). This effect was not associated with specific ARVs and was independent of changes in other lipids. The low-lipoprotein(a) group (baseline median 7 mg/dL) showed a small increase of median 2.6 mg/dL (week 24). Conclusions Marked increases in lipoprotein(a) after initiation of ART were mainly restricted to patients with high baseline levels. This may have clinical implications as patients with high lipoprotein(a) are at higher risk for myocardial infarction and stroke. [source]

    Diagnosed and undiagnosed HIV-infected populations in Europe

    HIV MEDICINE, Issue 2008
    FF Hamers
    This article aims to build a picture of HIV epidemiology in Europe by combining existing surveillance data to mathematical modelling to achieve observations closer to the dynamic reality of HIV infections across different parts of Europe. In the European Union (EU), where it is estimated that 30% of HIV-infected persons have not been diagnosed, the number of new HIV diagnoses has risen in recent years. However, trends must be interpreted with some caution around the differences and variations in surveillance systems and testing rates among affected populations and regions. By introducing mathematical models, we can build an overall picture from the pieces of information available. We present a mathematical model of the course of infection and the effect of ART which has been developed to fit as closely as possible to observed data from HIV cohorts. The preliminary estimates for the entire WHO European Region are that around 2.3 million people were living with HIV in Europe at the end of 2006, of whom around 50% have not been diagnosed. The model can also be used to assess the potential impact of earlier diagnoses. Observations show how a combination of surveillance data and modelling allows an estimation of the current state of the epidemic in Europe, though further developments in both areas are needed. [source]

    European AIDS Clinical Society (EACS) guidelines on the prevention and management of metabolic diseases in HIV,

    HIV MEDICINE, Issue 2 2008
    JD Lundgren
    Background Metabolic diseases are frequently observed in HIV-infected persons and, as the risk of contracting these diseases is age-related, their prevalence will increase in the future as a consequence of the benefits of antiretroviral therapy (ART). Summary of guidelines All HIV-infected persons should be screened at regular intervals for a history of metabolic disease, dyslipidaemia, diabetes mellitus, hypertension and alteration of body composition; cardiovascular risk and renal function should also be assessed. Efforts to prevent cardiovascular disease will vary in intensity depending on an individual's absolute risk of ischaemic heart disease and should be comprehensive in nature. Lifestyle interventions should focus on counselling to stop smoking, modify diet and take regular exercise. A healthy diet, exercise and maintaining normal body weight tend to reduce dyslipidaemia; if not effective, a change of ART should be considered, followed by use of lipid-lowering medication in high-risk patients. A pre-emptive switch from thymidine analogues is recommended to reduce the risk of development or progression of lipoatrophy. Intra-abdominal fat accumulation is best managed by exercise and diet. Prevention and management of type 2 diabetes mellitus and hypertension follow guidelines used in the general population. When using medical interventions to prevent and/or treat metabolic disease(s), impairment of the efficacy of ART should be avoided by considering the possibility of pharmacokinetic interactions and compromised adherence. Specialists in HIV and specialists in metabolic diseases should consult each other, in particular in difficult-to-treat cases. Conclusion Multiple and relatively simple approaches exist to prevent metabolic diseases in HIV-infected persons; priority should be given to patients at high risk of contracting these diseases. [source]

    CD4 cell count and initiation of antiretroviral therapy: trends in seven UK centres, 1997,2003

    HIV MEDICINE, Issue 3 2007
    W Stöhr
    Objectives We examined whether the timing of initiation of antiretroviral therapy (ART) in routine clinical practice reflected treatment guidelines, which have evolved towards recommending starting therapy at lower CD4 cell counts. Methods We analysed longitudinal data on 10 820 patients enrolled in the UK Collaborative HIV Cohort (UK CHIC) Study, which includes seven large clinical centres in south-east England. CD4 cell and viral load measurements performed in the period between 1 January 1997 and 31 December 2003 were classified according to whether ART was subsequently initiated or deferred, to estimate the probability of ART initiation by CD4 count and viral load over time. The effect of nonclinical factors (age, sex, ethnicity, and exposure category) was analysed by logistic regression. Kaplan,Meier analysis was used to estimate the proportion of patients who had initiated ART by a particular CD4 count among ,early' presenters (initial CD4 cell count >500 cells/,L). Results There was a tendency to initiate ART at lower CD4 cell counts over time in the years 1997,2000, especially in the range 200,500 cells/,L, with little change thereafter. An estimated 34% of HIV-infected individuals having presented early initiated ART at a CD4 count <200 cells/,L. We also found an independent influence of viral load, which was particularly pronounced for CD4 <350 cells/,L. Use of injection drugs was the only nonclinical factor associated with initiation of ART at lower CD4 cell counts. Conclusions The initiation of ART in the clinics included in this analysis reflected evolving treatment guidelines. However, an unexpectedly high proportion of patients started ART at lower CD4 counts than recommended, which is only partly explained by late presentation. [source]

    Safety of nevirapine in pregnancy

    HIV MEDICINE, Issue 1 2007
    U Natarajan
    Background Nevirapine has been widely used in pregnancy for its efficacy, low pill burden, bioavailability and rapid transplacental transfer. Concern about nevirapine toxicity during pregnancy has emerged over recent years. Objectives The aims of the study were to document the frequency of cutaneous and hepatic toxicity secondary to nevirapine use during pregnancy and to compare rates in women starting nevirapine during the current pregnancy with those in women who had commenced nevirapine prior to the current pregnancy. Design This was a retrospective, comparative, five-centre study carried out in London, UK, in 1997,2003. Methods All HIV-1-infected women who received nevirapine as part of combination antiretroviral therapy (ART) during pregnancy were included in the study. Data on demographics, HIV infection risk, Centers for Disease Control and Prevention (CDC) status, surrogate markers at initiation of therapy, other medications hepatitis B and C virus coinfection and clinical data relating to potential toxicity were collated and analysed. Results Fifteen of 235 eligible women (6.4%) developed rash and eight (3.4%) developed hepatotoxicity, including four with coexistent rash, giving a combined incidence of 19 potential cases of nevirapine toxicity during pregnancy (8.1%). Alternative causes of rash/hepatotoxicity were suspected in seven cases and only 10 mothers (5.8%) discontinued nevirapine. Of the 170 women who commenced nevirapine during this pregnancy, 13 (7.6%) developed rash and eight (4.7%) hepatotoxicity, a combined incidence of 10%. Only two of 65 women with nevirapine exposure prior to this pregnancy developed rash (3.1%). Conclusions Nevirapine-containing ART was well tolerated in this cohort of pregnant women. Although pregnancy did not appear to increase the risk of nevirapine-associated toxicity compared to published adult data, CD4 count may be less predictive of toxicity in pregnancy. [source]

    Prevalence of risk factors for cardiovascular disease in HIV-infected patients over time: the Swiss HIV Cohort Study

    HIV MEDICINE, Issue 6 2006
    TR Glass
    Objective Metabolic changes caused by antiretroviral therapy (ART) may increase the risk of coronary heart disease (CHD). We evaluated changes in the prevalence of cardiovascular risk factors (CVRFs) and 10-year risk of CHD in a large cohort of HIV-infected individuals. Methods All individuals from the Swiss HIV Cohort Study (SHCS) who completed at least one CVRF questionnaire and for whom laboratory data were available for the period February 2000 to February 2006 were included in the analysis. The presence of a risk factor was determined using cut-offs based on the guidelines of the National Cholesterol Education Program (NCEP ATP III), the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7), the American Diabetes Association, and the Swiss Society for Cardiology. Results Overall, 8033 individuals completed at least one CVRF questionnaire. The most common CVRFs in the first completed questionnaire were smoking (57.0%), low high-density lipoprotein (HDL) cholesterol (37.2%), high triglycerides (35.7%), and high blood pressure (26.1%). In total, 2.7 and 13.8% of patients were categorized as being at high (>20%) and moderate (10,20%) 10-year risk for CHD, respectively. Over 6 years the percentage of smokers decreased from 61.4 to 47.6% and the percentage of individuals with total cholesterol >6.2 mmol/L decreased from 21.1 to 12.3%. The prevalence of CVRFs and CHD risk was higher in patients currently on ART than in either pretreated or ART-naive patients. Conclusion During the 6-year observation period, the prevalence of CVRFs remains high in the SHCS. Time trends indicate a decrease in the percentage of smokers and individuals with high cholesterol. [source]

    Indinavir/ritonavir-based therapy in HIV-1-infected antiretroviral therapy-naive patients: comparison of 800/100 mg and 400/100 mg twice daily

    HIV MEDICINE, Issue 1 2005
    D Konopnicki
    Objectives To compare the efficacy and tolerability of indinavir (IDV)/ritonavir (RTV) at 800/100 and 400/100 mg twice daily (bid) in antiretroviral therapy (ART)-naive patients. Methods An open comparison of two groups of ART-naive patients treated with IDV/RTV 800/100 or 400/100 mg bid plus two nucleoside analogues was carried out. Viral load, CD4 cell count and tolerability were measured at baseline and at weeks 4, 12, 24 and 48. IDV plasma concentrations were measured retrospectively. Results A total of 107 patients were included in the study. Of these, 57 were treated with 800/100 and 50 with 400/100 mg IDV/RTV bid. At week 48, a viral load of <50 HIV-1 RNA copies/mL was achieved by 77 and 64% of the patients, respectively, and the median CD4 cell count increases were +171 and +164 cells/,L (intent-to-treat; P not significant), respectively. Side effects leading to protease inhibitor discontinuation occurred in 61% of subjects in the 800/100 mg group vs. 20% in the 400/100 mg group (P<0.0001). Switching from 800/100 to 400/100 mg dosage improved adverse events in 16 of 20 patients. IDV concentrations were above 0.15 mg/L in 89% of the 28 patients tested in the 400/100 mg group. Conclusions Indinavir/ritonavir 400/100 mg bid provided the same efficacy as 800/100 mg bid at 48 weeks in an ART-naive population, but safety and tolerance were significantly better for 400/100 mg, while convenience was also improved and cost was reduced. [source]

    Matched case,control study to evaluate risk factors for hyperlactataemia in HIV patients on antiretroviral therapy

    HIV MEDICINE, Issue 4 2003
    D Datta
    Background Lactic acidosis is a life-threatening event during antiretroviral therapy (ART). Hyperlactataemia may be a prelude to acidosis. Our database study suggested that female gender, intercurrent illness and didanosine (ddI)-based regimens may increase risk of lactic acidosis. The aim of this matched case,control study was to identify risk factors for hyperlactataemia requiring screening. Methods Cases were defined as patients with two consecutive lactate samples ,3.5 mmol/L taken more than 1 week apart. Cases were matched to two controls on gender, use of ddI and total duration of therapy using a 6-month window on either side. Controls never had raised lactate >2.5 mmol/L. A conditional logistic regression analysis using the PHREG procedure in SAS (SAS Institute Inc, Cary, NC) was performed with a discreet logistic model stratified by matching variables. Results Twenty-one cases were matched to 42 controls. In the univariate model, current use of stavudine (d4T), total cholesterol >5.3 mmol/L and glucose levels ,5.2 mmol/L gave increased likelihood of persistent hyperlactataemia. The multivariate model showed current use of d4T to be a significant independent predictor of persistent hyperlactataemia. Conclusions The results of this case,control study indicate that, when controlling for ddI use, d4T use is an additional risk factor for hyperlactataemia. [source]

    TRIZAL study: switching from successful HAART to TrizivirTM (abacavir-lamivudine-zidovudine combination tablet): 48 weeks efficacy, safety and adherence results

    HIV MEDICINE, Issue 2 2003
    C Katlama
    Objective To assess the antiviral efficacy, safety, and adherence in subjects who switched to TrizivirÔ following long-term HIV-1 RNA suppression. Study design A randomized, open-label, multicentre, 48-week comparative study in subjects who have received two nucleoside reverse transcriptase inhibitors plus a protease inhibitor or an nonnucleoside reverse transcriptase inhibitor or three nucleoside reverse transcriptase inhibitors for at least 6 months, with a history of undetectable plasma HIV-1 RNA since initiation of therapy and plasma viral load of < 50 HIV-1 RNA copies/mL at screening. Methods Subjects were randomized 1:1 to continue their current treatment or to switch to a simplified treatment with TrizivirÔ administered twice daily. Assessments included plasma HIV-1 RNA, lymphocyte counts, clinical laboratory evaluations, adverse events, and adherence to treatment (obtained via subject self-report). Treatment failure was defined as a plasma viral load of , 400 HIV-1 RNA copies/mL on two consecutive occasions or premature discontinuation of randomized treatment. Results At week 48, the proportion of treatment failures in TrizivirÔ arm (23/106, 22%) was noninferior to that observed in continued arm (23/103, 22%) with a treatment difference stratified by prior ART of 1.2%[-10.1; 12.5]. Incidence of adverse events was similar in both treatment groups. The incidence of possible hypersensitivity reaction in the TrizivirÔ arm was 10%. Significant reductions in cholesterol and triglyceride plasma levels were observed in the TrizivirÔ arm (P < 0.001 and P = 0.006, respectively). Conclusion Switching to TrizivirÔ offers a potent and simplified regimen with equivalent efficacy and significant improvement in lipid abnormalities compared to continued triple therapy. [source]

    A T2 cytokine environment may not limit T1 responses in human immunodeficiency virus patients with a favourable response to antiretroviral therapy

    IMMUNOLOGY, Issue 1 2006
    Patricia Price
    Summary Low-level production of interferon-, (IFN-,) marks human immunodeficiency virus (HIV)-induced immunodeficiency and has been ascribed to a bias towards T2 cytokines. This was investigated in two cross-sectional studies of HIV patients who were immunodeficient when they began antiretroviral therapy (ART) and had stable increases in CD4 T-cell counts. Blood leucocytes were assessed unstimulated or after stimulation with cytomegalovirus (CMV), anti-CD3 or mitogen. IFN-, and interleukin (IL)-5 responses were initially assessed by enzyme-linked immunosorbent spot-forming cell assay (ELISPOT) and enzyme-linked immunosorbent assay (ELISA). We then adopted a sensitive reverse transcription,polymerase chain reaction (RT,PCR) system to assess IFN-,, IL-5, IL-4 and IL-4,2 (an inhibitory splice variant of IL-4) mRNA. The results were correlated with putative serological markers of a T1 [lymphocyte activation gene-3 (LAG-3), CD26] or a T2 [CD30, immunoglobulin E (IgE)] cytokine environment. IL-5 production and IgE levels were elevated in patients. IgE levels did not correlate with IFN-,, but showed an inverse correlation with IL-5 released in culture (P = 0·05). The levels of IL-4, IFN-,, IL-5 and IL-4,2 mRNA were correlated after anti-CD3 stimulation, where IL-5 was the best predictor of IFN-, mRNA (P = 0·006). Weak positive correlations were evident between CD30 and cytokine mRNA levels, whilst IgE correlated inversely with IL-4, IL-4,2, IL-5 and IFN-, mRNA levels. These analyses provide no evidence for an inverse relationship between T1 and T2 cytokine responses in HIV patients, but suggest that the elevation of IgE marks low cytokine responses. [source]

    Factors associated with adherence to antiretroviral therapy for the treatment of HIV-infected women attending an urban care facility

    Heila E Aspeling RN MSN
    Adherence to antiretroviral therapy (ART) is often jeopardized by factors misapprehended by health-care providers. As South Africa is severely affected by HIV and AIDS, identifying factors that influence adherence in this specific context becomes essential. An exploratory and descriptive case study design was used to further explore this subject and to identify factors that could influence adherence to ART. A significant correlation with international data was found. Most participants indicated that their traditional beliefs and customs did not interfere with their adherence to ART, although the lack of HIV education might facilitate reversion to traditional customs. Adequate treatment preparation, comprehensive HIV education and a supportive patient,provider relationship seemed to impact adherence significantly. [source]