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Sample records for long-term hiv virological

  1. Early adherence to antiretroviral medication as a predictor of long-term HIV virological suppression: five-year follow up of an observational cohort.

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    Nathan Ford

    Full Text Available OBJECTIVE: Previous studies have demonstrated a cross-sectional relationship between antiretroviral adherence and HIV virological suppression. We assessed the predictive value of baseline adherence in determining long-term virological failure. DESIGN: We assessed baseline adherence via an adherence questionnaire between administered to all consenting patients attending antiretroviral clinics in Khayelitsha township, South Africa, between May 2002 and March 2004. Virological status was ascertained after five years of follow up and multivariate analysis used to model associations of baseline variables and medication adherence with time to viral suppression or failure. RESULTS: Our adherence cohort comprised 207 patients, among whom 72% were female. Median age was 30 years and median CD4 count at initiation was 55 cells/mm(3. We found no statistically significant differences between baseline characteristics and early adherence groups. Multivariate analysis adjusting for baseline CD4 and age found that patients with suboptimal baseline adherence had a hazard ratio of 2.82 (95% CI 1.19-6.66, p = 0.018 for progression to virological failure compared to those whose baseline adherence was considered optimal. CONCLUSIONS: Our longitudinal study provides further confirmation of adherence as a primary determinant of subsequent confirmed virological failure, and serves as a reminder of the importance of initial early investments in adherence counseling and support as an effective way to maximize long-term treatment success.

  2. Clinical outcome of HIV-infected patients with sustained virologic response to antiretroviral therapy: long-term follow-up of a multicenter cohort.

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    Félix Gutierrez

    Full Text Available BACKGROUND: Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART. METHODS: Using data collected from ten clinic-based cohorts in Spain, we selected all antiretroviral-naive adults who initiated HAART and maintained plasma HIV-1 RNA levels <500 copies/mL throughout follow-up. Factors associated with disease progression were determined by Cox proportional-hazards models. RESULTS: Of 2,613 patients who started HAART, 757 fulfilled the inclusion criteria. 61% of them initiated a protease inhibitor-based HAART regimen, 29.7% a nonnucleoside reverse-transcriptase inhibitor-based regimen, and 7.8% a triple-nucleoside regimen. During 2,556 person-years of follow-up, 22 (2.9% patients died (mortality rate 0.86 per 100 person-years, and 40 (5.3% died or developed a new AIDS-defining event. The most common causes of death were neoplasias and liver failure. Mortality was independently associated with a CD4-T cell response <50 cells/L after 12 months of HAART (adjusted hazard ratio [AHR], 4.26 [95% confidence interval {CI}, 1.68-10.83]; P = .002, and age at initiation of HAART (AHR, 1.06 per year; 95% CI, 1.02-1.09; P = .001. Initial antiretroviral regimen chosen was not associated with different risk of clinical progression. CONCLUSIONS: Patients with sustained virologic response on HAART have a low mortality rate over time. Long-term outcome of these patients is driven by immunologic response at the end of the first year of therapy and age at the time of HAART initiation, but not by the initial antiretroviral regimen selected.

  3. Virological response and resistance among HIV-infected children receiving long-term antiretroviral therapy without virological monitoring in Uganda and Zimbabwe: Observational analyses within the randomised ARROW trial.

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    Alexander J Szubert

    2017-11-01

    Full Text Available Although WHO recommends viral load (VL monitoring for those on antiretroviral therapy (ART, availability in low-income countries remains limited. We investigated long-term VL and resistance in HIV-infected children managed without real-time VL monitoring.In the ARROW factorial trial, 1,206 children initiating ART in Uganda and Zimbabwe between 15 March 2007 and 18 November 2008, aged a median 6 years old, with median CD4% of 12%, were randomised to monitoring with or without 12-weekly CD4 counts and to receive 2 nucleoside reverse transcriptase inhibitors (2NRTI, mainly abacavir+lamivudine with a non-nucleoside reverse transcriptase inhibitor (NNRTI or 3 NRTIs as long-term ART. All children had VL assayed retrospectively after a median of 4 years on ART; those with >1,000 copies/ml were genotyped. Three hundred and sixteen children had VL and genotypes assayed longitudinally (at least every 24 weeks. Overall, 67 (6% switched to second-line ART and 54 (4% died. In children randomised to WHO-recommended 2NRTI+NNRTI long-term ART, 308/378 (81% monitored with CD4 counts versus 297/375 (79% without had VL <1,000 copies/ml at 4 years (difference = +2.3% [95% CI -3.4% to +8.0%]; P = 0.43, with no evidence of differences in intermediate/high-level resistance to 11 drugs. Among children with longitudinal VLs, only 5% of child-time post-week 24 was spent with persistent low-level viraemia (80-5,000 copies/ml and 10% with VL rebound ≥5,000 copies/ml. No child resuppressed <80 copies/ml after confirmed VL rebound ≥5,000 copies/ml. A median of 1.0 (IQR 0.0,1.5 additional NRTI mutation accumulated over 2 years' rebound. Nineteen out of 48 (40% VLs 1,000-5,000 copies/ml were immediately followed by resuppression <1,000 copies/ml, but only 17/155 (11% VLs ≥5,000 copies/ml resuppressed (P < 0.0001. Main study limitations are that analyses were exploratory and treatment initiation used 2006 criteria, without pre-ART genotypes.In this study, children

  4. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study.

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    Asier Sáez-Cirión

    2013-03-01

    Full Text Available Combination antiretroviral therapy (cART reduces HIV-associated morbidities and mortalities but cannot cure the infection. Given the difficulty of eradicating HIV-1, a functional cure for HIV-infected patients appears to be a more reachable short-term goal. We identified 14 HIV patients (post-treatment controllers [PTCs] whose viremia remained controlled for several years after the interruption of prolonged cART initiated during the primary infection. Most PTCs lacked the protective HLA B alleles that are overrepresented in spontaneous HIV controllers (HICs; instead, they carried risk-associated HLA alleles that were largely absent among the HICs. Accordingly, the PTCs had poorer CD8+ T cell responses and more severe primary infections than the HICs did. Moreover, the incidence of viral control after the interruption of early antiretroviral therapy was higher among the PTCs than has been reported for spontaneous control. Off therapy, the PTCs were able to maintain and, in some cases, further reduce an extremely low viral reservoir. We found that long-lived HIV-infected CD4+ T cells contributed poorly to the total resting HIV reservoir in the PTCs because of a low rate of infection of naïve T cells and a skewed distribution of resting memory CD4+ T cell subsets. Our results show that early and prolonged cART may allow some individuals with a rather unfavorable background to achieve long-term infection control and may have important implications in the search for a functional HIV cure.

  5. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy

    NARCIS (Netherlands)

    Pakker, NG; Otto, SA; Hall, D; Wit, FWNM; Hamann, D; van der Ende, Marchina E.; Claessen, FAP; Kauffmann, RH; Koopmans, PP; Sprenger, HG; Weigel, HM; Montaner, JSG; Lange, JMA; Reiss, P; Schellekens, PTA; Miedema, F; Ten Napel, Chris H. H.

    1999-01-01

    Background: Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. Objectives: In this study, long-term immune reconstitution was investigated during highly active antiretroviral

  6. Risk of triple-class virological failure in children with HIV: a retrospective cohort study

    DEFF Research Database (Denmark)

    Castro, Hannah; Judd, Ali; Gibb, Diana M

    2011-01-01

    In adults with HIV treated with antiretroviral drug regimens from within the three original drug classes (nucleoside or nucleotide reverse transcriptase inhibitors [NRTIs], non-NRTIs [NNRTIs], and protease inhibitors), virological failure occurs slowly, suggesting that long-term virological...... failure to the three original drugs classes in children....

  7. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group

    NARCIS (Netherlands)

    Pakker, N. G.; Kroon, E. D.; Roos, M. T.; Otto, S. A.; Hall, D.; Wit, F. W.; Hamann, D.; van der Ende, M. E.; Claessen, F. A.; Kauffmann, R. H.; Koopmans, P. P.; Kroon, F. P.; ten Napel, C. H.; Sprenger, H. G.; Weigel, H. M.; Montaner, J. S.; Lange, J. M.; Reiss, P.; Schellekens, P. T.; Miedema, F.

    1999-01-01

    BACKGROUND: Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. OBJECTIVES: In this study, long-term immune reconstitution was investigated during highly active antiretroviral

  8. Long-term effectiveness of unboosted atazanavir plus abacavir/lamivudine in subjects with virological suppression

    DEFF Research Database (Denmark)

    Llibre, Josep M; Cozzi-Lepri, Alessandro; Pedersen, Court

    2016-01-01

    Effectiveness data of an unboosted atazanavir (ATV) with abacavir/lamivudine (ABC/3TC) switch strategy in clinical routine are scant.We evaluated treatment outcomes of ATV + ABC/3TC in pretreated subjects in the EuroSIDA cohort when started with undetectable plasma HIV-1 viral load (p......VL), performing a time to loss of virological response (TLOVR analysis at 48, 96, and 144 weeks. Virological failure (VF) was defined as confirmed pVL >50 copies/mL.We included 285 subjects, 67% male, with median baseline CD4 530 cells, and 44 months with pVL ≤50 copies/mL. The third......%/67%/59% (snapshot analysis), respectively. The rates of VF were 8%/8%/6%. Rates of adverse events leading to study discontinuation were 0.4%/1%/2%. The multivariable adjusted analysis showed an association between VF and nadir CD4+ (hazard ratio [HR] 0.63 [95% confidence interval [CI]: 0.42-0.93] per 100 cells...

  9. HIV-related politics in long-term perspective.

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    Friedman, S R

    1998-06-01

    Some long-term, large-scale socio-economic changes may affect the politics of HIV and other emerging viruses such as hepatitis C. It is useful to ask why the potential peace dividend of the early 1990s failed to provide adequate resources for HIV-related social and medical service delivery in developed or developing nations. This failure can be understood by looking at long-term global economic trends and the pressures they put on governments and corporations. They have produced a period in which fundamental issues of political and economic structure are at stake and, often, the response is a divide-and-rule politics to promote stability. National politics differ in terms of the extent to which such a 'politics of scapegoating' is institutionalized and in terms of which groups are scapegoated. Groups such as drug injectors, gay and bisexual men and sex traders are particularly likely to be targeted both by the scapegoaters and by HIV. Given this framework, how should public health professionals and activists engaged in HIV-related issues respond? Under what circumstances should we orient efforts upwards towards corporate, political or bureaucratic leaders? Under what circumstances, and how, should we orient towards popular forces? Relatedly, we need to consider an issue we often ignore: What do we have to offer potential allies? That is, in terms of their goals, philosophies and needs, why should they ally with us?

  10. Immune restoration does not invariably occur following long-term HIV-1 suppression during antiretroviral therapy. INCAS Study Group.

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    Pakker, N G; Kroon, E D; Roos, M T; Otto, S A; Hall, D; Wit, F W; Hamann, D; van der Ende, M E; Claessen, F A; Kauffmann, R H; Koopmans, P P; Kroon, F P; ten Napel, C H; Sprenger, H G; Weigel, H M; Montaner, J S; Lange, J M; Reiss, P; Schellekens, P T; Miedema, F

    1999-02-04

    Current antiretroviral treatment can induce significant and sustained virological and immunological responses in HIV-1-infected persons over at least the short- to mid-term. In this study, long-term immune reconstitution was investigated during highly active antiretroviral therapy. Patients enrolled in the INCAS study in The Netherlands were treated for 102 weeks (range 52-144 weeks) with nevirapine (NVP) + zidovudine (ZDV) (n = 9), didanosine (ddl) + ZDV (n = 10), or NVP + ddl + ZDV (n = 10). Memory and naïve CD4+ and CD8+ T cells were measured using CD45RA and CD27 monoclonal antibodies (mAb), T-cell function was assayed by CD3 + CD28 mAb stimulation, and plasma HIV-1 RNA load was measured by ultra-direct assay (cut-off < 20 copies/ml). Compared to both double combination regimens the triple combination regimen resulted in the most sustained increase in CD4+ T cells (change in CD4+, + 253 x 10(6) cells/l; standard error, 79 x 10(6) cells/l) and reduction of plasma HIV-1 RNA. In nine patients (31%) (ddl + ZDV, n = 2; NVP + ddl + ZDV, n = 7) plasma HIV-1 RNA levels remained below cut-off for at least 2 years. On average, these long-term virological responders demonstrated a significantly higher increase of naïve and memory CD4+ T cells (P = 0.01 and 0.02, respectively) as compared with patients with a virological failure, and showed improved T-cell function and normalization of the naïve; memory CD8+ T-cell ratio. However, individual virological success or failure did not predict the degree of immunological response. T-cell patterns were independent of baseline CD4+ T-cell count, T-cell function, HIV-1 RNA load or age. Low numbers of naïve CD4+ T cells at baseline resulted in modest long-term naïve T-cell recovery. Patients with prolonged undetectable plasma HIV-1 RNA levels during antiretroviral therapy do not invariably show immune restoration. Naïve T-cell recovery in the setting of complete viral suppression is a gradual process, similar to that reported

  11. Long-term effects of HIV treatment in sub-Saharan Africa: from access to quality

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    Boender, T.S.

    2016-01-01

    As HIV treatment programs in sub-Saharan Africa mature, there are rising concerns about the long-term sustainability and quality of these programs. Increasing levels of HIV drug resistance have been measured in sub-Saharan Africa, and could jeopardize long-term treatment success. This thesis

  12. Long term adverse drug reaction to Efavirenz in a HIV infected ...

    African Journals Online (AJOL)

    There is only one published case of serious adverse reaction to Efavirenz in an adolescent after long-term use. The case of a male HIV Positive Nigerian patient aged 13 years. He presented with five-day history of Difficulty sleeping, abnormal dreams, inability to concentrate, restlessness, irrational behavior and long-term ...

  13. Cognition, Emotional Health, and Immunological Markers in Children With Long-Term Nonprogressive HIV

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    Paul, Robert; Apornpong, Tanakorn; Prasitsuebsai, Wasana; Puthanakit, Thanyawee; Saphonn, Vonthanak; Aurpibul, Linda; Kosalaraksa, Pope; Kanjanavanit, Suparat; Luesomboon, Wicharn; Ngampiyaskul, Chaiwat; Suwanlerk, Tulathip; Chettra, Kea; Shearer, William T.; Valcour, Victor; Ananworanich, Jintanat; Kerr, Stephen

    2018-01-01

    HIV-infected children with long-term nonprogressive (LTNP) disease eventually convert to a progressive disease type, yet the extent to which these children experience the cognitive and emotional symptoms observed in typical progressive HIV (Progressors) is unknown. Eighty-eight LTNPs, 53

  14. Long term effectiveness of once-daily unboosted atazanavir plus abacavir/lamivudine as a switch strategy in subjects with virological suppression

    DEFF Research Database (Denmark)

    Llibre, Josep M; Cozzi-Lepri, Alessandro; La Rosa, Jorge Antonio Valencia

    2014-01-01

    routine however are scant. METHODS: We evaluated treatment outcomes of ATV400+ABC/3TC in pre-treated subjects in the EuroSIDA cohort with undetectable HIV-1 RNA, and previous ABC experience or assumed previous HLA B57*01 testing. We performed a time to loss of virologic response (TLOVR below 50 c...

  15. Long-term clinical outcome of human immunodeficiency virus-infected patients with discordant immunologic and virologic responses to a protease inhibitor-containing regimen.

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    Piketty, C; Weiss, L; Thomas, F; Mohamed, A S; Belec, L; Kazatchkine, M D

    2001-05-01

    Within a prospective cohort of 150 human immunodeficiency virus (HIV)-infected patients who began first-line protease inhibitor therapy in 1996, the outcome of 42 patients with discrepant virologic and immunologic responses to antiretroviral treatment at 12 months was analyzed at 30 months of treatment. The incidence of AIDS-defining events and deaths (14%) in the group of patients with immunologic responses in the absence of a virologic response was higher than that in full-responder patients (2%); yet, the incidence in this group was lower than that in patients with no immunologic response, despite a virologic response (21%), and was lower than that in patients without an immunologic or virologic response (67%; P<.0001, log-rank test). Differences in outcome were significant (relative risk, 6.9; 95% confidence interval, 1.9-39.3) when factors for progression were compared with those of responder patients. The results support the relevance of the CD4 cell marker over plasma HIV load for predicting clinical outcome in patients who do not achieve full immunologic and virologic responses.

  16. Performance and Logistical Challenges of Alternative HIV-1 Virological Monitoring Options in a Clinical Setting of Harare, Zimbabwe

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    Pascale Ondoa

    2014-01-01

    Full Text Available We evaluated a low-cost virological failure assay (VFA on plasma and dried blood spot (DBS specimens from HIV-1 infected patients attending an HIV clinic in Harare. The results were compared to the performance of the ultrasensitive heat-denatured p24 assay (p24. The COBAS AmpliPrep/COBAS TaqMan HIV-1 test, version 2.0, served as the gold standard. Using a cutoff of 5,000 copies/mL, the plasma VFA had a sensitivity of 94.5% and specificity of 92.7% and was largely superior to the VFA on DBS (sensitivity = 61.9%; specificity = 99.0% or to the p24 (sensitivity = 54.3%; specificity = 82.3% when tested on 302 HIV treated and untreated patients. However, among the 202 long-term ART-exposed patients, the sensitivity of the VFA decreased to 72.7% and to 35.7% using a threshold of 5,000 and 1,000 RNA copies/mL, respectively. We show that the VFA (either on plasma or on DBS and the p24 are not reliable to monitor long-term treated, HIV-1 infected patients. Moreover, achieving acceptable assay sensitivity using DBS proved technically difficult in a less-experienced laboratory. Importantly, the high level of virological suppression (93% indicated that quality care focused on treatment adherence limits virological failure even when PCR-based viral load monitoring is not available.

  17. Virological Mechanisms in the Coinfection between HIV and HCV

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    Maria Carla Liberto

    2015-01-01

    Full Text Available Due to shared transmission routes, coinfection with Hepatitis C Virus (HCV is common in patients infected by Human Immunodeficiency Virus (HIV. The immune-pathogenesis of liver disease in HIV/HCV coinfected patients is a multifactorial process. Several studies demonstrated that HIV worsens the course of HCV infection, increasing the risk of cirrhosis and hepatocellular carcinoma. Also, HCV might increase immunological defects due to HIV and risk of comorbidities. A specific cross-talk among HIV and HCV proteins in coinfected patients modulates the natural history, the immune responses, and the life cycle of both viruses. These effects are mediated by immune mechanisms and by a cross-talk between the two viruses which could interfere with host defense mechanisms. In this review, we focus on some virological/immunological mechanisms of the pathogenetic interactions between HIV and HCV in the human host.

  18. Socioeconomic position and ten-year survival and virologic outcomes in a Ugandan HIV cohort receiving antiretroviral therapy.

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    Andrew G Flynn

    Full Text Available Lifelong ART is essential to reducing HIV mortality and ending the epidemic, however the interplay between socioeconomic position and long-term outcomes of HIV-infected persons receiving antiretroviral therapy (ART in sub-Saharan Africa is unknown. Furthering the understanding of factors related to long-term ART outcomes in this important region will aid the successful scale-up of ART programs. We enrolled 559 HIV-infected Ugandan adults starting ART in 2004-2005 at the Infectious Diseases Institute in Kampala, Uganda and followed them for 10 years. We documented baseline employment status, regular household income, education level, housing description, physical ability, and CD4 count. Viral load was measured every six months. Proportional hazard regression tested for associations between baseline characteristics and 1 mortality, 2 virologic failure, and 3 mortality or virologic failure as a composite outcome. Over ten years 23% (n = 127 of participants died, 6% (n = 31 were lost-to-follow-up and 23% (107/472 experienced virologic treatment failure. In Kaplan-Meier analysis we observed an association between employment and mortality, with the highest cumulative probability of death occurring in unemployed individuals. In univariate analysis unemployment and disease severity were associated with mortality, but in multivariable analysis the only association with mortality was disease severity. We observed an association between higher household income and an increased incidence of both virologic failure and the combined outcome, and an association between self-employment and lower incidence of virologic failure and the combined outcome when compared to unemployment. Formal education level and housing status were unrelated to outcomes. It is feasible to achieve good ten-year survival, retention-in-care, and viral suppression in a socioeconomically diverse population in a resource-limited setting. Unemployment appears to be related to adverse 10

  19. Long-term nonprogression and broad HIV-1-specific proliferative T-cell responses

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    Nesrina eImami

    2013-03-01

    Full Text Available Complex mechanisms underlying the maintenance of fully functional, proliferative, HIV-1-specific T-cell responses involve processes from early T-cell development through to the final stages of T-cell differentiation and antigen recognition. Virus-specific proliferative CD4 and CD8 T-cell responses, important for the control of infection, are observed in some HIV-1+ patients during early stages of disease, and are maintained in long-term nonprogressing subjects. In the vast majority of HIV-1+ patients, full immune functionality is lost when proliferative HIV-1-specific T-cell responses undergo a variable progressive decline throughout the course of chronic infection. This appears irreparable despite administration of potent combination antiretroviral therapy, which to date is non-curative, necessitating life-long administration and the development of effective, novel, therapeutic interventions. While a sterilising cure, involving clearance of virus from the host, remains a primary aim, a functional cure may be a more feasible goal with considerable impact on worldwide HIV-1 infection. Such an approach would enable long-term co-existence of host and virus in the absence of toxic and costly drugs. Effective immune homeostasis coupled with a balanced response appropriately targeting conserved viral antigens, in a manner that avoids hyperactivation and exhaustion, may prove to be the strongest correlate of durable viral control. This review describes novel concepts underlying full immune functionality in the context of HIV-1 infection, which may be utilised in future strategies designed to improve upon existing therapy. The aim will be to induce long-term nonprogressor or elite controller status in every infected host, through immune-mediated control of viraemia and reduction of viral reservoirs, leading to lower HIV-1 transmission rates.

  20. Long-Term Efficacy, Tolerability, and Renal Safety of Atazanavir/Ritonavir-based Antiretroviral Therapy in a Cohort of Treatment-Naïve Patients with HIV-1 Infection: the REMAIN Study.

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    Teófilo, Eugénio; Rocha-Pereira, Nuno; Kuhlmann, Birger; Antela, Antonio; Knechten, Heribert; Santos, Jesús; Jiménez-Expósito, Maria Jesús

    2016-02-01

    Boosted protease inhibitors (PIs), including ritonavir-boosted atazanavir (ATV/r), are a recommended option for the initial treatment of HIV-1 infection based upon clinical trial data; however, long-term real-life clinical data are limited. We evaluated the long-term use of ATV/r as a component of antiretroviral combination therapy in the real-life setting in the REMAIN study. This was an observational cohort study conducted at sites across Germany, Portugal, and Spain. Retrospective historical and prospective longitudinal follow-up data were extracted every six months from medical records of HIV-infected treatment-naïve patients aged ≥ 18 years initiating a first-line ATV/r-containing regimen. Eligible patients (n = 517) were followed up for a median of 3.4 years. The proportion remaining on ATV/r at 5 years was 51.5% with an estimated Kaplan-Meier median time to treatment discontinuation of 4.9 years. Principal reasons for discontinuation were adverse events (15.9%; 8.9% due to hyperbilirubinemia) and virologic failure (6.8%). The Kaplan-Meier probability of not having virologic failure (HIV-1 RNA treatment-emergent major PI resistance occurred. ATV/r was generally well tolerated during long-term treatment with no significant changes in estimated glomerular filtration rate over five years. In a real-life clinical setting over five years, treatment-naïve patients with HIV-1 infection initiating an ATV/r-based regimen showed sustained virologic suppression, an overall treatment persistence rate of 51.5%, an absence of treatment-emergent major PI resistance mutations at virologic failure, a long-term safety profile consistent with that observed in clinical trials, and no significant decline in renal function.

  1. Drug resistance in HIV patients with virological failure or slow virological response to antiretroviral therapy in Ethiopia

    DEFF Research Database (Denmark)

    Abdissa, Alemseged; Yilma, Daniel; Fonager, Jannik

    2014-01-01

    BACKGROUND: The ongoing scale-up of antiretroviral therapy (ART) in sub-Saharan Africa has prompted the interest in surveillance of transmitted and acquired HIV drug resistance. Resistance data on virological failure and mutations in HIV infected populations initiating treatment in sub-Saharan Af...... mutations among failing patients justify increased vigilance by improving the availability and systematic use of VL testing to monitor ART response, and underlines the need for rapid, inexpensive tests to identify the most common drug resistance mutations....

  2. HIV-1 specific antibody titers and neutralization among chronically infected patients on long-term suppressive antiretroviral therapy (ART: a cross-sectional study.

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    Johannes S Gach

    Full Text Available The majority of potent and broadly neutralizing antibodies against HIV-1 have been isolated from untreated patients with acute or chronic infection. To assess the extent of HIV-1 specific antibody response and neutralization after many years of virologic suppression from potent combination ART, we examined antibody binding titers and neutralization of 51 patients with chronic HIV-1 infection on suppressive ART for at least three years. In this cross-sectional analysis, we found high antibody titers against gp120, gp41, and the membrane proximal external region (MPER in 59%, 43%, and 27% of patients, respectively. We observed significantly higher endpoint binding titers for gp120 and gp41 for patients with >10 compared to ≤ 10 years of detectable HIV RNA. Additionally, we observed higher median gp120 and gp41 antibody titers in patients with HIV RNA 10 years of detectable HIV RNA (8/20 [40.0%] versus 3/31 [9.7%] for ≤ 10 years, p = 0.02 and a trend toward greater neutralization in patients with ≤ 5 years of HIV RNA 5 years, p = 0.08. All patients with neutralizing activity mediated successful phagocytosis of VLPs by THP-1 cells after antibody opsonization. Our findings of highly specific antibodies to several structural epitopes of HIV-1 with antibody effector functions and neutralizing activity after long-term suppressive ART, suggest continuous antigenic stimulation and evolution of HIV-specific antibody response occurs before and after suppression with ART. These patients, particularly those with slower HIV progression and more time with detectable viremia prior to initiation of suppressive ART, are a promising population to identify and further study functional antibodies against HIV-1.

  3. Non-polarized cytokine profile of a long-term non-progressor HIV infected patient.

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    Pina, Ana Flávia; Matos, Vanessa Terezinha Gubert de; Bonin, Camila Mareti; Dal Fabbro, Márcia Maria Ferrairo Janini; Tozetti, Inês Aparecida

    The HIV-1 initial viral infection may present diverse clinical and laboratory course and lead to rapid, intermediate, or long-term progression. Among the group of non-progressors, the elite controllers are those who control the infection most effectively, in the absence of antiretroviral therapy (ART). In this paper, the TH1, TH2 and TH17 cytokines profiles are described, as well as clinical and laboratory aspects of an HIV-infected patient with undetectable viral load without antiretroviral therapy. Production of IL-6, IL-10, TNF-α, IFN-γ, and IL-17 was detected; in contrast IL-4 was identified. Host-related factors could help explain such a level of infection control, namely the differentiated modulation of the cellular immune response and a non-polarized cytokine response of the TH1 and TH2 profiles. Copyright © 2018 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  4. Increasing adolescent HIV prevalence in Eastern Zimbabwe--evidence of long-term survivors of mother-to-child transmission?

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    Jeffrey W Eaton

    Full Text Available Recent data from the Manicaland HIV/STD Prevention Project, a general-population open HIV cohort study, suggested that between 2004 and 2007 HIV prevalence amongst males aged 15-17 years in eastern Zimbabwe increased from 1.20% to 2.23%, and in females remained unchanged at 2.23% to 2.39%, while prevalence continued to decline in the rest of the adult population. We assess whether the more likely source of the increase in adolescent HIV prevalence is recent sexual HIV acquisition, or the aging of long-term survivors of perinatal HIV acquisition that occurred during the early growth of the epidemic. Using data collected between August 2006 and November 2008, we investigated associations between adolescent HIV and (1 maternal orphanhood and maternal HIV status, (2 reported sexual behaviour, and (3 reporting recurring sickness or chronic illness, suggesting infected adolescents might be in a late stage of HIV infection. HIV-infected adolescent males were more likely to be maternal orphans (RR = 2.97, p<0.001 and both HIV-infected adolescent males and females were more likely to be maternal orphans or have an HIV-infected mother (male RR = 1.83, p<0.001; female RR = 16.6, p<0.001. None of 22 HIV-infected adolescent males and only three of 23 HIV-infected females reported ever having had sex. HIV-infected adolescents were 60% more likely to report illness than HIV-infected young adults. Taken together, all three hypotheses suggest that recent increases in adolescent HIV prevalence in eastern Zimbabwe are more likely attributable to long-term survival of mother-to-child transmission rather than increases in risky sexual behaviour. HIV prevalence in adolescents and young adults cannot be used as a surrogate for recent HIV incidence, and health systems should prepare for increasing numbers of long-term infected adolescents.

  5. Long-Term Outcome of an HIV-Treatment Programme in Rural Africa: Viral Suppression despite Early Mortality

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    Roos E. Barth

    2011-01-01

    Results. 63% of patients (466/735 have a fully suppressed HIV-RNA, a median of three years after treatment initiation. Early mortality was high: 14% died within 3 months after treatment start. 16% of patients experienced virological failure, but only 4% was switched to second-line ART. Male gender and a low performance score were associated with treatment failure; immunological failure was a poor predictor of virological failure. Conclusions. An “all or nothing” phenomenon was observed in this rural South African ART programme: high early attrition, but good virological control in those remaining in care. Continued efforts are needed to enrol patients earlier. Furthermore, the observed viro-immunological dissociation emphasises the need to make HIV-RNA testing more widely available.

  6. Sustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection.

    Directory of Open Access Journals (Sweden)

    Swee Lin G Chen Yi Mei

    Full Text Available Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR in people with chronic hepatitis C (CHC infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart.CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM using transient elastography [FibroScan] were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa or advanced (METAVIR F3-4/ LSM >9.5 kPa. The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2 to advanced fibrosis at follow-up liver fibrosis assessment.131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54-62 years with median estimated duration of infection 33-years (IQR 29-38. At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12-17. 109 (83% participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002. The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343. However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F

  7. Sustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection.

    Science.gov (United States)

    Chen Yi Mei, Swee Lin G; Thompson, Alexander J; Christensen, Britt; Cunningham, Georgina; McDonald, Lucy; Bell, Sally; Iser, David; Nguyen, Tin; Desmond, Paul V

    2017-01-01

    Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR) in people with chronic hepatitis C (CHC) infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart. CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM) using transient elastography [FibroScan]) were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa) or advanced (METAVIR F3-4/ LSM >9.5 kPa). The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2) to advanced fibrosis at follow-up liver fibrosis assessment. 131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54-62) years with median estimated duration of infection 33-years (IQR 29-38). At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12-17). 109 (83%) participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002). The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343). However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F/U (p

  8. Perinatal acquisition of drug-resistant HIV-1 infection: mechanisms and long-term outcome

    Directory of Open Access Journals (Sweden)

    Dollfus Catherine

    2009-09-01

    Full Text Available Abstract Background Primary-HIV-1-infection in newborns that occurs under antiretroviral prophylaxis that is a high risk of drug-resistance acquisition. We examine the frequency and the mechanisms of resistance acquisition at the time of infection in newborns. Patients and Methods We studied HIV-1-infected infants born between 01 January 1997 and 31 December 2004 and enrolled in the ANRS-EPF cohort. HIV-1-RNA and HIV-1-DNA samples obtained perinatally from the newborn and mother were subjected to population-based and clonal analyses of drug resistance. If positive, serial samples were obtained from the child for resistance testing. Results Ninety-two HIV-1-infected infants were born during the study period. Samples were obtained from 32 mother-child pairs and from another 28 newborns. Drug resistance was detected in 12 newborns (20%: drug resistance to nucleoside reverse transcriptase inhibitors was seen in 10 cases, non-nucleoside reverse transcriptase inhibitors in two cases, and protease inhibitors in one case. For 9 children, the detection of the same resistance mutations in mothers' samples (6 among 10 available and in newborn lymphocytes (6/8 suggests that the newborn was initially infected by a drug-resistant strain. Resistance variants were either transmitted from mother-to-child or selected during subsequent temporal exposure under suboptimal perinatal prophylaxis. Follow-up studies of the infants showed that the resistance pattern remained stable over time, regardless of antiretroviral therapy, suggesting the early cellular archiving of resistant viruses. The absence of resistance in the mother of the other three children (3/10 and neonatal lymphocytes (2/8 suggests that the newborns were infected by a wild-type strain without long-term persistence of resistance when suboptimal prophylaxis was stopped. Conclusion This study confirms the importance of early resistance genotyping of HIV-1-infected newborns. In most cases (75%, drug

  9. A modified SILCS contraceptive diaphragm for long-term controlled release of the HIV microbicide dapivirine.

    Science.gov (United States)

    Major, Ian; Boyd, Peter; Kilbourne-Brook, Maggie; Saxon, Gene; Cohen, Jessica; Malcolm, R Karl

    2013-07-01

    There is considerable interest in developing new multipurpose prevention technologies to address women's reproductive health needs. This study describes an innovative barrier contraceptive device--based on the SILCS diaphragm--that also provides long-term controlled release of the lead candidate anti-HIV microbicide dapivirine. Diaphragm devices comprising various dapivirine-loaded polymer spring cores overmolded with a nonmedicated silicone elastomer sheath were fabricated by injection molding processes. In vitro release testing, thermal analysis and mechanical characterization were performed on the devices. A diaphragm device containing a polyoxymethylene spring core loaded with 10% w/w dapivirine provided continuous and controlled release of dapivirine over a 6-month period, with a mean in vitro daily release rate of 174 mcg/day. The mechanical properties of the new diaphragm were closely matched to the SILCS diaphragm. The study demonstrates proof of concept for a dapivirine-releasing diaphragm with daily release quantities potentially capable of preventing HIV transmission. In discontinuous clinical use, release of dapivirine may be readily extended over 1 or more years. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Brief Report: CYP2B6 516G>T Minor Allele Protective of Late Virologic Failure in Efavirenz-Treated HIV-Infected Patients in Botswana.

    Science.gov (United States)

    Vujkovic, Marijana; Bellamy, Scarlett L; Zuppa, Athena F; Gastonguay, Marc; Moorthy, Ganesh S; Ratshaa, Bakgaki R; Han, Xiaoyan; Steenhoff, Andrew P; Mosepele, Mosepele; Strom, Brian L; Aplenc, Richard; Bisson, Gregory P; Gross, Robert

    2017-08-01

    CYP2B6 polymorphisms that affect efavirenz (EFV) concentrations are common, but the effect of this polymorphism on HIV virologic failure in clinical practice settings has not fully been elucidated. Our objective was to investigate the relationship between the CYP2B6 516G>T genotype and late virologic failure in patients treated with EFV in Gaborone, Botswana. We performed a case-control study that included 1338 HIV-infected black Batswana on EFV-based antiretroviral therapy (ART). Patients were approached for enrollment during regular visits at one of the outpatient HIV clinics between July 2013 and April 2014. Cases experienced late HIV failure, defined as plasma HIV RNA >1000 copies/mL after maintaining viral suppression (ART for at least 6 months. Logistic regression was used to determine the adjusted odds of late HIV failure by 516G>T genotype. After adjustment for the confounding variables age and CD4 count, the CYP2B6 516 T-allele was protective against late HIV virologic breakthrough, adjusted OR 0.70; 95% CI: 0.50 to 0.97. The CYP2B6 516 T-allele was protective against late virologic breakthrough in patients with initial (6 month) HIV RNA suppression on EFV-based ART. Future studies are needed to assess long-term viral benefits of identifying and offering EFV containing ART to black African HIV-infected patients with CYP2B6 T-alleles, especially given the wider availability of a single pill EFV in this setting.

  11. The effect of long-term treatment with granulocyte colony-stimulating factor on hematopoiesis in HIV-infected individuals

    DEFF Research Database (Denmark)

    Nielsen, S D; Sørensen, T U; Aladdin, H

    2000-01-01

    This randomized, placebo-controlled trial examine the long-term effect of granulocyte colony-stimulating factor (G-CSF) on absolute numbers of CD34+ progenitor cells and progenitor cell function in human immunodeficiency virus (HIV)-infected patients. G-CSF (300 microg filgrastim) or placebo was ...

  12. Resting-state subcortical functional connectivity in HIV-infected patients on long-term cART

    NARCIS (Netherlands)

    Janssen, M.A.M.; Hinne, M.; Janssen, R.J.; Gerven, M.A.J. van; Steens, S.C.; Góraj, B.M.; Koopmans, P.P.; Kessels, R.P.C.

    2017-01-01

    Despite long-term successful treatment with cART, impairments in cognitive functioning are still being reported in HIV-infected patients. Since changes in cognitive function may be preceded by subtle changes in brain function, neuroimaging techniques, such as resting-state functional magnetic

  13. Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052.

    Directory of Open Access Journals (Sweden)

    Philip J Palumbo

    Full Text Available Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART. We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM assay was used to analyze baseline (pre-treatment HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008. The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

  14. Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052.

    Science.gov (United States)

    Palumbo, Philip J; Wilson, Ethan A; Piwowar-Manning, Estelle; McCauley, Marybeth; Gamble, Theresa; Kumwenda, Newton; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James G; Hosseinipour, Mina C; Melo, Marineide G; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H; Fogel, Jessica M

    2017-01-01

    Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

  15. Long-term hepatitis B virus (HBV response to lamivudine-containing highly active antiretroviral therapy in HIV-HBV co-infected patients in Thailand.

    Directory of Open Access Journals (Sweden)

    Woottichai Khamduang

    Full Text Available Approximately 4 million of people are co-infected with HIV and Hepatitis B virus (HBV. In resource-limited settings, the majority of HIV-infected patients initiate first-line highly active antiretroviral therapy containing lamivudine (3TC-containing-HAART and long-term virological response of HBV to lamivudine-containing HAART in co-infected patients is not well known.HIV-HBV co-infected patients enrolled in the PHPT cohort (ClinicalTrials.gov NCT00433030 and initiating a 3TC-containing-HAART regimen were included. HBV-DNA, HIV-RNA, CD4+ T-cell counts and alanine transaminase were measured at baseline, 3 months, 12 months and then every 6 months up to 5 years. Kaplan-Meier analysis was used to estimate the cumulative rates of patients who achieved and maintained HBV-DNA suppression. Of 30 co-infected patients, 19 were positive for HBe antigen (HBeAg. At initiation of 3TC-containing-HAART, median HBV DNA and HIV RNA levels were 7.35 log(10 IU/mL and 4.47 log(10 copies/mL, respectively. At 12 months, 67% of patients achieved HBV DNA suppression: 100% of HBeAg-negative patients and 47% of HBeAg-positive. Seventy-three percent of patients had HIV RNA below 50 copies/mL. The cumulative rates of maintained HBV-DNA suppression among the 23 patients who achieved HBV-DNA suppression were 91%, 87%, and 80% at 1, 2, and 4 years respectively. Of 17 patients who maintained HBV-DNA suppression while still on 3TC, 4 (24% lost HBsAg and 7 of 8 (88% HBeAg-positive patients lost HBeAg at their last visit (median duration, 59 months. HBV breakthrough was observed only in HBeAg-positive patients and 6 of 7 patients presenting HBV breakthrough had the rtM204I/V mutations associated with 3TC resistance along with rtL180M and/or rtV173L.All HBeAg-negative patients and 63% of HBeAg-positive HIV-HBV co-infected patients achieved long-term HBV DNA suppression while on 3TC-containing-HAART. This study provides information useful for the management of co-infected patients

  16. Predicting long-term outcomes for children affected by HIV and AIDS: perspectives from the scientific study of children's development.

    Science.gov (United States)

    Stein, Alan; Desmond, Christopher; Garbarino, James; Van IJzendoorn, Marinus H; Barbarin, Oscar; Black, Maureen M; Stein, Aryeh D; Hillis, Susan D; Kalichman, Seth C; Mercy, James A; Bakermans-Kranenburg, Marian J; Rapa, Elizabeth; Saul, Janet R; Dobrova-Krol, Natasha A; Richter, Linda M

    2014-07-01

    The immediate and short-term consequences of adult HIV for affected children are well documented. Little research has examined the long-term implications of childhood adversity stemming from caregiver HIV infection. Through overviews provided by experts in the field, together with an iterative process of consultation and refinement, we have extracted insights from the broader field of child development of relevance to predicting the long-term consequences to children affected by HIV and AIDS. We focus on what is known about the impact of adversities similar to those experienced by HIV-affected children, and for which there is longitudinal evidence. Cautioning that findings are not directly transferable across children or contexts, we examine findings from the study of parental death, divorce, poor parental mental health, institutionalization, undernutrition, and exposure to violence. Regardless of the type of adversity, the majority of children manifest resilience and do not experience any long-term negative consequences. However, a significant minority do and these children experience not one, but multiple problems, which frequently endure over time in the absence of support and opportunities for recovery. As a result, they are highly likely to suffer numerous and enduring impacts. These insights suggest a new strategic approach to interventions for children affected by HIV and AIDS, one that effectively combines a universal lattice of protection with intensive intervention targeted to selected children and families.

  17. Factors associated with collagen deposition in lymphoid tissue in long-term treated HIV-infected patients.

    Science.gov (United States)

    Diaz, Alba; Alós, Llúcia; León, Agathe; Mozos, Anna; Caballero, Miguel; Martinez, Antonio; Plana, Montserrat; Gallart, Teresa; Gil, Cristina; Leal, Manuel; Gatell, Jose M; García, Felipe

    2010-08-24

    The factors associated with fibrosis in lymphoid tissue in long-term treated HIV-infected patients and their correlation with immune reconstitution were assessed. Tonsillar biopsies were performed in seven antiretroviral-naive patients and 29 successfully treated patients (median time on treatment, 61 months). Twenty patients received protease inhibitors-sparing regimens and nine protease inhibitor-containing regimens. Five tonsillar resections of HIV-negative individuals were used as controls. Lymphoid tissue architecture, collagen deposition (fibrosis) and the mean interfollicular CD4(+) cell count per mum were assessed. Naive and long-term treated HIV-infected patients had a higher proportion of fibrosis than did HIV-uninfected persons (P lymphoid tissue (P = 0.03) and smaller increase in peripheral CD4(+) T cells (r = -0.40, P = 0.05). The factors independently associated with fibrosis in lymphoid tissue were age (P lymphoid tissue viral load when compared with patients with undetectable lymphoid tissue viral load (median 5 vs. 12%, respectively, P = 0.017) and patients receiving a protease inhibitor-sparing vs. a protease inhibitor-containing regimen (median 8 vs. 2.5%, respectively, P = 0.04). Fibrosis in lymphoid tissue was associated with a poor reconstitution of CD4(+) T cells and long-term antiretroviral therapy did not reverse this abnormality. HIV infection, older age, a detectable level of lymphoid tissue viral load in treated patients and protease inhibitor-sparing regimens seem to favour fibrosis in lymphoid tissue.

  18. Long-Term Changes of Subcutaneous Fat Mass in HIV-Infected Children on Antiretroviral Therapy: A Retrospective Analysis of Longitudinal Data from Two Pediatric HIV-Cohorts

    NARCIS (Netherlands)

    Cohen, Sophie; Innes, Steve; Geelen, Sibyl P. M.; Wells, Jonathan C. K.; Smit, Colette; Wolfs, Tom F. W.; van Eck-Smit, Berthe L. F.; Kuijpers, Taco W.; Reiss, Peter; Scherpbier, Henriette J.; Pajkrt, Dasja; Bunders, Madeleine J.

    2015-01-01

    Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected children in

  19. Long-Term Changes of Subcutaneous Fat Mass in HIV-Infected Children on Antiretroviral Therapy : A Retrospective Analysis of Longitudinal Data from Two Pediatric HIV-Cohorts

    NARCIS (Netherlands)

    Cohen, Sophie; Innes, Steve; Geelen, SPM; Wells, Jonathan C. K.; Smit, Colette; Wolfs, Tom F. W.; van Eck-Smit, Berthe L. F.; Kuijpers, Taco W.; Reiss, Peter; Scherpbier, Henriette J.; Pajkrt, Dasja; Bunders, Madeleine J.

    2015-01-01

    Objective Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected

  20. HIV-associated cognitive performance and psychomotor impairment in a Thai cohort on long-term cART.

    Science.gov (United States)

    Do, Tanya C; Kerr, Stephen J; Avihingsanon, Anchalee; Suksawek, Saowaluk; Klungkang, Supalak; Channgam, Taweesak; Odermatt, Christoph C; Maek-A-Nantawat, Wirach; Ruxtungtham, Kiat; Ananworanich, Jintanat; Valcour, Victor; Reiss, Peter; Wit, Ferdinand W

    2018-01-01

    To assess cognitive performance and psychomotor impairment in an HIV-positive cohort, well-suppressed on combination antiretroviral therapy (cART), in an Asian resource-limited setting. Cross-sectional sociodemographic and cognitive data were collected in 329 HIV-positive and 510 HIV-negative participants. Cognitive performance was assessed using the International HIV Dementia Scale (IHDS), Montreal Cognitive Assessment (MoCA), WAIS-III Digit Symbol, Trail Making A, and Grooved Pegboard (both hands). Psychomotor test scores in the HIV-positive participants were converted to Z-scores using scores of the HIV-negative participants as normative data. Psychomotor impairment was defined as performance on two tests more than 1 standard deviation (SD) from controls or more than 2 SD on one test. Multivariate linear and logistic regression analyses were used to investigate associations between HIV and non-HIV-related covariates and poorer cognitive performance and psychomotor impairment. HIV-positive participants, mean age 45 (SD 7.69) years received cART for a median of 12.1 years (interquartile range [IQR] 9.1-14.4). Median CD4 cell count was 563 cells/mm 3 (IQR 435-725), and 92.77% had plasma HIV RNA performance (tests all P 90% on long-term cART, we found that inferior cognitive performance and psychomotor impairment were primarily associated with non-HIV-related factors.

  1. Prevalence of low bone mineral density among HIV patients on long-term suppressive antiretroviral therapy in resource limited setting of western India.

    Science.gov (United States)

    Dravid, Ameet; Kulkarni, Milind; Borkar, Amit; Dhande, Sachin

    2014-01-01

    Bone mineral density (BMD) assessment in HIV patients is sparsely done in resource limited settings. We conducted a cross-sectional study of BMD amongst HIV patients following up in our clinic from 1 June to 1 December 2013 by performing dual-energy X-ray absorptiometry scan (Lunar Prodigy Advanced DXA System, GE Healthcare) of lumbar spine and hip. Patients on long term (≥12 months), virologically suppressive antiretroviral therapy (ART) were included. Patients who were ART naïve were included as control population. Virologic failures were excluded. Low BMD was defined by WHO T-score criteria (normal: T score ≥-1;osteopenia: T score between -1 and -2.5 SD; osteoporosis: T score ≤-2.5 SD). Baseline risk factors associated with low BMD like age, low BMI, lipoatrophy, diabetes mellitus, current smoking, current alcohol intake, steroid exposure and menopause were recorded. ART-related factors associated with low BMD like ART duration, exposure to tenofovir and exposure to protease inhibitors (PI) were studied. A total of 536 patients (66% males, 496 ART experienced and 40 ART naïve) were included in this analysis. Median age was 42 years, mean BMI 23.35 kg/m(2) and median CD4 count 146 cells/mm(3). All ART experienced patients had plasma viral loadpatients in our cohort is a matter of deep concern due to its association with pathological fractures. Bone mineral loss was seen irrespective of ART used. Association of low BMD with low baseline CD4 count strengthens the case for early ART.

  2. HIV sero-positivity in recently admitted and long-term psychiatric in ...

    African Journals Online (AJOL)

    HIV rapid testing, HIV ELISA, syphilis-RPR and TPHA testing were performed. Results: The HIV prevalence of 11% in the sample was significantly associated with 'gender-and-duration-of-admission' categories (p=0.003). No significant association between HIV infection and psychiatric diagnoses or intravenous drug use ...

  3. Long-Term Effect of HAART on Biochemical Profiles of HIV/AIDS ...

    African Journals Online (AJOL)

    Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. ... Purpose: To assess the long-term effect of highly active antiretroviral therapy (HAART) on .... allowed to clot at room temperature for 45 min.

  4. Long term adverse drug reaction to Efavirenz in a HIV infected ...

    African Journals Online (AJOL)

    Arun Kumar Agnihotri

    2015-08-31

    Aug 31, 2015 ... presented with five-day history of Difficulty sleeping, abnormal dreams, inability to ... He regained his memory, no longer had bad dreams or demonstrated any irrational .... concentration of Efavirenz on long term. Efavirenz ...

  5. Long-term effectiveness of highly active antiretroviral therapy (HAART) in perinatally HIV-infected children in Denmark

    DEFF Research Database (Denmark)

    Bracher, Linda; Valerius, Niels Henrik; Rosenfeldt, Vibeke

    2007-01-01

    children treated with HAART. Initial HAART included 2 nucleoside reverse-transcriptase inhibitors in combination with either a protease inhibitor (n =38) or a non-nucleoside reverse-transcriptase inhibitor (n =12). 19 (39%) patients were previously treated with mono- or dual therapy. Baseline......The long-term impact of highly active antiretroviral therapy (HAART) on HIV-1 infected children is not well known. The Danish Paediatric HIV Cohort Study includes all patients ... characteristics were median CD4 percentage 14% and HIV-RNA viral load 4.9 log(10). Within the first 12 weeks of therapy approximately 60% achieved HIV-RNA viral load children changed the components of HAART. The proportion of children with CD4...

  6. Impact of long-term civil disorders and wars on the trajectory of HIV epidemics in sub-Saharan Africa.

    Science.gov (United States)

    Gisselquist, David

    2004-08-01

    From the mid-1970s, seven countries in sub-Saharan Africa have experienced civil disorders and wars lasting for at least 10 years. In two-- Sierra Leone during 1991-2002, and Somalia from 1988 and continuing--adult HIV prevalence remained below 1%. In the Democratic Republic of the Congo, HIV prevalence appears to have stabilised during post-1991 civil disorder and war. Limited information from Angola (civil war 1975 -2002) and Liberia (civil disorder and war from 1989 and continuing) suggests low HIV prevalence. Mozambique's HIV prevalence was near 1% after its 1975 - 1992 civil war, but increased dramatically in the first post-war decade. Across African countries with long-term wars, HIV seems to have spread more slowly than in most neighbouring countries at peace. This evidence contributes to the ongoing debate about the factors that explain differential epidemic trajectories, a debate which is crucial to the design of HIV prevention programmes. One possible explanation for slow epidemic growth in wartime is that unsterile health care accounts for an important proportion of HIV transmission during peacetime, but much less when wars disrupt health services. However, other explanations are also possible. The roles of sex and blood exposures in HIV epidemics in war and peace await empirical determination.

  7. The impact of nevirapine- versus protease inhibitor-based regimens on virological markers of HIV-1 persistence during seemingly suppressive ART.

    Science.gov (United States)

    Kiselinova, Maja; Anna, Maria; Malatinkova, Eva; Vervish, Karen; Beloukas, Apostolos; Messiaen, Peter; Bonczkowski, Pawel; Trypsteen, Wim; Callens, Steven; Verhofstede, Chris; De Spiegelaere, Ward; Vandekerckhove, Linos

    2014-01-01

    The source and significance of residual plasma HIV-1 RNA detection during suppressive ART remain controversial. It has been proposed that nevirapine (NVP)-based regimens achieve a greater HIV-1 RNA suppression than regimens containing a protease inhibitor (PI). The aim of this study was to compare the effect of receiving NVP- vs PI-based ART on the virological markers of HIV persistence in peripheral blood. The study population comprised 161 HIV-1 infected patients receiving either NVP-based (n=81) or PI-based (n=80) ART and showing a HIV-1 RNA load stably suppressed ART, with median (IQR) levels of 5 (3-6) and 5 (3-8) copies/mL, respectively. HIV-1 RNA detection was associated with shorter duration of suppressive ART regardless of treatment arm (p=0.007), and lower CD4 nadir (p=0.015). HIV-1 DNA levels were median 282 (120-484) and 213 (87-494) copies/106 PBMCs in the two groups respectively, and were lowest (ART HIV-1 RNA load (p=0.0001). In this comprehensive characterization of patients on long-term suppressive ART, we did not observe evidence for a greater suppressive activity of NVP-based over PI-based therapy on plasma and intracellular markers of virus persistence. Overall excellent correlation was observed between the markers, allowing the identification of a subset of treated patients with low HIV-1 expression as an important cohort for future HIV cure studies.

  8. Comparison of HIV-1 genotypic resistance test interpretation systems in predicting virological outcomes over time

    NARCIS (Netherlands)

    D. Frentz (Dineke); C.A.B. Boucher (Charles); M. Assel (Matthias); A. de Luca (Andrea); M. Fabbiani (Massimiliano); F. Incardona (Francesca); P. Libin (Pieter); N. Manca (Nino); V. Müller (Viktor); B.O. Nualláin (Breanndán); R. Paredes (Roger); M. Prosperi (Mattia); E. Quiros-Roldan (Eugenia); L. Ruiz (Lidia); P.M.A. Sloot (Peter); C. Torti (Carlo); A.M. Vandamme (Anne Mieke); K. Laethem (Kristel); M. Zazzi (Maurizio); D.A.M.C. van de Vijver (David)

    2010-01-01

    textabstractBackground: Several decision support systems have been developed to interpret HIV-1 drug resistance genotyping results. This study compares the ability of the most commonly used systems (ANRS, Rega, and Stanford's HIVdb) to predict virological outcome at 12, 24, and 48 weeks.

  9. Risk factors of virologic failure and slow response to art among HIV ...

    African Journals Online (AJOL)

    Risk factors of virologic failure and slow response to art among HIV-infected children and adolescents in Nairobi. J. M. Kabogo, S. Gupta, A. K. Maina, M. Ochwoto, R. W. Omange, R. N. Musoke, R. W. Lihana, E. Muniu, F. W. Wamunyokoli, B. Liang, E. M. Songok ...

  10. Clinical outcomes of elite controllers, viremic controllers, and long-term nonprogressors in the US Department of Defense HIV natural history study.

    Science.gov (United States)

    Okulicz, Jason F; Marconi, Vincent C; Landrum, Michael L; Wegner, Scott; Weintrob, Amy; Ganesan, Anuradha; Hale, Braden; Crum-Cianflone, Nancy; Delmar, Judith; Barthel, Vincent; Quinnan, Gerald; Agan, Brian K; Dolan, Matthew J

    2009-12-01

    Durable control of human immunodeficiency virus (HIV) replication and lack of disease progression in the absence of antiretroviral therapy were studied in a military cohort of 4586 subjects. We examined groups of elite controllers (ie, subjects with plasma HIV RNA levels of <50 copies/mL; prevalence, 0.55% [95% confidence interval {CI}, 0.35%-0.80%]), viremic controllers (ie, subjects with plasma HIV RNA levels of 50-2000 copies/mL; prevalence, 3.34% [95% CI, 2.83%-3.91%]), and subjects with a lack of disease progression (ie, long-term nonprogressors [LTNPs]) through 7 years of follow-up (LTNP7s; prevalence, 3.32% [95% CI, 2.70%-4.01%]) or 10 years of follow-up (LTNP10s; prevalence, 2.04% [95% CI, 1.52%-2.68%]). For elite and viremic controllers, spontaneous virologic control was established early and was typically observed when the initial viral load measurement was obtained within 1 year of estimated seroconversion. Elite controllers had favorable time to development of AIDS (P=.048), a CD4 cell count of 350 cells/microL (P= .009), and more-stable CD4 cell trends, compared with viremic controllers. LTNPs defined by 10-year versus 7-year criteria had a longer survival time (P=.001), even after adjustment for differing periods of invulnerability (P= .042). Definitions of controllers and LTNPs describe distinct populations whose differing clinical outcomes improve with the stringency of criteria, underscoring the need for comparability between study populations.

  11. Resting regulatory CD4 T cells: a site of HIV persistence in patients on long-term effective antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Tu-Anh Tran

    Full Text Available BACKGROUND: In HIV-infected patients on long-term HAART, virus persistence in resting long-lived CD4 T cells is a major barrier to curing the infection. Cell quiescence, by favouring HIV latency, reduces the risk of recognition and cell destruction by cytotoxic lymphocytes. Several cell-activation-based approaches have been proposed to disrupt cell quiescence and then virus latency, but these approaches have not eradicated the virus. CD4+CD25+ regulatory T cells (Tregs are a CD4+ T-cell subset with particular activation properties. We investigated the role of these cells in virus persistence in patients on long-term HAART. METHODOLOGY/PRINCIPAL FINDINGS: We found evidence of infection of resting Tregs (HLADR(-CD69(-CD25(hiFoxP3+CD4+ T cells purified from patients on prolonged HAART. HIV DNA harbouring cells appear more abundant in the Treg subset than in non-Tregs. The half-life of the Treg reservoir was estimated at 20 months. Since Tregs from patients on prolonged HAART showed hyporesponsiveness to cell activation and inhibition of HIV-specific cytotoxic T lymphocyte-related functions upon activation, therapeutics targeting cell quiescence to induce virus expression may not be appropriate for purging the Treg reservoir. CONCLUSIONS: Our results identify Tregs as a particular compartment within the latent reservoir that may require a specific approach for its purging.

  12. Loss of long term protection with the inclusion of HIV pol to a DNA vaccine encoding gag.

    Science.gov (United States)

    Garrod, Tamsin J; Gargett, Tessa; Yu, Wenbo; Major, Lee; Burrell, Christopher J; Wesselingh, Steven; Suhrbier, Andreas; Grubor-Bauk, Branka; Gowans, Eric J

    2014-11-04

    Traditional vaccine strategies that induce antibody responses have failed to protect against HIV infection in clinical trials, and thus cell-mediated immunity is now an additional criterion. Recent clinical trials that aimed to induce strong T cell responses failed to do so. Therefore, to enhance induction of protective T cell responses, it is crucial that the optimum antigen combination is chosen. Limited research has been performed into the number of antigens selected for an HIV vaccine. This study aimed to compare DNA vaccines encoding either a single HIV antigen or a combination of two antigens, using intradermal vaccination of C57BL/6 mice. Immune assays were performed on splenocytes, and in vivo protection was examined by challenge with a chimeric virus, EcoHIV, able to infect mouse but not human leukocytes, at 10 days (short term) and 60 days (long term) post final vaccination. At 60 days there was significantly lower frequency of induced antigen-specific CD8(+) T cells in the spleens of pCMVgag-pol-vaccinated mice compared with mice which received pCMVgag only. Most importantly, short term viral control of EcoHIV was similar for pCMVgag and pCMVgag-pol-vaccinated mice at day 10, but only the pCMVgag-vaccinated significantly controlled EcoHIV at day 60 compared with pCMV-vaccinated mice, showing that control was reduced with the inclusion of the HIV pol gene. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Long Term Follow-up of HIV-1 Exposed Children in Nairobi

    International Nuclear Information System (INIS)

    Ndinya-Achola, J.O; Datta, P.; Maitha, G.; Embree, J.E.; Kreiss, J.K.; Achola, P.S.; Holmes, K.K.; Plummer, F.A.

    1992-01-01

    Transmission of HIV-1 from an infected mother to her infant is the major route of transmission of this infection to children. In sub-Saharan Africa where heterosexual transmission of HIV is the commonest mode of spread, high prevalence of HIV infection in women of child bearing age is bound to lead to increased paediatric AIDS as a result of vertical transmission. In recognizing these epidemiological factors, the University of Nairobi HIV-1 Perinatal Transmission and Paediatric AIDS Project was initiated in 1986. Antenatal mothers attending Pumwani Maternity Hospital were enrolled during labour and screened for HIV-1 infection by ELISA. Those reacting positive were to participate in the study. An equal number of negative controls were also recruited. The mothers and babies of both groups were followed for varying periods over the next five years. A total of 360 babies born to HIV infected mothers and 360 babies born to HIV negative mothers were examined. The mortality rate observed in the HIV-1 exposed was substantially higher than that observed in controls (RR 2.8, 95% CI 1.3-6.1). Common causes of death among infected infants were pneumonia, measles, malaria, gastroenteritis, tuberculosis, and septicaemia. The five year survival was 85% among HIV infected children. Maternal risk factors associated with transmission were marital status, duration of sexual activity and the age of the first intercourse

  14. Long Term Follow-up of HIV-1 Exposed Children in Nairobi

    Energy Technology Data Exchange (ETDEWEB)

    Ndinya-Achola, J O; Datta, P; Maitha, G [Department of Microbiology, University of Nairobi, (Kenya); Embree, J E; Kreiss, J K; Achola, P S [Health Department, Nairobi City Commission, Nairobi, (Kenya); Holmes, K K [Dept. of Medicine, Harboview Medical Centre, University of Washington, Seattle (United States); Plummer, F A [Dept. of Medical Microbiology, University of Manitoba (Canada)

    1992-05-15

    Transmission of HIV-1 from an infected mother to her infant is the major route of transmission of this infection to children. In sub-Saharan Africa where heterosexual transmission of HIV is the commonest mode of spread, high prevalence of HIV infection in women of child bearing age is bound to lead to increased paediatric AIDS as a result of vertical transmission. In recognizing these epidemiological factors, the University of Nairobi HIV-1 Perinatal Transmission and Paediatric AIDS Project was initiated in 1986. Antenatal mothers attending Pumwani Maternity Hospital were enrolled during labour and screened for HIV-1 infection by ELISA. Those reacting positive were to participate in the study. An equal number of negative controls were also recruited. The mothers and babies of both groups were followed for varying periods over the next five years. A total of 360 babies born to HIV infected mothers and 360 babies born to HIV negative mothers were examined. The mortality rate observed in the HIV-1 exposed was substantially higher than that observed in controls (RR 2.8, 95% CI 1.3-6.1). Common causes of death among infected infants were pneumonia, measles, malaria, gastroenteritis, tuberculosis, and septicaemia. The five year survival was 85% among HIV infected children. Maternal risk factors associated with transmission were marital status, duration of sexual activity and the age of the first intercourse.

  15. Impact of long-term viral suppression in CD4+ recovery of HIV-children on Highly Active Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Gurbindo-Gutierrez Dolores

    2006-01-01

    Full Text Available Abstract Background The effects of HAART may differ between children and adults because children have a developing immune system, and the long-term immunological outcome in HIV-infected children on HAART is not well-known. A major aim of our study was to determine CD4+ evolution associated with long-term VL control during 4 years of observation on HAART. Methods We carried out a retrospective study on a cohort of 160 vertically HIV-infected children. It was carried out from 1996 to 2004 in six large Spanish pediatric referral hospitals. We compared 33 children who had long-term VL suppression (VL ≤400 copies/ml in the first 12 months of follow-up and maintained that level throughout follow-up (Responders-group, and 127 children with persistently detectable VL in spite of ART switches (Non-Responders-group. Results We observed a quick initial and significant increase in CD4+ counts from the baseline to 12 months on HAART in both groups (p Non-Responders group sustained CD4+ increases and most of these children maintained high CD4+ level counts (≥25%. The Non-Responders group reached a plateau between 26% and 27% CD4+ at the first 12 months of follow-up that remained stable during the following 3 years. However, the Responders group reached a plateau between 30% and 32% CD4+ at 24, 36 and 48 months of follow-up. We found that the Responders group had higher CD4+ count values and higher percentages of children with CD4+ ≥25% than the Non-Responders group (p Conclusion Long-term VL suppression in turn induces large beneficial effects in immunological responses. However, it is not indispensable to recover CD4+ levels.

  16. Long-term financing needs for HIV control in sub-Saharan Africa in 2015–2050: a modelling study

    Science.gov (United States)

    Atun, Rifat; Chang, Angela Y; Ogbuoji, Osondu; Silva, Sachin; Resch, Stephen; Hontelez, Jan; Bärnighausen, Till

    2016-01-01

    Objectives To estimate the present value of current and future funding needed for HIV treatment and prevention in 9 sub-Saharan African (SSA) countries that account for 70% of HIV burden in Africa under different scenarios of intervention scale-up. To analyse the gaps between current expenditures and funding obligation, and discuss the policy implications of future financing needs. Design We used the Goals module from Spectrum, and applied the most up-to-date cost and coverage data to provide a range of estimates for future financing obligations. The four different scale-up scenarios vary by treatment initiation threshold and service coverage level. We compared the model projections to current domestic and international financial sources available in selected SSA countries. Results In the 9 SSA countries, the estimated resources required for HIV prevention and treatment in 2015–2050 range from US$98 billion to maintain current coverage levels for treatment and prevention with eligibility for treatment initiation at CD4 count of <500/mm3 to US$261 billion if treatment were to be extended to all HIV-positive individuals and prevention scaled up. With the addition of new funding obligations for HIV—which arise implicitly through commitment to achieve higher than current treatment coverage levels—overall financial obligations (sum of debt levels and the present value of the stock of future HIV funding obligations) would rise substantially. Conclusions Investing upfront in scale-up of HIV services to achieve high coverage levels will reduce HIV incidence, prevention and future treatment expenditures by realising long-term preventive effects of ART to reduce HIV transmission. Future obligations are too substantial for most SSA countries to be met from domestic sources alone. New sources of funding, in addition to domestic sources, include innovative financing. Debt sustainability for sustained HIV response is an urgent imperative for affected countries and donors

  17. Factors associated with HIV-1 virological failure in an outpatient clinic for HIV-infected people in Haiphong, Vietnam

    DEFF Research Database (Denmark)

    Huong, D T M; Bannister, W; Phong, P T

    2011-01-01

    starting ART, 23% had detectable HIV-1 viral load (= 400 copies/mL). Patients who had developed a World Health Organization (WHO) clinical stage 4 condition at the time of initiation of ART were more likely to experience virological failure than those in stages 1-3, odds ratio (OR): 5.20 (95% confidence...

  18. Astrocytes sustain long-term productive HIV-1 infection without establishment of reactivable viral latency.

    Science.gov (United States)

    Barat, Corinne; Proust, Alizé; Deshiere, Alexandre; Leboeuf, Mathieu; Drouin, Jean; Tremblay, Michel J

    2018-02-21

    The "shock and kill" HIV-1 cure strategy proposes eradication of stable cellular reservoirs by clinical treatment with latency-reversing agents (LRAs). Although resting CD4 + T cells latently infected with HIV-1 constitute the main reservoir that is targeted by these approaches, their consequences on other reservoirs such as the central nervous system are still unknown and should be taken into consideration. We performed experiments aimed at defining the possible role of astrocytes in HIV-1 persistence in the brain and the effect of LRA treatments on this viral sanctuary. We first demonstrate that the diminished HIV-1 production in a proliferating astrocyte culture is due to a reduced proliferative capacity of virus-infected cells compared with uninfected astrocytes. In contrast, infection of non-proliferating astrocytes led to a robust HIV-1 infection that was sustained for over 60 days. To identify astrocytes latently infected with HIV-1, we designed a new dual-color reporter virus called NL4.3 eGFP-IRES-Crimson that is fully infectious and encodes for all viral proteins. Although we detected a small fraction of astrocytes carrying silent HIV-1 proviruses, we did not observe any reactivation using various LRAs and even strong inducers such as tumor necrosis factor, thus suggesting that these proviruses were either not transcriptionally competent or in a state of deep latency. Our findings imply that astrocytes might not constitute a latent reservoir per se but that relentless virus production by this brain cell population could contribute to the neurological disorders seen in HIV-1-infected persons subjected to combination antiretroviral therapy. © 2018 Wiley Periodicals, Inc.

  19. Development of 5' LTR DNA methylation of latent HIV-1 provirus in cell line models and in long-term-infected individuals

    Czech Academy of Sciences Publication Activity Database

    Trejbalová, K.; Kovářová, D.; Blažková, J.; Machala, L.; Jilich, D.; Weber, Jan; Kučerová, D.; Vencálek, O.; Hirsch, Ivan; Hejnar, J.

    2016-01-01

    Roč. 8, Feb 19 (2016), č. článku 19. ISSN 1868-7083 Institutional support: RVO:61388963 Keywords : HIV-1 * latent reservoir * DNA methylation * chromatin conformation * latent HIV-1 provirus reactivation * HIV-1-infected individuals Subject RIV: EE - Microbiology, Virology Impact factor: 4.987, year: 2016 http://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-016-0185-6

  20. Associations between HIV-RNA-based indicators and virological and clinical outcomes

    DEFF Research Database (Denmark)

    Laut, Kamilla G; Shepherd, Leah C; Pedersen, Court

    2016-01-01

    OBJECTIVES: To evaluate and compare the performance of six HIV-RNA-based quality of care indicators for predicting short-term and long-term outcomes. DESIGN: Multinational cohort study. METHODS: We included EuroSIDA patients on antiretroviral therapy (ART) with at least three viral load measureme......OBJECTIVES: To evaluate and compare the performance of six HIV-RNA-based quality of care indicators for predicting short-term and long-term outcomes. DESIGN: Multinational cohort study. METHODS: We included EuroSIDA patients on antiretroviral therapy (ART) with at least three viral load...... measurements after baseline (the latest of 01/01/2001 or entry into EuroSIDA). Using multivariate Poisson regression, we modelled the association between short-term (resistance, triple-class failure) and long-term (all-cause mortality, any AIDS/non-AIDS clinical event) outcomes and the indicators: viraemia...

  1. Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

    DEFF Research Database (Denmark)

    Chereau, Fanny; Madec, Yoann; Sabin, Caroline

    2017-01-01

    OBJECTIVE: HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control. MET...

  2. Postpartum Engagement in HIV Care: An Important Predictor of Long-term Retention in Care and Viral Suppression.

    Science.gov (United States)

    Adams, Joëlla W; Brady, Kathleen A; Michael, Yvonne L; Yehia, Baligh R; Momplaisir, Florence M

    2015-12-15

    Human immunodeficiency virus (HIV)-infected women are at risk of virologic failure postpartum. We evaluated factors influencing retention in care and viral suppression in postpartum HIV-infected women. We conducted a retrospective cohort analysis (2005-2011) of 695 deliveries involving 561 HIV-infected women in Philadelphia. Multivariable logistic regression evaluated factors, including maternal age, race/ethnicity, substance use, antiretroviral therapy during pregnancy, timing of HIV diagnosis, previous pregnancy with HIV, adequacy of prenatal care, and postpartum HIV care engagement (≥ 1 CD4 count or viral load [VL] test within 90 days of delivery), associated with retention in care (≥ 1 CD4 count or VL test in each 6-month interval of the period with ≥ 60 days between tests) and viral suppression (VL ≤ 200 copies/mL at the last measure in the period) at 1 and 2 years postpartum. Overall, 38% of women engaged in HIV care within 90 days postpartum; with 39% and 31% retained in care and virally suppressed, respectively, at 1 year postpartum, and 25% and 34% retained in care and virally suppressed, respectively, at 2 years postpartum. In multivariable analyses, women who engaged in HIV care within 90 days of delivery were more likely to be retained (adjusted odds ratio [AOR], 11.38; 95% confidence interval [CI], 7.74-16.68) and suppressed (AOR, 2.60 [95% CI, 1.82-3.73]) at 1 year postpartum. This association persisted in the second year postpartum for both retention (AOR, 6.19 [95% CI, 4.04-9.50]) and suppression (AOR, 1.40 [95% CI, 1.01-1.95]). The prevalence of postpartum HIV-infected women retained in care and maintaining viral suppression is low. Interventions seeking to engage women in care shortly after delivery have the potential to improve clinical outcomes. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Clinical, Virologic, Immunologic Outcomes and Emerging HIV Drug Resistance Patterns in Children and Adolescents in Public ART Care in Zimbabwe.

    Directory of Open Access Journals (Sweden)

    A T Makadzange

    Full Text Available To determine immunologic, virologic outcomes and drug resistance among children and adolescents receiving care during routine programmatic implementation in a low-income country.A cross-sectional evaluation with collection of clinical and laboratory data for children (0-<10 years and adolescents (10-19 years attending a public ART program in Harare providing care for pediatric patients since 2004, was conducted. Longitudinal data for each participant was obtained from the clinic based medical record.Data from 599 children and adolescents was evaluated. The participants presented to care with low CD4 cell count and CD4%, median baseline CD4% was lower in adolescents compared with children (11.0% vs. 15.0%, p<0.0001. The median age at ART initiation was 8.0 years (IQR 3.0, 12.0; median time on ART was 2.9 years (IQR 1.7, 4.5. On ART, median CD4% improved for all age groups but remained below 25%. Older age (≥ 5 years at ART initiation was associated with severe stunting (HAZ <-2: 53.3% vs. 28.4%, p<0.0001. Virologic failure rate was 30.6% and associated with age at ART initiation. In children, nevirapine based ART regimen was associated with a 3-fold increased risk of failure (AOR: 3.5; 95% CI: 1.3, 9.1, p = 0.0180. Children (<10 y on ART for ≥4 years had higher failure rates than those on ART for <4 years (39.6% vs. 23.9%, p = 0.0239. In those initiating ART as adolescents, each additional year in age above 10 years at the time of ART initiation (AOR 0.4 95%CI: 0.1, 0.9, p = 0.0324, and each additional year on ART (AOR 0.4, 95%CI 0.2, 0.9, p = 0.0379 were associated with decreased risk of virologic failure. Drug resistance was evident in 67.6% of sequenced virus isolates.During routine programmatic implementation of HIV care for children and adolescents, delayed age at ART initiation has long-term implications on immunologic recovery, growth and virologic outcomes.

  4. Virologic And Immunologic Outcome Of Treatment Of Hiv ...

    African Journals Online (AJOL)

    This study was to determine the effectiveness (CD4 count and viral load) of a safe herbal concoction, a-Zam used by clients seeking herbal remedy for treatment of HIV infection in Nigeria. 51 patients taking a-Zam as complementary and alternative therapy through the herbal therapist were studied for a period of 16 months.

  5. Long-term foscarnet therapy remodels thymidine analogue mutations and alters resistance to zidovudine and lamivudine in HIV-1

    DEFF Research Database (Denmark)

    Mathiesen, Sofie; Dam, Elisabeth; Roge, Birgit

    2007-01-01

    OBJECTIVE: To study the evolution of multi-drug-resistant HIV-1 in treatment-experienced patients receiving foscarnet (PFA) as part of salvage therapy and to investigate the virological consequences of emerging mutations. METHODS: Genotypic and phenotypic resistance tests were performed on plasma...... viruses from seven patients at baseline and during treatment with PFA. The phenotypic effects of mutations suspected to be associated with PFA resistance were evaluated by site-directed mutagenesis of wild-type or thymidine analogue mutations (TAM)-carrying pNL4-3. Reversion of single mutations...... was performed in a patient-derived recombinant clone. RESULTS: Baseline multi-drug-resistant isolates exhibited hypersusceptibility to PFA. In two patients who received > 12 months of PFA treatment, a novel mutation pattern including K70G, V75T, K219R and L228R emerged. These viruses had 3-6-fold resistance...

  6. Influence of transportation cost on long-term retention in clinic for HIV patients in rural Haiti.

    Science.gov (United States)

    Sowah, Leonard A; Turenne, Franck V; Buchwald, Ulrike K; Delva, Guesly; Mesidor, Romaine N; Dessaigne, Camille G; Previl, Harold; Patel, Devang; Edozien, Anthony; Redfield, Robert R; Amoroso, Anthony

    2014-12-01

    With improved access to antiretroviral therapy in resource-constrained settings, long-term retention in HIV clinics has become an important means of reducing costs and improving outcomes. Published data on retention in HIV clinics beyond 24 months are, however, limited. In our clinic in rural Haiti, we hypothesized that individuals residing in locations with higher transportation costs to clinic would have poorer retention than those who had lower costs. We used a retrospective cohort design to evaluate potential predictors of HIV clinic retention. Patient information was abstracted from the electronic medical records. Cox proportional hazards regression was used to identify independent predictors of 4-year clinic retention. There were 410 patients in our cohort, 266 (64.9%) females and 144 (35.1%) males. Forty-five (11%) patients lived in locations with transportation costs >$2. Males were 1.5 times more likely to live in municipalities with transportation costs to clinic of >$2. Multivariate analysis suggested that age transportation cost were independent predictors of loss to follow-up (LTFU): risk ratio of 2.98, 95% confidence interval (CI): 1.73 to 4.96, P transportation costs greater than $2 were 1.9 times more likely to be lost to care compared with those who paid less for transportation. HIV treatment programs in resource-constrained settings may need to pay closer attention to issues related to transportation cost to improve patient retention.

  7. Long-term results after cardiac surgery in patients infected with the human immunodeficiency virus type-1 (HIV-1).

    Science.gov (United States)

    Mestres, Carlos A; Chuquiure, Javier E; Claramonte, Xavier; Muñoz, Josefa; Benito, Natividad; Castro, Miguel A; Pomar, José L; Miró, José M

    2003-06-01

    Assessment of long-term results of immunodeficiency virus type-1 (HIV-1)-infected patients undergoing cardiac surgery. Retrospective analysis of profile and outcomes of 31 HIV-1-infected patients (35 operations, 1985-2002). Twenty-seven males and four females (mean age 34.67) in three groups: acute infective endocarditis (AIE) 21 (67.74%), coronary (CAD) 5 (16.13%) and non-infective valvular disease (NIVD) 5 (16.13%). HIV factors: drug addiction (23-74.19%), homosexuality (5-16.12%), heterosexuality (3-9.67%), hemodialysis (1-3.22%). HIV stage: A (17), B (2), C (2) in AIE; A (2), B (3) in CAD and A (3), C (2) in NIVD. Mean preoperative CD4 count was 278 cells/microL (12infected patients requiring cardiac surgery, a decrease in AIE, however NIVD and CAD increasingly seen. Cardiac surgery did not blunt CD4 response induced by antiretrovirals. The late cause of death were not AIDS-related events.

  8. Long-term financing needs for HIV control in sub-Saharan Africa in 2015-2050: a modelling study.

    Science.gov (United States)

    Atun, Rifat; Chang, Angela Y; Ogbuoji, Osondu; Silva, Sachin; Resch, Stephen; Hontelez, Jan; Bärnighausen, Till

    2016-03-06

    To estimate the present value of current and future funding needed for HIV treatment and prevention in 9 sub-Saharan African (SSA) countries that account for 70% of HIV burden in Africa under different scenarios of intervention scale-up. To analyse the gaps between current expenditures and funding obligation, and discuss the policy implications of future financing needs. We used the Goals module from Spectrum, and applied the most up-to-date cost and coverage data to provide a range of estimates for future financing obligations. The four different scale-up scenarios vary by treatment initiation threshold and service coverage level. We compared the model projections to current domestic and international financial sources available in selected SSA countries. In the 9 SSA countries, the estimated resources required for HIV prevention and treatment in 2015-2050 range from US$98 billion to maintain current coverage levels for treatment and prevention with eligibility for treatment initiation at CD4 count of <500/mm(3) to US$261 billion if treatment were to be extended to all HIV-positive individuals and prevention scaled up. With the addition of new funding obligations for HIV--which arise implicitly through commitment to achieve higher than current treatment coverage levels--overall financial obligations (sum of debt levels and the present value of the stock of future HIV funding obligations) would rise substantially. Investing upfront in scale-up of HIV services to achieve high coverage levels will reduce HIV incidence, prevention and future treatment expenditures by realising long-term preventive effects of ART to reduce HIV transmission. Future obligations are too substantial for most SSA countries to be met from domestic sources alone. New sources of funding, in addition to domestic sources, include innovative financing. Debt sustainability for sustained HIV response is an urgent imperative for affected countries and donors. Published by the BMJ Publishing Group

  9. HIV/AIDS status disclosure increases support, behavioural change and, HIV prevention in the long term: a case for an Urban Clinic, Kampala, Uganda.

    Science.gov (United States)

    Atuyambe, Lynn Muhimbuura; Ssegujja, Eric; Ssali, Sarah; Tumwine, Christopher; Nekesa, Nicolate; Nannungi, Annette; Ryan, Gery; Wagner, Glenn

    2014-06-21

    Disclosure of HIV status supports risk reduction and facilitates access to prevention and care services, but can be inhibited by the fear of negative repercussions. We explored the short and long-term outcomes of disclosure among clients attending an urban HIV clinic in Uganda. Qualitative semi-structured interviews were administered to a purposeful sample of 40 adult HIV clients that was stratified by gender. The information elicited included their lived experiences and outcomes of disclosure in the short and long term. A text data management software (ATLAS.ti) was used for data analysis. Codes were exported to MS Excel and pivot tables, and code counts made to generate statistical data. Of the 134 short-term responses elicited during the interview regarding disclosure events, most responses were supportive including encouragement, advice and support regarding HIV care and treatment. The results show on-disclosing to spouse, there was more trust, and use of condoms for HIV prevention. Only one third were negative responses, like emotional shock and feeling of distress. The negative reactions to the spouses included rejection, shock and distress in the short term. Even then, none of these events led to drastic change such as divorce. Other responses reflected HIV prevention and call for behavioural change and advice to change sexual behaviour, recipient seeking HIV testing or care. Women reported more responses of encouragement compared to men. Men reported more preventive behaviour compared to women. Of the 137 long-term outcomes elicited during disclosure, three quarters were positive followed by behavioral change and prevention, and then negative responses. Men reported increased care and support when they disclosed to fellow men compared to when women disclosed to women. There was better or not change in relationship when women disclosed to women than when women disclosed to men. There is overwhelming support to individuals that disclose their HIV status

  10. Long-term outcomes of oral rehabilitation with dental implants in HIV-positive patients: A retrospective case series.

    Science.gov (United States)

    Gay-Escoda, C; Pérez-Álvarez, D; Camps-Font, O; Figueiredo, R

    2016-05-01

    The existing information on oral rehabilitations with dental implants in VIH-positive patients is scarce and of poor quality. Moreover, no long-term follow-up studies are available. Hence, the aims of this study were to describe the long-term survival and success rates of dental implants in a group of HIV-positive patients and to identify the most common postoperative complications, including peri-implant diseases. A retrospective case series of HIV-positive subjects treated with dental implants at the School of Dentistry of the University of Barcelona (Spain) was studied. Several clinical parameters were registered, including CD4 cell count, viral load and surgical complications. Additionally, the patients were assessed for implant survival and success rates and for the prevalence of peri-implant diseases. A descriptive statistical analysis of the data was performed. Nine participants (57 implants) were included. The patients' median age was 42 years (IQR=13.5 years). The implant survival and success rates were 98.3% and 68.4%, respectively, with a mean follow-up of 77.5 months (SD=16.1 months). The patient-based prevalence of peri-implant mucositis and peri-implantitis were 22.2% and 44.4% respectively at the last appointment. Patients that attended regular periodontal maintenance visits had significantly less mean bone loss than non-compliant patients (1.3 mm and 3.9 mm respectively). Oral rehabilitation with dental implants in HIV-positive patients seems to provide satisfactory results. In order to reduce the considerably high prevalence of peri-implant diseases, strict maintenance programmes must be implemented.

  11. Disability and Living with HIV: Baseline from a Cohort of People on Long Term ART in South Africa.

    Science.gov (United States)

    Hanass-Hancock, Jill; Myezwa, Hellen; Carpenter, Bradley

    2015-01-01

    Through access to life saving antiretroviral treatment (ART) in southern Africa, HIV has been reconceptualised as a chronic disease. This comes with new challenges of HIV-related co-morbidities and disabilities. We still lack an understanding of the types and scope of disabilities experienced by people on long term ART and how this impacts health, adherence, and livelihood. This paper describes the results of a cohort study examining the new health- and disability-related needs of the millions of people on ART in the region. Data was collected from a cohort of people who had been on ART for six months or longer in a semi-urban public health care setting in South Africa. 1042 adults (18 and older) participated in the cross-sectional study which investigated disabilities/activity limitations, health, ART adherence, depression symptoms, and livelihood. We analysed the associations between these constructs using descriptive statistics, and bivariate and multivariate analyses. A large number of participants (35.5%) obtained a weighted score of two or more on the WHODAS 2.0 indicating possible activity limitations. A positive relationship was found between activity limitations and depression symptoms, adherence, and worse health outcomes, while none was found for BMI or CD4 count. These associations varied by type of activity limitations and, in some cases, by gender. Activity limitations are potentially experienced by a large portion of people on ART in southern Africa which impacts health and ART adherence negatively. These results highlight the importance of better understanding the new health-related needs of people who are on long term ART, as well as the nuances of the disability they experience. This is urgently needed in order to enable HIV-endemic countries to better prepare for the new health-related needs of the millions of people on ART in southern Africa.

  12. Disability and Living with HIV: Baseline from a Cohort of People on Long Term ART in South Africa.

    Directory of Open Access Journals (Sweden)

    Jill Hanass-Hancock

    Full Text Available Through access to life saving antiretroviral treatment (ART in southern Africa, HIV has been reconceptualised as a chronic disease. This comes with new challenges of HIV-related co-morbidities and disabilities. We still lack an understanding of the types and scope of disabilities experienced by people on long term ART and how this impacts health, adherence, and livelihood. This paper describes the results of a cohort study examining the new health- and disability-related needs of the millions of people on ART in the region.Data was collected from a cohort of people who had been on ART for six months or longer in a semi-urban public health care setting in South Africa. 1042 adults (18 and older participated in the cross-sectional study which investigated disabilities/activity limitations, health, ART adherence, depression symptoms, and livelihood. We analysed the associations between these constructs using descriptive statistics, and bivariate and multivariate analyses.A large number of participants (35.5% obtained a weighted score of two or more on the WHODAS 2.0 indicating possible activity limitations. A positive relationship was found between activity limitations and depression symptoms, adherence, and worse health outcomes, while none was found for BMI or CD4 count. These associations varied by type of activity limitations and, in some cases, by gender.Activity limitations are potentially experienced by a large portion of people on ART in southern Africa which impacts health and ART adherence negatively. These results highlight the importance of better understanding the new health-related needs of people who are on long term ART, as well as the nuances of the disability they experience. This is urgently needed in order to enable HIV-endemic countries to better prepare for the new health-related needs of the millions of people on ART in southern Africa.

  13. Management of Long-Term Complications of HIV Disease: Focus on Cardiovascular Disease.

    Science.gov (United States)

    Currier, Judith S

    2018-04-01

    HIV-infected individuals on effective antiretroviral therapy experience a number of non-AIDS noncommunicable diseases, such as cardiovascular disease, more frequently than uninfected individuals. Common pathways for such diseases are chronic immune activation and inflammation, including the prolonged inflammation associated with lower nadir CD4+ cell count. Prevention and treatment of non-AIDS conditions include treatment of traditional risk factors, lifestyle interventions, earlier initiation of antiretroviral therapy, and potentially therapies specifically targeting inflammation and immune activation (eg, statins). This article summarizes a presentation by Judith S. Currier, MD, at the IAS-USA continuing education program, Improving the Management of HIV Disease, held in New York, New York, in February 2017.

  14. Sexual life and fertility desire in long-term HIV serodiscordant couples in Addis Ababa, Ethiopia: a grounded theory study

    Directory of Open Access Journals (Sweden)

    Hailemariam Tewodros G

    2012-10-01

    Full Text Available Abstract Background Even though remarkable progress has been achieved, HIV/AIDS continues to be a major global health priority. HIV discordant relationship is one of the emerging issues in HIV prevention endeavour. In Ethiopia, very little is known about HIV-serodiscordant couples particularly how they manage their sexual relationship and fertility desire. Therefore, we conduct this study with the aim of exploring the experiences of HIV discordant couples about their sexual life, and fertility desire in the context of long-term relationships in Addis Ababa, Ethiopia. Methods A grounded theory approach was employed using in-depth interviews among 36 informants in ART/PMTCT centers of three public hospitals, a health center and one PLHIV association in Addis Ababa. Theoretical sampling was used to recruit 28 clients who lived in a discordant relationship and eight health care providers as key informants. Data collection and analysis were undertaken simultaneously using a constant comparison. The analysis was facilitated using OpenCode software. Results A grounded theory pertaining to sexual life and desire to have a child among HIV discordant couples emerged as “maintaining the relationship” as a core category. Couples pass through a social process of struggle to maintain their relationship. The causal conditions for couples to enter into the process of struggle to maintain their relationship were collectively categorized as “Entering in-to a transition” (knowing HIV serostatus and this includes mismatch of desire to have a child, controversy on safe sex versus desire to have a child, and undeniable change in sexual desire and practice through time were the features in entering into-transition. Then after the transition, couples engaged in certain actions/strategies that are categorized as “dealing with discordancy” such as entertaining partner’s interest by scarifying once self interest to maintain their relationship. Conclusions

  15. Illness Representations of HIV Positive Patients Are Associated with Virologic Success.

    Science.gov (United States)

    Leone, Daniela; Borghi, Lidia; Lamiani, Giulia; Barlascini, Luca; Bini, Teresa; d'Arminio Monforte, Antonella; Vegni, Elena

    2016-01-01

    Introduction: It is important for HIV positive patients to be engaged in their care and be adherent to treatment in order to reduce disease progression and mortality. Studies found that illness representations influence adherence through the mediating role of coping behaviors. However, no study has ever tested if patient engagement to the visits mediate the relationship between illness perceptions and adherence. This study aimed to explore illness representations of HIV positive patients and test the hypothesis that illness representations predict adherence through the mediating role of a component of behavioral engagement. Methods: HIV-positive patients treated with highly active antiretroviral therapy (HAART) for at least one year and presenting to a check-up visit were eligible to participate in the study. Patients completed the Illness Perception Questionnaire-Revised. Behavioral engagement was measured based on the patients' clinical attendance to the check-up visits; adherence to HAART was measured by viral load. Undetectable viral load or HIV-RNA perception that the disease does not have serious consequences on patient's life and the prevalence of negative emotions toward HIV were associated with virologic success. On the contrary, the patient's perception that the disease has serious consequences on his/her life and the prevalence of positive emotions were associated with virologic failure. This model showed good fit indexes (CFI = 1; TLI = 1; RMSEA = 0.00; and WRMSR = 0.309). Discussion: Results do not support the mediating role of behavioral engagement in the relationship between illness representations and adherence. As perception of serious consequences coupled with positive emotions are directly associated with virologic failure, clinicians should take them into account to promote treatment adherence.

  16. Characterization of broadly neutralizing antibody responses to HIV-1 in a cohort of long term non-progressors.

    Science.gov (United States)

    González, Nuria; McKee, Krisha; Lynch, Rebecca M; Georgiev, Ivelin S; Jimenez, Laura; Grau, Eulalia; Yuste, Eloísa; Kwong, Peter D; Mascola, John R; Alcamí, José

    2018-01-01

    Only a small fraction of HIV-1-infected patients develop broadly neutralizing antibodies (bNAbs), a process generally associated to chronic antigen stimulation. It has been described that rare aviremic HIV-1-infected patients can generate bNAbs but this issue remains controversial. To address this matter we have assessed bNAb responses in a large cohort of long-term non-progressors (LTNPs) with low or undetectable viremia. Samples from the LTNP cohort of the Spanish AIDS Research Network (87 elite and 42 viremic controllers) and a control population of 176 viremic typical-progressors (TPs) were screened for bNAbs using Env-recombinant viruses. bNAb specificities were studied by ELISA using mutated gp120, neutralization assays with mutated viruses, and peptide competition. Epitope specificities were also elucidated from the serum pattern of neutralization against a panel of diverse HIV-1 isolates. Broadly neutralizing sera were found among 9.3% LTNPs, both elite (7%) and viremic controllers (14%). Within the broadly neutralizing sera, CD4 binding site antibodies were detected by ELISA in 4/12 LTNPs (33%), and 16/33 of TPs (48%). Anti-MPER antibodies were detected in 6/12 LTNPs (50%) and 14/33 TPs (42%) whereas glycan-dependent HIV-1 bNAbs were more frequent in LTNPs (11/12, 92%) as compared to TPs (12/33, 36%). A good concordance between standard serum mapping and neutralization-based mapping was observed. LTNPs, both viremic and elite controllers, showed broad humoral immune responses against HIV-1, including activity against many major epitopes involved in bNAbs-mediated protection.

  17. Linking women who test HIV-positive in pregnancy-related services to long-term HIV care and treatment services: a systematic review.

    Science.gov (United States)

    Ferguson, Laura; Grant, Alison D; Watson-Jones, Deborah; Kahawita, Tanya; Ong'ech, John O; Ross, David A

    2012-05-01

    To quantify attrition between women testing HIV-positive in pregnancy-related services and accessing long-term HIV care and treatment services in low- or middle-income countries and to explore the reasons underlying client drop-out by synthesising current literature on this topic. A systematic search in Medline, EMBASE, Global Health and the International Bibliography of the Social Sciences of literature published 2000-2010. Only studies meeting pre-defined quality criteria were included. Of 2543 articles retrieved, 20 met the inclusion criteria. Sixteen (80%) drew on data from sub-Saharan Africa. The pathway between testing HIV-positive in pregnancy-related services and accessing long-term HIV-related services is complex, and attrition was usually high. There was a failure to initiate highly active antiretroviral therapy (HAART) among 38-88% of known-eligible women. Providing 'family-focused care', and integrating CD4 testing and HAART provision into prevention of mother-to-child HIV transmission services appear promising for increasing women's uptake of HIV-related services. Individual-level factors that need to be addressed include financial constraints and fear of stigma. Too few women negotiate the many steps between testing HIV-positive in pregnancy-related services and accessing HIV-related services for themselves. Recent efforts to stem patient drop-out, such as the MTCT-Plus Initiative, hold promise. Addressing barriers and enabling factors both within health facilities and at the levels of the individual woman, her family and society will be essential to improve the uptake of services. © 2012 Blackwell Publishing Ltd.

  18. Long-term Outcomes of a Cell Phone–Delivered Intervention for Smokers Living With HIV/AIDS

    Science.gov (United States)

    Gritz, Ellen R.; Danysh, Heather E.; Fletcher, Faith E.; Tami-Maury, Irene; Fingeret, Michelle Cororve; King, Rachel Marks; Arduino, Roberto C.; Vidrine, Damon J.

    2013-01-01

    Background. People living with human immunodeficiency virus (HIV)/AIDS (PLWHA) have a substantially higher prevalence of cigarette smoking compared to the general population. In addition, PLWHA are particularly susceptible to the adverse health effects of smoking. Our primary objective was to design and test the efficacy over 12 months of a smoking cessation intervention targeting PLWHA. Methods. Participants were enrolled from an urban HIV clinic with a multiethnic and economically disadvantaged patient population. Participants received smoking cessation treatment either through usual care (UC) or counseling delivered by a cell phone intervention (CPI). The 7-day point prevalence abstinence was evaluated at 3, 6, and 12 months using logistic regression and generalized linear mixed models. Results. We randomized 474 HIV-positive smokers to either the UC or CPI group. When evaluating the overall treatment effect (7-day abstinence outcomes from 3-, 6-, and 12-month follow-ups), participants in the CPI group were 2.41 times (P = .049) more likely to demonstrate abstinence compared to the UC group. The treatment effect was strongest at the 3-month follow-up (odds ratio = 4.3, P .05). Conclusions. Cell phone–delivered smoking cessation treatment has a positive impact on abstinence rates compared to a usual care approach. Future research should focus on strategies for sustaining the treatment effect in the long term. PMID:23704120

  19. Long-term outcomes of a cell phone-delivered intervention for smokers living with HIV/AIDS.

    Science.gov (United States)

    Gritz, Ellen R; Danysh, Heather E; Fletcher, Faith E; Tami-Maury, Irene; Fingeret, Michelle Cororve; King, Rachel Marks; Arduino, Roberto C; Vidrine, Damon J

    2013-08-01

    People living with human immunodeficiency virus (HIV)/AIDS (PLWHA) have a substantially higher prevalence of cigarette smoking compared to the general population. In addition, PLWHA are particularly susceptible to the adverse health effects of smoking. Our primary objective was to design and test the efficacy over 12 months of a smoking cessation intervention targeting PLWHA. Participants were enrolled from an urban HIV clinic with a multiethnic and economically disadvantaged patient population. Participants received smoking cessation treatment either through usual care (UC) or counseling delivered by a cell phone intervention (CPI). The 7-day point prevalence abstinence was evaluated at 3, 6, and 12 months using logistic regression and generalized linear mixed models. We randomized 474 HIV-positive smokers to either the UC or CPI group. When evaluating the overall treatment effect (7-day abstinence outcomes from 3-, 6-, and 12-month follow-ups), participants in the CPI group were 2.41 times (P = .049) more likely to demonstrate abstinence compared to the UC group. The treatment effect was strongest at the 3-month follow-up (odds ratio = 4.3, P .05). Cell phone-delivered smoking cessation treatment has a positive impact on abstinence rates compared to a usual care approach. Future research should focus on strategies for sustaining the treatment effect in the long term.

  20. Long-term recall of social relationships related to addiction and HIV risk behaviors.

    Science.gov (United States)

    Stout, R L; Janssen, T; Braciszewski, J M; Vose-O'Neal, A

    2017-08-01

    Social relationships have been demonstrated as a key predictor of relapse among addicted persons and are likely to be important determinants of HIV risk behaviors also. However, the degree to which this population can reliably and consistently identify important people (IPs) in retrospect has been understudied. Using the modified Important People and Activities questionnaire, we investigated to what degree IPs were dropped, added, or retained, and whether data about individual IPs were reported accurately on 6- and 12-month follow up periods using a sample of 50 drug or alcohol abusing participants. We found that IPs were largely retained, and that those retained versus dropped/added differed by their reaction to participant alcohol/drug use, as well as frequency of contact. We further found that there were differences in reliability of data describing specific IPs. While both 6- and 12-month follow up periods led to reliabilities ranging from excellent to fair, we found poorer reliability on responses to recall of "frequency of contact" and "reactions to drinking", as well as "reactions to drug use". Future investigations of reliability of social relationships recalled retrospectively should attempt to examine possible systematic biases in addition to the reliability of specific IP data. More sophisticated studies are needed on factors associated with systematic variation in reporting of aspects of social relationships that are associated with addictions or HIV risk outcomes. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Time from HIV infection to virological suppression: dramatic fall from 2007 to 2016.

    Science.gov (United States)

    Medland, Nicholas A; Nicholson, Suellen; Chow, Eric P F; Read, Timothy R H; Bradshaw, Catriona S; Denham, Ian; Fairley, Christopher K

    2017-11-13

    Time from HIV infection to virological suppression: dramatic fall from 2007 to 2016. We examined the time from HIV infection to virological suppression in MSM who were first diagnosed at Melbourne Sexual Health Centre between 2007 and 2016. Retrospective cohort. Date of infection was imputed from the testing history or serological evidence of recent infection (negative or indeterminate western blot) or baseline CD4 cell count. Date of virological suppression was determined using clinical viral load data. We analysed predictors of diagnosis with serological evidence of recent infection (logistic regression) and time from diagnosis to suppression and from infection to suppression (Cox regression) using demographic, clinical, and behavioral covariates. Between 2007 and 2016, the median time from HIV infection to diagnosis fell from 6.8 to 4.3 months (P = 0.001), from diagnosis to suppression fell from 22.7 to 3.2 months (P < 0.0001), and from infection to suppression fell from 49.0 to 9.6 months (P < 0.0001). Serological evidence of recent infection increased from 15.6 to 34.3% (P < 0.0001) of diagnoses. In the multivariate analyses, age, being recently arrived from a non-English speaking country, history of IDU, other sexually transmitted infections, and sexual risk were not associated with any of these measures. The duration of infectiousness in MSM diagnosed with HIV infection at Melbourne Sexual Health Centre in Victoria has fallen dramatically between 2007 and 2016 and the proportion diagnosed with serological evidence of recent infection has increased. This effect is observed across all population subgroups and marks a positive milestone for the treatment as prevention paradigm.

  2. High exposure to nevirapine in plasma is associated with an improved virological response in HIV-1-infected individuals

    NARCIS (Netherlands)

    Veldkamp, A. I.; Weverling, G. J.; Lange, J. M.; Montaner, J. S.; Reiss, P.; Cooper, D. A.; Vella, S.; Hall, D.; Beijnen, J. H.; Hoetelmans, R. M.

    2001-01-01

    OBJECTIVE: To explore relationships between exposure to nevirapine and the virological response in HIV-1-infected individuals participating in the INCAS trial. METHODS: The elimination rate constant of plasma HIV-1 RNA (k) was calculated during the first 2 weeks of treatment with nevirapine,

  3. Clinical, immunological and virological response to different antiretroviral regimens in a cohort of HIV-2-infected patients

    NARCIS (Netherlands)

    van der Ende, Marchina E.; Prins, Jan M.; Brinkman, Kees; Keuter, Monique; Veenstra, Jan; Danner, Sven A.; Niesters, Hubert G. M.; Osterhaus, Albert D. M. E.; Schutten, Martin

    2003-01-01

    Objective: To assess the clinical, immunological and virological response and the emergence of resistance towards antiretroviral therapy (ART) in a cohort of HIV-2-infected patients. Design: Observational study. Patients: HIV-2-infected patients residing in the Netherlands. Results: From 1995 to

  4. HIV-1 DNA predicts disease progression and post-treatment virological control

    Science.gov (United States)

    Williams, James P; Hurst, Jacob; Stöhr, Wolfgang; Robinson, Nicola; Brown, Helen; Fisher, Martin; Kinloch, Sabine; Cooper, David; Schechter, Mauro; Tambussi, Giuseppe; Fidler, Sarah; Carrington, Mary; Babiker, Abdel; Weber, Jonathan

    2014-01-01

    In HIV-1 infection, a population of latently infected cells facilitates viral persistence despite antiretroviral therapy (ART). With the aim of identifying individuals in whom ART might induce a period of viraemic control on stopping therapy, we hypothesised that quantification of the pool of latently infected cells in primary HIV-1 infection (PHI) would predict clinical progression and viral replication following ART. We measured HIV-1 DNA in a highly characterised randomised population of individuals with PHI. We explored associations between HIV-1 DNA and immunological and virological markers of clinical progression, including viral rebound in those interrupting therapy. In multivariable analyses, HIV-1 DNA was more predictive of disease progression than plasma viral load and, at treatment interruption, predicted time to plasma virus rebound. HIV-1 DNA may help identify individuals who could safely interrupt ART in future HIV-1 eradication trials. Clinical trial registration: ISRCTN76742797 and EudraCT2004-000446-20 DOI: http://dx.doi.org/10.7554/eLife.03821.001 PMID:25217531

  5. Pregnancy Outcomes in HIV-Infected Women Receiving Long-Term Isoniazid Prophylaxis for Tuberculosis and Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Allan W. Taylor

    2013-01-01

    Full Text Available Objective. While 6- to 12-month courses of isoniazid for tuberculosis prevention are considered safe in pregnant women, the effects of longer-term isoniazid prophylaxis or isoniazid in combination with antiretroviral therapy (ART are not established in human-immunodeficiency-virus-(HIV- infected women who experience pregnancy during the course of therapy. Design. Nested study of pregnancy outcomes among HIV-infected women participating in a placebo-controlled, TB-prevention trial using 36 months daily isoniazid. Pregnancy outcomes were collected by interview and record review. Results. Among 196 pregnant women, 103 (52.6% were exposed to isoniazid during pregnancy; all were exposed to antiretroviral drugs. Prior to pregnancy they had received a median of 341 days (range 1–1095 of isoniazid. We observed no isoniazid-associated hepatitis or other severe isoniazid-associated adverse events in the 103 women. Pregnancy outcomes were 132 term live births, 42 premature births, 11 stillbirths, 8 low birth weight, 6 spontaneous abortions, 4 neonatal deaths, and 1 congenital abnormality. In a multivariable model, neither isoniazid nor ART exposure during pregnancy was significantly associated with adverse pregnancy outcome (adjusted odds ratios 0.6, 95% CI: 0.3–1.1 and 1.8, 95% CI 0.9–3.6, resp.. Conclusions. Long-term isoniazid prophylaxis was not associated with adverse pregnancy outcomes, such as preterm delivery, even in the context of ART exposure.

  6. Clinical, virologic, and immunologic outcomes in lymphoma survivors and in cancer-free, HIV-1-infected patients: a matched cohort study.

    Science.gov (United States)

    Spagnuolo, Vincenzo; Travi, Giovanna; Galli, Laura; Cossarini, Francesca; Guffanti, Monica; Gianotti, Nicola; Salpietro, Stefania; Lazzarin, Adriano; Castagna, Antonella

    2013-08-01

    < .0001). HIV-infected lymphoma survivors experienced more clinical events than controls, especially during the first year of follow-up, but they reached similar long-term immunologic and virologic outcomes. © 2013 American Cancer Society.

  7. Multiple proviral integration events after virological synapse-mediated HIV-1 spread

    International Nuclear Information System (INIS)

    Russell, Rebecca A.; Martin, Nicola; Mitar, Ivonne; Jones, Emma; Sattentau, Quentin J.

    2013-01-01

    HIV-1 can move directly between T cells via virological synapses (VS). Although aspects of the molecular and cellular mechanisms underlying this mode of spread have been elucidated, the outcomes for infection of the target cell remain incompletely understood. We set out to determine whether HIV-1 transfer via VS results in productive, high-multiplicity HIV-1 infection. We found that HIV-1 cell-to-cell spread resulted in nuclear import of multiple proviruses into target cells as seen by fluorescence in-situ hybridization. Proviral integration into the target cell genome was significantly higher than that seen in a cell-free infection system, and consequent de novo viral DNA and RNA production in the target cell detected by quantitative PCR increased over time. Our data show efficient proviral integration across VS, implying the probability of multiple integration events in target cells that drive productive T cell infection. - Highlights: • Cell-to-cell HIV-1 infection delivers multiple vRNA copies to the target cell. • Cell-to-cell infection results in productive infection of the target cell. • Cell-to-cell transmission is more efficient than cell-free HIV-1 infection. • Suggests a mechanism for recombination in cells infected with multiple viral genomes

  8. Gene expression profile in long-term non progressor HIV infected patients: in search of potential resistance factors.

    Science.gov (United States)

    Luque, Maria Carolina; Santos, Camila C; Mairena, Eliane C; Wilkinson, Peter; Boucher, Genèvieve; Segurado, Aluisio C; Fonseca, Luiz A; Sabino, Ester; Kalil, Jorge E; Cunha-Neto, Edecio

    2014-11-01

    Long-term non-progressors (LTNP) represent a minority (1-5%) of HIV-infected individuals characterized by documented infection for more than 7-10 years, a stable CD4+ T cell count over 500/mm(3) and low viremia in the absence of antiretroviral treatment. Protective factors described so far such as the CCR5delta32 deletion, protective HLA alleles, or defective viruses fail to fully explain the partial protection phenotype. The existence of additional host resistance mechanisms in LTNP patients was investigated here using a whole human genome microarray study comparing gene expression profiles of unstimulated peripheral blood mononuclear cells from LTNP patients, HIV-1 infected patients under antiretroviral therapy with CD4+ T cell levels above 500/mm(3) (ST), as well as healthy individuals. Genes that were up- or downregulated exclusively in LTNP, ST or in both groups in comparison to controls were identified and classified in functional categories using Ingenuity Pathway Analysis. ST and LTNP patient groups revealed distinct genetic profiles, regarding gene number in each category and up- or downregulation of specific genes, which could have a bearing on the outcome of each group. We selected some relevant genes to validate the differential expression using quantitative real-time qRT-PCR. Among others, we found several genes related to the canonical Wnt/beta-catenin signaling pathway. Our results identify new possible host genes and molecules that could be involved in the mechanisms leading to the slower progression to AIDS and sustained CD4+ T cell counts that is peculiar to LTNP patients. Copyright © 2014. Published by Elsevier Ltd.

  9. Different Immunological Phenotypes Associated with Preserved CD4+ T Cell Counts in HIV-Infected Controllers and Viremic Long Term Non-Progressors

    DEFF Research Database (Denmark)

    Gaardbo, Julie Christine; Hartling, Hans J; Ronit, Andreas

    2013-01-01

    HIV-infected controllers control viral replication and maintain normal CD4+ T cell counts. Long Term Non-Progressors (LTNP) also maintain normal CD4+ T cell counts, but have on-going viral replication. We hypothesized that different immunological mechanisms are responsible for preserved CD4+ T cell...

  10. Long-Term Changes of Subcutaneous Fat Mass in HIV-Infected Children on Antiretroviral Therapy: A Retrospective Analysis of Longitudinal Data from Two Pediatric HIV-Cohorts.

    Science.gov (United States)

    Cohen, Sophie; Innes, Steve; Geelen, Sibyl P M; Wells, Jonathan C K; Smit, Colette; Wolfs, Tom F W; van Eck-Smit, Berthe L F; Kuijpers, Taco W; Reiss, Peter; Scherpbier, Henriette J; Pajkrt, Dasja; Bunders, Madeleine J

    2015-01-01

    Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected children in need for lifelong treatment. We assessed regional fat distribution over time, measured with sequential DEXA-scans in HIV-infected children on cART in cohorts from South Africa (SA) and the Netherlands (NL), and in healthy controls (SA). Limb and trunk fat Z-scores were calculated with the lambda-mu-sigma (LMS) method. Multivariable linear regression models with mixed effects were used to investigate the effect of cART compounds on body fat distribution over time. In total, 218 children underwent 445 DEXA assessments with a median follow-up of 3.5 years. Fat mass in all limbs was decreased in HIV-infected children compared to controls (arm fat Z-score: coefficient -0.4813; P = 0.006, leg fat Z-score: coefficient -0.4345; P = 0.013). In the HIV-infected group, stavudine treatment was associated with lower subcutaneous fat mass (arm fat Z-score: coefficient -0.5838; P = 0.001), with an additional cumulative exposure effect (arm fat Z-score: coefficient -0.0867; P = 0.003). Our study shows that subcutaneous fat loss is still prevalent in HIV-infected children on cART, and is strongly associated with cumulative stavudine exposure. These results underline the need for early detection of subcutaneous fat loss and alternative treatment options for HIV-infected children globally.

  11. Live Imaging of HIV-1 Transfer across T Cell Virological Synapse to Epithelial Cells that Promotes Stromal Macrophage Infection.

    Science.gov (United States)

    Real, Fernando; Sennepin, Alexis; Ganor, Yonatan; Schmitt, Alain; Bomsel, Morgane

    2018-05-08

    During sexual intercourse, HIV-1 crosses epithelial barriers composing the genital mucosa, a poorly understood feature that requires an HIV-1-infected cell vectoring efficient mucosal HIV-1 entry. Therefore, urethral mucosa comprising a polarized epithelium and a stroma composed of fibroblasts and macrophages were reconstructed in vitro. Using this system, we demonstrate by live imaging that efficient HIV-1 transmission to stromal macrophages depends on cell-mediated transfer of the virus through virological synapses formed between HIV-1-infected CD4 + T cells and the epithelial cell mucosal surface. We visualized HIV-1 translocation through mucosal epithelial cells via transcytosis in regions where virological synapses occurred. In turn, interleukin-13 is secreted and HIV-1 targets macrophages, which develop a latent state of infection reversed by lipopolysaccharide (LPS) activation. The live observation of virological synapse formation reported herein is key in the design of vaccines and antiretroviral therapies aimed at blocking HIV-1 access to cellular reservoirs in genital mucosa. Copyright © 2018. Published by Elsevier Inc.

  12. HIV Stigma and Depressive Symptoms are Related to Adherence and Virological Response to Antiretroviral Treatment Among Immigrant and Indigenous HIV Infected Patients

    NARCIS (Netherlands)

    Sumari-de Boer, I. Marion; Sprangers, Mirjam A. G.; Prins, Jan M.; Nieuwkerk, Pythia T.

    2012-01-01

    We compared adherence to cART and viro-logical response between indigenous and immigrant HIV-infected patients in the Netherlands, and investigated if a possible difference was related to a difference in the psychosocial variables: HIV-stigma, quality-of-life, depression and beliefs about

  13. Respiratory health status is impaired in UK HIV-positive adults with virologically suppressed HIV infection.

    Science.gov (United States)

    Brown, J; McGowan, J A; Chouial, H; Capocci, S; Smith, C; Ivens, D; Johnson, M; Sathia, L; Shah, R; Lampe, F C; Rodger, A; Lipman, M

    2017-09-01

    We sought to evaluate whether people living with HIV (PLWH) using effective antiretroviral therapy (ART) have worse respiratory health status than similar HIV-negative individuals. We recruited 197 HIV-positive and 93 HIV-negative adults from HIV and sexual health clinics. They completed a questionnaire regarding risk factors for respiratory illness. Respiratory health status was assessed using the St George's Respiratory Questionnaire (SGRQ) and the Medical Research Council (MRC) breathlessness scale. Subjects underwent spirometry without bronchodilation. PLWH had worse respiratory health status: the median SGRQ Total score was 12 [interquartile range (IQR) 6-25] in HIV-positive subjects vs. 6 (IQR 2-14) in HIV-negative subjects (P respiratory health appears more common in HIV-positive adults, and has a significant impact on health-related quality of life. © 2017 The Authors HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

  14. Age and CD4 count at initiation of antiretroviral therapy in HIV-infected children: effects on long-term T-cell reconstitution.

    Science.gov (United States)

    Lewis, Joanna; Walker, A Sarah; Castro, Hannah; De Rossi, Anita; Gibb, Diana M; Giaquinto, Carlo; Klein, Nigel; Callard, Robin

    2012-02-15

    Effective therapies and reduced AIDS-related morbidity and mortality have shifted the focus in pediatric human immunodeficiency virus (HIV) from minimizing short-term disease progression to maintaining optimal long-term health. We describe the effects of children's age and pre-antiretroviral therapy (ART) CD4 count on long-term CD4 T-cell reconstitution. CD4 counts in perinatally HIV-infected, therapy-naive children in the Paediatric European Network for the Treatment of AIDS 5 trial were monitored following initiation of ART for a median 5.7 years. In a substudy, naive and memory CD4 counts were recorded. Age-standardized measurements were analyzed using monophasic, asymptotic nonlinear mixed-effects models. One hundred twenty-seven children were studied. Older children had lower age-adjusted CD4 counts in the long term and at treatment initiation (P memory CD4 counts increased less, albeit on a faster timescale. It appears the immature immune system can recover well from HIV infection via the naive pool. However, this potential is progressively damaged with age and/or duration of infection. Current guidelines may therefore not optimize long-term immunological health.

  15. Pretreatment HIV drug resistance results in virological failure and accumulation of additional resistance mutations in Ugandan children

    NARCIS (Netherlands)

    Kityo, Cissy; Boerma, Ragna S.; Sigaloff, Kim C. E.; Kaudha, Elizabeth; Calis, Job C. J.; Musiime, Victor; Balinda, Sheila; Nakanjako, Rita; Boender, T. Sonia; Mugyenyi, Peter N.; Rinke de Wit, Tobias F.

    2017-01-01

    Background: Pretreatment HIV drug resistance (PDR) can impair virological response to ART, jeopardizing effective treatment for children. Methods: Children aged <12 years initiated first-line ART in Uganda during 2010-11. Baseline and 6 monthly viral load (VL) and genotypic resistance testing if VL.

  16. Transient nature of long-term nonprogression and broad virus-specific proliferative T-cell responses with sustained thymic output in HIV-1 controllers.

    Directory of Open Access Journals (Sweden)

    Samantha J Westrop

    Full Text Available HIV-1(+ individuals who, without therapy, conserve cellular anti-HIV-1 responses, present with high, stable CD4(+ T-cell numbers, and control viral replication, facilitate analysis of atypical viro-immunopathology. In the absence of universal definition, immune function in such HIV controllers remains an indication of non-progression.CD4 T-cell responses to a number of HIV-1 proteins and peptide pools were assessed by IFN-gamma ELISpot and lymphoproliferative assays in HIV controllers and chronic progressors. Thymic output was assessed by sjTRECs levels. Follow-up of 41 HIV-1(+ individuals originally identified as "Long-term non-progressors" in 1996 according to clinical criteria, and longitudinal analysis of two HIV controllers over 22 years, was also performed. HIV controllers exhibited substantial IFN-gamma producing and proliferative HIV-1-specific CD4 T-cell responses to both recombinant proteins and peptide pools of Tat, Rev, Nef, Gag and Env, demonstrating functional processing and presentation. Conversely, HIV-specific T-cell responses were limited to IFN-gamma production in chronic progressors. Additionally, thymic output was approximately 19 fold higher in HIV controllers than in age-matched chronic progressors. Follow-up of 41 HIV-1(+ patients identified as LTNP in 1996 revealed the transitory characteristics of this status. IFN-gamma production and proliferative T-cell function also declines in 2 HIV controllers over 22 years.Although increased thymic output and anti-HIV-1 T-cell responses are observed in HIV controllers compared to chronic progressors, the nature of nonprogressor/controller status appears to be transitory.

  17. Relationship of long-term highly active antiretroviral therapy on salivary flow rate and CD4 Count among HIV-infected patients.

    Science.gov (United States)

    Kumar, J Vijay; Baghirath, P Venkat; Naishadham, P Parameswar; Suneetha, Sujai; Suneetha, Lavanya; Sreedevi, P

    2015-01-01

    To determine if long-term highly active antiretroviral therapy (HAART) therapy alters salivary flow rate and also to compare its relation of CD4 count with unstimulated and stimulated whole saliva. A cross-sectional study was performed on 150 individuals divided into three groups. Group I (50 human immunodeficiency virus (HIV) seropositive patients, but not on HAART therapy), Group II (50 HIV-infected subjects and on HAART for less than 3 years called short-term HAART), Group III (50 HIV-infected subjects and on HAART for more than or equal to 3 years called long-term HAART). Spitting method proposed by Navazesh and Kumar was used for the measurement of unstimulated and stimulated salivary flow rate. Chi-square test and analysis of variance (ANOVA) were used for statistical analysis. The mean CD4 count was 424.78 ± 187.03, 497.82 ± 206.11 and 537.6 ± 264.00 in the respective groups. Majority of the patients in all the groups had a CD4 count between 401 and 600. Both unstimulated and stimulated whole salivary (UWS and SWS) flow rates in Group I was found to be significantly higher than in Group II (P flow rate between Group II and III subjects were also found to be statistically significant (P relationship in Group II (P flow rates of HIV-infected individuals who are on long-term HAART.

  18. Effectiveness and Risk Factors for Virological Outcome of Raltegravir-Based Therapy for Treatment-Experienced HIV-Infected Patients.

    Science.gov (United States)

    Mata-Marín, José Antonio; Smeke, Ariane Estrella Weiser; Rodriguez, Mariana Rotzinger; Chávez-García, Marcelino; Banda-Lara, Marco Isaac; Rios, Alma Minerva Pérez; Nuñez-Rodríguez, Nohemí; Domínguez-Hermosillo, Juan Carlos; Sánchez, Alberto Chaparro; Juarez-Kasusky, Irene; Herrera, Javier Enrique Cruz; Ramírez, Jorge Luis Sandoval; Gaytán-Martínez, Jesús

    2017-03-01

    We evaluated the effectiveness of a raltegravir (RAL)-containing regimen plus an optimized background regimen in HIV-1 highly treatment-experienced patients. A retrospective cohort, multicentre study was conducted. Adult (>16 years old) HIV treatment-experience patients starting therapy with a RAL-containing regimen were included. Effectiveness was evaluated as the percentage of patients with an undetectable HIV-1 RNA viral load (treatment failure. Of the 107 patients in the cohort, 86% were men, the median age was 45 years [interquartile range (IQR) 40-52] and the median number of previous regimens was six (IQR 4-7). After 48 weeks of treatment, 73% (IQR 63-80%) of patients (n = 78) had a viral load of HIV-1 RNA of 40 years [odds ratio (OR) 5.61; 95% confidence interval (CI) 1.61-18.84; P = 0.006] and use of tenofovir in the regimen (OR 0.16; 95% CI 0.03-0.80; P = 0.026). In this Mexican cohort, RAL achieved high rates of virological suppression and an increase in CD4+ cell count in highly treatment-experienced patients infected with HIV-1. Age >40 years was associated with a good virological outcome, contrary to tenofovir use, which was associated with a poor virological outcome.

  19. Phenotype and envelope gene diversity of nef-deleted HIV-1 isolated from long-term survivors infected from a single source

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    Sullivan John S

    2007-07-01

    Full Text Available Abstract Background The Sydney blood bank cohort (SBBC of long-term survivors consists of multiple individuals infected with attenuated, nef-deleted variants of human immunodeficiency virus type 1 (HIV-1 acquired from a single source. Long-term prospective studies have demonstrated that the SBBC now comprises slow progressors (SP as well as long-term nonprogressors (LTNP. Convergent evolution of nef sequences in SBBC SP and LTNP indicates the in vivo pathogenicity of HIV-1 in SBBC members is dictated by factors other than nef. To better understand mechanisms underlying the pathogenicity of nef-deleted HIV-1, we examined the phenotype and env sequence diversity of sequentially isolated viruses (n = 2 from 3 SBBC members. Results The viruses characterized here were isolated from two SP spanning a three or six year period during progressive HIV-1 infection (subjects D36 and C98, respectively and from a LTNP spanning a two year period during asymptomatic, nonprogressive infection (subject C18. Both isolates from D36 were R5X4 phenotype and, compared to control HIV-1 strains, replicated to low levels in peripheral blood mononuclear cells (PBMC. In contrast, both isolates from C98 and C18 were CCR5-restricted. Both viruses isolated from C98 replicated to barely detectable levels in PBMC, whereas both viruses isolated from C18 replicated to low levels, similar to those isolated from D36. Analysis of env by V1V2 and V3 heteroduplex tracking assay, V1V2 length polymorphisms, sequencing and phylogenetic analysis showed distinct intra- and inter-patient env evolution. Conclusion Independent evolution of env despite convergent evolution of nef may contribute to the in vivo pathogenicity of nef-deleted HIV-1 in SBBC members, which may not necessarily be associated with changes in replication capacity or viral coreceptor specificity.

  20. HIV-DNA in the genital tract of women on long-term effective therapy is associated to residual viremia and previous AIDS-defining illnesses.

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    Thierry Prazuck

    Full Text Available OBJECTIVES: To assess the impact of long-term combined antiretroviral therapy (cART on HIV-RNA and HIV-DNA levels in cervicovaginal secretions of HIV-1-infected women with sustained undetectable plasma RNA viral load (PVL; to explore factors predictive of residual viral shedding; and to evaluate the risk of heterosexual transmission. METHODS: Women with undetectable PVL (6 months were included in this cross-sectional study. HIV-RNA and HIV-DNA were measured in blood and cervicovaginal lavage fluid (CVL. Women were systematically tested for genital infections. The risk of transmission to male partners during unprotected intercourse was estimated. RESULTS: Eighty-one women composed the study population: all had HIV-RNA <40 copies/mL in CVL. HIV-DNA was detectable in CVL of 29/78 patients (37%. There was a weak positive correlation between HIV-DNA levels in PBMCs and CVL (r = 0.20; p = 0.08. In multivariate analysis, two factors were associated with HIV-DNA detection in CVL: previous AIDS-defining illnesses (OR = 11; 95%CI = 2-61 and current residual viremia (20HIV-DNA detection in CVL. Twenty-eight percent of the women had unprotected intercourse with their regular HIV-seronegative male partner, for between 8 and 158 months. None of their male partners became infected, after a total of 14 000 exposures. CONCLUSION: In our experience, HIV-RNA was undetectable in the genital tract of women with sustained control of PVL on cART. HIV-DNA shedding persisted in about one third of cases, with no substantial evidence of residual infectiousness.

  1. Long-term follow-up of HIV-1-infected adults who received the F4/AS01B HIV-1 vaccine candidate in two randomised controlled trials.

    Science.gov (United States)

    Harrer, Thomas; Dinges, Warren; Roman, François

    2018-05-03

    This Phase I/II, open, long-term follow-up study was conducted in antiretroviral therapy (ART)-naïve (N = 212) and ART-treated (N = 19) human immunodeficiency virus 1 (HIV-1)-infected adults, who received an HIV-1 investigational vaccine (F4/AS01 B ) or placebo in two previous studies (NCT00814762 and NCT01218113). After a minimum of two years and a maximum of four years of follow-up post-vaccination per patient, no significant differences were observed between F4/AS01 B and placebo groups in terms of viral load, CD4 + T-cell count and incidence of specific clinical events. Vaccine-induced polyfunctional CD4 + T-cells persisted up to study end and no relevant vaccine-related safety events were reported in F4/AS01 B groups. This study has been registered at ClinicalTrials.gov (NCT01092611). Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Discordant CSF/plasma HIV-1 RNA in individuals on virologically suppressive antiretroviral therapy in Western India.

    Science.gov (United States)

    Dravid, Ameet N; Natrajan, Kartik; Kulkarni, Milind M; Saraf, Chinmay K; Mahajan, Uma S; Kore, Sachin D; Rathod, Niranjan M; Mahajan, Umakant S; Wadia, Rustom S

    2018-02-01

    Aim of this study was to estimate the prevalence of cerebrospinal fluid (CSF)/Plasma HIV-1 RNA discordance in virologically suppressed individuals presenting with incident neurologic symptoms.In this retrospective cohort study conducted between March 1, 2009, and March 1, 2017, HIV-1 infected adults exposed to atleast 12 months of antiretroviral therapy (ART) and having plasma viral load (VL) CSF/Plasma HIV-1 RNA discordance by measuring HIV-1 RNA in collected plasma and CSF samples. CSF/plasma HIV-1 RNA discordance was defined as either detectable CSF HIV-1 RNA (VL > 20 copies/mL) with an undetectable plasma RNA (complete viral suppression, VL ≤20 copies/mL) or CSF HIV-1 RNA ≥ 0.5 log10 higher than plasma RNA when plasma VL was between 20 and 1000 copies/mL (low-level viremia, LLV).Out of 1584 virologically suppressed patients, 71 (4.4%) presented with incident neurologic symptoms. Twenty out of 71 (28.2%) patients were diagnosed with CSF/Plasma HIV-1 discordance. Median plasma and CSF VL in patients with discordance was 120 [interquartile range (IQR): CSF HIV-1 genotypic resistance testing was done showed mutations that would compromise efficacy of prescribed ART regimen. Prevalence of CSF/plasma HIV-1 RNA discordance was higher among neurologically symptomatic patients with plasma LLV as compared with those with complete viral suppression (70% vs 11.8%, P CSF/plasma HIV-1 RNA discordance indicates replication of HIV-1 that has adapted to the CNS or has developed antiretroviral drug resistance. Larger studies should be performed to study incidence of discordance in India. This will help in managing patients presenting with neurologic symptoms on suppressive ART with appropriate neuroeffective therapy.

  3. Assessment of BED HIV-1 incidence assay in seroconverter cohorts: effect of individuals with long-term infection and importance of stable incidence.

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    Janet M McNicholl

    Full Text Available BACKGROUND: Performance of the BED assay in estimating HIV-1 incidence has previously been evaluated by using longitudinal specimens from persons with incident HIV infections, but questions remain about its accuracy. We sought to assess its performance in three longitudinal cohorts from Thailand where HIV-1 CRF01_AE and subtype B' dominate the epidemic. DESIGN: BED testing was conducted in two longitudinal cohorts with only incident infections (a military conscript cohort and an injection drug user cohort and in one longitudinal cohort (an HIV-1 vaccine efficacy trial cohort that also included long-term infections. METHODS: Incidence estimates were generated conventionally (based on the number of annual serocoversions and by using BED test results in the three cohorts. Adjusted incidence was calculated where appropriate. RESULTS: For each longitudinal cohort the BED incidence estimates and the conventional incidence estimates were similar when only newly infected persons were tested, whether infected with CRF01_AE or subtype B'. When the analysis included persons with long-term infections (to mimic a true cross-sectional cohort, BED incidence estimates were higher, although not significantly, than the conventional incidence estimates. After adjustment, the BED incidence estimates were closer to the conventional incidence estimates. When the conventional incidence varied over time, as in the early phase of the injection drug user cohort, the difference between the two estimates increased, but not significantly. CONCLUSIONS: Evaluation of the performance of incidence assays requires the inclusion of a substantial number of cohort-derived specimens from individuals with long-term HIV infection and, ideally, the use of cohorts in which incidence remained stable. Appropriate adjustments of the BED incidence estimates generate estimates similar to those generated conventionally.

  4. Factors associated with conversion of long-term non-progressors to progressors: A prospective study of HIV perinatally infected paediatric survivors

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    Muttineni Radhakrishna

    2013-01-01

    Full Text Available Background & objectives : Survival pattern among children infected with the human immune deficiency virus (HIV follows a bimodel distribution. Some children survive beyond 9 years age and are known as long term survivers (LTS while others had a more rapid course to death during the first few years of life. In the LTS group of children, two sub-populations have emerged, the long term non-progressors (LTNP who have remained asymptomatic over a period of years and those who have survived despite clinical and laboratory evidence of disease progression, the long term progressors (LTP. The aim of the present study was to determine the factors influencing the conversion of LTNPs to LTPs in a group of perinatally HIV infected children who were followed up for five years. Methods : A total of 26 HIV seropositive paediatric patients were monitored from 2006 to 2011 with CD4 cell counts, onset of clinical manifestations, body weight, biochemical, haematological and immunological parameters. Statistical analyses, both qualitative and quantitative, were used to determine the degree of conversion of non-progressors to progressors. Results : All 26 (13 female and 13 male perinatally HIV infected children, born during1991-1996 were healthy until 2006. But by 2011, 18 were placed in progressors group with antiretroviral therapy (ART, while six remained in non progressors group and two died. As per the Kaplan-Meier survival analysis, AIDS free median survival period (years in LTP group (CD4 count of the cohort was 10΁0.66 (350, P=<0.05. Intercurrent and opportunistic infections (OIs were observed in LTPs only. The incidence of OI in LTPs was higher when compared to general paediatric population. Interpretation & conclusions : Our findings show that CD4 counts and OIs play an important role in influencing the survival chances of perinatally HIV infected children.

  5. Failure to achieve immunological recovery in HIV-infected patients with clinical and virological success after 10 years of combined ART: role of treatment course.

    Science.gov (United States)

    Raffi, François; Le Moing, Vincent; Assuied, Alex; Habak, Sofiane; Spire, Bruno; Cazanave, Charles; Billaud, Eric; Dellamonica, Pierre; Ferry, Tristan; Fagard, Catherine; Leport, Catherine

    2017-01-01

    We assessed factors, including treatment course, associated with failure to obtain a 10 year immunological response after starting first-generation PI-containing combined ART (cART). In the prospective COPILOTE cohort of HIV-infected patients started on a first-generation PI-containing regimen in 1997-99, the impact of cART history on the failure to achieve immunological response measured at 10 years was assessed by multivariate logistic regression models in the 399 patients with clinical and virological success of cART. Failure of CD4 response (CD4 >500/mm 3 ) was associated with age ≥40 years at baseline (P failure to achieve complete immunological response (CD4 >500/mm 3 and CD4:CD8 ratio >1) were CD4:CD8 ratio ≤0.8 at month 8 (P success. Lack of treatment interruption may improve long-term immunological outcome in HIV infection. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Factors Influencing Antiretroviral Adherence and Virological Outcomes in People Living with HIV in the Highlands of Papua New Guinea.

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    Janet Gare

    Full Text Available Adherence to antiretroviral therapy (ART is paramount for virological suppression and positive treatment outcomes. ART has been rapidly scaled up in Papua New Guinea (PNG in recent years, however clinical monitoring of HIV+ individuals on ART is limited. A cross-sectional study was conducted at two major sexual health clinics in high HIV prevalence provinces in the Highlands Region of PNG to assess ART adherence, factors affecting adherence and the relationship between ART adherence and virological outcomes. Ninety-five HIV+ individuals were recruited and administered a questionnaire to gather demographic and ART adherence information whilst clinical data and pill counts were extracted from patient charts and blood was collected for viral load testing. Bivariate analysis was performed to identify independent predictors of ART adherence. Fourteen percent (n = 12 of participants showed evidence of virological failure. Although the majority of participants self-reported excellent ART adherence in the last seven days (78.9%, 75/91, pill count measurements indicated only 40% (34/84 with >95% adherence in the last month. Taking other medications while on ART (p = 0.01 and taking ART for ≥1 year (p = 0.037 were positively associated with adherence by self-report and pill count, respectively. Participants who had never heard of drug resistance were more likely to show virological failure (p = 0.033. Misconception on routes of HIV transmission still persists in the studied population. These findings indicate that non-adherence to ART is high in this region of PNG and continued education and strategies to improve adherence are required to ensure the efficacy of ART and prevent HIV drug resistance.

  7. Liver stiffness is not associated with short- and long-term plasma HIV RNA replication in immunocompetent patients with HIV infection and with HIV/HCV coinfection

    Science.gov (United States)

    Parisi, Saverio Giuseppe; Basso, Monica; Mengoli, Carlo; Scaggiante, Renzo; Andreis, Samantha; Franzetti, Marzia Maria; Cattelan, Anna Maria; Zago, Daniela; Cruciani, Mario; Andreoni, Massimo; Piovesan, Sara; Palù, Giorgio; Alberti, Alfredo

    2017-01-01

    Background Human immunodeficiency virus (HIV) may be directly responsible for liver damage but there are contrasting data regarding the influence of detectable plasma viremia. We analyzed the influence of plasma HIV RNA (pHIV) detectability and of other clinical and viro-immunological variables on liver stiffness (LS) measurement in adult immunocompetent HIV-monoinfected patients and in patients coinfected with hepatitis C virus (HCV). Methods Logistic regression analysis was performed using the value of LS>7.1 kPa as the dependent variable. A linear regression model was applied using LS measurement after log10 transformation (lkpa) as the dependent variable and we analyzed the predicted values versus the observed lkpa values; pHIV was classified as detectable or undetectable in the 12- and 36-month study periods before LS measurement. Results We studied 251 patients (178 with HIV monoinfection), most of whom were on antiviral treatment; 36-month study time was available for 154 subjects. The mean CD4+ cell count was 634 cells/mm3 in HIV-monoinfected patients and 606 cells/mm3 in coinfected patients. No difference in LS was found between patients with detectable or undetectable pHIV in either the 12- or the 36-month study period before transient elastography. The mean LS was higher in HIV/HCV coinfected patients (P<0.0001) than in the HIV-monoinfected subjects; lkpa was positively correlated with HCV coinfection (P<0.0001) and aspartate aminotransferase levels (P<0.0001). Detectable pHIV failed to reach significance. Eight HIV-monoinfected patients had a predicted LS measurement lower than the observed one, while eight patients had the opposite result. Conclusion LS was not correlated with ongoing HIV replication during the 12- and 36-month study periods in immunocompetent HIV-monoinfected and HIV/HCV-coinfected patients. PMID:28845109

  8. Timing of pregnancy, postpartum risk of virologic failure and loss to follow-up among HIV-positive women.

    Science.gov (United States)

    Onoya, Dorina; Sineke, Tembeka; Brennan, Alana T; Long, Lawrence; Fox, Matthew P

    2017-07-17

    We assessed the association between the timing of pregnancy with the risk of postpartum virologic failure and loss from HIV care in South Africa. This is a retrospective cohort study of 6306 HIV-positive women aged 15-49 at antiretroviral therapy (ART) initiation, initiated on ART between January 2004 and December 2013 in Johannesburg, South Africa. The incidence of virologic failure (two consecutive viral load measurements of >1000 copies/ml) and loss to follow-up (>3 months late for a visit) during 24 months postpartum were assessed using Cox proportional hazards modelling. The rate of postpartum virologic failure was higher following an incident pregnancy on ART [adjusted hazard ratio 1.8, 95% confidence interval (CI): 1.1-2.7] than among women who initiated ART during pregnancy. This difference was sustained among women with CD4 cell count less than 350 cells/μl at delivery (adjusted hazard ratio 1.8, 95% CI: 1.1-3.0). Predictors of postpartum virologic failure were being viremic, longer time on ART, being 25 or less years old and low CD4 cell count and anaemia at delivery, as well as initiating ART on stavudine-containing or abacavir-containing regimen. There was no difference postpartum loss to follow-up rates between the incident pregnancies group (hazard ratio 0.9, 95% CI: 0.7-1.1) and those who initiated ART in pregnancy. The risk of virologic failure remains high among postpartum women, particularly those who conceive on ART. The results highlight the need to provide adequate support for HIV-positive women with fertility intention after ART initiation and to strengthen monitoring and retention efforts for postpartum women to sustain the benefits of ART.

  9. Prevalence of HIV Antiretroviral Drug Resistance and Its Impacts on HIV-1 Virological Failures in Jiangsu, China: A Cross-Sectional Study

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    Ying Zhou

    2016-01-01

    Full Text Available Antiretroviral therapy (ART has been shown to improve survival of patients with Human Immunodeficiency Virus (HIV infection and to reduce HIV-1 transmission. Therefore, the Chinese central government initiated a national program to provide ART free of charge to HIV-1 patients. We conducted a cross-sectional survey in Jiangsu province to determine the level of drug resistance (DR in HIV-1 infected patients and the correlates of DR in virological failures in 2012. Approximately 10.4% of the HIV-1 patients in the study experienced virological failure after one year of ART and were divided into drug sensitive and drug resistant groups based on genotype determination. The viral loads (VLs in the drug resistant group were significantly lower than the drug sensitive group. There were two independent predictors of virological failure: male gender and increasing duration of treatment. The primary mutations observed in the study were against nucleoside reverse transcriptase inhibitors (NRTIs which were M184V (79.45% and K103N (33.70% in nonnucleoside reverse transcriptase inhibitors (NNRTIs. The overall rate of DR in Jiangsu province is still relatively low among treated patients. However, close monitoring of drug resistance in male patients in the early stages of treatment is vital to maintaining and increasing the benefits of HIV ART achieved to date.

  10. Patient Characteristics Associated with HCV Treatment Adherence, Treatment Completion, and Sustained Virologic Response in HIV Coinfected Patients

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    Glenn Wagner

    2011-01-01

    Full Text Available Background. Hepatitis C (HCV treatment efficacy among HIV patients is limited by poor treatment adherence and tolerance, but few studies have examined the psychosocial determinants of treatment adherence and outcomes. Methods. Chart abstracted and survey data were collected on 72 HIV patients who had received pegylated interferon and ribavirin to assess correlates of treatment adherence, completion, and sustained virologic response (SVR. Results. Nearly half (46% the sample had active psychiatric problems and 13% had illicit drug use at treatment onset; 28% reported <100% treatment adherence, 38% did not complete treatment (mostly due to virologic nonresponse, and intent to treat SVR rate was 49%. Having a psychiatric diagnosis was associated with nonadherence, while better HCV adherence was associated with both treatment completion and SVR. Conclusions. Good mental health may be an indicator of HCV treatment adherence readiness, which is in turn associated with treatment completion and response, but further research is needed with new HCV treatments emerging.

  11. Long-term high-physiological-dose growth hormone reduces intra-abdominal fat in HIV-infected patients with a neutral effect on glucose metabolism

    DEFF Research Database (Denmark)

    Hansen, B R; Haugaard, S B; Jensen, Frank Krieger

    2010-01-01

    , glucose tolerance, and total plasma cholesterol and triglycerides did not significantly change during intervention. CONCLUSIONS: Daily 0.7 mg rhGH treatment for 40 weeks reduced abdominal visceral fat and trunk fat mass in HIV-infected patients. This treatment appeared to be safe with respect to glucose......OBJECTIVES: The aim of the study was to investigate the effect of long-term high-physiological-dose recombinant human growth hormone (rhGH) therapy on fat distribution and glucose metabolism in HIV-infected patients. METHODS: Forty-six HIV-infected Caucasian men on highly active antiretroviral...... between 1 and 3 pm for 40 weeks. Endpoints included changes in visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), limb fat mass, percentage of limb fat, plasma lipids, insulin resistance and glucose tolerance. RESULTS: VAT and trunk fat mass decreased significantly in the GH group compared...

  12. Immunoregulatory T Cells May Be Involved in Preserving CD4 T Cell Counts in HIV-Infected Long-Term Nonprogressors and Controllers

    DEFF Research Database (Denmark)

    Gaardbo, Julie C; Ronit, Andreas; Hartling, Hans J

    2014-01-01

    BACKGROUND: HIV-infected controllers control viral replication and maintain normal CD4 T cell counts. Long-term nonprogressors (LTNPs) also maintain normal CD4 T cell counts but have ongoing viral replication. We hypothesized that immunoregulatory mechanisms are involved in preserved CD4 T cell...... of patients and controls. However, both ECs and LTNPs displayed a large proportion of activated Tregs suggesting immunoregulatory mechanisms to be involved in preserving CD4 T cell counts in HIV-infected nonprogressors....... counts in controllers and in LTNPs. METHODS: Twenty HIV-infected viremic controllers, 5 elite controllers (ECs), and 14 LTNPs were included in this cross-sectional study. For comparison, 25 progressors and 34 healthy controls were included. Regulatory T cells (Tregs), Treg subpopulations, CD161+Th17...

  13. Tuberculosis among people living with HIV/AIDS in the German ClinSurv HIV Cohort: long-term incidence and risk factors.

    Science.gov (United States)

    Karo, Basel; Haas, Walter; Kollan, Christian; Gunsenheimer-Bartmeyer, Barbara; Hamouda, Osamah; Fiebig, Lena

    2014-03-19

    Tuberculosis (TB) still presents a leading cause of morbidity and mortality among people living with HIV/AIDS (PLWHA), including those on antiretroviral therapy. In this study, we aimed to determine the long-term incidence density rate (IDR) of TB and risk factors among PLWHA in relation to combination antiretroviral therapy (cART)-status. Data of PLWHA enrolled from 2001 through 2011 in the German ClinSurv HIV Cohort were investigated using survival analysis and Cox regression. TB was diagnosed in 233/11,693 PLWHA either at enrollment (N = 62) or during follow-up (N = 171). The TB IDR during follow-up was 0.37 cases per 100 person-years (PY) overall [95% CI, 0.32-0.43], and was higher among patients who never started cART and among patients originating from Sub-Saharan Africa (1.23 and 1.20 per 100PY, respectively). In two multivariable analyses, both patients (I) who never started cART and (II) those on cART shared the same risk factors for TB, namely: originating from Sub-Saharan Africa compared to Germany (I, hazard ratio (HR); [95% CI]) 4.05; [1.87-8.78] and II, HR 5.15 [2.76-9.60], CD4+ cell count 5 log10 copies/ml (I, HR 2.51 [1.33-4.75] and II, HR 1.77 [1.11-2.82]). Gender, age or HIV-transmission risk group were not independently associated with TB. In the German ClinSurv HIV cohort, patients originating from Sub-Saharan Africa, with low CD4+ cell count or high viral load at enrollment were at increased risk of TB even after cART initiation. As patients might be latently infected with Mycobacterium tuberculosis complex, early screening for latent TB infection and implementing isoniazid preventive therapy in line with available recommendations is crucial.

  14. Use of Nonantiretroviral Medications That May Impact Neurocognition: Patterns and Predictors in a Large, Long-Term HIV Cohort Study.

    Science.gov (United States)

    Radtke, Kendra K; Bacchetti, Peter; Anastos, Kathryn; Merenstein, Daniel; Crystal, Howard; Karim, Roksana; Weber, Kathleen M; Edmonds, Andrew; Sheth, Anandi N; Fischl, Margaret A; Vance, David; Greenblatt, Ruth M; Rubin, Leah H

    2018-06-01

    Neurocognitive impairment is a frequent and often disabling comorbidity of HIV infection. In addition to antiretroviral therapies, individuals with HIV infection may commonly use nonantiretroviral medications that are known to cause neurocognitive adverse effects (NC-AE). The contribution of NC-AE to neurocognitive impairment is rarely considered in the context of HIV and could explain part of the variability in neurocognitive performance among individuals with HIV. Women's Interagency HIV Study, a prospective, multisite, observational study of US women with and without HIV. After a literature review, 79 medications (excluding statins) with NC-AE were identified and reported by Women's Interagency HIV Study participants. We examined factors associated with self-reported use of these medications over a 10-year period. Generalized estimating equations for binary outcomes were used to assess sociodemographic, behavioral, and clinical characteristics associated with NC-AE medication use. Three thousand three hundred women (71% with HIV) and data from ∼42,000 visits were studied. HIV infection was associated with NC-AE medication use (odds ratio = 1.52; 95% confidence interval: 1.35 to 1.71). After adjustment for HIV infection status, other predictors of NC-AE medication use included having health insurance, elevated depressive symptoms, prior clinical AIDS, noninjection recreational drug use, and an annual household income of <$12,000 (Ps < 0.004). NC-AE medication use was less likely among women who drank 1-7 or 8-12 alcoholic drinks/week (vs. abstaining) (P < 0.04). HIV infection was associated with NC-AE medication use, which may influence determinations of HIV-associated neurocognitive impairment. Providers should consider the impact of NC-AE medications when evaluating patients with HIV and concurrent neurocognitive symptoms.

  15. Experiences of patients with HIV/AIDS receiving mid- and long-term care in Japan: A qualitative study

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    Yoko Imazu, R.N., P.H.N., Ph.D.

    2017-04-01

    Conclusions: Some participants accepted themselves as HIV-positive, some did not when they were diagnosis. This difference of reaction had effect on attitudes toward HIV therapy. But all participants continued mid- and long-treatments owing to feeling well and receiving support from professionals. Additionally, it found that patients were felt stigma of HIV-positive similarly to another Asian countries. Therefore, we should provide the entire Japanese society with knowledge about HIV/AIDS and be early and constant intervention by professional teams after being infected.

  16. Persistence of attenuated HIV-1 rev alleles in an epidemiologically linked cohort of long-term survivors infected with nef-deleted virus

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    Wesselingh Steven L

    2007-07-01

    Full Text Available Abstract Background The Sydney blood bank cohort (SBBC of long-term survivors consists of multiple individuals infected with nef-deleted, attenuated strains of human immunodeficiency virus type 1 (HIV-1. Although the cohort members have experienced differing clinical courses and now comprise slow progressors (SP as well as long-term nonprogressors (LTNP, longitudinal analysis of nef/long-terminal repeat (LTR sequences demonstrated convergent nef/LTR sequence evolution in SBBC SP and LTNP. Thus, the in vivo pathogenicity of attenuated HIV-1 strains harboured by SBBC members is dictated by factors other than nef/LTR. Therefore, to determine whether defects in other viral genes contribute to attenuation of these HIV-1 strains, we characterized dominant HIV-1 rev alleles that persisted in 4 SBBC subjects; C18, C64, C98 and D36. Results The ability of Rev derived from D36 and C64 to bind the Rev responsive element (RRE in RNA binding assays was reduced by approximately 90% compared to Rev derived from HIV-1NL4-3, C18 or C98. D36 Rev also had a 50–60% reduction in ability to express Rev-dependent reporter constructs in mammalian cells. In contrast, C64 Rev had only marginally decreased Rev function despite attenuated RRE binding. In D36 and C64, attenuated RRE binding was associated with rare amino acid changes at 3 highly conserved residues; Gln to Pro at position 74 immediately N-terminal to the Rev activation domain, and Val to Leu and Ser to Pro at positions 104 and 106 at the Rev C-terminus, respectively. In D36, reduced Rev function was mapped to an unusual 13 amino acid extension at the Rev C-terminus. Conclusion These findings provide new genetic and mechanistic insights important for Rev function, and suggest that Rev function, not Rev/RRE binding may be rate limiting for HIV-1 replication. In addition, attenuated rev alleles may contribute to viral attenuation and long-term survival of HIV-1 infection in a subset of SBBC members.

  17. Restoration of the CD4 T cell compartment after long-term highly active antiretroviral therapy without phenotypical signs of accelerated immunological aging

    NARCIS (Netherlands)

    Vrisekoop, Nienke; van Gent, Rogier; de Boer, Anne Bregje; Otto, Sigrid A.; Borleffs, Jan C. C.; Steingrover, Radjin; Prins, Jan M.; Kuijpers, Taco W.; Wolfs, Tom F. W.; Geelen, Sibyl P. M.; Vulto, Irma; Lansdorp, Peter; Tesselaar, Kiki; Borghans, José A. M.; Miedema, Frank

    2008-01-01

    It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery.

  18. Restoration of the CD4 T cell compartment after long-term highly active Antiretroviral therapy without phenotypical signs of accelerated immunological aging

    NARCIS (Netherlands)

    Vrisekoop, Nienke; van Gent, Rogier; de Boer, Anne Bregje; Otto, Sigrid A.; Borleffs, Jan C. C.; Stemgrover, Radjin; Prins, Jan M.; Kuijpers, Taco W.; Wolfs, Tom F. W.; Geelen, Sibyl P. M.; Vulto, Irma; Lansdorp, Peter; Tesselaar, Kiki; Borghans, Jose A. M.; Miedema, Frank

    2008-01-01

    It remains uncertain whether full T cell reconstitution can be established in HIV-infected children and adults with long-term sustained virological control by highly active antiretroviral therapy (HAART). In this study, we comprehensively analyzed various phenotypical markers of CD4 T cell recovery.

  19. Acute HIV infection (AHI) in a specialized clinical setting: case-finding, description of virological, epidemiological and clinical characteristics.

    Science.gov (United States)

    Ammassari, Adriana; Abbate, Isabella; Orchi, Nicoletta; Pinnetti, Carmela; Rozera, Gabriella; Libertone, Raffaella; Pierro, Paola; Martini, Federico; Puro, Vincenzo; Girardi, Enrico; Antinori, Andrea; Capobianchi, Maria Rosaria

    2014-01-01

    Diagnosis of HIV infection during early stages is mandatory to catch up with the challenge of limiting HIV viral replication and reservoirs formation, as well as decreasing HIV transmissions by immediate cART initiation. Aims were to describe (a) virological characteristics of AHI identified, (b) epidemiological and clinical factors associated with being diagnosed with AHI. Cross-sectional, retrospective study. All individuals diagnosed with AHI according to Fiebig's staging between Jan 2013 and Mar 2014 at the INMI "L. Spallanzani" were included. Serum samples reactive to a fourth generation HIV-1/2 assay (Architect HIV Ag/Ab Combo, Abbott) were retested with another fourth generation assay (VIDAS DUO HIV Ultra, Biomérieux) and underwent confirmation with HIV-1 WB (New Lav I Bio-Rad) and/or with Geenius confirmatory assay (Bio-Rad). WHO criteria (two env products reactivity) were used to establish positivity of confirmatory assays. In case of clinically suspected AHI, HIV-1 RNA (Real time, Abbott) and p24 assay (VIDAS HIV P24 Bio-Rad) were also performed. Avidity test was carried out, on confirmed positive samples lacking p31 reactivity, to discriminate between recent (true Fiebig V phase) and late infections; to avoid possible misclassifications, clinical data were also used. Demographic, epidemiological, clinical and laboratory data are routinely, and anonymously recorded in the SENDIH and SIREA studies. During the study period, we observed 483 newly HIV diagnosed individuals, of whom 40 were identified as AHI (8.3%). Fiebig classification showed: 7 stage II/III, 13 stage IV, 20 stage V. Demographic, epidemiological, and clinical characteristics of patients are shown in the Table. Overall, the study population had a median S/Co ratio at fourth generation EIA (Architect) of 49.50 (IQR, 23.54-98.05): values were significantly lower in Fiebig II-IV than in Fiebig V (38.68 [IQR, 20.08-54.84] vs 75.72 [IQR, 42.66-249.80], p=0.01). Overall, median HIV-1 RNA was 5

  20. The road to success. Long-term prognosis for persons living with HIV in Denmark - time trends and risk factors

    DEFF Research Database (Denmark)

    Lohse, Nicolai

    2016-01-01

    compared temporal trends in quality and quantity of ART introduction in Den-mark and Greenland. Despite similar levels of health worker education and economic resources, ART implementation and mortality decline in Greenland lacked several years behind Denmark. The study reminded us that although economy...... another 39 years, only 12.2 years less than a person in a matched general population cohort would survive. With improved survival and declining HIV-related co-morbidity, non-HIV related co-morbidity became a more visible contributor to the health status of persons with HIV. We assessed the impact of non......-HIV related comorbidity acquired before the person became infected with HIV. We found that 32% of the observed mortality in our cohort was due to HCV and co-morbidities measured by the Charlson Comorbidity Index, 13% corresponded to the background mortality in the population, and that only 55...

  1. Central memory CD4 T cells are associated with incomplete restoration of the CD4 T cell pool after treatment-induced long-term undetectable HIV viraemia.

    Science.gov (United States)

    Rallón, Norma; Sempere-Ortells, José M; Soriano, Vincent; Benito, José M

    2013-11-01

    It is unclear to what extent T cell reconstitution may be possible in HIV-1-infected individuals on continuous successful highly active antiretroviral therapy (HAART). Herein, we analysed distinct phenotypic markers of immune recovery in patients with undetectable viraemia for 8 years, taking as reference untreated patients and healthy controls. Seventy-two subjects were examined: 28 HIV-1+ patients on successful long-term HAART, 24 HIV-1+ untreated viraemic patients and 20 age-matched healthy controls. Analysis of naive and memory CD4 and CD8 T cells was combined with measurements of activation status (expression of CD38) and with thymic function (expression of CD31). Statistical significance was determined by non-parametric tests. After long-term HAART, the majority of parameters were normalized compared with age-matched control values, including T cell activation and thymic function. However, absolute counts of naive and central memory CD4 T cells remained below normal levels. The only parameters significantly associated with CD4 counts at the end of follow-up were the pre-HAART CD4 count ( β ± SD = 0.54 ± 0.16, P = 0.003) and the level of CD4 central memory cells at the end of follow-up (β ± SD = 1.18 ± 0.23, P 350 cells/mm(3) reached a complete normalization of CD4 counts. Even after long-term successful HAART, complete CD4 restoration may be attainable only in patients starting therapy with moderately high CD4 counts, prompting early initiation of antiretroviral therapy. Incomplete CD4 restoration may be associated with a defective restoration of central memory CD4 T cells, a cell subset with a pivotal role in T cell homeostasis.

  2. Clinical, virological and immunological responses in Danish HIV patients receiving raltegravir as part of a salvage regimen

    Directory of Open Access Journals (Sweden)

    Frederik N Engsig

    2010-05-01

    Full Text Available Frederik N Engsig1, Jan Gerstoft1, Gitte Kronborg2, Carsten S Larsen3, Gitte Pedersen4, Anne M Audelin5, Louise B Jørgensen5, Niels Obel11Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark; 2Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; 3Department of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark; 4Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark; 5Department of Virology, Statens Serum Institute, Copenhagen, DenmarkBackground: Raltegravir is the first integrase inhibitor approved for treatment of HIV-infected patients harboring multiresistant viruses.Methods: From a Danish population-based nationwide cohort of HIV patients we identified the individuals who initiated a salvage regimen including raltegravir and a matched cohort of HIV-infected patients initiating HAART for the first time. We compared these two cohorts for virological suppression, gain in CD4 count, and time to first change of initial regimen.Results: We identified 32 raltegravir patients and 64 HIV patients who initiated HAART for the first time in the period 1 January 2006 to 1 July 2009. The virological and immunological responses in the raltegravir patients were comparable to those seen in the control cohort. No patients in the two cohorts died and no patients terminated raltegravir treatment in the observation period. Time to first change of initial regimen was considerably shorter for HAART-naïve patients.Conclusion: We conclude that salvage regimens including raltegravir have high effectiveness in the everyday clinical setting. The effectiveness of the regimens is comparable to that observed for patients initiating HAART for the first time. The risk of change in the salvage regimens after initiation of raltegravir is low.Keywords: HIV, raltegravir, salvage regime, efficacy, matched cohort

  3. Cerebrospinal fluid analysis for HIV replication and biomarkers of immune activation and neurodegeneration in long-term atazanavir/ritonavir monotherapy treated patients.

    Science.gov (United States)

    Ferretti, Francesca; Bigoloni, Alba; Passeri, Laura; Galli, Laura; Longo, Valeria; Gerevini, Simonetta; Spagnuolo, Vincenzo; Gisslen, Magnus; Zetterberg, Henrik; Fuchs, Dietmar; Cattaneo, Dario; Caramatti, Giada; Lazzarin, Adriano; Cinque, Paola; Castagna, Antonella

    2016-07-01

    Cerebrospinal fluid (CSF) viral escape is a concern in ritonavir-boosted protease inhibitors monotherapy. The aim was to assess HIV-RNA, biomarkers of immune activation and neurodegeneration, and atazanavir concentrations in CSF of patients on successful long-term atazanavir/ritonavir (ATV/r) monotherapy. This is a substudy of the multicentric, randomized, open-label, noninferiority trial monotherapy once a day with atazanavir/ritonavir (NCT01511809), comparing the ongoing ATV/r along with 2 nucleoside retrotranscriptase inhibitors (NRTIs) regimen to a simplified ATV/r monotherapy. Patients with plasma HIV-RNA < 50 copies/mL after at least 96 study weeks were eligible.We assessed HIV-RNA, soluble (s)CD14, sCD163, CCL2, CXCL10, interleukin-6, and YKL40 by enzyme-linked immunosorbent assay; neopterin, tryptophan, kynurenine, and neurofilament by immunoassays; and ATV concentrations by liquid chromatography-mass spectrometry in paired plasma and CSF samples. Variables were compared with Wilcoxon rank-sum or Fisher exact test, as appropriate. HIV-RNA was detected in the CSF of 1/11 patients on ATV/r monotherapy (114 copies/mL), without neurological symptoms, who was successfully reintensified with his previous 2NRTIs, and in none of the 12 patients on ATV/r + 2NRTIs. CSF biomarkers and ATV concentrations did not differ between the 2 arms. CSF escape was uncommon in patients on long-term ATV/r monotherapy and was controlled with reintensification.

  4. Long-term control of HIV-1 in hemophiliacs carrying slow-progressing allele HLA-B*5101.

    Science.gov (United States)

    Kawashima, Yuka; Kuse, Nozomi; Gatanaga, Hiroyuki; Naruto, Takuya; Fujiwara, Mamoru; Dohki, Sachi; Akahoshi, Tomohiro; Maenaka, Katsumi; Goulder, Philip; Oka, Shinichi; Takiguchi, Masafumi

    2010-07-01

    HLA-B*51 alleles are reported to be associated with slow disease progression to AIDS, but the mechanism underlying this association is still unclear. In the present study, we analyzed the effect of HLA-B*5101 on clinical outcome for Japanese hemophiliacs who had been infected with HIV-1 before 1985 and had been recruited in 1998 for this study. HLA-B*5101(+) hemophiliacs exhibited significantly slow progression. The analysis of HLA-B*5101-restricted HIV-1-specific cytotoxic T-lymphocyte (CTL) responses to 4 HLA-B*-restricted epitopes in 10 antiretroviral-therapy (ART)-free HLA-B*5101(+) hemophiliacs showed that the frequency of Pol283-8-specific CD8(+) T cells was inversely correlated with the viral load, whereas the frequencies of CD8(+) T cells specific for 3 other epitopes were positively correlated with the viral load. The HLA-B*5101(+) hemophiliacs whose HIV-1 replication had been controlled for approximately 25 years had HIV-1 possessing the wild-type Pol283-8 sequence or the Pol283-8V mutant, which does not critically affect T-cell recognition, whereas other HLA-B*5101(+) hemophiliacs had HIV-1 with escape mutations in this epitope. The results suggest that the control of HIV-1 over approximately 25 years in HLA-B*5101-positive hemophiliacs is associated with a Pol283-8-specific CD8(+) T-cell response and that lack of control of HIV-1 is associated with the appearance of Pol283-8-specific escape mutants.

  5. Long-Term Control of HIV-1 in Hemophiliacs Carrying Slow-Progressing Allele HLA-B*5101▿ †

    Science.gov (United States)

    Kawashima, Yuka; Kuse, Nozomi; Gatanaga, Hiroyuki; Naruto, Takuya; Fujiwara, Mamoru; Dohki, Sachi; Akahoshi, Tomohiro; Maenaka, Katsumi; Goulder, Philip; Oka, Shinichi; Takiguchi, Masafumi

    2010-01-01

    HLA-B*51 alleles are reported to be associated with slow disease progression to AIDS, but the mechanism underlying this association is still unclear. In the present study, we analyzed the effect of HLA-B*5101 on clinical outcome for Japanese hemophiliacs who had been infected with HIV-1 before 1985 and had been recruited in 1998 for this study. HLA-B*5101+ hemophiliacs exhibited significantly slow progression. The analysis of HLA-B*5101-restricted HIV-1-specific cytotoxic T-lymphocyte (CTL) responses to 4 HLA-B*-restricted epitopes in 10 antiretroviral-therapy (ART)-free HLA-B*5101+ hemophiliacs showed that the frequency of Pol283-8-specific CD8+ T cells was inversely correlated with the viral load, whereas the frequencies of CD8+ T cells specific for 3 other epitopes were positively correlated with the viral load. The HLA-B*5101+ hemophiliacs whose HIV-1 replication had been controlled for approximately 25 years had HIV-1 possessing the wild-type Pol283-8 sequence or the Pol283-8V mutant, which does not critically affect T-cell recognition, whereas other HLA-B*5101+ hemophiliacs had HIV-1 with escape mutations in this epitope. The results suggest that the control of HIV-1 over approximately 25 years in HLA-B*5101-positive hemophiliacs is associated with a Pol283-8-specific CD8+ T-cell response and that lack of control of HIV-1 is associated with the appearance of Pol283-8-specific escape mutants. PMID:20410273

  6. T-cell responses targeting HIV Nef uniquely correlate with infected cell frequencies after long-term antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Allison S Thomas

    2017-09-01

    Full Text Available HIV-specific CD8+ T-cell responses limit viral replication in untreated infection. After the initiation of antiretroviral therapy (ART, these responses decay and the infected cell population that remains is commonly considered to be invisible to T-cells. We hypothesized that HIV antigen recognition may persist in ART-treated individuals due to low-level or episodic protein expression. We posited that if persistent recognition were occurring it would be preferentially directed against the early HIV gene products Nef, Tat, and Rev as compared to late gene products, such as Gag, Pol, and Env, which have higher barriers to expression. Using a primary cell model of latency, we observed that a Nef-specific CD8+ T-cell clone exhibited low-level recognition of infected cells prior to reactivation and robust recognition shortly thereafter. A Gag-specific CD8+ T-cell clone failed to recognized infected cells under these conditions, corresponding with a lack of detectable Gag expression. We measured HIV-specific T-cell responses in 96 individuals who had been suppressed on ART for a median of 7 years, and observed a significant, direct correlation between cell-associated HIV DNA levels and magnitudes of IFN-γ-producing Nef/Tat/Rev-specific T-cell responses. This correlation was confirmed in an independent cohort (n = 18. Correlations were not detected between measures of HIV persistence and T-cell responses to other HIV antigens. The correlation with Nef/Tat/Rev-specific T-cells was attributable to Nef-specific responses, the breadth of which also correlated with HIV DNA levels. These results suggest that ongoing Nef expression in ART-treated individuals drives preferential maintenance and/or expansion of T-cells reactive to this protein, implying sensing of infected cells by the immune system. The direct correlation, however, suggests that recognition does not result in efficient elimination of infected cells. These results raise the possibility that

  7. The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda

    NARCIS (Netherlands)

    Bartelink, Imke H.; Savic, Rada M.; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J.; Capparelli, Edmund; Jullien, Vincent; Young, Sera L.; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

    2015-01-01

    Malnutrition may impact the pharmacokinetics (PKs) of antiretroviral medications and virologic responses in HIV-infected children. The authors therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected

  8. Prime-Boost Vaccination Using Chemokine-Fused gp120 DNA and HIV Envelope Peptides Activates Both Immediate and Long-Term Memory Cellular Responses in Rhesus Macaques

    Directory of Open Access Journals (Sweden)

    Hong Qin

    2010-01-01

    Full Text Available HIV vaccine candidates with improved immunogenicity and induction of mucosal T-cell immunity are needed. A prime-boost strategy using a novel HIV glycoprotein 120 DNA vaccine was employed to immunize rhesus macaques. The DNA vaccine encoded a chimeric gp120 protein in fusion with monocyte chemoattractant protein-3, which was hypothesized to improve the ability of antigen-presenting cells to capture viral antigen through chemokine receptor-mediated endocytosis. DNA vaccination induced virus-reactive T cells in peripheral blood, detectable by T cell proliferation, INFγ ELISPOT and sustained IL-6 production, without humoral responses. With a peptide-cocktail vaccine containing a set of conserved polypeptides of HIV-1 envelope protein, given by nasogastric administration, primed T-cell immunity was significantly boosted. Surprisingly, long-term and peptide-specific mucosal memory T-cell immunity was detected in both vaccinated macaques after one year. Therefore, data from this investigation offer proof-of-principle for potential effectiveness of the prime-boost strategy with a chemokine-fused gp120 DNA and warrant further testing in the nonhuman primate models for developing as a potential HIV vaccine candidate in humans.

  9. Virological failure and all-cause mortality in HIV-positive adults with low-level viremia during antiretroviral treatment.

    Directory of Open Access Journals (Sweden)

    Olof Elvstam

    Full Text Available Although most HIV-infected individuals achieve undetectable viremia during antiretroviral therapy (ART, a subset have low-level viremia (LLV of varying duration and magnitude. The impact of LLV on treatment outcomes is unclear. We investigated the association between LLV and virological failure and/or all-cause mortality among Swedish patients receiving ART.HIV-infected patients from two Swedish HIV centers were identified from the nationwide register InfCare HIV. Subjects aged ≥15 years with triple agent ART were included at 12 months after treatment initiation if ≥2 following viral load measurements were available. Patients with 2 consecutive HIV RNA values ≥1000 copies/mL at this time point were excluded. Participants were stratified into four categories depending on viremia profiles: permanently suppressed viremia (<50 copies/mL, LLV 50-199 copies/mL, LLV 200-999 copies/mL and viremia ≥1000 copies/mL. Association between all four viremia categories and all-cause death was calculated using survival analysis with viremia as a time-varying covariate, so that patients could change viremia category during follow-up. Association between the three lower categories and virological failure (≥2 consecutive measurements ≥1000 copies/mL was calculated in a similar manner.LLV 50-199 copies/mL was recorded in 70/1015 patients (6.9% and LLV 200-999 copies/mL in 89 (8.8% during 7812 person-years of follow-up (median 6.5 years. LLV 200-999 copies/mL was associated with virological failure (adjusted hazard ratio 3.14 [95% confidence interval 1.41-7.03, p<0.01], whereas LLV 50-199 copies/mL was not (1.01 [0.34-4.31, p = 0.99]; median follow-up 4.5 years. LLV 200-999 copies/mL had an adjusted mortality hazard ratio of 2.29 (0.98-5.32, p = 0.05 and LLV 50-199 copies/mL of 2.19 (0.90-5.37, p = 0.09.In this Swedish cohort followed during ART for a median of 4.5 years, LLV 200-999 copies/mL was independently associated with virological failure. Patients

  10. Viremic long-term nonprogressive HIV-1 infection is not associated with abnormalities in known Nef functions

    NARCIS (Netherlands)

    Heigele, Anke; Camerini, David; van't Wout, Angélique B.; Kirchhoff, Frank

    2014-01-01

    A small minority of HIV-1-infected individuals show low levels of immune activation and do not develop immunodeficiency despite high viral loads. Since the accessory viral Nef protein modulates T cell activation and plays a key role in the pathogenesis of AIDS, we investigated whether specific

  11. HIV gender-based vulnerabilities of women using drugs in long-term heterosexual relationships: baseline results from a randomized trial in Ukraine

    Directory of Open Access Journals (Sweden)

    Shulga, Liudmyla

    2012-07-01

    Full Text Available BACKGROUND: Sexual way of HIV transmission in Ukraine outweighs parenteral route since 2007. In response to situation change couple’s counseling for IDUs was introduced and is currently tested within randomized trial.METHODS: Baseline data were collected in June-September 2011: 548 IDU couples in 10 cities were surveyed and screened for HIV and Hepatitis C. Participants were recruited using respondent-driven sampling method. RESULTS: The average age of participants varied between 30 – 33 years old with women being 3 years younger. On many aspects drug using couples in long-term relationships share the same values as non-drug using couples. However, drug use resulted into specific HIV/STIs risks for the couple. Common reasons of being with the current partner included mutual understanding (98%; similar life styles (90%; understanding life with addiction (88%; and love (87%. At the same time, looking at the quality time partners spend together, it was found that mostly, they are connected by their drug use, fear of social exclusion and economical reasons. Although these factors are important for both men and women, they have a bigger impact on women and put them into more vulnerable position: 25% have children who in 59% of cases mostly live with mother and her partner; 40% live in a partner’s house; 30% are financially supported by partners; 77% women get drugs from partners and only 20% are first one to be injected. Trust also seems to be an issue. Thus, 83% of respondents believe that they know the HIV/STI status of their partner and 90% of those believe it to be negative, while 20% of those surveyed appeared to be HIV positive and about 30% Hepatitis C positive. CONCLUSIONS: Understanding characteristics of sexual partners is crucial for HIV prevention programme design and implementation.

  12. Antiretroviral therapy initiation before, during, or after pregnancy in HIV-1-infected women: maternal virologic, immunologic, and clinical response.

    Directory of Open Access Journals (Sweden)

    Vlada V Melekhin

    2009-09-01

    Full Text Available Pregnancy has been associated with a decreased risk of HIV disease progression in the highly active antiretroviral therapy (HAART era. The effect of timing of HAART initiation relative to pregnancy on maternal virologic, immunologic and clinical outcomes has not been assessed.We conducted a retrospective cohort study from 1997-2005 among 112 pregnant HIV-infected women who started HAART before (N = 12, during (N = 70 or after pregnancy (N = 30.Women initiating HAART before pregnancy had lower CD4+ nadir and higher baseline HIV-1 RNA. Women initiating HAART after pregnancy were more likely to receive triple-nucleoside reverse transcriptase inhibitors. Multivariable analyses adjusted for baseline CD4+ lymphocytes, baseline HIV-1 RNA, age, race, CD4+ lymphocyte count nadir, history of ADE, prior use of non-HAART ART, type of HAART regimen, prior pregnancies, and date of HAART start. In these models, women initiating HAART during pregnancy had better 6-month HIV-1 RNA and CD4+ changes than those initiating HAART after pregnancy (-0.35 vs. 0.10 log(10 copies/mL, P = 0.03 and 183.8 vs. -70.8 cells/mm(3, P = 0.03, respectively but similar to those initiating HAART before pregnancy (-0.32 log(10 copies/mL, P = 0.96 and 155.8 cells/mm(3, P = 0.81, respectively. There were 3 (25% AIDS-defining events or deaths in women initiating HAART before pregnancy, 3 (4% in those initiating HAART during pregnancy, and 5 (17% in those initiating after pregnancy (P = 0.01. There were no statistical differences in rates of HIV disease progression between groups.HAART initiation during pregnancy was associated with better immunologic and virologic responses than initiation after pregnancy.

  13. Clinical Outcomes of Virologically-Suppressed Patients with Pre-existing HIV-1 Drug Resistance Mutations Switching to Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in the SPIRIT Study.

    Science.gov (United States)

    Porter, Danielle P; Toma, Jonathan; Tan, Yuping; Solberg, Owen; Cai, Suqin; Kulkarni, Rima; Andreatta, Kristen; Lie, Yolanda; Chuck, Susan K; Palella, Frank; Miller, Michael D; White, Kirsten L

    2016-02-01

    Antiretroviral regimen switching may be considered for HIV-1-infected, virologically-suppressed patients to enable treatment simplification or improve tolerability, but should be guided by knowledge of pre-existing drug resistance. The current study examined the impact of pre-existing drug resistance mutations on virologic outcomes among virologically-suppressed patients switching to Rilpivirine (RPV)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF). SPIRIT was a phase 3b study evaluating the safety and efficacy of switching to RPV/FTC/TDF in virologically-suppressed HIV-1-infected patients. Pre-existing drug resistance at baseline was determined by proviral DNA genotyping for 51 RPV/FTC/TDF-treated patients with known mutations by historical RNA genotype and matched controls and compared with clinical outcome at Week 48. Drug resistance mutations in protease or reverse transcriptase were detected in 62.7% of patients by historical RNA genotype and in 68.6% by proviral DNA genotyping at baseline. Proviral DNA sequencing detected 89% of occurrences of NRTI and NNRTI resistance-associated mutations reported by historical genotype. Mutations potentially affecting RPV activity, including E138A/G/K/Q, Y181C, and H221Y, were detected in isolates from 11 patients by one or both assays. None of the patients with single mutants had virologic failure through Week 48. One patient with pre-existing Y181Y/C and M184I by proviral DNA genotyping experienced virologic failure. Nineteen patients with K103N present by historical genotype were confirmed by proviral DNA sequencing and 18/19 remained virologically-suppressed. Virologic success rates were high among virologically-suppressed patients with pre-existing NRTI and NNRTI resistance-associated mutations who switched to RPV/FTC/TDF in the SPIRIT study. While plasma RNA genotyping remains preferred, proviral DNA genotyping may provide additional value in virologically-suppressed patients for whom historical resistance

  14. Any impact of blips and low-level viraemia episodes among HIV-infected patients with sustained virological suppression on ART?

    Science.gov (United States)

    Pernas, Berta; Grandal, Marta; Pertega, Sonia; Cañizares, Angelina; Castro-Iglesias, Ángeles; Mena, Álvaro; Rodriguez-Osorio, Iria; Tabernilla, Andrés; Pedreira, José D; Poveda, Eva

    2016-04-01

    The objective of this study was to evaluate the prevalence of blips and risk of virological failure (VF) among HIV-infected patients with sustained virological suppression (HIV-RNA ART. Newly diagnosed (2004-13) HIV-infected patients with sustained virological suppression on ART (minimum follow-up of 3 months) were identified. Risk of VF was evaluated according to different plasma HIV-RNA quantification values based on the limits of quantification/detection of current commercial assays (20 copies/mL). Kaplan-Meier and Cox proportional hazards models were used to compare the cumulative incidence of VF. A total of 565 newly diagnosed HIV-infected patients were identified: 453 started ART and 354 achieved virological suppression. Prevalence of blips (isolated HIV-RNA ranging from 50 to 200 copies/mL) and VF (HIV-RNA ≥50 copies/mL) was 22.7% and 8.8%, respectively (mean follow-up of 42 months). Multivariate analysis identified differences between HIV-RNA values as an independent predictor of VF (P = 0.008); risk of VF was higher for patients with blips [HR 2.500 (95% CI 0.524-11.926)] and for those with at least three consecutive detected, but not quantified, HIV-RNA determinations (HIV-RNA 200 copies/mL [33.7% at 24 and 60 months versus ART. HIV patients with blips and at least three consecutive detected, but not quantified, HIV-RNA determinations (<20 copies/mL) had a higher risk of VF. These findings highlight the relevance of maintaining HIV-RNA levels below the limits of quantification of current assays (<20 copies/mL). © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. Genomic analysis of HIV type 1 strains derived from a mother and child pair of long-term nonprogressors

    Czech Academy of Sciences Publication Activity Database

    Reiniš, Milan; Weiser, B.; Kuiken, C.; Dong, T.; Lang, D.; Nachman, S.; Zhang, Y.; Rowland-Jones, S.; Burger, H.

    2007-01-01

    Roč. 23, č. 2 (2007), s. 309-315 ISSN 0889-2229 Grant - others:U.S. National Institue of Allergy and Infectious Disease (US) RO1-AI-42555; Fogarty International Center, the National Institute on Drug Abuse, and the National Heart Lung and Blood Institute(US) D43 TW000233 Institutional research plan: CEZ:AV0Z50520514 Keywords : HIV-1 * genomic analysis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.022, year: 2007

  16. How important are human immunodeficiency virus (HIV) clinical markers to the long-term formal employment among people living with HIV in developing countries? A study in South Africa.

    Science.gov (United States)

    Odek, W O; Glendinning, A; Charalambous, S

    2014-01-01

    To examine the relationship of Human Immunodeficiency Virus (HIV) clinical markers and socio-demographic characteristics with long-term formal employment among people living with HIV (PLHIV). 554 adults, 55% females, on HIV treatment for at least two years at two public hospitals in Johannesburg, South Africa. A retrospective cohort design, tracing changes in study participants' formal employment status since the first HIV-positive diagnosis. Data collection included historical medical records review and interviewer-administered questionnaires. 44% of all study participants (39% and 49% among males and females, respectively) were formally employed at the time of the study, primarily in low-skilled jobs in the private sector. The majority (83%) of males and 60% of females remained in formal employment since being diagnosed as HIV-positive. Female gender, education to grade 12 or higher, a smaller household size and being married were significantly associated with current formal employment. Formal employment was unrelated to HIV treatment indicators (CD4 count, viral load and duration since diagnosis). Of those in formal employment, 68 (28%) were aware of HIV policies at their workplaces, which was also positively associated with the duration in their current employment. PLHIV in developing country contexts can enter into and maintain formal employment, especially when treatment and workplace support are available. Thus, employer organisations should implement effective workplace HIV policies to enhance employment experiences of their workforce living with HIV. Care and support services for people on HIV treatment should also address their career development needs.

  17. HIV is Now a Manageable Long-Term Condition, But What Makes it Unique? A Qualitative Study Exploring Views About Distinguishing Features from Multi-Professional HIV Specialists in North West England.

    Science.gov (United States)

    Jelliman, Pauline; Porcellato, Lorna

    HIV is evolving from a life-threatening infection to a long-term, manageable condition because of medical advances, radical changes in health and social care policy, and the impact of an aging population. However, HIV remains complex, presenting unique characteristics distinguishing it from other long-term conditions (LTCs). Our aim in this qualitative descriptive study was to identify and explore these features in the context of LTCs. A focus group (FG) method was used to gather the views and experiences of multi-professional HIV specialists who worked in North West England. Twenty-four staff participated in FGs (n = 3), which were audio recorded, manually transcribed, and thematically analyzed. We found four main themes: (a) stigma, (b) challenges faced by HIV specialists, (c) lack HIV-related knowledge, and (d) unique features, termed "stand alone." We concluded that these distinguishing features hindered full recognition and acceptance of HIV as an LTC. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  18. Replication Capacity in Relation to Immunologic and Virologic Outcomes in HIV-1 infected, Treatment-Naïve Subjects

    Science.gov (United States)

    Skowron, Gail; Spritzler, John G.; Weidler, Jodi; Robbins, Gregory K.; Johnson, Victoria A.; Chan, Ellen S.; Asmuth, David M.; Gandhi, Rajesh T.; Lie, Yolanda; Bates, Michael; Pollard, Richard B.

    2012-01-01

    Objectives To evaluate the association between baseline (BL) replication capacity (RC) [RCBL] and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1 infected subjects initiating antiretroviral therapy. Methods RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naïve subjects from ACTG384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. Results Higher RCBL was associated with lower baseline CD4 (CD4BL) (r=−0.23, p<0.0001), higher baseline HIV-1 (RNABL) (r=0.25, p<0.0001), higher CD4BL activation percent (r=0.23, p<0.0001) and lower CD4BL memory count (r=−0.21, p=0.0002). In a multivariable model, week 48 CD4 increase (ΔCD448) was associated with lower CD4BL memory count and higher CD4BL naive percent (p=0.004, p=0.015, respectively). The interaction between CD4BL and RCBL was significant (p=0.018), with a positive association between RCBL and ΔCD448 in subjects with higher CD4BL, and a negative association at lower absCD4BL. Conclusions At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different baseline CD4 counts. PMID:19194319

  19. Replication capacity in relation to immunologic and virologic outcomes in HIV-1-infected treatment-naive subjects.

    Science.gov (United States)

    Skowron, Gail; Spritzler, John G; Weidler, Jodi; Robbins, Gregory K; Johnson, Victoria A; Chan, Ellen S; Asmuth, David M; Gandhi, Rajesh T; Lie, Yolanda; Bates, Michael; Pollard, Richard B

    2009-03-01

    To evaluate the association between baseline (BL) replication capacity (RC) (RCBL) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy. RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. Higher RCBL was associated with lower baseline CD4 (CD4BL) (r = -0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4BL activation percent (r = 0.23, P < 0.0001), and lower CD4BL memory count (r = -0.21, P = 0.0002). In a multivariable model, week 48 CD4 increase (DeltaCD448) was associated with lower CD4BL memory count and higher CD4BL-naive percent (P = 0.004, P = 0.015, respectively). The interaction between CD4BL and RCBL was significant (P = 0.018), with a positive association between RCBL and DeltaCD448 in subjects with higher CD4BL and a negative association at lower absCD4BL. At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts.

  20. Point-of-Care Virologic Testing to Improve Outcomes of HIV-Infected Children in Zambia: A Clinical Trial Protocol.

    Science.gov (United States)

    Chibwesha, Carla J; Ford, Catherine E; Mollan, Katie R; Stringer, Jeffrey S A

    2016-08-01

    In the absence of early infant diagnosis (EID) and immediate antiretroviral therapy (ART), some 50% of untreated HIV-infected infants die before age 2. Conventional EID requires sophisticated instruments that are typically placed in centralized or reference laboratories. In low-resource settings, centralized systems often lead to result turnaround times of several months, long delays in diagnosis, and adverse outcomes for HIV-infected children. Our clinical trial tests the effectiveness of a new point-of-care (POC) diagnostic technology to identify HIV-infected infants and start providing them life-saving ART as soon as possible. The study uses a randomized, controlled design to test whether the Alere q platform for HIV DNA polymerase chain reaction (PCR) testing improves outcomes of HIV-infected children in Zambia. We aim to enroll 2867 HIV-exposed infants aged 4-12 weeks and to follow those who are HIV infected for 12 months as they receive HIV care at 6 public health facilities in Lusaka. The trial's primary endpoint is the proportion of HIV-infected infants in each study arm who start ART and remain alive, in care, and virally suppressed 12 months after their diagnostic blood draw. Our trial will provide evidence for the incremental benefit of implementing a POC EID strategy in low-resource settings where only off-site PCR services are currently available. The results will be useful in guiding future decisions regarding investments in POC virologic testing as part of overall pediatric AIDS mitigation strategies in sub-Saharan Africa. clinicaltrials.gov NCT02682810.

  1. Long-term effect of depot medroxyprogesterone acetate on vaginal microbiota, epithelial thickness and HIV target cells.

    Science.gov (United States)

    Mitchell, Caroline M; McLemore, Leslie; Westerberg, Katharine; Astronomo, Rena; Smythe, Kimberly; Gardella, Carolyn; Mack, Matthias; Magaret, Amalia; Patton, Dorothy; Agnew, Kathy; McElrath, M Juliana; Hladik, Florian; Eschenbach, David

    2014-08-15

    Depot medroxyprogesterone acetate (DMPA) has been linked to human immunodeficiency virus type 1 (HIV-1) acquisition. Vaginal microbiota of women using DMPA for up to 2 years were cultured. Mucosal immune cell populations were measured by immunohistological staining. Over 12 months, the proportion with H2O2-positive lactobacilli decreased (n = 32; 53% vs 27%; P = .03). Median vaginal CD3(+) cells also decreased (n = 15; 355 vs 237 cells/mm(2); P = .03), as did CD3(+)CCR5(+) cells (195 vs 128 cells/mm(2); P = .04), HLA-DR(+) cells (130 vs 96 cells/mm(2); P = .27), and HLA-DR(+)CCR5(+) cells (18 vs 10 cells/mm(2); P = .33). DMPA contraception does not increase vaginal mucosal CCR5(+) HIV target cells but does decrease CD3(+) T lymphocytes and vaginal H2O2-producing lactobacilli. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Long-term persistence and function of hematopoietic stem cell-derived chimeric antigen receptor T cells in a nonhuman primate model of HIV/AIDS.

    Directory of Open Access Journals (Sweden)

    Anjie Zhen

    2017-12-01

    Full Text Available Chimeric Antigen Receptor (CAR T-cells have emerged as a powerful immunotherapy for various forms of cancer and show promise in treating HIV-1 infection. However, significant limitations are persistence and whether peripheral T cell-based products can respond to malignant or infected cells that may reappear months or years after treatment remains unclear. Hematopoietic Stem/Progenitor Cells (HSPCs are capable of long-term engraftment and have the potential to overcome these limitations. Here, we report the use of a protective CD4 chimeric antigen receptor (C46CD4CAR to redirect HSPC-derived T-cells against simian/human immunodeficiency virus (SHIV infection in pigtail macaques. CAR-containing cells persisted for more than 2 years without any measurable toxicity and were capable of multilineage engraftment. Combination antiretroviral therapy (cART treatment followed by cART withdrawal resulted in lower viral rebound in CAR animals relative to controls, and demonstrated an immune memory-like response. We found CAR-expressing cells in multiple lymphoid tissues, decreased tissue-associated SHIV RNA levels, and substantially higher CD4/CD8 ratios in the gut as compared to controls. These results show that HSPC-derived CAR T-cells are capable of long-term engraftment and immune surveillance. This study demonstrates for the first time the safety and feasibility of HSPC-based CAR therapy in a large animal preclinical model.

  3. A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy

    DEFF Research Database (Denmark)

    Paredes, Roger; Puertas, Maria Carmen; Bannister, Wendy

    2011-01-01

    Background. The clinical relevance of mutations in the connection subdomain and the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain. Methods. The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated...... in NNRTI-naive patients who started NNRTIs in the EuroSIDA study after July 1997 according to preexisting substitutions in the connection subdomain and the RNase H domain of HIV-1 RT. An observed association between A376S and virological failure was further investigated by testing in vitro NNRTI...... = .013). A376S conferred selective low-level nevirapine resistance in vitro, and led to greater affinity for double-stranded DNA. Conclusions. The A376S substitution in the connection subdomain of HIV-1 RT causes selective nevirapine resistance and confers an increased risk of virological failure...

  4. Dual Therapy Treatment Strategies for the Management of Patients Infected with HIV: A Systematic Review of Current Evidence in ARV-Naive or ARV-Experienced, Virologically Suppressed Patients.

    Science.gov (United States)

    Baril, Jean-Guy; Angel, Jonathan B; Gill, M John; Gathe, Joseph; Cahn, Pedro; van Wyk, Jean; Walmsley, Sharon

    2016-01-01

    We reviewed the current literature regarding antiretroviral (ARV)-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection. A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations. Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels. The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable insights into the

  5. Dual Therapy Treatment Strategies for the Management of Patients Infected with HIV: A Systematic Review of Current Evidence in ARV-Naive or ARV-Experienced, Virologically Suppressed Patients.

    Directory of Open Access Journals (Sweden)

    Jean-Guy Baril

    Full Text Available We reviewed the current literature regarding antiretroviral (ARV-sparing therapy strategies to determine whether these novel regimens can be considered appropriate alternatives to standard regimens for the initial treatment of ARV-naive patients or as switch therapy for those patients with virologically suppressed HIV infection.A search for studies related to HIV dual therapy published from January 2000 through April 2014 was performed using Biosis, Derwent Drug File, Embase, International Pharmaceutical Abstracts, Medline, Pascal, SciSearch, and TOXNET databases; seven major trial registries, and the abstracts of major conferences. Using predetermined criteria for inclusion, an expert review committee critically reviewed and qualitatively evaluated all identified trials for efficacy and safety results and potential limitations.Sixteen studies of dual therapy regimens were critiqued for the ARV-naive population. Studies of a protease inhibitor/ritonavir in combination with the integrase inhibitor raltegravir or the nucleoside reverse transcriptase inhibitor lamivudine provided the most definitive evidence supporting a role for dual therapy. In particular, lopinavir/ritonavir or darunavir/ritonavir combined with raltegravir and lopinavir/ritonavir combined with lamivudine demonstrated noninferiority to standard of care triple therapy after 48 weeks of treatment. Thirteen trials were critiqued in ARV-experienced, virologically suppressed patients. The virologic efficacy outcomes were mixed. Although overall data regarding toxicity are limited, when compared with standard triple therapy, certain dual therapy regimens may offer advantages in renal function, bone mineral density, and limb fat changes; however, some dual combinations may elevate lipid or bilirubin levels.The potential benefits of dual therapy regimens include reduced toxicity, improved tolerability and adherence, and reduced cost. Although the data reviewed here provide valuable

  6. Characterization of HIV-1 from patients with virological failure to a boosted protease inhibitor regimen

    DEFF Research Database (Denmark)

    Lillemark, Marie Rathcke; Gerstoft, Jan; Obel, Niels

    2011-01-01

    The use of highly active antiretroviral treatment (HAART) regimens with unboosted protease inhibitors (PIs) has resulted in a high level of virological failure primarily due to the development of resistant virus. Current boosted PI regimens combine successfully low-dose ritonavir (r) with a second.......3%) experienced virological failure, of whom 19 (83%) started PI/r treatment before 2001. Patients from Copenhagen (n=19) were selected to study the development of protease (PR) and gag cleavage site (CS) mutations during PI/r treatment and PI plasma levels at the time of virological failure. Three patients (16......%) developed major PI resistance mutations. Mutations in the p7/p1 and p1/p6 gag CS only developed in patients with major or minor mutations in PR. Drug concentrations were low or undetectable in 10 out of the 19 patients. In total PR resistance mutations and low drug levels could account for 12 (63...

  7. Long-term Mortality in HIV-Positive Individuals Virally Suppressed for >3 Years With Incomplete CD4 Recovery

    DEFF Research Database (Denmark)

    Engsig, Frederik N; Zangerle, Robert; Katsarou, Olga

    2014-01-01

    BACKGROUND: Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/µL after 3 years...... of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery (≤200 cells/µL) and Cox regression to identify associations with mortality. RESULTS: Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/µL after 3 years of suppression. Increasing...... age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/µL. Individuals with CD4 ≤200 cells/µL after 3...

  8. Access to HIV Care and Resilience in a Long-Term Conflict Setting: A Qualitative Assessment of the Experiences of Living with Diagnosed HIV in Mogadishu, Somali.

    Science.gov (United States)

    Kulane, Asli; Owuor, John O A; Sematimba, Douglas; Abdulahi, Sacdia Abdisamad; Yusuf, Hamdi Moalim; Mohamed, Lul M

    2017-07-05

    Human Immunodeficiency Virus (HIV) continues to take a heavy toll on the lives of many people, with the worst impact on health and wellbeing for the affected individuals in fragile states. The HIV situation in Somalia is not clearly known and experiences of the people living with HIV in this war-torn region are often unexpressed. This pilot qualitative study sought to explore the experiences of people diagnosed with HIV living in Mogadishu, and their resilience in access to care and social support. Participants were recruited through drug dispensers at the HIV clinic in Banadir Hospital. Face-to-face in-depth interviews were conducted in Somali in May 2013 among patients who were receiving antiretroviral therapy (ART) from the HIV clinic in Mogadishu. These were tape-recorded, transcribed, and translated for content analysis. Three women and four men who were living with HIV shared the following narratives. Their perception was that they had either got HIV from their spouses or through health care contamination. They were very knowledgeable about the realities of HIV, how the medication works, nutritional requirements, and drug adherence. They were always willing to go an extra mile to secure a good life for themselves. However, the external HIV stigma impacted their access to care. They faced challenges in their homes and at work which compelled them to seek support from non-governmental organizations (NGOs) or close family members. This stigma often affected their disclosure to the wider community due to the uncertainty of the repercussions, leading to a life of extreme loneliness and financial difficulties. The participants' coping mechanisms included living together and starting their own NGO for support with very strong optimism about their prognosis. The people diagnosed with HIV living in Mogadishu are highly knowledgeable about HIV transmission, the realities of living with a diagnosed HIV infection, and the efficacy of HIV treatment. Our small sample

  9. Access to HIV Care and Resilience in a Long-Term Conflict Setting: A Qualitative Assessment of the Experiences of Living with Diagnosed HIV in Mogadishu, Somali

    Science.gov (United States)

    Kulane, Asli; Owuor, John O. A.; Abdulahi, Sacdia Abdisamad; Yusuf, Hamdi Moalim; Mohamed, Lul M.

    2017-01-01

    Background: Human Immunodeficiency Virus (HIV) continues to take a heavy toll on the lives of many people, with the worst impact on health and wellbeing for the affected individuals in fragile states. The HIV situation in Somalia is not clearly known and experiences of the people living with HIV in this war-torn region are often unexpressed. This pilot qualitative study sought to explore the experiences of people diagnosed with HIV living in Mogadishu, and their resilience in access to care and social support. Methods: Participants were recruited through drug dispensers at the HIV clinic in Banadir Hospital. Face-to-face in-depth interviews were conducted in Somali in May 2013 among patients who were receiving antiretroviral therapy (ART) from the HIV clinic in Mogadishu. These were tape-recorded, transcribed, and translated for content analysis. Results: Three women and four men who were living with HIV shared the following narratives. Their perception was that they had either got HIV from their spouses or through health care contamination. They were very knowledgeable about the realities of HIV, how the medication works, nutritional requirements, and drug adherence. They were always willing to go an extra mile to secure a good life for themselves. However, the external HIV stigma impacted their access to care. They faced challenges in their homes and at work which compelled them to seek support from non-governmental organizations (NGOs) or close family members. This stigma often affected their disclosure to the wider community due to the uncertainty of the repercussions, leading to a life of extreme loneliness and financial difficulties. The participants’ coping mechanisms included living together and starting their own NGO for support with very strong optimism about their prognosis. Conclusions: The people diagnosed with HIV living in Mogadishu are highly knowledgeable about HIV transmission, the realities of living with a diagnosed HIV infection, and the

  10. Low Virologic Failure and Drug Resistance among HIV-Infected Patients Receiving Hospital-Based ART While Care and Outreach through Community in Guangxi, China.

    Science.gov (United States)

    Liang, Shujia; Shen, Zhiyong; Yan, Jing; Liang, Fuxiong; Tang, Zhenzhu; Liu, Wei; Kan, Wei; Liao, Lingjie; Leng, Xuebing; Ruan, Yuhua; Xing, Hui; Shao, Yiming

    2015-01-01

    To investigate human immunodeficiency virus (HIV) virologic suppression and drug resistance among HIV-infected patients receiving first-line antiretroviral treatment (ART) in hospitals while community care and outreach through local health workers in Guangxi, China. This was a series of cross-sectional surveys from 2004 to 2012 in Guangxi, supported by the Chinese National HIVDR Surveillance and Monitoring Network Working Group. Guangxi, China. Demographic, ART, and laboratory data (CD4(+) cell count, viral load, and drug resistance) were analyzed. Factors associated with virologic suppression were identified by logistic regression analysis. A total of 780 patients were included in this study. The median treatment duration was 20.6 months (IQR 6.6-35.9). Of 780 study participants, 95.4% of patients (744/780) had HIV virologic suppression. Among these, of the 143 patients who were infected through drug injection, only 10 (7.0%) experienced virologic failure, and the overall prevalence of HIV drug resistance was 2.8% (22/789). Factors associated with virologic suppression in the final multivariate models included self-reported missing doses in the past month (compared to not missing doses in the past month, AOR = 0.2, 95% CI: 0.1-0.6) and initial ART regimen without 3TC (compared to initial ART regimen with 3TC, AOR = 0.2, 95% CI: 0.1-0.4). Moreover, the trend chi-square test showed that the proportion of virologic suppression increased over time from 2004 to 2012 (P = 0.002). This study first demonstrated that HIV patients infected through various transmission routes can achieve an excellent treatment outcome in hospitals at or above the county level for free first-line ART in Guangxi. It is an important of ART education and adherence to intervention for achieving better treatment outcomes.

  11. A decade of HAART in Latin America: Long term outcomes among the first wave of HIV patients to receive combination therapy.

    Science.gov (United States)

    Wolff, Marcelo J; Giganti, Mark J; Cortes, Claudia P; Cahn, Pedro; Grinsztejn, Beatriz; Pape, Jean W; Padgett, Denis; Sierra-Madero, Juan; Gotuzzo, Eduardo; Duda, Stephany N; McGowan, Catherine C; Shepherd, Bryan E

    2017-01-01

    In Latin America, the first wave of HIV-infected patients initiated highly active antiretroviral therapy (HAART) 10 or more years ago. Characterizing their treatment experience and corresponding outcomes across a decade of HAART may yield insights relevant to the ongoing care of such patients and those initiating HAART more recently in similar clinical settings. This retrospective study included adults initiating HAART before 2004 at 8 sites in Argentina, Brazil, Chile, Haiti, Honduras, and Mexico. Patient status (in care, dead, or lost to follow-up [LTFU]) was assessed at 6-month intervals for 10 years, along with CD4 count and HIV-1 viral load (VL) for patients in care. 4,975 patients (66% male) started HAART prior to 2004; 45% were not antiretroviral-naïve. At 1, 5, and 10 years, rates of mortality were 4.2%, 9.0%, and 13.6% respectively. LTFU rates for the same periods were 2.4%, 10.9%, and 24.2%. Among patients remaining in care at 10 years, 84.4% were estimated to have VL≤400 copies/mL (Haiti excluded) and median baseline CD4 increased from 158 to 525 cells/mm3. Only 11.4% of all patients remained on their first regimen, 12.6% were on their second, 11.5% were on their third, and 23.0% were on their fourth or subsequent regimen. Outcomes were generally better for patients who were not antiretroviral-naïve, except for viral suppression. Heterogeneity among sites was substantial. Despite advanced disease and predominant use of older antiretrovirals, a large percentage of early HAART initiators in this Latin American cohort were alive and in care with sustained virologic suppression and progressive immune recovery after 10 years.

  12. A decade of HAART in Latin America: Long term outcomes among the first wave of HIV patients to receive combination therapy

    Science.gov (United States)

    Wolff, Marcelo J.; Giganti, Mark J.; Cortes, Claudia P.; Cahn, Pedro; Grinsztejn, Beatriz; Pape, Jean W.; Padgett, Denis; Sierra-Madero, Juan; Gotuzzo, Eduardo; Duda, Stephany N.; McGowan, Catherine C.; Shepherd, Bryan E.

    2017-01-01

    Background In Latin America, the first wave of HIV-infected patients initiated highly active antiretroviral therapy (HAART) 10 or more years ago. Characterizing their treatment experience and corresponding outcomes across a decade of HAART may yield insights relevant to the ongoing care of such patients and those initiating HAART more recently in similar clinical settings. Methods This retrospective study included adults initiating HAART before 2004 at 8 sites in Argentina, Brazil, Chile, Haiti, Honduras, and Mexico. Patient status (in care, dead, or lost to follow-up [LTFU]) was assessed at 6-month intervals for 10 years, along with CD4 count and HIV-1 viral load (VL) for patients in care. Results 4,975 patients (66% male) started HAART prior to 2004; 45% were not antiretroviral-naïve. At 1, 5, and 10 years, rates of mortality were 4.2%, 9.0%, and 13.6% respectively. LTFU rates for the same periods were 2.4%, 10.9%, and 24.2%. Among patients remaining in care at 10 years, 84.4% were estimated to have VL≤400 copies/mL (Haiti excluded) and median baseline CD4 increased from 158 to 525 cells/mm3. Only 11.4% of all patients remained on their first regimen, 12.6% were on their second, 11.5% were on their third, and 23.0% were on their fourth or subsequent regimen. Outcomes were generally better for patients who were not antiretroviral-naïve, except for viral suppression. Heterogeneity among sites was substantial. Conclusions Despite advanced disease and predominant use of older antiretrovirals, a large percentage of early HAART initiators in this Latin American cohort were alive and in care with sustained virologic suppression and progressive immune recovery after 10 years. PMID:28651014

  13. Nucleocapsid promotes localization of HIV-1 gag to uropods that participate in virological synapses between T cells.

    Science.gov (United States)

    Llewellyn, G Nicholas; Hogue, Ian B; Grover, Jonathan R; Ono, Akira

    2010-10-28

    T cells adopt a polarized morphology in lymphoid organs, where cell-to-cell transmission of HIV-1 is likely frequent. However, despite the importance of understanding virus spread in vivo, little is known about the HIV-1 life cycle, particularly its late phase, in polarized T cells. Polarized T cells form two ends, the leading edge at the front and a protrusion called a uropod at the rear. Using multiple uropod markers, we observed that HIV-1 Gag localizes to the uropod in polarized T cells. Infected T cells formed contacts with uninfected target T cells preferentially via HIV-1 Gag-containing uropods compared to leading edges that lack plasma-membrane-associated Gag. Cell contacts enriched in Gag and CD4, which define the virological synapse (VS), are also enriched in uropod markers. These results indicate that Gag-laden uropods participate in the formation and/or structure of the VS, which likely plays a key role in cell-to-cell transmission of HIV-1. Consistent with this notion, a myosin light chain kinase inhibitor, which disrupts uropods, reduced virus particle transfer from infected T cells to target T cells. Mechanistically, we observed that Gag copatches with antibody-crosslinked uropod markers even in non-polarized cells, suggesting an association of Gag with uropod-specific microdomains that carry Gag to uropods. Finally, we determined that localization of Gag to the uropod depends on higher-order clustering driven by its NC domain. Taken together, these results support a model in which NC-dependent Gag accumulation to uropods establishes a preformed platform that later constitutes T-cell-T-cell contacts at which HIV-1 virus transfer occurs.

  14. Nucleocapsid promotes localization of HIV-1 gag to uropods that participate in virological synapses between T cells.

    Directory of Open Access Journals (Sweden)

    G Nicholas Llewellyn

    2010-10-01

    Full Text Available T cells adopt a polarized morphology in lymphoid organs, where cell-to-cell transmission of HIV-1 is likely frequent. However, despite the importance of understanding virus spread in vivo, little is known about the HIV-1 life cycle, particularly its late phase, in polarized T cells. Polarized T cells form two ends, the leading edge at the front and a protrusion called a uropod at the rear. Using multiple uropod markers, we observed that HIV-1 Gag localizes to the uropod in polarized T cells. Infected T cells formed contacts with uninfected target T cells preferentially via HIV-1 Gag-containing uropods compared to leading edges that lack plasma-membrane-associated Gag. Cell contacts enriched in Gag and CD4, which define the virological synapse (VS, are also enriched in uropod markers. These results indicate that Gag-laden uropods participate in the formation and/or structure of the VS, which likely plays a key role in cell-to-cell transmission of HIV-1. Consistent with this notion, a myosin light chain kinase inhibitor, which disrupts uropods, reduced virus particle transfer from infected T cells to target T cells. Mechanistically, we observed that Gag copatches with antibody-crosslinked uropod markers even in non-polarized cells, suggesting an association of Gag with uropod-specific microdomains that carry Gag to uropods. Finally, we determined that localization of Gag to the uropod depends on higher-order clustering driven by its NC domain. Taken together, these results support a model in which NC-dependent Gag accumulation to uropods establishes a preformed platform that later constitutes T-cell-T-cell contacts at which HIV-1 virus transfer occurs.

  15. Clinical and virological efficacy of etravirine plus two active Nucleos(tide analogs in an heterogeneous HIV-infected population.

    Directory of Open Access Journals (Sweden)

    Luis F López-Cortés

    Full Text Available Etravirine (ETV is recommended in combination with a boosted protease inhibitor plus an optimized background regimen for salvage therapy, but there is limited experience with its use in combination with two nucleos(tide reverse-transcriptase inhibitors (NRTIs. This multicenter study aimed to assess the efficacy of this combination in two scenarios: group A subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors (NNRTIs switched due to adverse events and group B subjects switched after a virologic failure on an efavirenz- or nevirapine-based regimen. The primary endpoint was efficacy at 52 weeks analysed by intention-to-treat. Virologic failure was defined as the inability to suppress plasma HIV-RNA to 200 copies/mL in patients who had previously achieved a viral suppression or had an undetectable viral load at inclusion. Two hundred eighty seven patients were included. Treatment efficacy rates in group A and B were 88.0% (CI95, 83.9-92.1% and 77.4% (CI95, 65.0-89.7%, respectively; the rates reached 97.2% (CI95, 95.1-99.3% and 90.5% (CI95, 81.7-99.3, by on-treatment analysis. The once-a-day ETV treatment was as effective as the twice daily dosing regimen. Grade 1-2 adverse events were observed motivating a treatment switch in 4.2% of the subjects. In conclusion, ETV (once- or twice daily plus two analogs is a suitable, well-tolerated combination both as a switching strategy and after failure with first generation NNRTIs, ensuring full drug activity.ClinicalTrials.gov NCT01437241.

  16. A376S in the connection subdomain of HIV-1 reverse transcriptase confers increased risk of virological failure to nevirapine therapy

    NARCIS (Netherlands)

    Paredes, Roger; Puertas, Maria Carmen; Bannister, Wendy; Kisic, Mónica; Cozzi-Lepri, Alessandro; Pou, Christian; Bellido, Rocío; Betancor, Gilberto; Bogner, Johannes; Gargalianos, Panagiotis; Bánhegyi, Dénes; Clotet, Bonaventura; Lundgren, Jens; Menéndez-Arias, Luis; Martinez-Picado, Javier; Losso, M.; Elias, C.; Vetter, N.; Zangerle, R.; Karpov, I.; Vassilenko, A.; Mitsura, V. M.; Suetnov, O.; Clumeck, N.; de Wit, S.; Poll, B.; Colebunders, R.; Vandekerckhove, L.; Hadziosmanovic, V.; Kostov, K.; Begovac, J.; Machala, L.; Rozsypal, H.; Sedlacek, D.; Nielsen, J.; Kronborg, G.; Benfield, T.; Larsen, M.; Gerstoft, J.; Katzenstein, T.; Hansen, A.-B. E.; Skinhøj, P.; Pedersen, C.; Oestergaard, L.; Zilmer, K.; Ristola, M.; Katlama, C.; Viard, J.-P.; Girard, P.-M.; Livrozet, J. M.; Vanhems, P.; Pradier, C.; Dabis, F.; Neau, D.; Rockstroh, J.; Schmidt, R.; van Lunzen, J.; Degen, O.; Stellbrink, H. J.; Staszewski, S.; Fätkenheuer, G.; Kosmidis, J.; Gargalianos, P.; Xylomenos, G.; Perdios, J.; Panos, G.; Filandras, A.; Karabatsaki, E.; Sambatakou, H.; Banhegyi, D.; Mulcahy, F.; Yust, I.; Turner, D.; Burke, M.; Pollack, S.; Hassoun, G.; Maayan, S.; Vella, S.; Esposito, R.; Mazeu, I.; Mussini, C.; Arici, C.; Pristera, R.; Mazzotta, F.; Gabbuti, A.; Vullo, V.; Lichtner, M.; Chirianni, A.; Montesarchio, E.; Gargiulo, M.; Antonucci, G.; Iacomi, F.; Narciso, P.; Vlassi, C.; Zaccarelli, M.; Lazzarin, A.; Finazzi, R.; Galli, M.; Ridolfo, A.; d'Arminio, A.; Rozentale, B.; Aldins, P.; Chaplinskas, S.; Hemmer, R.; Staub, T.; Reiss, P.; Ormaasen, V.; Maeland, A.; Brunn, J.; Knysz, B.; Gasiorowski, J.; Horban, A.; Bakowska, E.; Prokopowicz, D.; Flisiak, R.; Boron-Kaczmarska, A.; Pynka, M.; Beniowski, M.; Mularska, E.; Trocha, H.; Jablonowska, E.; Malolepsza, E.; Wojcik, K.; Antunes, F.; Valadas, E.; Mansinho, K.; Maltez, F.; Duiculescu, D.; Rakhmanova, A.; Vinogradova, E.; Buzunova, S.; Jevtovic, D.; Mokrás, M.; Staneková, D.; Tomazic, J.; González-Lahoz, J.; Soriano, V.; Martin-Carbonero, L.; Labarga, P.; Moreno, S.; Clotet, B.; Jou, A.; Paredes, R.; Tural, C.; Puig, J.; Bravo, I.; Gatell, J. M.; Miró, J. M.; Domingo, P.; Gutierrez, M.; Mateo, G.; Sambeat, M. A.; Karlsson, A.; Persson, P. O.; Ledergerber, B.; Weber, R.; Francioli, P.; Cavassini, M.; Hirschel, B.; Boffi, E.; Furrer, H.; Battegay, M.; Elzi, L.; Kravchenko, E.; Chentsova, N.; Kutsyna, G.; Servitskiy, S.; Krasnov, M.; Barton, S.; Johnson, A. M.; Mercey, D.; Phillips, A.; Johnson, M. A.; Murphy, M.; Weber, J.; Scullard, G.; Fisher, M.; Leen, C.; Gatell, J.; Gazzard, B.; Lundgren, J.; d'Arminio Monforte, A.; Kirk, O.; Mocroft, A.; Cozzi-Lepri, A.; Grint, D.; Ellefson, M.; Podlekareva, D.; Kjaer, J.; Peters, L.; Reekie, J.; Kowalska, J.; Tverland, J.; Fischer, A. H.

    2011-01-01

    The clinical relevance of mutations in the connection subdomain and the ribonuclease (RNase) H domain of HIV-1 reverse transcriptase (RT) is uncertain. The risk of virological failure to nonnucleoside RT inhibitor (NNRTI)-based antiretroviral therapy (ART) was evaluated in NNRTI-naive patients who

  17. Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes

    DEFF Research Database (Denmark)

    Ledergerber, Bruno; Lundgren, Jens D; Walker, A Sarah

    2014-01-01

    Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure....

  18. Hepatitis C virus coinfection does not influence the CD4 cell recovery in HIV-1-infected patients with maximum virologic suppression

    DEFF Research Database (Denmark)

    Peters, Lars; Mocroft, Amanda; Soriano, Vincent

    2009-01-01

    BACKGROUND: Conflicting data exist whether hepatitis C virus (HCV) affects the CD4 cell recovery in patients with HIV starting antiretroviral treatment. OBJECTIVE: To investigate the influence of HCV coinfection on the CD4 recovery in patients with maximum virologic suppression within the EuroSIDA...

  19. Predictors of CD4(+) T-Cell Counts of HIV Type 1–Infected Persons After Virologic Failure of All 3 Original Antiretroviral Drug Classes

    DEFF Research Database (Denmark)

    Costagliola, Dominique; Ledergerber, Bruno; Torti, Carlo

    2013-01-01

    Low CD4(+) T-cell counts are the main factor leading to clinical progression in human immunodeficiency virus type 1 (HIV-1) infection. We aimed to investigate factors affecting CD4(+) T-cell counts after triple-class virological failure....

  20. Characteristics associated with virologic failure in high-risk HIV-positive participants with prior failure: a post hoc analysis of ACTG 5251.

    Science.gov (United States)

    Robbins, Gregory K; Cohn, Susan E; Harrison, Linda J; Smeaton, Laura; Moran, Laura; Rusin, David; Dehlinger, Marjorie; Flynn, Theresa; Lammert, Sara; Wu, Albert W; Safren, Steven A; Reynolds, Nancy R

    2016-07-01

    Patients with prior virologic failure (VF) are at an increased risk of subsequent failure, emergence of resistance, and death. This analysis identifies outcomes and correlates of VF in a high-risk population. A5251 was designed to evaluate an enhanced adherence counseling intervention delivered by nurses from a central call site on virologic suppression. Due to slow enrollment, the study was closed prematurely and revised study endpoints were evaluated (week 24 VF (HIV-1 RNA ≥200 copies/ml) and non-perfect adherence (antiretroviral regimen changes were three and the co-morbidity in this population was higher than typical for HIV clinical trials. At week 24 (n = 41), 24 (59%) failed to reach virologic suppression (HIV-1 RNA perceptions (IPQ-B) were associated with week 24 non-adherence. Early clinical assessments (week 12 HIV-RNA ≥200 copies/mL and non-perfect adherence) as well as higher depression and adverse illness perceptions were associated with week 24 VF. In this high-risk population, the proportion of participants with suboptimal adherence and VF was unacceptably high. Interventions to address this treatment gap are clearly needed. Depression and a higher illness perception score, failure to achieve virologic suppression by week 12, and less than perfect adherence could be used to target individuals for early interventions in treatment-experienced, high-risk individuals at high risk for VF.

  1. Proportion of long-term injection drug users as an indicator to characterize the state and prognosis of HIV-epidemic within a certain territory

    Directory of Open Access Journals (Sweden)

    Andreeva, Tatiana

    2012-07-01

    Full Text Available BACKGROUND: Epidemics of drug use and thus the spread of HIV have different duration in different regions, and, therefore, the prognosis of these epidemics may differ. We aimed to assess indicators measuring the peculiarities of injection drug use epidemics by region, informative for prevention activities among vulnerable to HIV groups. METHODS: Data from cross-sectional survey of 4026 injection drug users (IDUs conducted in 2007 in Ukraine were analyzed. The outcome measure was a binary variable depicting whether a respondent injects drugs for 20 years and over. Binary Logistic Regression in SPSS software was used to test associations with socio-demographic characteristics. RESULTS: More respondents from Odessa, Mykolayiv, Dnipropetrovsk, Cherkassy, Poltava, and Crimea regions inject over 20 years. Older respondents were more likely to belong to the group of long-term users. Men were more likely to inject over 20 years than women. Those respondents who were married, but did not live with their spouse or other sexual partner were more likely to inject longer than 20 years compared to those single or in a stable marriage. Those respondents who use opiates or combine them with stimulants were more likely to inject over 20 years and those who use only stimulants were more likely to inject less than 20 years. CONCLUSION: Injection drug use in Ukraine started earlier among men, on certain territories and was associated with opiate use. Percentage of IDUs who inject for more than 20 years was found to be a good indicator to distinguish territories with long-lasting epidemics.

  2. Long-term outcomes in adolescents perinatally infected with HIV-1 and followed up since birth in the French perinatal cohort (EPF/ANRS CO10).

    Science.gov (United States)

    Dollfus, C; Le Chenadec, J; Faye, A; Blanche, S; Briand, N; Rouzioux, C; Warszawski, J

    2010-07-15

    BACKGROUND. Increasing numbers of children perinatally infected with human immunodeficiency virus (HIV) are reaching adolescence, largely because of advances in treatment over the past 10 years, but little is known about their current health status. We describe here the living conditions and clinical and immunovirologic outcomes at last evaluation among this pioneering generation of adolescents who were born before the introduction of prophylaxis for vertical transmission and whose infections were diagnosed at a time when treatment options were limited. METHODS. The eligible population consisted of HIV-1-infected children who were born before December 1993 and who were included at birth in the prospective national French Perinatal Cohort (EPF/ANRS CO10). RESULTS. Of the 348 eligible children, 210 (60%; median age, 15 years) were still alive and regularly followed up. Current treatment was highly active antiretroviral therapy (HAART) in 77% and 2 nucleoside analogues in 5.0%; 16% had stopped treatment, and 2% had never been treated. The median CD4 cell count was 557 cells/microL, and 200 cells/microL was exceeded in 94% of patients. The median viral load was 200 copies/mL. Viral load was undetectable in 43% of the adolescents and in 54.5% of those receiving HAART. Median height, weight, and body mass index were similar to French reference values for age, and school achievement was similar to nationwide statistics. Better immunologic status was associated with being younger and with having begun HAART earlier. Undetectable viral load was associated with maternal geographic origin and current HAART. CONCLUSIONS. Given the limited therapeutic options available during the early years of these patients' lives and the challenge presented by treatment adherence during adolescence, the long-term outcomes among this population are encouraging.

  3. Pregnancy and infant outcomes among HIV-infected women taking long-term ART with and without tenofovir in the DART trial.

    Science.gov (United States)

    Gibb, Diana M; Kizito, Hilda; Russell, Elizabeth C; Chidziva, Ennie; Zalwango, Eva; Nalumenya, Ruth; Spyer, Moira; Tumukunde, Dinah; Nathoo, Kusum; Munderi, Paula; Kyomugisha, Hope; Hakim, James; Grosskurth, Heiner; Gilks, Charles F; Walker, A Sarah; Musoke, Phillipa

    2012-01-01

    Few data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART) in pregnancy. This is particularly true for World Health Organization (WHO)-recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure. Pregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART) trial, which compared routine laboratory monitoring (CD4; toxicity) versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models. 382 pregnancies occurred in 302/1,867 (16%) women (4.4/100 woman-years [95% CI 4.0-4.9]). 226/390 (58%) outcomes were live-births, 27 (7%) stillbirths (≥22 wk), and 137 (35%) terminations/miscarriages (0.4). Of 219 surviving infants, 182 (83%) enrolled in the follow-up study; median (interquartile range [IQR]) age at last visit was 25 (12-38) months. From mothers' ART, 62/9/111 infants had no/20%-89%/≥90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested). Only 73/182(40%) infants were breast-fed for median 94 (IQR 75-212) days. Overall, 14 infants died at median (IQR) age 9 (3-23) months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three), sepsis (two), burns (one), measles (one), unknown (one). During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16) or two (three) in 14

  4. Pregnancy and infant outcomes among HIV-infected women taking long-term ART with and without tenofovir in the DART trial.

    Directory of Open Access Journals (Sweden)

    Diana M Gibb

    Full Text Available Few data have described long-term outcomes for infants born to HIV-infected African women taking antiretroviral therapy (ART in pregnancy. This is particularly true for World Health Organization (WHO-recommended tenofovir-containing first-line regimens, which are increasingly used and known to cause renal and bone toxicities; concerns have been raised about potential toxicity in babies due to in utero tenofovir exposure.Pregnancy outcome and maternal/infant ART were collected in Ugandan/Zimbabwean HIV-infected women initiating ART during The Development of AntiRetroviral Therapy in Africa (DART trial, which compared routine laboratory monitoring (CD4; toxicity versus clinically driven monitoring. Women were followed 15 January 2003 to 28 September 2009. Infant feeding, clinical status, and biochemistry/haematology results were collected in a separate infant study. Effect of in utero ART exposure on infant growth was analysed using random effects models. 382 pregnancies occurred in 302/1,867 (16% women (4.4/100 woman-years [95% CI 4.0-4.9]. 226/390 (58% outcomes were live-births, 27 (7% stillbirths (≥22 wk, and 137 (35% terminations/miscarriages (0.4. Of 219 surviving infants, 182 (83% enrolled in the follow-up study; median (interquartile range [IQR] age at last visit was 25 (12-38 months. From mothers' ART, 62/9/111 infants had no/20%-89%/≥90% in utero tenofovir exposure; most were also zidovudine/lamivudine exposed. All 172 infants tested were HIV-negative (ten untested. Only 73/182(40% infants were breast-fed for median 94 (IQR 75-212 days. Overall, 14 infants died at median (IQR age 9 (3-23 months, giving 5% 12-month mortality; six of 14 were HIV-uninfected; eight untested infants died of respiratory infection (three, sepsis (two, burns (one, measles (one, unknown (one. During follow-up, no bone fractures were reported to have occurred; 12/368 creatinines and seven out of 305 phosphates were grade one (16 or two (three in 14 children

  5. Impact of body weight on virological and immunological responses to efavirenz-containing regimens in HIV-infected, treatment-naive adults

    DEFF Research Database (Denmark)

    Marzolini, Catia; Sabin, Caroline; Raffi, François

    2015-01-01

    OBJECTIVE: The prevalence of overweight and obesity is increasing among HIV-infected patients. Whether standard antiretroviral drug dosage is adequate in heavy individuals remains unresolved. We assessed the virological and immunological responses to initial efavirenz (EFV)-containing regimens...... individuals had significantly higher CD4 cell count at baseline, CD4 cell recovery at 6 and 12 months after EFV initiation was comparable to normal-weight individuals. CONCLUSION: Virological and immunological responses to initial EFV-containing regimens were not impaired in heavy individuals, suggesting...

  6. Time of HIV Diagnosis and Engagement in Prenatal Care Impact Virologic Outcomes of Pregnant Women with HIV

    OpenAIRE

    Momplaisir, Florence M.; Brady, Kathleen A.; Fekete, Thomas; Thompson, Dana R.; Diez Roux, Ana; Yehia, Baligh R.

    2015-01-01

    Background HIV suppression at parturition is beneficial for maternal, fetal and public health. To eliminate mother-to-child transmission of HIV, an understanding of missed opportunities for antiretroviral therapy (ART) use during pregnancy and HIV suppression at delivery is required. Methodology We performed a retrospective analysis of 836 mother-to-child pairs involving 656 HIV-infected women in Philadelphia, 2005-2013. Multivariable regression examined associations between patient (age, rac...

  7. Long-term exposure to tenofovir continuously decrease renal function in HIV-1-infected patients with low body weight: results from 10 years of follow-up.

    Science.gov (United States)

    Nishijima, Takeshi; Kawasaki, Yohei; Tanaka, Noriko; Mizushima, Daisuke; Aoki, Takahiro; Watanabe, Koji; Kinai, Ei; Honda, Haruhito; Yazaki, Hirohisa; Tanuma, Junko; Tsukada, Kunihisa; Teruya, Katsuji; Kikuchi, Yoshimi; Gatanaga, Hiroyuki; Oka, Shinichi

    2014-08-24

    To investigate the effect of long-term tenofovir disoproxil fumarate (TDF) use on renal function, especially in patients with low body weight who are vulnerable to TDF nephrotoxicity. A single-center, observational study in Tokyo, Japan. We performed a 10 years cohort study of 792 HIV-1-infected patients. The effect of long-term TDF use on estimated glomerular filtration rate (eGFR) was investigated on treatment-naive patients who started TDF-containing antiretroviral therapy (n = 422) and those who started abacavir-containing antiretroviral therapy as control (n = 370). Three renal endpoints were examined by the logistic regression model: decrement in eGFR of higher than 10 ml/min per 1.73 m relative to the baseline, more than 25% decrement in eGFR, and eGFR lower than 60 ml/min per 1.73 m at least 3 months apart. The loss in eGFR was estimated using linear mixed models for repeated measures. The median weight at baseline was 63 kg. TDF use increased the risk of all three renal outcomes compared with the control group: higher than 10 ml/min per 1.73 m decrement in eGFR [adjusted odds ratio (OR) = 2.1, 95% confidence interval (CI) 1.45-3.14, P decrement (adjusted OR = 2.1, 95% CI 1.50-2.90, P < 0.001), and eGFR lower than 60 ml/min per 1.73 m at least 3 months apart (adjusted OR = 3.9, 95% CI 1.62-9.36, P = 0.002). The cumulative mean loss relative to the control after 1, 2, 3, 4, and 5 years of TDF exposure was -3.8, -3.6, -5.5, -6.6, and -10.3 ml/min per 1.73 m, respectively, indicating that the loss in eGFR increased over time (P < 0.001). In this cohort of patients with low body weight, TDF exposure increased the risk of renal dysfunction. Furthermore, the loss in eGFR relative to the control increased continuously up to 5 years.

  8. Long-term collections

    CERN Multimedia

    Collectes à long terme

    2007-01-01

    The Committee of the Long Term Collections (CLT) asks for your attention for the following message from a young Peruvian scientist, following the earthquake which devastated part of her country a month ago.

  9. Contribution of immunological and virological factors to extremely severe primary HIV-1 infection

    Science.gov (United States)

    Dalmau, Judith; Puertas, Maria Carmen; Azuara, Marta; Mariño, Ana; Frahm, Nicole; Mothe, Beatriz; Izquierdo-Useros, Nuria; Buzón, Maria José; Paredes, Roger; Matas, Lourdes; Allen, Todd M.; Brander, Christian; Rodrigo, Carlos; Clotet, Bonaventura; Martinez-Picado, Javier

    2009-01-01

    Background During acute HIV infection, high viral loads and the induction of host immune responses typically coincide with the onset of clinical symptoms. However, clinically severe presentations during acute HIV-1 infection, including AIDS-defining symptoms, are unusual. Methods Virus isolates were tested for clade, drug susceptibility, coreceptor usage, and growth rate for two cases of clinically severe sexual transmission. HLA genotype was determined, and HIV-1-specific CTL responses to an overlapping peptide set spanning the entire HIV clade A and clade B proteome were assayed. Results The virus isolated from the two unrelated cases of severe primary HIV-1 infection showed R5/X4 dual/mixed tropism, belonged to clade B and CRF02-AG, and were highly replicative in peripheral blood mononuclear cell culture. Impaired humoral responses were paralleled by a profound absence of HIV-1-specific CTL responses to the entire viral proteome in the two study cases. One case for which the virus source was available, showed a remarkable HLA similarity between the transmission pair as all 4 HLA-A and -B alleles were HLA supertype-matched between the subjects involved in the transmission case. Conclusions The data suggest that concurrence of viral and host factors contribute to the clinical severity of primary HIV-1 infection and that subjects infected with highly replicative dual tropic viruses are more prone to develop AIDS-defining symptoms during acute infection if they are unable to mount humoral and cellular HIV-1-specific immune responses. Concordant HLA supertypes might facilitate the preferential transmission of HLA-adapted viral variants, further accelerating disease progression. PMID:19093810

  10. Priming B cell-mediated anti-HIV envelope responses by vaccination allows for the long-term control of infection in macaques exposed to a R5-tropic SHIV

    International Nuclear Information System (INIS)

    Buckner, Clarisa; Gines, Leoned G.; Saunders, Cheryl J.; Vojtech, Lucia; Srivastava, Indresh; Gettie, Agegnehu; Bohm, Rudolph; Blanchard, James; Barnett, Susan W.; Safrit, Jeffrey T.; Stamatatos, Leonidas

    2004-01-01

    The potential of vaccine-elicited anti-HIV envelope antibodies to control HIV-infection was evaluated by immunizing macaques with the HIV envelope protein and transiently depleting them of their CD8+ cells before intravenous challenge with the pathogenic CCR5-tropic SIV/HIV chimeric virus, SHIV SF162P4 . Although sterilizing immunity was not achieved, all vaccinated animals effectively controlled infection and remained free of disease for the duration of observation (over 3 years). In contrast, during the same period, the control animals progressed to disease. Both the vaccinees and the controls developed robust cell-mediated antiviral and neutralizing antibody responses following infection. A comparative analysis of these responses suggests that the more effective long-term control of infection by the vaccinated animals is due to the more rapid development of anti-HIV envelope antibodies. These studies suggest that priming by vaccination of B cell anti-HIV envelope responses maybe crucial for the long-term control of HIV infection

  11. A Prognostic Model for Estimating the Time to Virologic Failure in HIV-1 Infected Patients Undergoing a New Combination Antiretroviral Therapy Regimen

    Directory of Open Access Journals (Sweden)

    Micheli Valeria

    2011-06-01

    Full Text Available Abstract Background HIV-1 genotypic susceptibility scores (GSSs were proven to be significant prognostic factors of fixed time-point virologic outcomes after combination antiretroviral therapy (cART switch/initiation. However, their relative-hazard for the time to virologic failure has not been thoroughly investigated, and an expert system that is able to predict how long a new cART regimen will remain effective has never been designed. Methods We analyzed patients of the Italian ARCA cohort starting a new cART from 1999 onwards either after virologic failure or as treatment-naïve. The time to virologic failure was the endpoint, from the 90th day after treatment start, defined as the first HIV-1 RNA > 400 copies/ml, censoring at last available HIV-1 RNA before treatment discontinuation. We assessed the relative hazard/importance of GSSs according to distinct interpretation systems (Rega, ANRS and HIVdb and other covariates by means of Cox regression and random survival forests (RSF. Prediction models were validated via the bootstrap and c-index measure. Results The dataset included 2337 regimens from 2182 patients, of which 733 were previously treatment-naïve. We observed 1067 virologic failures over 2820 persons-years. Multivariable analysis revealed that low GSSs of cART were independently associated with the hazard of a virologic failure, along with several other covariates. Evaluation of predictive performance yielded a modest ability of the Cox regression to predict the virologic endpoint (c-index≈0.70, while RSF showed a better performance (c-index≈0.73, p Conclusions GSSs of cART and several other covariates were investigated using linear and non-linear survival analysis. RSF models are a promising approach for the development of a reliable system that predicts time to virologic failure better than Cox regression. Such models might represent a significant improvement over the current methods for monitoring and optimization of cART.

  12. Mortality and loss to follow-up among HIV-infected persons on long-term antiretroviral therapy in Latin America and the Caribbean

    Science.gov (United States)

    Carriquiry, Gabriela; Fink, Valeria; Koethe, John Robert; Giganti, Mark Joseph; Jayathilake, Karu; Blevins, Meridith; Cahn, Pedro; Grinsztejn, Beatriz; Wolff, Marcelo; Pape, Jean William; Padgett, Denis; Madero, Juan Sierra; Gotuzzo, Eduardo; McGowan, Catherine Carey; Shepherd, Bryan Earl

    2015-01-01

    Introduction Long-term survival of HIV patients after initiating highly active antiretroviral therapy (ART) has not been sufficiently described in Latin America and the Caribbean, as compared to other regions. The aim of this study was to describe the incidence of mortality, loss to follow-up (LTFU) and associated risk factors for patients enrolled in the Caribbean, Central and South America Network (CCASAnet). Methods We assessed time from ART initiation (baseline) to death or LTFU between 2000 and 2014 among ART-naïve adults (≥18 years) from sites in seven countries included in CCASAnet: Argentina, Brazil, Chile, Haiti, Honduras, Mexico and Peru. Kaplan-Meier techniques were used to estimate the probability of mortality over time. Risk factors for death were assessed using Cox regression models stratified by site and adjusted for sex, baseline age, nadir pre-ART CD4 count, calendar year of ART initiation, clinical AIDS at baseline and type of ART regimen. Results A total of 16,996 ART initiators were followed for a median of 3.5 years (interquartile range (IQR): 1.6–6.2). The median age at ART initiation was 36 years (IQR: 30–44), subjects were predominantly male (63%), median CD4 count was 156 cells/µL (IQR: 60–251) and 26% of subjects had clinical AIDS prior to starting ART. Initial ART regimens were predominantly non-nucleoside reverse transcriptase inhibitor based (86%). The cumulative incidence of LTFU five years after ART initiation was 18.2% (95% confidence interval (CI) 17.5–18.8%). A total of 1582 (9.3%) subjects died; the estimated probability of death one, three and five years after ART initiation was 5.4, 8.3 and 10.3%, respectively. The estimated five-year mortality probability varied substantially across sites, from 3.5 to 14.0%. Risk factors for death were clinical AIDS at baseline (adjusted hazard ratio (HR)=1.65 (95% CI 1.47–1.87); p<0.001), lower baseline CD4 (HR=1.95 (95% CI 1.63–2.32) for 50 vs. 350 cells/µL; p<0.001) and

  13. Virological and immunological response to antiretroviral regimens containing maraviroc in HIV type 1-infected patients in clinical practice: role of different tropism testing results and of concomitant treatments.

    Science.gov (United States)

    Rossetti, Barbara; Bianco, Claudia; Bellazzi, Lara Ines; Bruzzone, Bianca; Colao, Grazia; Corsi, Paola; Monno, Laura; Pagano, Gabriella; Paolucci, Stefania; Punzi, Grazia; Setti, Maurizio; Zazzi, Maurizio; De Luca, Andrea

    2014-01-01

    We assessed the immunovirological response to antiretroviral regimens containing maraviroc in HIV-infected viremic patients with viral tropism predicted by different assays. We selected antiretroviral treatment-experienced HIV-1-infected patients initiating regimens containing maraviroc after different phenotypic or genotypic viral tropism assays, with at least one HIV-1 RNA determination during follow-up. Survival analysis was employed to assess the virological response as time to HIV-1 RNA immunological response as time to a CD4 cell count increase of ≥ 100/μl from baseline. Predictors of these outcomes were analyzed by multivariate Cox regression models. In 191 treatments with maraviroc, virological response was achieved in 65.4% and the response was modestly influenced by the baseline viral load and concomitant drug activity but not influenced by the type of tropism assay employed. Immunological response was achieved in 58.1%; independent predictors were baseline HIV-1 RNA (per log10 higher: HR 1.29, 95% CI 1.05-1.60) and concomitant therapy with enfuvirtide (HR 2.05, 0.96-4.39) but not tropism assay results. Of 17 patients with baseline R5-tropic virus and available tropism results while viremic during follow-up on maraviroc, seven (41%) showed a tropism switch to non-R5 virus. A significant proportion of experienced patients treated with regimens containing maraviroc achieved virological response. The tropism test type used was not associated with immunovirological response and concomitant treatment with enfuvirtide increased the chance of immunological response. More than half of virological failures with maraviroc were not accompanied by tropism switch.

  14. High Rates of Baseline Drug Resistance and Virologic Failure Among ART-naive HIV-infected Children in Mali.

    Science.gov (United States)

    Crowell, Claudia S; Maiga, Almoustapha I; Sylla, Mariam; Taiwo, Babafemi; Kone, Niaboula; Oron, Assaf P; Murphy, Robert L; Marcelin, Anne-Geneviève; Traore, Ban; Fofana, Djeneba B; Peytavin, Gilles; Chadwick, Ellen G

    2017-11-01

    Limited data exist on drug resistance and antiretroviral treatment (ART) outcomes in HIV-1-infected children in West Africa. We determined the prevalence of baseline resistance and correlates of virologic failure (VF) in a cohort of ART-naive HIV-1-infected children baseline (before ART) and at 6 months. Resistance was defined according to the Stanford HIV Genotypic Resistance database. VF was defined as viral load ≥1000 copies/mL after 6 months of ART. Logistic regression was used to evaluate factors associated with VF or death >1 month after enrollment. Post hoc, antiretroviral concentrations were assayed on baseline samples of participants with baseline resistance. One-hundred twenty children with a median age 2.6 years (interquartile range: 1.6-5.0) were included. Eighty-eight percent reported no prevention of mother-to-child transmission exposure. At baseline, 27 (23%), 4 (3%) and none had non-nucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor or protease inhibitor resistance, respectively. Thirty-nine (33%) developed VF and 4 died >1 month post-ART initiation. In multivariable analyses, poor adherence [odds ratio (OR): 6.1, P = 0.001], baseline NNRTI resistance among children receiving NNRTI-based ART (OR: 22.9, P baseline NNRTI resistance (OR: 5.8, P = 0.018) were significantly associated with VF/death. Ten (38%) with baseline resistance had detectable levels of nevirapine or efavirenz at baseline; 7 were currently breastfeeding, but only 2 reported maternal antiretroviral use. Baseline NNRTI resistance was common in children without reported NNRTI exposure and was associated with increased risk of treatment failure. Detectable NNRTI concentrations were present despite few reports of maternal/infant antiretroviral use.

  15. Stable Caloric Intake and Continued Virologic Suppression for HIV-Positive Antiretroviral Treatment-Experienced Women After Switching to a Single-Tablet Regimen of Emtricitabine, Rilpivirine, and Tenofovir Disoproxil Fumarate.

    Science.gov (United States)

    Menezes, Prema; Mollan, Katie; Hoffman, Erin; Xie, Zimeng; Wills, Jennifer; Marcus, Cheryl; Rublein, John; Hudgens, Michael; Eron, Joseph J

    2018-05-02

    Benefits of switching to a single-tablet regimen (STR) of emtricitabine/rilpivirine/tenofovir (FTC/RPV/TDF) in virologically suppressed antiretroviral treatment (ART) experienced HIV-positive women include pregnancy category B rating and lack of clinically significant drug interactions between RPV and oral contraceptives. Unfortunately, studies involving switching to FTC/RPV/TDF enrolled fewer than 25% women. We undertook this 48-week study to assess the ability of virologically suppressed HIV-positive women switching to RPV STR to remain virologically suppressed and comply with the caloric intake requirement. HIV-positive women on ART with viral load phone calls on randomly chosen dates. For each 3-day food diary, the daily median caloric intake and median value for each macronutrient consumed concurrent with FTC/RPV/TDF were computed. Medication adherence was measured using a visual analog scale. We enrolled 33 women, 73% of whom were African American. At week 48, virologic suppression (HIV RNA phone call. Median kcal intake (food diary) did not change significantly from baseline (684 kcal) to week 48 (820 kcal); median change 102 kcal, p = .15. Women who reported noncompliance with a ≥400 kcal meal did not experience virologic failure. Significant concordance between caloric adherence and virologic suppression was not detected. Our study demonstrated that HIV-positive women who switched to STR FTC/RPV/TDF continued to experience virologic suppression and were readily able to comply with the recommended caloric intake requirement.

  16. Time of HIV Diagnosis and Engagement in Prenatal Care Impact Virologic Outcomes of Pregnant Women with HIV.

    Directory of Open Access Journals (Sweden)

    Florence M Momplaisir

    Full Text Available HIV suppression at parturition is beneficial for maternal, fetal and public health. To eliminate mother-to-child transmission of HIV, an understanding of missed opportunities for antiretroviral therapy (ART use during pregnancy and HIV suppression at delivery is required.We performed a retrospective analysis of 836 mother-to-child pairs involving 656 HIV-infected women in Philadelphia, 2005-2013. Multivariable regression examined associations between patient (age, race/ethnicity, insurance status, drug use and clinical factors such as adequacy of prenatal care measured by the Kessner index which classifies prenatal care as inadequate, intermediate, or adequate prenatal care; timing of HIV diagnosis; and the outcomes: receipt of ART during pregnancy and viral suppression at delivery.Overall, 25% of the sample was diagnosed with HIV during pregnancy; 39%, 38%, and 23% were adequately, intermediately, and inadequately engaged in prenatal care. Eight-five percent of mother-to-child pairs received ART during pregnancy but only 52% achieved suppression at delivery. Adjusting for patient factors, pairs diagnosed with HIV during pregnancy were less likely to receive ART (AOR 0.39, 95% CI 0.25-0.61 and achieve viral suppression (AOR 0.70, 95% CI 0.49-1.00 than those diagnosed before pregnancy. Similarly, women with inadequate prenatal care were less likely to receive ART (AOR 0.06, 95% CI 0.03-0.11 and achieve viral suppression (AOR 0.31, 95% CI 0.20-0.47 than those with adequate prenatal care.Targeted interventions to diagnose HIV prior to pregnancy and engage HIV-infected women in prenatal care have the potential to improve HIV related outcomes in the perinatal period.

  17. Time of HIV Diagnosis and Engagement in Prenatal Care Impact Virologic Outcomes of Pregnant Women with HIV.

    Science.gov (United States)

    Momplaisir, Florence M; Brady, Kathleen A; Fekete, Thomas; Thompson, Dana R; Diez Roux, Ana; Yehia, Baligh R

    2015-01-01

    HIV suppression at parturition is beneficial for maternal, fetal and public health. To eliminate mother-to-child transmission of HIV, an understanding of missed opportunities for antiretroviral therapy (ART) use during pregnancy and HIV suppression at delivery is required. We performed a retrospective analysis of 836 mother-to-child pairs involving 656 HIV-infected women in Philadelphia, 2005-2013. Multivariable regression examined associations between patient (age, race/ethnicity, insurance status, drug use) and clinical factors such as adequacy of prenatal care measured by the Kessner index which classifies prenatal care as inadequate, intermediate, or adequate prenatal care; timing of HIV diagnosis; and the outcomes: receipt of ART during pregnancy and viral suppression at delivery. Overall, 25% of the sample was diagnosed with HIV during pregnancy; 39%, 38%, and 23% were adequately, intermediately, and inadequately engaged in prenatal care. Eight-five percent of mother-to-child pairs received ART during pregnancy but only 52% achieved suppression at delivery. Adjusting for patient factors, pairs diagnosed with HIV during pregnancy were less likely to receive ART (AOR 0.39, 95% CI 0.25-0.61) and achieve viral suppression (AOR 0.70, 95% CI 0.49-1.00) than those diagnosed before pregnancy. Similarly, women with inadequate prenatal care were less likely to receive ART (AOR 0.06, 95% CI 0.03-0.11) and achieve viral suppression (AOR 0.31, 95% CI 0.20-0.47) than those with adequate prenatal care. Targeted interventions to diagnose HIV prior to pregnancy and engage HIV-infected women in prenatal care have the potential to improve HIV related outcomes in the perinatal period.

  18. The development of artificial neural networks to predict virological response to combination HIV therapy

    NARCIS (Netherlands)

    Larder, Brendan; Wang, Dechao; Revell, Andrew; Montaner, Julio; Harrigan, Richard; de Wolf, Frank; Lange, Joep; Wegner, Scott; Ruiz, Lidia; Pérez-Elías, Maria Jésus; Emery, Sean; Gatell, Jose; D'Arminio Monforte, Antonella; Torti, Carlo; Zazzi, Maurizio; Lane, Clifford

    2007-01-01

    When used in combination, antiretroviral drugs are highly effective for suppressing HIV replication. Nevertheless, treatment failure commonly occurs and is generally associated with viral drug resistance. The choice of an alternative regimen may be guided by a drug-resistance test. However,

  19. High Virologic Failure Rates with Maraviroc-Based Salvage Regimens Among Indian Patients: A Preliminary Analysis-Maraviroc Effectiveness in HIV-1 Subtype C.

    Science.gov (United States)

    Pujari, Sanjay; Gaikwad, Sunil; Bele, Vivek; Joshi, Kedar; Dabhade, Digamber

    2018-01-01

    There is no information on the clinical effectiveness of Maraviroc (MVC) amongst People Living with HIV (PLHIV) in India infected with HIV-1 Subtype C viruses. We conducted a retrospective chart review of adult PLHIV on MVC based Antiretroviral (ARV) regimens for at least 6 months. Maraviroc was initiated amongst PLHIV with documented R5 tropic viruses (determined by in-house population sequencing of the V3 loop in triplicate and interpreted using the Geno2Pheno algorithm) in combination with an Optimized Background regimen (designed using genotypic resistance testing and past ARV history). Plasma viral loads (PVL) are performed 6 months post-initiation and annually thereafter. Primary outcome d. Median duration on MVC treatment was 1.8 years (range 1-2.9 years) while median duration of ART prior to switching to MVC was 13 years. Maraviroc was combined with Darunavir/ritonavir (DRV/r) (n=10), Atazanavir/r (ATV/r) (n=2) and Lopinavir/r (LPV/r) (n=1). All PLHIV were infected with HIV-1 Subtype C. Only 23.3% PLHIV achieved virologic suppression at 6 months and sustained it for 2.3 years. Median CD4 count change from baseline was +117 (n=13), +228 (n=10), +253 (n=9), and +331 (n=4) at 6, 12, 18 and 24 months respectively. Repeat tropism among patients with virologic failure demonstrated R5 virus. High rates of virologic failure was seen when MVC was used amongst treatment experienced PLHIV infected with HIV-1 Subtype C in India. was the proportion of PLHIV with virologic success (PVL<50 copies/ml) at last follow up visit. Data on 13 PLHIV were analyze.

  20. Assessment of metabolic and mitochondrial dynamics in CD4+ and CD8+ T cells in virologically suppressed HIV-positive individuals on combination antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Jesse J R Masson

    Full Text Available Metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and mitochondrial biogenesis in subpopulations of CD4+ and CD8+ T cells from 18 virologically-suppressed HIV-positive individuals on combination antiretroviral therapy (cART; median CD4+ cell count: 728 cells/μl and 13 HIV seronegative controls. Mitochondrial membrane potential (MMP and reactive oxygen species (ROS production were also analysed in total CD4+ and CD8+ T cells. Among HIV+/cART individuals, expression of glucose transporter (Glut1 and mitochondrial density were highest within central memory and naïve CD4+ T cells, and lowest among effector memory and transitional memory T cells, with similar trends in HIV-negative controls. Compared to HIV-negative controls, there was a trend towards higher percentage of circulating CD4+Glut1+ T cells in HIV+/cART participants. There were no significant differences in mitochondrial dynamics between subject groups. Glut1 expression was positively correlated with mitochondrial density and MMP in total CD4+ T cells, while MMP was also positively correlated with ROS production in both CD4+ and CD8+ T cells. Our study characterizes specific metabolic features of CD4+ and CD8+ T cells in HIV-negative and HIV+/cART individuals and will invite future studies to explore the immunometabolic consequences of HIV infection.

  1. Long-Term Collections

    CERN Multimedia

    Comité des collectes à long terme

    2011-01-01

    It is the time of the year when our fireman colleagues go around the laboratory for their traditional calendars sale. A part of the money of the sales will be donated in favour of the long-term collections. We hope that you will welcome them warmly.

  2. Virological failure of staggered and simultaneous treatment interruption in HIV patients who began Efavirenz-based regimens after allergic reactions to nevirapine

    Directory of Open Access Journals (Sweden)

    Siripassorn Krittaecho

    2013-01-01

    Full Text Available Abstract Objective The objective of this work was to study the virological outcomes associated with two different types of treatment interruption strategies in patients with allergic reactions to nevirapine (NVP. We compared the virological outcomes of (1 HIV-1-infected patients who discontinued an initial NVP-based regimen because of cutaneous allergic reactions to NVP; different types of interruption strategies were used, and second-line regimen was based on efavirenz (EFV; and (2 HIV-1-infected patients who began an EFV-based regimen as a first-line therapy (controls. Methods This retrospective cohort included patients who began an EFV-based regimen, between January 2002 and December 2008, as either an initial regimen or as a subsequent regimen after resolving a cutaneous allergic reaction against an initial NVP-based regimen. The study ended in March 2010. The primary outcome was virological failure, which was defined as either (a two consecutive plasma HIV-1 RNA levels >400 copies/mL or (b a plasma HIV-1 RNA level >1,000 copies/mL plus any genotypic resistance mutation. Results A total of 559 patients were stratified into three groups: (a Simultaneous Interruption, in which the subjects simultaneously discontinued all the drugs in an NVP-based regimen following an allergic reaction (n=161; (b Staggered Interruption, in which the subjects discontinued NVP treatment while continuing nucleoside reverse transcriptase inhibitor (NRTI backbone therapy for a median of 7 days (n=82; and (c Control, in which the subjects were naïve to antiretroviral therapy (n=316. The overall median follow-up time was 43 months. Incidence of virological failure in Simultaneous Interruption was 12.9 cases per 1,000 person-years, which trended toward being higher than the incidences in Staggered Interruption (5.4 and Control (6.6. However, differences were not statistically significant. Conclusions Among the patients who had an acute allergic reaction to first

  3. Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe

    DEFF Research Database (Denmark)

    Judd, A; Lodwick, R; Noguera-Julian, A

    2017-01-01

    OBJECTIVES: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. METHODS...... compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4-111) vs. 8 (IQR 2-38) weeks, respectively], and highest in perinatally infected participants aged 10-14 years [49 (IQR 9-267) weeks]. The cumulative proportion with TCVF 5 years after starting ART......: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged

  4. The role of virologic and immunologic factors in mother-to-child transmission of HIV-1.

    Science.gov (United States)

    Colognesi, C; Halapi, E; Jansson, M; Hodara, V; Steuer, G; Tresoldi, E; Leitner, T; Scarlatti, G

    1997-09-01

    More than 90% of human immunodeficiency virus type 1 (HIV-1) infection in children is acquired by mother-to-child transmission. However, infection of the child occurs in between 14 and 35% of cases. To understand the mechanisms involved in HIV-1 transmission, we have investigated the antigenic, molecular, and phenotypic characteristics of the virus harbored in infected mothers and their children. A clear correlation was observed between the transmission of the virus and the isolation of viral variants with a rapidly replicating and syncytium-inducing phenotype from the mother. Furthermore, non-transmitting mothers were able to neutralize several primary isolates more frequently than transmitting mothers. The comparison of the viral phenotype and genotype of mother-child pairs showed that the transmitted virus did not have common features, suggesting that transmission is usually not a selective process. This study suggests that transmission is governed by an interaction of both viral and immunological factors. The results obtained indicate that different strategies can be applied for the prevention of transmission.

  5. Factors Associated with Low-Level Viraemia and Virological Failure: Results from the Austrian HIV Cohort Study.

    Directory of Open Access Journals (Sweden)

    Gisela Leierer

    Full Text Available In human immunodeficiency virus treatment adequate virological suppression is warranted, nevertheless for some patients it remains a challenge. We investigated factors associated with low-level viraemia (LLV and virological failure (VF under combined antiretroviral therapy (cART.We analysed patients receiving standard regimens between 1st July 2012 and 1st July 2013 with at least one viral load (VL measurement below the quantification limit (BLQ in their treatment history. After a minimum of 6 months of unmodified cART, the next single VL measurement within 6 months was analysed. VF was defined as HIV RNA levels ≥ 200 copies/mL and all other quantifiable measurements were classified as LLV. Factors associated with LLV and VF compared to BLQ were identified by logistic regression models.Of 2276 participants, 1972 (86.6% were BLQ, 222 (9.8% showed LLV and 82 (3.6% had VF. A higher risk for LLV and VF was shown in patients with cART interruptions and in patients with boosted PI therapy. The risk for LLV and VF was lower in patients from centres using the Abbott compared to the Roche assay to measure VL. A higher risk for LLV but not for VF was found in patients with a higher VL before cART [for >99.999 copies/mL: aOR (95% CI: 4.19 (2.07-8.49; for 10.000-99.999 copies/mL: aOR (95% CI: 2.52 (1.23-5.19] and shorter cART duration [for <9 months: aOR (95% CI: 2.59 (1.38-4.86]. A higher risk for VF but not for LLV was found in younger patients [for <30 years: aOR (95% CI: 2.76 (1.03-7.35; for 30-50 years: aOR (95% CI: 2.70 (1.26-5.79], people originating from high prevalence countries [aOR (95% CI: 2.20 (1.09-4.42] and in male injecting drug users [aOR (95% CI: 2.72 (1.38-5.34].For both VF and LLV, factors associated with adherence play a prominent role. Furthermore, performance characteristics of the diagnostic assay used for VL quantification should also be taken into consideration.

  6. The association between cigarette smoking, virologic suppression, and CD4+ lymphocyte count in HIV-Infected Russian women.

    Science.gov (United States)

    Brown, Jennifer L; Winhusen, Theresa; DiClemente, Ralph J; Sales, Jessica M; Rose, Eve S; Safonova, Polina; Levina, Olga; Belyakov, Nikolay; Rassokhin, Vadim V

    2017-09-01

    Cigarette smoking among people living with HIV/AIDS is associated with significant morbidity and mortality, but findings regarding the association between cigarette smoking and HIV viral load and CD4+ lymphocyte counts have been inconsistent. This study characterized the prevalence of cigarette smoking among HIV-infected Russian women and examined the association between smoking frequency and quantity and HIV viral load and CD4+ lymphocyte counts. HIV-infected Russian women (N = 250; M age = 30.0) in St. Petersburg, Russia, completed an audio computer-assisted self-interview survey assessing cigarette use, antiretroviral medication adherence, and provided blood samples assayed for HIV viral load and CD4+ lymphocyte counts. The majority (60.4%) reported cigarette smoking in the past month; 49.0% of recent smokers were classified as moderate or heavy smokers, defined as smoking ≥10 cigarettes daily. Viral load status did not differ between infrequent smokers and regular smokers. However, moderate/heavy smokers (relative to light smokers) were more likely to have a detectable viral load (AOR = 2.3, 95% CI: 1.1, 5.1). There were no significant differences in CD4+ lymphocyte counts by smoking frequency or quantity of cigarettes smoked. Results highlight the need for additional research to examine the association between cigarette smoking and virologic suppression and markers of HIV disease progression. Adverse health consequences of cigarette smoking coupled with a potential link between heavy smoking and poor virologic suppression highlight the need for assessment of cigarette use and provision of evidence-based smoking-cessation interventions within HIV medical care.

  7. Trends on epidemiological, virological, and clinical features among newly diagnosed HIV-1 persons in Northwest Spain over the last 10 years.

    Science.gov (United States)

    Pernas, B; Mena, A; Cañizares, A; Grandal, M; Castro-Iglesias, A; Pértega, S; Pedreira, J D; Poveda, E

    2015-08-01

    To describe temporal trend and characteristics of newly HIV-diagnosed patients in a medical care area in Northwest Spain over the last 10 years. All newly diagnosed patients for HIV-infection from 2004 to 2013 at a reference medical care area in Northwest of Spain were identified. Epidemiological, virological, immunological, and clinical data, as well as HIV genotype and drug resistance information were recorded. A total of 565 newly HIV-diagnosed patients were identified. The number of new cases increased in the last 5 years (66 cases/year). Overall, 53.1% had a median CD4 counts study period was 3.7%, but a decreased to 2.6% was observed in the last 5 years. The most prevalent TDR mutations were: T215 revertants (1.5%), K219QENR (1.2%), for NRTIs; K103N (1.9%), for NNRTIs; L90M (0.3%), for PIs. Overall, 73.2% of patients started antiretroviral treatment and 9.9% of patients died during follow-up. The number of newly HIV diagnosed patients increased since year 2009. There is a high prevalence of late diagnosis (53%) and 33% had an AIDS defining criteria. Interestingly, the most prevalent non-B subtype in our population was F (25.8%). These findings support the need to facilitate the access for HIV testing to reduce the rate of late HIV diagnosis, improve the clinical outcome and prevent HIV transmission. © 2015 Wiley Periodicals, Inc.

  8. Long-Term Collections

    CERN Multimedia

    Staff Association

    2016-01-01

    45 years helping in developing countries! CERN personnel have been helping the least fortunate people on the planet since 1971. How? With the Long-Term Collections! Dear Colleagues, The Staff Association’s Long-Term Collections (LTC) Committee is delighted to share this important milestone in the life of our Laboratory with you. Indeed, whilst the name of CERN is known worldwide for scientific discoveries, it also shines in the many humanitarian projects which have been supported by the LTC since 1971. Several schools and clinics, far and wide, carry its logo... Over the past 45 years, 74 projects have been supported (9 of which are still ongoing). This all came from a group of colleagues who wanted to share a little of what life offered them here at CERN, in this haven of mutual understanding, peace and security, with those who were less fortunate elsewhere. Thus, the LTC were born... Since then, we have worked as a team to maintain the dream of these visionaries, with the help of regular donat...

  9. Long-Term Collection

    CERN Multimedia

    Staff Association

    2016-01-01

    Dear Colleagues, As previously announced in Echo (No. 254), your delegates took action to draw attention to the projects of the Long-Term Collections (LTC), the humanitarian body of the CERN Staff Association. On Tuesday, 11 October, at noon, small Z-Cards were widely distributed at the entrances of CERN restaurants and we thank you all for your interest. We hope to have achieved an important part of our goal, which was to inform you, convince you and find new supporters among you. We will find out in the next few days! An exhibition of the LTC was also set up in the Main Building for the entire week. The Staff Association wants to celebrate the occasion of the Long-Term Collection’s 45th anniversary at CERN because, ever since 1971, CERN personnel have showed great support in helping the least fortunate people on the planet in a variety of ways according to their needs. On a regular basis, joint fundraising appeals are made with the Directorate to help the victims of natural disasters around th...

  10. Collectes à long terme

    CERN Multimedia

    Collectes à long terme

    2014-01-01

    En cette fin d’année 2014 qui approche à grands pas, le Comité des Collectes à Long Terme remercie chaleureusement ses fidèles donatrices et donateurs réguliers pour leurs contributions à nos actions en faveur des plus démunis de notre planète. C’est très important, pour notre Comité, de pouvoir compter sur l’appui assidu que vous nous apportez. Depuis plus de 40 ans maintenant, le modèle des CLT est basé principalement sur des actions à long terme (soit une aide pendant 4-5 ans par projet, mais plus parfois selon les circonstances), et sa planification demande une grande régularité de ses soutiens financiers. Grand MERCI à vous ! D’autres dons nous parviennent au cours de l’année, et ils sont aussi les bienvenus. En particulier, nous tenons à remercier...

  11. The effect of malnutrition on the pharmacokinetics and virologic outcomes of lopinavir, efavirenz and nevirapine in food insecure HIV-infected children in Tororo, Uganda.

    Science.gov (United States)

    Bartelink, Imke H; Savic, Rada M; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J; Capparelli, Edmund; Jullien, Vincent; Young, Sera L; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

    2015-03-01

    Malnutrition may impact the pharmacokinetics (PKs) of antiretroviral medications and virologic responses in HIV-infected children. The authors therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected Ugandan children. Sparse dried blood spot samples from Ugandan children were used to estimate plasma concentrations. Historical PK data from children from 3 resource-rich countries (RRC) were utilized to develop the PK models. Concentrations in 330 dried blood spot from 163 Ugandan children aged 0.7-7 years were analyzed in reference to plasma PK data (1189 samples) from 204 children from RRC aged 0.5-12 years. Among Ugandan children, 48% was malnourished (underweight, thin or stunted). Compared to RRC, Ugandan children exhibited reduced bioavailability of EFV and LPV; 11% (P=0.045) and 18% (P=0.008), respectively. In contrast, NVP bioavailability was 46% higher in Ugandan children (PChildren receiving LPV, EFV or NVP had comparable risk of virologic failure. Among children on NVP, low height and weight for age Z scores were associated with reduced risk of virologic failure (P=0.034, P=0.068, respectively). Ugandan children demonstrated lower EFV and LPV and higher NVP exposure compared to children in RRC, perhaps reflecting the consequence of malnutrition on bioavailability. In children receiving NVP, the relation between exposure, malnutrition and outcome turned out to be marginally significant. Further investigations are warranted using more intensive PK measurements and adequate adherence assessments, to further assess causes of virologic failure in Ugandan children.

  12. Immunological responses during a virologically failing antiretroviral regimen are associated with in vivo synonymous mutation rates of HIV type-1 env

    DEFF Research Database (Denmark)

    Mens, Helene; Jørgensen, Louise Bruun; Kronborg, Gitte

    2009-01-01

    BACKGROUND: Little is known about the underlying causes of differences in immunological response to antiretroviral therapy during multidrug-resistant (MDR) HIV type-1 (HIV-1) infection. This study aimed to identify virological factors associated with immunological response during therapy failure...... for analysis. In a longitudinal mixed-effects model, plasma HIV-1 RNA only tended to predict immunological response (P=0.06), whereas minor protease inhibitor (PI) and nucleoside reverse transcriptase (NRTI) mutations at baseline correlated significantly with CD4+ T-cell count slopes (r= -0.56, P=0.04 and r......= -0.64, P=0.008, respectively). Interestingly, synonymous mutations of env correlated inversely with CD4+ T-cell count slopes (r=-0.60; P=0.01) and individuals with codons under positive selection had significantly better CD4+ T-cell responses than individuals without (0.42 versus -5.34; P=0...

  13. Development of 5 ' LTR DNA methylation of latent HIV-1 provirus in cell line models and in long-term-infected individuals

    Czech Academy of Sciences Publication Activity Database

    Trejbalová, Kateřina; Kovářová, Denisa; Blažková, Jana; Machala, L.; Jilich, D.; Weber, J.; Kučerová, Dana; Vencálek, O.; Hirsch, Ivan; Hejnar, Jiří

    2016-01-01

    Roč. 8, zima (2016), č. článku 19. ISSN 1868-7083 R&D Projects: GA ČR GAP304/12/1736 Institutional support: RVO:68378050 Keywords : HIV-1 * latent reservoir * DNA methylation * chromatin conformation * latent HIV-1 provirus reactivation * HIV-1-infected individuals Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.987, year: 2016

  14. A randomized controlled trial to promote long-term contraceptive use among HIV-serodiscordant and concordant positive couples in Zambia.

    Science.gov (United States)

    Stephenson, Rob; Vwalika, Bellington; Greenberg, Lauren; Ahmed, Yusuf; Vwalika, Cheswa; Chomba, Elwyn; Kilembe, William; Tichacek, Amanda; Allen, Susan

    2011-04-01

    Countries facing high HIV prevalence often also experience high levels of fertility and low contraceptive use, suggesting high levels of unmet need for contraceptive services. In particular, the unique needs of couples with one or both partners HIV positive are largely missing from many current family planning efforts, which focus on the prevention of pregnancies in the absence of reduction of the risk of HIV and other sexually transmitted infections (STIs). This article presents an examination of contraceptive method uptake among a cohort of HIV serodiscordant and concordant positive study participants in Zambia. Baseline contraceptive use was low; however, exposure to a video-based intervention that provided information on contraceptive methods and modeled desirable future planning behaviors dramatically increased the uptake of modern contraceptive methods. Including information on family planning in voluntary counseling and testing (VCT) services in addition to tailoring the delivery of family planning information to meet the needs and concerns of HIV-positive women or those with HIV-positive partners is an essential step in the delivery of services and prevention efforts to reduce the transmission of HIV. Family planning and HIV prevention programs should integrate counseling on dual method use, combining condoms for HIV/STI prevention with a long-acting contraceptive for added protection against unplanned pregnancy.

  15. Virologic failure of protease inhibitor-based second-line antiretroviral therapy without resistance in a large HIV treatment program in South Africa.

    Directory of Open Access Journals (Sweden)

    Julie H Levison

    Full Text Available We investigated the prevalence of wild-type virus (no major drug resistance and drug resistance mutations at second-line antiretroviral treatment (ART failure in a large HIV treatment program in South Africa.HIV-infected patients ≥ 15 years of age who had failed protease inhibitor (PI-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%. Mean duration on ART (SD prior to initiation of second-line ART was 23 (17 months, and time from second-line ART initiation to failure was 10 (9 months. Plasma samples were obtained 7(9 months from confirmed failure. At second-line failure, 22 patients (67% had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5 months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged.Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure.

  16. TLR-4 engagement of dendritic cells confers a BST-2/tetherin-mediated restriction of HIV-1 infection to CD4+ T cells across the virological synapse

    Directory of Open Access Journals (Sweden)

    Blanchet Fabien P

    2013-01-01

    Full Text Available Abstract Background Dendritic cells and their subsets, located at mucosal surfaces, are among the first immune cells to encounter disseminating pathogens. The cellular restriction factor BST-2/tetherin (also known as CD317 or HM1.24 potently restricts HIV-1 release by retaining viral particles at the cell surface in many cell types, including primary cells such as macrophages. However, BST-2/tetherin does not efficiently restrict HIV-1 infection in immature dendritic cells. Results We now report that BST-2/tetherin expression in myeloid (myDC and monocyte-derived dendritic cells (DC can be significantly up-regulated by IFN-α treatment and TLR-4 engagement with LPS. In contrast to HeLa or 293T cells, infectious HIV-1 release in immature DC and IFN-α–matured DC was only modestly affected in the absence of Vpu compared to wild-type viruses. Strikingly, immunofluorescence analysis revealed that BST-2/tetherin was excluded from HIV containing tetraspanin-enriched microdomains (TEMs in both immature DC and IFN-α–matured DC. In contrast, in LPS-mediated mature DC, BST-2/tetherin exerted a significant restriction in transfer of HIV-1 infection to CD4+ T cells. Additionally, LPS, but not IFN-α stimulation of immature DC, leads to a dramatic redistribution of cellular restriction factors to the TEM as well as at the virological synapse between DC and CD4+ T cells. Conclusions In conclusion, we demonstrate that TLR-4 engagement in immature DC significantly up-regulates the intrinsic antiviral activity of BST-2/tetherin, during cis-infection of CD4+ T cells across the DC/T cell virological synapse. Manipulating the function and potency of cellular restriction factors such as BST-2/tetherin to HIV-1 infection, has implications in the design of antiviral therapeutic strategies.

  17. The impact of HIV-1 co-infection on long-term mortality in patients with hepatitis C: a population-based cohort study

    DEFF Research Database (Denmark)

    Omland, L H; Jepsen, P; Skinhøj, P

    2009-01-01

    OBJECTIVE: To investigate the impact of HIV co-infection on mortality in patients infected with hepatitis C virus (HCV). METHODS: From a nationwide Danish database of HCV-infected patients, we identified individuals diagnosed with HCV subsequent to an HIV diagnosis. For each co-infected patient...

  18. Nevirapine Concentration in Hair Samples Is a Strong Predictor of Virologic Suppression in a Prospective Cohort of HIV-Infected Patients.

    Directory of Open Access Journals (Sweden)

    Sanjiv M Baxi

    Full Text Available Effective antiretroviral (ARV therapy depends on adequate drug exposure, yet methods to assess ARV exposure are limited. Concentrations of ARV in hair are the product of steady-state pharmacokinetics factors and longitudinal adherence. We investigated nevirapine (NVP concentrations in hair as a predictor of treatment response in women receiving ARVs. In participants of the Women's Interagency HIV Study, who reported NVP use for >1 month from 2003-2008, NVP concentrations in hair were measured via liquid-chromatography-tandem mass-spectrometry. The outcome was virologic suppression (plasma HIV RNA below assay threshold at the time of hair sampling and the primary predictor was nevirapine concentration categorized into quartiles. We controlled for age, race/ethnicity, pre-treatment HIV RNA, CD4 cell count, and self-reported adherence over the 6-month visit interval (categorized ≤ 74%, 75%-94% or ≥ 95%. We also assessed the relation of NVP concentration with changes in hepatic transaminase levels via multivariate random intercept logistic regression and linear regression analyses. 271 women contributed 1089 person-visits to the analysis (median 3 of semi-annual visits. Viral suppression was least frequent in concentration quartile 1 (86/178 (48.3% and increased in higher quartiles (to 158/204 (77.5% for quartile 4. The odds of viral suppression in the highest concentration quartile were 9.17 times (95% CI 3.2-26, P < 0.0001 those in the lowest. African-American race was associated with lower rates of virologic suppression independent of NVP hair concentration. NVP concentration was not significantly associated with patterns of serum transaminases. Concentration of NVP in hair was a strong independent predictor of virologic suppression in women taking NVP, stronger than self-reported adherence, but did not appear to be strongly predictive of hepatotoxicity.

  19. Ribavirin Concentrations Do Not Predict Sustained Virological Response in HIV/HCV-Coinfected Patients Treated with Ribavirin and Pegylated Interferon in the Swiss HIV Cohort Study.

    Directory of Open Access Journals (Sweden)

    Helen Kovari

    Full Text Available Ribavirin (RBV is an essential component of most current hepatitis C (HCV treatment regimens and still standard of care in the combination with pegylated interferon (pegIFN to treat chronic HCV in resource limited settings. Study results in HIV/HCV-coinfected patients are contradicting as to whether RBV concentration correlates with sustained virological response (SVR.We included 262 HCV treatment naïve HIV/HCV-coinfected Swiss HIV Cohort Study (SHCS participants treated with RBV and pegIFN between 01.01.2001-01.01.2010, 134 with HCV genotype (GT 1/4, and 128 with GT 2/3 infections. RBV levels were measured retrospectively in stored plasma samples obtained between HCV treatment week 4 and end of therapy. Uni- and multivariable logistic regression analyses were used to evaluate the association between RBV concentration and SVR in GT 1/4 and GT 2/3 infections. The analyses were repeated stratified by treatment phase (week 4-12, 13-24, >24 and IL28B genotype (CC versus CT/TT.SVR rates were 35.1% in GT 1/4 and 70.3% in GT 2/3 infections. Overall, median RBV concentration was 2.0 mg/L in GT 1/4, and 1.9 mg/L in GT 2/3, and did not change significantly across treatment phases. Patients with SVR had similar RBV concentrations compared to patients without SVR in both HCV genotype groups. SVR was not associated with RBV levels ≥2.0 mg/L (GT 1/4, OR 1.19 [0.5-2.86]; GT 2/3, 1.94 [0.78-4.80] and ≥2.5 mg/L (GT 1/4, 1.56 [0.64-3.84]; GT 2/3 2.72 [0.85-8.73], regardless of treatment phase, and IL28B genotype.In HIV/HCV-coinfected patients treated with pegIFN/RBV, therapeutic drug monitoring of RBV concentrations does not enhance the chance of HCV cure, regardless of HCV genotype, treatment phase and IL28B genotype.

  20. Genotypic drug resistance and long-term mortality in patients with triple-class antiretroviral drug failure

    DEFF Research Database (Denmark)

    Lohse, Nicolai; Jørgensen, LB; Kronborg, G

    2007-01-01

    OBJECTIVE: To examine the prevalence of drug-resistance-associated mutations in HIV patients with triple-drug class virological failure (TCF) and their association with long-term mortality. DESIGN: Population-based study from the Danish HIV Cohort Study (DHCS). METHODS: We included all patients...... range 2-10), and 81 (61%) patients had mutations conferring resistance towards all three major drug classes. In a regression model adjusted for CD4+ T-cell count, HIV RNA, year of TCF, age, gender and previous inferior antiretroviral therapy, harbouring > or =9 versus ... in the DHCS who experienced TCF between January 1995 and November 2004, and we performed genotypic resistance tests for International AIDS Society (IAS)-USA primary mutations on virus from plasma samples taken around the date of TCF. We computed time to all-cause death from date of TCF. The relative risk...

  1. Impacts of HIV infection and long-term use of antiretroviral therapy on the prevalence of oral human papilloma virus type 16.

    Science.gov (United States)

    Amornthatree, Korntip; Sriplung, Hutcha; Mitarnun, Winyou; Nittayananta, Wipawee

    2012-04-01

    The objectives of this study were to determine (i) the prevalence and the copy numbers of oral human papilloma virus type 16 (HPV-16) in HIV-infected patients compared with non-HIV controls, and (ii) the effects of antiretroviral therapy (ART) and its duration on the virus. A cross-sectional study was carried out in HIV-infected patients with and without ART and in non-HIV controls. Saliva samples were collected, and the DNA extracted from those samples was used as a template to detect HPV-16 E6 and E7 by quantitative polymerase chain reaction. Student's t-test and ANOVA test were performed to determine the prevalence rates among groups. Forty-nine HIV-infected patients: 37 on ART (age range, 23-54 years; mean, 37 years), 12 not on ART (age range, 20-40 years; mean, 31 years), and 20 non-HIV controls (age range, 19-53 years; mean, 31 years) were enrolled. The prevalence of oral HPV-16 infection and the copy numbers of the virus were significantly higher in HIV-infected patients than in non-HIV controls when using E6 assay (geometric mean = 10696 vs. 563 copies/10(5) cells, P prevalence of oral HPV-16 infection and the copy numbers of the virus (P = 0.567). We conclude that the prevalence of oral HPV-16 infection and the copy numbers of the virus are increased by HIV infection. Neither the use of ART nor its duration significantly affected the virus. © 2011 John Wiley & Sons A/S.

  2. Introduction: Long term prediction

    International Nuclear Information System (INIS)

    Beranger, G.

    2003-01-01

    Making a decision upon the right choice of a material appropriate to a given application should be based on taking into account several parameters as follows: cost, standards, regulations, safety, recycling, chemical properties, supplying, transformation, forming, assembly, mechanical and physical properties as well as the behaviour in practical conditions. Data taken from a private communication (J.H.Davidson) are reproduced presenting the life time range of materials from a couple of minutes to half a million hours corresponding to applications from missile technology up to high-temperature nuclear reactors or steam turbines. In the case of deep storage of nuclear waste the time required is completely different from these values since we have to ensure the integrity of the storage system for several thousand years. The vitrified nuclear wastes should be stored in metallic canisters made of iron and carbon steels, stainless steels, copper and copper alloys, nickel alloys or titanium alloys. Some of these materials are passivating metals, i.e. they develop a thin protective film, 2 or 3 nm thick - the so-called passive films. These films prevent general corrosion of the metal in a large range of chemical condition of the environment. In some specific condition, localized corrosion such as the phenomenon of pitting, occurs. Consequently, it is absolutely necessary to determine these chemical condition and their stability in time to understand the behavior of a given material. In other words the corrosion system is constituted by the complex material/surface/medium. For high level nuclear wastes the main features for resolving problem are concerned with: geological disposal; deep storage in clay; waste metallic canister; backfill mixture (clay-gypsum) or concrete; long term behavior; data needed for modelling and for predicting; choice of appropriate solution among several metallic candidates. The analysis of the complex material/surface/medium is of great importance

  3. Long-Term Symbolic Learning

    National Research Council Canada - National Science Library

    Kennedy, William G; Trafton, J. G

    2007-01-01

    What are the characteristics of long-term learning? We investigated the characteristics of long-term, symbolic learning using the Soar and ACT-R cognitive architectures running cognitive models of two simple tasks...

  4. Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe.

    Science.gov (United States)

    Judd, A; Lodwick, R; Noguera-Julian, A; Gibb, D M; Butler, K; Costagliola, D; Sabin, C; van Sighem, A; Ledergerber, B; Torti, C; Mocroft, A; Podzamczer, D; Dorrucci, M; De Wit, S; Obel, N; Dabis, F; Cozzi-Lepri, A; García, F; Brockmeyer, N H; Warszawski, J; Gonzalez-Tome, M I; Mussini, C; Touloumi, G; Zangerle, R; Ghosn, J; Castagna, A; Fätkenheuer, G; Stephan, C; Meyer, L; Campbell, M A; Chene, G; Phillips, A

    2017-03-01

    The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI. The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4-111) vs. 8 (IQR 2-38) weeks, respectively], and highest in perinatally infected participants aged 10-14 years [49 (IQR 9-267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0-12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9-5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10-14 years when starting ART (27.7%; 95% CI 13.2-42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10-14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4. The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development. © 2016 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.

  5. Novel HIV-1 knockdown targets identified by an enriched kinases/phosphatases shRNA library using a long-term iterative screen in Jurkat T-cells.

    Directory of Open Access Journals (Sweden)

    Sylvie Rato

    2010-02-01

    Full Text Available HIV-1 is a complex retrovirus that uses host machinery to promote its replication. Understanding cellular proteins involved in the multistep process of HIV-1 infection may result in the discovery of more adapted and effective therapeutic targets. Kinases and phosphatases are a druggable class of proteins critically involved in regulation of signal pathways of eukaryotic cells. Here, we focused on the discovery of kinases and phosphatases that are essential for HIV-1 replication but dispensable for cell viability. We performed an iterative screen in Jurkat T-cells with a short-hairpin-RNA (shRNA library highly enriched for human kinases and phosphatases. We identified 14 new proteins essential for HIV-1 replication that do not affect cell viability. These proteins are described to be involved in MAPK, JNK and ERK pathways, vesicular traffic and DNA repair. Moreover, we show that the proteins under study are important in an early step of HIV-1 infection before viral integration, whereas some of them affect viral transcription/translation. This study brings new insights for the complex interplay of HIV-1/host cell and opens new possibilities for antiviral strategies.

  6. LONG TERM COLLECTIONS

    CERN Multimedia

    STAFF ASSOCIATION

    2010-01-01

    ACKNOWLEDGMENTS The Long-Term Collections (CLT) committee would like to warmly thank its faithful donors who, year after year, support our actions all over the world. Without you, all this would not be possible. We would like to thank, in particular, the CERN Firemen’s Association who donated 5000 CHF in the spring thanks to the sale of their traditional calendar, and the generosity of the CERN community. A huge thank you to the firemen for their devotion to our cause. And thank you to all those who have opened their door, their heart, and their purses! Similarly, we warmly thank the CERN Yoga Club once again for its wonderful donation of 2000 CHF we recently received. We would also like to tell you that all our projects are running well. Just to remind you, we are currently supporting the activities of the «Réflexe-Partage» Association in Mali; the training centre of «Education et Développement» in Abomey, Benin; and the orphanage and ...

  7. On the front line of HIV virological monitoring: barriers and facilitators from a provider perspective in resource-limited settings.

    Science.gov (United States)

    Rutstein, S E; Golin, C E; Wheeler, S B; Kamwendo, D; Hosseinipour, M C; Weinberger, M; Miller, W C; Biddle, A K; Soko, A; Mkandawire, M; Mwenda, R; Sarr, A; Gupta, S; Mataya, R

    2016-01-01

    Scale-up of viral load (VL) monitoring for HIV-infected patients on antiretroviral therapy (ART) is a priority in many resource-limited settings, and ART providers are critical to effective program implementation. We explored provider-perceived barriers and facilitators of VL monitoring. We interviewed all providers (n = 17) engaged in a public health evaluation of dried blood spots for VL monitoring at five ART clinics in Malawi. All ART clinics were housed within district hospitals. We grouped themes at patient, provider, facility, system, and policy levels. Providers emphasized their desire for improved ART monitoring strategies, and frustration in response to restrictive policies for determining which patients were eligible to receive VL monitoring. Although many providers pled for expansion of monitoring to include all persons on ART, regardless of time on ART, the most salient provider-perceived barrier to VL monitoring implementation was the pressure of work associated with monitoring activities. The work burden was exacerbated by inefficient data management systems, highlighting a critical interaction between provider-, facility-, and system-level factors. Lack of integration between laboratory and clinical systems complicated the process for alerting providers when results were available, and these communication gaps were intensified by poor facility connectivity. Centralized second-line ART distribution was also noted as a barrier: providers reported that the time and expenses required for patients to collect second-line ART frequently obstructed referral. However, provider empowerment emerged as an unexpected facilitator of VL monitoring. For many providers, this was the first time they used an objective marker of ART response to guide clinical management. Providers' knowledge of a patient's virological status increased confidence in adherence counseling and clinical decision-making. Results from our study provide unique insight into provider

  8. Evaluating long term forecasts

    Energy Technology Data Exchange (ETDEWEB)

    Lady, George M. [Department of Economics, College of Liberal Arts, Temple University, Philadelphia, PA 19122 (United States)

    2010-03-15

    The U.S. Department of Energy's Energy Information Administration (EIA), and its predecessor organizations, has published projections of U.S. energy production, consumption, distribution and prices annually for over 30 years. A natural issue to raise in evaluating the projections is an assessment of their accuracy compared to eventual outcomes. A related issue is the determination of the sources of 'error' in the projections that are due to differences between the actual versus realized values of the associated assumptions. One way to do this would be to run the computer-based model from which the projections are derived at the time the projected values are realized, using actual rather than assumed values for model assumptions; and, compare these results to the original projections. For long term forecasts, this approach would require that the model's software and hardware configuration be archived and available for many years, possibly decades, into the future. Such archival creates many practical problems; and, in general, it is not being done. This paper reports on an alternative approach for evaluating the projections. In the alternative approach, the model is run many times for cases in which important assumptions are changed individually and in combinations. A database is assembled from the solutions and a regression analysis is conducted for each important projected variable with the associated assumptions chosen as exogenous variables. When actual data are eventually available, the regression results are then used to estimate the sources of the differences in the projections of the endogenous variables compared to their eventual outcomes. The results presented here are for residential and commercial sector natural gas and electricity consumption. (author)

  9. The Virological and Immunological Characteristics of the HIV-1-Infected Population in Brazil: From Initial Diagnosis to Impact of Antiretroviral Use.

    Directory of Open Access Journals (Sweden)

    Ricardo Sobhie Diaz

    Full Text Available Immunological and virological status of HIV-infected individuals entering the Brazilian public system over time was analyzed. We evaluated the impact of ART on virological, immunological and antiretroviral resistance over time.CD4+ T cell counts, viral loads and genotypes from patients over 13 years old from 2001-2011 were analyzed according to demographic data. We compared groups using parametric t-tests and linear regression analysis in the R statistical software language.Mean baseline CD4+ T cell counts varied from 348 (2003 to 389 (2009 and was higher among women (p = 1.1 x 10(-8, lower in older patients (p< 1 x 10(-8 and lower in less developed regions (p = 1.864 x 10(-5. Percentage of treated patients with undetectable viral loads increased linearly from 46% (2001 to 77% (2011, was lower among women (p = 2.851 x 10(-6, younger ages (p = 1 x 10(-3, and in less developed regions (p = 1.782 x 10(-4. NRTI acquired resistance was 86% in 2001-3 and decreased over time. NNRTI resistance increased from 2001-3(50% to 2006-9 (60%, PI resistance decreased from 2001-3 (60% to 2009 (40%, and 3-class resistance was stable over time around 25%. Subtype prevalence comprised B (75.3%, B/F recombinants (12.2%, C (5.7%, F (5.3% and B/C recombinants (1.5%, with regional variations. Three-class resistance was 26.5% among Bs, 22.4% among Fs and 17.2% among Cs.HIV diagnosis occurs late, especially among elderly Brazilians. Younger individuals need special attention due to poor virological response to treatment. Antiretroviral Resistance profile is subtype related.

  10. Optimal antiretroviral therapy adherence as evaluated by CASE index score tool is associated with virological suppression in HIV-infected adults in Dakar, Senegal.

    Science.gov (United States)

    Byabene, A K; Fortes-Déguénonvo, L; Niang, K; Manga, M N; Bulabula, A N H; Nachega, J B; Seydi, M

    2017-06-01

    To determine the prevalence and factors associated with optimal antiretroviral therapy (ART) adherence and virological failure (VLF) among HIV-infected adults enrolled in the national ART programme at the teaching hospital of Fann, Dakar, Senegal. Cross-sectional study from 1 September 2013 to 30 January 2014. (1) optimal ART adherence by the Center for Adherence Support Evaluation (CASE) Index Score (>10) and (2) VLF (HIV RNA > 1000 copies/ml). Diagnostic accuracy of CASE Index Score assessed using sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and corresponding 95% confidence intervals (CIs). Multivariate logistic regression analysis was performed to identify independent factors associated with optimal adherence and VLF. Of 98 HIV-infected patients on ART, 68% were female. The median (IQR) age was 42 (20-50) years. A total of 57 of 98 (60%) were on ART more than 3 years, and majority (88%) were on NNRTI-based first-line ART regimen. A total of 79 of 98 (80%) patients reported optimal ART adherence, and only five of 84 (5.9%) had documented VLF. Patients with VLF were significantly more likely to have suboptimal ART adherence (17.7% vs. 2.9%; P = 0.02). CASE Index Score showed the best trade-off in Se (78.9%, 95% CI: 54.4-93.9%), Sp (20.0%, 95% CI: 11.1-31.7), PPV (22.4, 95% CI: 13.1-34.2%) and NPV (76.5%, 95% CI: 50.1-93.2), when used VLF threshold of HIV RNA >50 copies/ml. Factors independently associated with VLF were CASE Index Score CASE Index Score was independently associated with virological outcomes, supporting usefulness of this low-cost ART adherence monitoring tool in this setting. © 2017 John Wiley & Sons Ltd.

  11. The Effect of Malnutrition on the Pharmacokinetics and Virologic Outcomes of Lopinavir, Efavirenz and Nevirapine in Food Insecure HIV-Infected Children in Tororo, Uganda

    Science.gov (United States)

    Bartelink, Imke H.; Savic, Rada M.; Dorsey, Grant; Ruel, Theodore; Gingrich, David; Scherpbier, Henriette J.; Capparelli, Edmund; Jullien, Vincent; Young, Sera L.; Achan, Jane; Plenty, Albert; Charlebois, Edwin; Kamya, Moses; Havlir, Diane; Aweeka, Francesca

    2014-01-01

    Background Malnutrition may impact the pharmacokinetics (PK) of antiretroviral medications and virologic responses in HIV-infected children. We therefore evaluated the PK of nevirapine (NVP), efavirenz (EFV) and lopinavir (LPV) in associations with nutritional status in a cohort of HIV-infected Ugandan children. Methods Sparse dried blood spot (DBS) samples from Ugandan children were used to estimate plasma concentrations. Historical PK data from children from three resource-rich countries (RRC) were utilized to develop the PK models. Results Concentrations in 330 DBS from 163 Ugandan children aged 0.7–7 years were analyzed in reference to plasma PK data (1189 samples) from 204 children from RRC aged 0.5–12 years. Among Ugandan children 48% was malnourished (underweight, thin or stunted). Compared to RRC, Ugandan children exhibited reduced bioavailability of EFV and LPV; 11% (P=0.045) and 18% (P=0.008) respectively. In contrast, NVP bioavailability was 46% higher in Ugandan children (Pmalnutrition on bioavailability. In children receiving NVP, the relation between exposure, malnutrition and outcome turned out to be marginally significant. Further investigations are warranted using more intensive PK measurements and adequate adherence assessements, to further assess causes of virologic failure in Ugandan children. PMID:25742090

  12. Factors predicting discordant virological and immunological responses to antiretroviral therapy in HIV-1 clade C infected Zulu/Xhosa in South Africa.

    Directory of Open Access Journals (Sweden)

    Boris Julg

    Full Text Available Factors predicting suboptimal CD4 cell recovery have been studied in HIV clade-B infected US and European populations. It is, however, uncertain to what extent these results are applicable to HIV clade-C infected African populations. Multivariate analysis using logistic regression and longitudinal analyses using mixed models were employed to assess the impact of age, gender, baseline CD4 cell count, hemoglobin, body mass index (BMI, tuberculosis and other opportunistic co-infections, and frequencies of regimen change on CD4 cell recovery at 12 and 30 months and on overtime change in CD4 cells among 442 virologically suppressed South Africans. Despite adequate virological response 37% (95% CI:32%-42% and 83% (95% CI:79%-86% of patients on antiretroviral therapy failed to restore CD4 cell counts ≥ 200 cells/mm(3 after 12 and ≥ 500 cells/mm(3 after 30 months, respectively, in this South African cohort. Critical risk factors for inadequate recovery were older age (p = 0.001 and nadir CD4 cell count at ART initiation (p<0.0001, while concurrent TB co-infection, BMI, baseline hemoglobin, gender and antiretroviral regimen were not significant risk factors. These data suggest that greater efforts are needed to identify and treat HAART-eligible patients prior to severe CD4 cell decline or achievement of advanced age.

  13. Factors predicting discordant virological and immunological responses to antiretroviral therapy in HIV-1 clade C infected Zulu/Xhosa in South Africa.

    Science.gov (United States)

    Julg, Boris; Poole, Danielle; Ghebremichael, Musie; Castilla, Carmen; Altfeld, Marcus; Sunpath, Henry; Murphy, Richard A; Walker, Bruce D

    2012-01-01

    Factors predicting suboptimal CD4 cell recovery have been studied in HIV clade-B infected US and European populations. It is, however, uncertain to what extent these results are applicable to HIV clade-C infected African populations. Multivariate analysis using logistic regression and longitudinal analyses using mixed models were employed to assess the impact of age, gender, baseline CD4 cell count, hemoglobin, body mass index (BMI), tuberculosis and other opportunistic co-infections, and frequencies of regimen change on CD4 cell recovery at 12 and 30 months and on overtime change in CD4 cells among 442 virologically suppressed South Africans. Despite adequate virological response 37% (95% CI:32%-42%) and 83% (95% CI:79%-86%) of patients on antiretroviral therapy failed to restore CD4 cell counts ≥ 200 cells/mm(3) after 12 and ≥ 500 cells/mm(3) after 30 months, respectively, in this South African cohort. Critical risk factors for inadequate recovery were older age (p = 0.001) and nadir CD4 cell count at ART initiation (p<0.0001), while concurrent TB co-infection, BMI, baseline hemoglobin, gender and antiretroviral regimen were not significant risk factors. These data suggest that greater efforts are needed to identify and treat HAART-eligible patients prior to severe CD4 cell decline or achievement of advanced age.

  14. INTERVENTIONAL STUDY OF IMMEDIATE AND LONG TERM CHANGES IN HIV/AIDS KNOWLEDGE AND ATTITUDE AMONG SCHOOL STUDENTS IN AN URBAN SLUM IN MUMBAI

    Directory of Open Access Journals (Sweden)

    Manasi Shekhar Padhyegurjar

    2012-03-01

    Full Text Available Background: Education sector plays an important role in imparting vital information regarding HIV AIDS to large number of adolescents. The present study was carried out to assess the baseline level of knowledge and attitude regarding HIV / AIDS and retention of various aspects of information over the period of one year among ninth standard school students in Mumbai. Methods and Material: The present study was designed as a school based interventional follow up study. Health education sessions on HIV/AIDS were conducted. Pre test, immediate post test, along with a follow up post test at six months and one year were administered. SPSS (Version 16 and Excel software were used for statistical analysis. Z tests for difference between proportions were applied. Results: The proportion of correct responses regarding some of the aspects of knowledge of HIV / AIDS significantly increased on health education intervention. However, no significant change in the proportion of correct responses regarding blood donation leading to HIV transmission was observed. Significant waning (p < 0.01 away of the effect of health education has been observed in some important aspects especially regarding spread without being aware of transmission, involvement of infected needles, condoms as mode of prevention and no complete cure till date. Though there is a general acceptance of HIV positive patients, attitudes involving sexual mode of transmission, drug abuse and homosexuality did not show positive change post intervention. Conclusions: Health education sessions were very effective in increasing knowledge. However, students tend to lose information regarding certain aspects. We thus need strategies for reinforcing knowledge as well as attitude aspect in school AIDS education.

  15. Persisting Inflammation and Chronic Immune Activation but Intact Cognitive Function in HIV-Infected Patients After Long-Term Treatment With Combination Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Pedersen, Karin K; Pedersen, Maria; Gaardbo, Julie C

    2013-01-01

    Impaired cognitive function in HIV-infected patients has been suggested. Treatment with combination antiretroviral therapy (cART) restores CD4⁺ cell counts and suppresses viral replication, but immune activation and inflammation may persist. The aim of the study was to examine if cognitive function...

  16. Long-term analysis of resistance development in HIV-1 positive patients treated with protease and reverse transcriptase inhibitors: Correlation of the genotype and disease progression

    Czech Academy of Sciences Publication Activity Database

    Prejdová, Jana; Weber, Jan; Machala, L.; Reiniš, Milan; Linka, M.; Brůčková, M.; Vandasová, M.; Staňková, M.; Konvalinka, Jan

    2005-01-01

    Roč. 49, č. 1 (2005), 29-36 ISSN 0001-723X R&D Projects: GA MZd(CZ) NI6339 Grant - others:5th Framework(XE) QLK2-CT-2001-02360 Institutional research plan: CEZ:AV0Z4055905 Keywords : HIV * protease inhibitors * resistance development Subject RIV: CE - Biochemistry Impact factor: 0.696, year: 2005

  17. Evolution of drug resistance in HIV infected patients remaining on a virologically failing cART regimen

    DEFF Research Database (Denmark)

    Cozzi-Lepri, A; Phillips, AN; Ruiz, L

    2007-01-01

    OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...

  18. Modelled in vivo HIV fitness under drug selective pressure and estimated genetic barrier towards resistance are predictive for virological response

    DEFF Research Database (Denmark)

    Deforche, Koen; Cozzi-Lepri, Alessandro; Theys, Kristof

    2008-01-01

    landscapes (nelfinavir [NFV] and zidovudine [AZT] plus lamivudine [3TC]) to predict week 12 viral load (VL) change for 176 treatment change episodes (TCEs) and probability of week 48 virological failure for 90 TCEs, in treatment experienced patients starting these drugs in combination. RESULTS: A higher...

  19. Optimal antiviral switching to minimize resistance risk in HIV therapy.

    Directory of Open Access Journals (Sweden)

    Rutao Luo

    Full Text Available The development of resistant strains of HIV is the most significant barrier to effective long-term treatment of HIV infection. The most common causes of resistance development are patient noncompliance and pre-existence of resistant strains. In this paper, methods of antiviral regimen switching are developed that minimize the risk of pre-existing resistant virus emerging during therapy switches necessitated by virological failure. Two distinct cases are considered; a single previous virological failure and multiple virological failures. These methods use optimal control approaches on experimentally verified mathematical models of HIV strain competition and statistical models of resistance risk. It is shown that, theoretically, order-of-magnitude reduction in risk can be achieved, and multiple previous virological failures enable greater success of these methods in reducing the risk of subsequent treatment failures.

  20. No impact of HIV-1 protease minority resistant variants on the virological response to a first-line PI-based regimen containing darunavir or atazanavir.

    Science.gov (United States)

    Perrier, Marine; Visseaux, Benoit; Landman, Roland; Joly, Véronique; Todesco, Eve; Yazdanpanah, Yazdan; Calvez, Vincent; Marcelin, Anne-Geneviève; Descamps, Diane; Charpentier, Charlotte

    2018-01-01

    To evaluate, in a clinical cohort of HIV-1-infected patients, the prevalence of PI minority resistant variants (MRV) at ART baseline and their impact on the virological response to a first-line PI-based regimen. In an observational single-centre cohort, we assessed all ART-naive patients initiating a first-line regimen including two NRTI and one boosted PI, darunavir/ritonavir or atazanavir/ritonavir, between January 2012 and March 2015. Ultra-deep sequencing of the pol gene was performed using Illumina® technology. Protease mutations were identified using the WHO transmitted drug resistance list and major PI resistance mutations (IAS-USA drug resistance mutations list). Ninety-four and 16 patients initiating a darunavir/ritonavir-based regimen and an atazanavir/ritonavir-based regimen, respectively, were assessed. Twenty-eight percent of the patients were HIV-1 subtype B, 39% CRF02_AG and 33% other non-B subtypes. Thirteen patients (13.8%) in the darunavir group and three patients (18.8%) in the atazanavir group experienced a virological failure (VF). Overall, 13 (11.8%) subjects had PI MRV at baseline in the median proportion of 1.3% (IQR = 1.1-1.7). The most prevalent PI MRV were G73C (n = 5) and M46I (n = 3). The proportion of patients harbouring baseline PI MRV was similar between those with virological success (10.6%) and those experiencing VF (18.8%) (P = 0.40). No difference was observed in the rate of PI MRV by viral subtype (P = 0.51) or by PI drug (P = 0.40). This study showed a prevalence of 11.8% of PI MRV among 110 ART-naive subjects, without significant impact on the virological response to a first-line PI-based regimen containing darunavir or atazanavir. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Long Term Financing of Infrastructure

    OpenAIRE

    Sinha, Sidharth

    2014-01-01

    Infrastructure projects, given their long life, require long term financing. The main sources of long term financings are insurance and pension funds who seek long term investments with low credit risk. However, in India household financial savings are mainly invested in bank deposits. Insurance and pension funds account for only a small percentage of household financial savings. In addition most infrastructure projects do not qualify for investment by insurance and pension funds because of t...

  2. Circulating sCD14 is associated with virological response to pegylated-interferon-alpha/ribavirin treatment in HIV/HCV co-infected patients.

    Directory of Open Access Journals (Sweden)

    Giulia Marchetti

    Full Text Available Microbial translocation (MT through the gut accounts for immune activation and CD4+ loss in HIV and may influence HCV disease progression in HIV/HCV co-infection. We asked whether increased MT and immune activation may hamper anti-HCV response in HIV/HCV patients.98 HIV/HCV patients who received pegylated-alpha-interferon (peg-INF-alpha/ribavirin were retrospectively analyzed. Baseline MT (lipopolysaccharide, LPS, host response to MT (sCD14, CD38+HLA-DR+CD4+/CD8+, HCV genotype, severity of liver disease were assessed according to Early Virological Response (EVR: HCV-RNA <50 IU/mL at week 12 of therapy or ≥2 log(10 reduction from baseline after 12 weeks of therapy and Sustained Virological Response (SVR: HCV-RNA <50 IU/mL 24 weeks after end of therapy. Mann-Whitney/Chi-square test and Pearson's correlation were used. Multivariable regression was performed to determine factors associated with EVR/SVR.71 patients displayed EVR; 41 SVR. Patients with HCV genotypes 1-4 and cirrhosis presented a trend to higher sCD14, compared to patients with genotypes 2-3 (p = 0.053 and no cirrhosis (p = 0.052. EVR and SVR patients showed lower levels of circulating sCD14 (p = 0.0001, p = 0.026, respectively, but similar T-cell activation compared to Non-EVR (Null Responders, NR and Non-SVR (N-SVR subjects. sCD14 resulted the main predictive factor of EVR (0.145 for each sCD14 unit more, 95%CI 0.031-0.688, p = 0.015. SVR was associated only with HCV genotypes 2-3 (AOR 0.022 for genotypes 1-4 vs 2-3, 95%CI 0.001-0.469, p = 0.014.In HIV/HCV patients sCD14 correlates with the severity of liver disease and predicts early response to peg-INF-alpha/ribavirin, suggesting MT-driven immune activation as pathway of HIV/HCV co-infection and response to therapy.

  3. Detecting virological failure in HIVinfected Tanzanian children ...

    African Journals Online (AJOL)

    Background. The performance of clinical and immunological criteria to predict virological failure in HIV-infected children receiving antiretroviral therapy (ART) is not well documented. Objective. To determine the validity of clinical and immunological monitoring in detecting virological failure in children on ART. Methods.

  4. HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia

    Science.gov (United States)

    Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick CK; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher KC; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

    2014-01-01

    Introduction First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. Methods We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance – Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥2 TAMs; or M184V+≥1 TAM. Virological suppression was defined as viral load (VL) Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥2 TAMs; and 32 with M184V+≥1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤200 cells/µL at genotyping (OR=4.43, 95% CI [1.59–12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39–16.36], p<0.001). Among 87/105 patients with available VL at 12 months after switch to second-line ART, virological suppression was achieved in 85%. The median genotypic susceptibility score (GSS) for the second-line regimen was 2.00. Patients with ART adherence ≥95% were more likely to be virologically suppressed (OR=9.33, 95% CI (2.43–35.81), p=0.001). Measures of patient resistance to second-line ART, including the GSS, were not significantly associated with virological outcome. Conclusions Multi-NRTI RAMs at first-line failure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving

  5. Incident and long-term HIV-1 infection among pregnant women in Brazil: Transmitted drug resistance and mother-to-child transmission.

    Science.gov (United States)

    Lima, Yanna Andressa Ramos; Cardoso, Ludimila Paula Vaz; Reis, Mônica Nogueira da Guarda; Stefani, Mariane Martins Araújo

    2016-11-01

    Primary infection, seroconversion, and transmitted drug resistance (TDR) during pregnancy may influence the risk of mother-to-child-transmission (MTCT) of HIV-1 infection. This study estimated recent seroconversion, TDR rates, HIV-1 subtypes and pregnancy outcomes among 95 recently diagnosed, antiretroviral (ARV)-naïve pregnant women recruited during antenatal care in central western Brazil. Recent seroconversion was defined by BED-capture enzyme immunoassay (HIV-1 subtypes were defined by REGA and phylogenetic analyses. The median age of participants was 25 years; the median gestational age at diagnosis was 20.5 weeks. Based on serology and sequence polymorphism, recent infection was identified in 11.6% (11/95) and, 9 of them (82%), probably seroconverted during pregnancy; one MTCT case was observed among them. Three cases of stillbirth were observed among chronic infected patients (3.6%; 3/84). Moderate rate of TDR was observed (9/90, 10%, CI95% 4.7-18.1%). Subtype B was 60% (54/90), 13.3% (12/90) was subtype C, 6.7% (6/90) was subtype F1. Recombinant B(PR) /F1(RT) and F1(PR) /B(RT) viruses comprised 15.5% (14/90); B(PR) /C(RT) mosaics represented 4.4% (4/90). Seroconversion during pregnancy, late presentation to antenatal care and moderate TDR identified in this study represent significant challenges for the MTCT elimination. J. Med. Virol. 88:1936-1943, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia.

    Directory of Open Access Journals (Sweden)

    Hubert Barennes

    Full Text Available INTRODUCTION: In resource limited settings, patients entering an antiretroviral therapy (ART program comprise ART naive and ART pre-treated patients who may show differential virological outcomes. METHODS: This retrospective study, conducted in 2010-2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia assessed virological failure (VF rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF (>1,000 copies/ml underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms. RESULTS: On a total of 209 patients, 164 (78.4% were naive and 45 (21.5% were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30-194 and 279 cells/mm3 (IQR: 103-455 (p<0.001, respectively. Twenty seven patients (12.9% exhibited VF (95% CI: 8.6-18.2%, including 10 naive (10/164, 6.0% and 17 pre-treated (17/45, 37.8% patients (p<0.001. Among these viremic patients, twenty-two (81.4% were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3% harbored ≥1 drug resistance mutations (DRMs whereas 3 (all belonging to pre-treated patients harbored wild-types viruses. The most frequent DRMs were M184V (86.3%, K103N (45.5% and thymidine analog mutations (TAMs (40.9%. Two (13.3% pre-treated patients harbored viruses that showed a multi-nucleos(tide resistance including Q151M, K65R, E33A/D, E44A/D mutations. CONCLUSION: In Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for ART pre

  7. Mucosal immunology and virology

    National Research Council Canada - National Science Library

    Tyring, Stephen

    2006-01-01

    .... A third chapter focuses on the proximal end of the gastrointestinal tract (i.e. the oral cavity). The mucosal immunology and virology of the distal end of the gastrointestinal tract is covered in the chapter on the anogenital mucosa. Mucosa-associated lymphoid tissue (MALT) plays a role in protection against all viral (and other) infections except those that enter the body via a bite (e.g. yellow fever or dengue from a mosquito or rabies from a dog) or an injection or transfusion (e.g. HIV, Hepatitis B). ...

  8. Effect of pretreatment HIV-1 drug resistance on immunological, virological, and drug-resistance outcomes of first-line antiretroviral treatment in sub-Saharan Africa: a multicentre cohort study

    NARCIS (Netherlands)

    Hamers, Raph L.; Schuurman, Rob; Sigaloff, Kim C. E.; Wallis, Carole L.; Kityo, Cissy; Siwale, Margaret; Mandaliya, Kishor; Ive, Prudence; Botes, Mariette E.; Wellington, Maureen; Osibogun, Akin; Wit, Ferdinand W.; van Vugt, Michèle; Stevens, Wendy S.; de Wit, Tobias F. Rinke

    2012-01-01

    Background The effect of pretreatment HIV-1 drug resistance on the response to first-line combination antiretroviral therapy (ART) in sub-Saharan Africa has not been assessed. We studied pretreatment drug resistance and virological, immunological, and drug-resistance treatment outcomes in a large

  9. Long-term urethral catheterisation.

    Science.gov (United States)

    Turner, Bruce; Dickens, Nicola

    This article discusses long-term urethral catheterisation, focusing on the relevant anatomy and physiology, indications for the procedure, catheter selection and catheter care. It is important that nurses have a good working knowledge of long-term catheterisation as the need for this intervention will increase with the rise in chronic health conditions and the ageing population.

  10. HIV multi-drug resistance at first-line antiretroviral failure and subsequent virological response in Asia.

    Science.gov (United States)

    Jiamsakul, Awachana; Sungkanuparph, Somnuek; Law, Matthew; Kantor, Rami; Praparattanapan, Jutarat; Li, Patrick C K; Phanuphak, Praphan; Merati, Tuti; Ratanasuwan, Winai; Lee, Christopher K C; Ditangco, Rossana; Mustafa, Mahiran; Singtoroj, Thida; Kiertiburanakul, Sasisopin

    2014-01-01

    First-line antiretroviral therapy (ART) failure often results from the development of resistance-associated mutations (RAMs). Three patterns, including thymidine analogue mutations (TAMs), 69 Insertion (69Ins) and the Q151M complex, are associated with resistance to multiple-nucleoside reverse transcriptase inhibitors (NRTIs) and may compromise treatment options for second-line ART. We investigated patterns and factors associated with multi-NRTI RAMs at first-line failure in patients from The TREAT Asia Studies to Evaluate Resistance - Monitoring study (TASER-M), and evaluated their impact on virological responses at 12 months after switching to second-line ART. RAMs were compared with the IAS-USA 2013 mutations list. We defined multi-NRTI RAMs as the presence of either Q151M; 69Ins; ≥ 2 TAMs; or M184V+≥ 1 TAM. Virological suppression was defined as viral load (VL) failure and (2) factors associated with virological suppression after 12 months on second-line. A total of 105 patients from 10 sites in Thailand, Hong Kong, Indonesia, Malaysia and Philippines were included. There were 97/105 (92%) patients harbouring ≥ 1 RAMs at first-line failure, 39/105 with multi-NRTI RAMs: six with Q151M; 24 with ≥ 2 TAMs; and 32 with M184V+≥ 1 TAM. Factors associated with multi-NRTI RAMs were CD4 ≤ 200 cells/µL at genotyping (OR=4.43, 95% CI [1.59-12.37], p=0.004) and ART duration >2 years (OR=6.25, 95% CI [2.39-16.36], pfailure were associated with low CD4 level and longer duration of ART. With many patients switching to highly susceptible regimens, good adherence was still crucial in achieving virological response. This emphasizes the importance of continued adherence counselling well into second-line therapy.

  11. Herpes viruses and HIV-1 drug resistance mutations influence the virologic and immunologic milieu of the male genital tract.

    Science.gov (United States)

    Gianella, Sara; Morris, Sheldon R; Anderson, Christy; Spina, Celsa A; Vargas, Milenka V; Young, Jason A; Richman, Douglas D; Little, Susan J; Smith, Davey M

    2013-01-02

    To further understand the role that chronic viral infections of the male genital tract play on HIV-1 dynamics and replication. Retrospective, observational study including 236 paired semen and blood samples collected from 115 recently HIV-1 infected antiretroviral naive men who have sex with men. In this study, we evaluated the association of seminal HIV-1 shedding to coinfections with seven herpes viruses, blood plasma HIV-1 RNA levels, CD4 T-cell counts, presence of transmitted drug resistance mutations (DRMs) in HIV-1 pol, participants' age and stage of HIV-infection using multivariate generalized estimating equation methods. Associations between herpes virus shedding, seminal HIV-1 levels, number and immune activation of seminal T-cells was also investigated (Mann-Whitney). Seminal herpes virus shedding was observed in 75.7% of individuals. Blood HIV-1 RNA levels (P herpes virus (HHV)-8 levels (P herpes viruses seminal shedding in our cohort. Shedding of CMV, EBV and HHV-8 and absence of DRM were associated with increased frequency of HIV-1 shedding and/or higher levels of HIV-1 RNA in semen, which are likely important cofactors for HIV-1 transmission.

  12. HIV-infected viremic long-term non-progressors and controllers display different immunological mechanisms for preserved CD4+cell counts

    DEFF Research Database (Denmark)

    Gaardbo, J; Ronit, A; Hartling, H

    2012-01-01

    of viral replication cannot explain non-progression in LTNP. Therefore we hypothesized that the immunological mechanism responsible for preserved CD4 counts in LTNP is different from that in VC. Methods: 69 treatment naïve HIV-infected patients were included in a cross-sectional study. A total of 14 LTNP...... ratio in LTNP compared to VC were found (3.8 vs. 5.5, P=0.068) while ratios in LTNP and PR were similar (4.0, P>0.05). Conclusion: LTNP displayed high levels of immune activation, apoptotic cells and reduced Th17/Treg ratio compared to VC, while LTNP were similar to PR. Thus, the immunological mechanism...... responsible for preserved CD4 counts in LTNP is still unclear but seems to be different from that in VC....

  13. Long-term Therapeutic Impact of the Timing of Antiretroviral Therapy in Patients Diagnosed With Primary Human Immunodeficiency Virus Type 1 Infection.

    Science.gov (United States)

    Novelli, Sophie; Lécuroux, Camille; Avettand-Fenoel, Véronique; Seng, Rémonie; Essat, Asma; Morlat, Philippe; Viard, Jean-Paul; Rouzioux, Christine; Meyer, Laurence; Goujard, Cécile

    2018-05-02

    We aimed to determine the consequences of delayed human immunodeficiency virus type 1 (HIV-1) infection diagnosis by comparing long-term outcomes depending on the time of combination antiretroviral therapy (cART) initiation in patients diagnosed during primary HIV infection (PHI). We selected patients from the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) PRIMO cohort, treated for ≥36 months, with sustained HIV RNA 12 months after infection (deferred ART). We measured inflammatory biomarkers from PHI through the last visit on cART, and CD4+ and CD8+ T-cell activation and plasma ultrasensitive HIV RNA at the last visit. Inflammation/activation levels were compared with those of uninfected controls. We modeled CD4+ count, CD4:CD8 ratio, and HIV DNA dynamics on cART. The decrease of HIV DNA levels was more marked in the immediate than deferred ART group, leading to a sustained mean difference of -0.6 log10 copies/106 peripheral blood mononuclear cells. Immediate ART led to improved CD4+ T-cell counts and CD4:CD8 ratios over the first 4 years of cART. At the last visit (median, 82 months), there was no difference between groups in CD4+ counts, CD4:CD8 ratio, ultrasensitive HIV RNA, or inflammation/activation marker levels. Long-term suppressive cART failed to normalize inflammation levels, which were not associated with immunovirological markers. Antiretroviral therapy initiated during PHI promotes long-term reduction of HIV reservoir size. In patients with sustained virologic suppression, inflammation may be driven by non-HIV-related factors.

  14. Effect of probiotics (Saccharomyces boulardii) on microbial translocation and inflammation in HIV-treated patients: a double-blind, randomized, placebo-controlled trial.

    Science.gov (United States)

    Villar-García, Judit; Hernández, Juan J; Güerri-Fernández, Robert; González, Alicia; Lerma, Elisabet; Guelar, Ana; Saenz, David; Sorlí, Lluisa; Montero, Milagro; Horcajada, Juan P; Knobel Freud, Hernando

    2015-03-01

    Microbial translocation has been associated with an increase in immune activation and inflammation in HIV infection despite effective highly active antiretroviral therapy. It has been shown that some probiotics have a beneficial effect by reducing intestinal permeability and, consequently, microbial translocation. To assess changes in microbial translocation and inflammation after treatment with probiotics (Saccharomyces boulardii) in HIV-1-infected patients with virologic suppression. A double-blind, randomized, placebo-controlled trial was conducted in 44 nonconsecutive HIV-1-infected patients with viral load of boulardii decreases microbial translocation (LBP) and inflammation parameters (IL-6) in HIV-1-infected patients with long-term virologic suppression.

  15. Translational HIV-1 research: from routine diagnostics to new virology insights in Amsterdam, the Netherlands during 1983-2013

    NARCIS (Netherlands)

    van der Kuyl, Antoinette C.; Bakker, Margreet; Jurriaans, Suzanne; Back, Nicole K. T.; Pasternak, Alexander O.; Cornelissen, Marion; Berkhout, Ben

    2013-01-01

    An HIV-1 diagnostic laboratory was established in the Academic Medical Center (AMC) of the University of Amsterdam after the discovery of human immunodeficiency virus (HIV) as the cause of the acquired immunodeficiency syndrome (AIDS). The first AIDS patients were diagnosed here in 1981 and since

  16. Long term complications of diabetes

    Science.gov (United States)

    ... medlineplus.gov/ency/patientinstructions/000327.htm Long-term complications of diabetes To use the sharing features on this page, ... other tests. All these may help you keep complications of diabetes away. You will need to check your blood ...

  17. Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study.

    Science.gov (United States)

    Thibault, Vincent; Gaudy-Graffin, Catherine; Colson, Philippe; Gozlan, Joël; Schnepf, Nathalie; Trimoulet, Pascale; Pallier, Coralie; Saune, Karine; Branger, Michel; Coste, Marianne; Thoraval, Francoise Roudot

    2013-03-15

    Chronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infected individuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwide cross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identify parameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBV viremia. A multicenter collaborative cross-sectional study was launched in 19 French University hospitals distributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiological characteristics of 223 HBV-HIV co-infected patients with an HBV replication over 1000 IU/mL were investigated. Patients were mostly male (82%, mean age 42 years). Genotype distribution (A 52%; E 23.3%; D 16.1%) was linked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic pattern highlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) under antiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypic lamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4 count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesions were observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viral load or genotype. Immune escape HBsAg variants were seldom detected. Despite the detection of advanced liver lesions in most patients, few were not receiving anti-HBV drugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimal adherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver disease progression. These findings are strong arguments to further optimize clinical management

  18. Nucleocapsid promotes localization of HIV-1 gag to uropods that participate in virological synapses between T cells.

    OpenAIRE

    G Nicholas Llewellyn; Ian B Hogue; Jonathan R Grover; Akira Ono

    2010-01-01

    T cells adopt a polarized morphology in lymphoid organs, where cell-to-cell transmission of HIV-1 is likely frequent. However, despite the importance of understanding virus spread in vivo, little is known about the HIV-1 life cycle, particularly its late phase, in polarized T cells. Polarized T cells form two ends, the leading edge at the front and a protrusion called a uropod at the rear. Using multiple uropod markers, we observed that HIV-1 Gag localizes to the uropod in polarized T cells. ...

  19. [Long-term psychiatric hospitalizations].

    Science.gov (United States)

    Plancke, L; Amariei, A

    2017-02-01

    Long-term hospitalizations in psychiatry raise the question of desocialisation of the patients and the inherent costs. Individual indicators were extracted from a medical administrative database containing full-time psychiatric hospitalizations for the period 2011-2013 of people over 16 years old living in the French region of Nord-Pas-de-Calais. We calculated the proportion of people who had experienced a hospitalization with a duration of 292 days or more during the study period. A bivariate analysis was conducted, then ecological data (level of health-care offer, the deprivation index and the size of the municipalities of residence) were included into a multilevel regression model in order to identify the factors significantly related to variability of long-term hospitalization rates. Among hospitalized individuals in psychiatry, 2.6% had had at least one hospitalization of 292 days or more during the observation period; the number of days in long-term hospitalization represented 22.5% of the total of days of full-time hospitalization in psychiatry. The bivariate analysis revealed that seniority in the psychiatric system was strongly correlated with long hospitalization rates. In the multivariate analysis, the individual indicators the most related to an increased risk of long-term hospitalization were: total lack of autonomy (OR=9.0; 95% CI: 6.7-12.2; P<001); diagnoses of psychological development disorders (OR=9.7; CI95%: 4.5-20.6; P<.001); mental retardation (OR=4.5; CI95%: 2.5-8.2; P<.001): schizophrenia (OR=3.0; CI95%: 1.7-5.2; P<.001); compulsory hospitalization (OR=1.7; CI95%: 1.4-2.1; P<.001); having experienced therapeutic isolation (OR=1.8; CI95%: 1.5-2.1; P<.001). Variations of long-term hospitalization rates depending on the type of establishment were very high, but the density of hospital beds or intensity of ambulatory activity services were not significantly linked to long-term hospitalization. The inhabitants of small urban units had

  20. Immuno-Virological Discordance and the Risk of NonAIDS and AIDS Events in a Large Observational Cohort of HIV-Patients in Europe

    DEFF Research Database (Denmark)

    Zoufaly, Alexander; Cozzi-Lepri, Alessandro; Reekie, Joanne

    2014-01-01

    The impact of immunosuppression despite virological suppression (immuno-virological discordance, ID) on the risk of developing fatal and non-fatal AIDS/non-AIDS events is unclear and remains to be elucidated....

  1. Potential Impact of a Free Online HIV Treatment Response Prediction System for Reducing Virological Failures and Drug Costs after Antiretroviral Therapy Failure in a Resource-Limited Setting

    Directory of Open Access Journals (Sweden)

    Andrew D. Revell

    2013-01-01

    Full Text Available Objective. Antiretroviral drug selection in resource-limited settings is often dictated by strict protocols as part of a public health strategy. The objective of this retrospective study was to examine if the HIV-TRePS online treatment prediction tool could help reduce treatment failure and drug costs in such settings. Methods. The HIV-TRePS computational models were used to predict the probability of response to therapy for 206 cases of treatment change following failure in India. The models were used to identify alternative locally available 3-drug regimens, which were predicted to be effective. The costs of these regimens were compared to those actually used in the clinic. Results. The models predicted the responses to treatment of the cases with an accuracy of 0.64. The models identified alternative drug regimens that were predicted to result in improved virological response and lower costs than those used in the clinic in 85% of the cases. The average annual cost saving was $364 USD per year (41%. Conclusions. Computational models that do not require a genotype can predict and potentially avoid treatment failure and may reduce therapy costs. The use of such a system to guide therapeutic decision-making could confer health economic benefits in resource-limited settings.

  2. Evolution of drug resistance in HIV infected patients remaining on a virologically failing cART regimen

    DEFF Research Database (Denmark)

    Cozzi-Lepri, A; Phillips, AN; Ruiz, L

    2007-01-01

    OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...... (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1...... January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). RESULTS: At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance...

  3. Evolution of drug resistance in HIV-infected patients remaining on a virologically failing combination antiretroviral therapy regimen

    DEFF Research Database (Denmark)

    Cozzi-Lepri, Alessandro; Phillips, Andrew N; Ruiz, Lidia

    2007-01-01

    OBJECTIVE: To estimate the extent of drug resistance accumulation in patients kept on a virologically failing regimen and its determinants in the clinical setting. DESIGN: The study focused on 110 patients of EuroSIDA on an unchanged regimen who had two genotypic tests performed at two time points...... (t0 and t1) when viral load was > 400 copies/ml. METHODS: Accumulation of resistance between t0 and t1 was measured using genotypic susceptibility scores (GSS) obtained by counting the total number of active drugs (according to the Rega system v6.4.1) among all licensed antiretrovirals as of 1...... January 2006. Patients were grouped according to the number of active drugs in the failing regimen at t0 (GSS_f-t0). RESULTS: At t0, patients had been on the failing combination antiretroviral therapy (cART) for a median of 11 months (range, 6-50 months). Even patients with extensive resistance...

  4. High rate of virologic suppression with darunavir/ritonavir plus optimized background therapy among highly antiretroviral-experienced HIV-infected patients: results of a prospective cohort study in São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    José Ernesto Vidal

    Full Text Available OBJECTIVES: To assess the virologic and immunological response of darunavir/ritonavir plus optimized background therapy in highly antiretroviral-experienced HIV-infected patients in Brazil. METHODS: Prospective cohort study carried out in a tertiary center in Sao Paulo, Brazil. Three-class antiretroviral-experienced patients with confirmed virologic failure began darunavir/ritonavir plus optimized background therapy (nucleoside/tide reverse transcriptase inhibitors ± raltegravir ± enfuvirtide ± maraviroc after performing a genotypic resistance assay. Clinical evaluation and laboratory tests were collected at baseline and at weeks 12, 24, and 48. Multivariate analysis was performed to identify predictors of virologic response at 48 weeks. RESULTS: Ninety-two patients were included. The median of darunavir resistant mutation was 1 (range 0-6. The median genotypic sensitivity score in the optimized background therapy was 2 (interquartile range 1-2. At week 48, 83% (95% CI: 75-90% had an HIV RNA level 100 000 copies/mL was inversely associated with virologic success at week 48 (HR: 0.22, 95% CI: 0.06-0.85, p = 0.028. CONCLUSIONS: Darunavir/ritonavir plus optimized background therapy was a highly effective salvage regimen under clinical routine conditions in a referral center in Brazil, which is similar to the reported in high-income countries.

  5. High rate of virologic suppression with darunavir/ritonavir plus optimized background therapy among highly antiretroviral-experienced HIV-infected patients: results of a prospective cohort study in São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    José Ernesto Vidal

    2013-02-01

    Full Text Available OBJECTIVES: To assess the virologic and immunological response of darunavir/ritonavir plus optimized background therapy in highly antiretroviral-experienced HIV-infected patients in Brazil. METHODS: Prospective cohort study carried out in a tertiary center in Sao Paulo, Brazil. Three-class antiretroviral-experienced patients with confirmed virologic failure began darunavir/ritonavir plus optimized background therapy (nucleoside/tide reverse transcriptase inhibitors ± raltegravir ± enfuvirtide ± maraviroc after performing a genotypic resistance assay. Clinical evaluation and laboratory tests were collected at baseline and at weeks 12, 24, and 48. Multivariate analysis was performed to identify predictors of virologic response at 48 weeks. RESULTS: Ninety-two patients were included. The median of darunavir resistant mutation was 1 (range 0-6. The median genotypic sensitivity score in the optimized background therapy was 2 (interquartile range 1-2. At week 48, 83% (95% CI: 75-90% had an HIV RNA level 100 000 copies/mL was inversely associated with virologic success at week 48 (HR: 0.22, 95% CI: 0.06-0.85, p = 0.028. CONCLUSIONS: Darunavir/ritonavir plus optimized background therapy was a highly effective salvage regimen under clinical routine conditions in a referral center in Brazil, which is similar to the reported in high-income countries.

  6. Virological Blips and Predictors of Post Treatment Viral Control After Stopping ART Started in Primary HIV Infection.

    Science.gov (United States)

    Fidler, Sarah; Olson, Ashley D; Bucher, Heiner C; Fox, Julie; Thornhill, John; Morrison, Charles; Muga, Roberto; Phillips, Andrew; Frater, John; Porter, Kholoud

    2017-02-01

    Few individuals commencing antiretroviral therapy (ART) in primary HIV infection (PHI) maintain undetectable viremia after treatment cessation. Associated factors remain unclear given the importance of the phenomenon to cure research. Using CASCADE data of seroconverters starting ART in PHI (≤6 months from seroconversion), we estimated proportions experiencing viral blips (>400 copies followed by HIV-RNA/mL without alteration of regimen) while on ART. We used Cox models to examine the association between time from ART stop to loss of control (2 consecutive measurements >1000 copies per milliliter) and magnitude and frequency of blips while on ART, time from seroconversion to ART, time on ART, adjusting for mean number of HIV-RNA measurements/year while on ART, and other confounders. Seven hundred seventy-eight seroconverters started ART in PHI with ≥3 HIV-RNA measurements. Median interquartile range (IQR) ART duration was 16.2 (8.0-35.9) months, within which we observed 13% with ≥1 blip. Of 228 who stopped ART, 119 rebounded; time to loss of control was associated with longer interval between seroconversion and ART initiation [hazard ratio (HR) = 1.16 per month; 1.04, 1.28], and blips while on ART (HR = 1.71 per blip; 95% confidence interval = 0.94 to 3.10). Longer time on ART (HR = 0.84 per additional month; 0.76, 0.92) was associated with lower risk of losing control. Of 228 stopping ART, 22 (10%) maintained post treatment control (PTC), ie, HIV-RNA HIV viral blips on therapy are associated with subsequent viral rebound on stopping ART among individuals treated in PHI. Longer duration on ART is associated with a greater chance of PTC.

  7. Triple-class virologic failure in HIV-infected patients undergoing antiretroviral therapy for up to 10 years

    DEFF Research Database (Denmark)

    Lodwick, Rebecca; Costagliola, Dominique; Reiss, Peter

    2010-01-01

    /r) from 1998 onwards. We also focused on TCVF in patients who started a PI/r-containing regimen after a first-line NNRTI-containing regimen failed. RESULTS: Of 45 937 patients followed up for a median (interquartile range) of 3.0 (1.5-5.0) years, 980 developed TCVF (2.1%). By 5 and 9 years after starting...... ART, an estimated 3.4% (95% confidence interval [CI], 3.1%-3.6%) and 8.6% (95% CI, 7.5%-9.8%) of patients, respectively, had developed TCVF. The incidence of TCVF rose during the first 3 to 4 years on ART but plateaued thereafter. There was no significant difference in the risk of TCVF according...... to whether the initial regimen was NNRTI or PI/r based (P = .11). By 5 years after starting a PI/r regimen as second-line therapy, 46% of patients had developed TCVF. CONCLUSIONS: The rate of virologic failure of the 3 original drug classes is low, but not negligible, and does not appear to diminish over...

  8. Virological responses to lamivudine or emtricitabine when combined with tenofovir and a protease inhibitor in treatment-naïve HIV-1-infected patients in the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort.

    Science.gov (United States)

    Rokx, C; Gras, L; van de Vijver, Damc; Verbon, A; Rijnders, Bja

    2016-09-01

    Lamivudine (3TC) and emtricitabine (FTC) are considered interchangeable in recommended tenofovir disoproxil-fumarate (TDF)-containing combination antiretroviral therapies (cARTs). This statement of equivalence has not been systematically studied. We compared the treatment responses to 3TC and FTC combined with TDF in boosted protease inhibitor (PI)-based cART for HIV-1-infected patients. An observational study in the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort was carried out between 2002 and 2013. Virological failure rates, time to HIV RNA suppression treatment failure were analysed using multivariable logistic regression and Cox proportional hazard models. Sensitivity analyses included propensity score-adjusted models. A total of 1582 ART-naïve HIV-1-infected patients initiated 3TC or FTC with TDF and ritonavir-boosted darunavir (29.6%), atazanavir (41.5%), lopinavir (27.1%) or another PI (1.8%). Week 48 virological failure rates on 3TC and FTC were comparable (8.9% and 5.6%, respectively; P = 0.208). The multivariable adjusted odds ratio of virological failure when using 3TC instead of FTC with TDF in PI-based cART was 0.75 [95% confidence interval (CI) 0.32-1.79; P = 0.51]. Propensity score-adjusted models showed comparable results. The adjusted hazard ratio (HR) for treatment failure of 3TC compared with FTC was 1.15 (95% CI 0.58-2.27) within 240 weeks after cART initiation. The time to two consecutive HIV RNA measurements treatment failure after suppression treatment-naïve HIV-1-infected patients starting either 3TC/TDF or FTC/TDF and a ritonavir-boosted PI. © 2016 British HIV Association.

  9. Nuclear Energy, Long Term Requirements

    International Nuclear Information System (INIS)

    Knapp, V.

    2006-01-01

    There are serious warnings about depletion of oil and gas and even more serious warnings about dangers of climate change caused by emission of carbon dioxide. Should developed countries be called to replace CO2 emitting energy sources as soon as possible, and the time available may not be longer then few decades, can nuclear energy answer the call and what are the requirements? Assuming optimistic contribution of renewable energy sources, can nuclear energy expand to several times present level in order to replace large part of fossil fuels use? Paper considers intermediate and long-term requirements. Future of nuclear power depends on satisfactory answers on several questions. First group of questions are those important for near and intermediate future. They deal with economics and safety of nuclear power stations in the first place. On the same time scale a generally accepted concept for radioactive waste disposal is also required. All these issues are in the focus of present research and development. Safer and more economical reactors are targets of international efforts in Generation IV and INPRO projects, but aiming further ahead these innovative projects are also addressing issues such as waste reduction and proliferation resistance. However, even assuming successful technical development of these projects, and there is no reason to doubt it, long term and large-scale nuclear power use is thereby not yet secured. If nuclear power is to play an essential role in the long-term future energy production and in reduction of CO2 emission, than several additional questions must be replied. These questions will deal with long-term nuclear fuel sufficiency, with necessary contribution of nuclear power in sectors of transport and industrial processes and with nuclear proliferation safety. This last issue is more political then technical, thus sometimes neglected by nuclear engineers, yet it will have essential role for the long-term prospects of nuclear power. The

  10. Effect of HIV type 1 subtype on virological and immunological response to combination antiretroviral therapy: evidence for a more rapid viral suppression for subtype A than subtype B-infected Greek individuals.

    Science.gov (United States)

    Paraskevis, Dimirios; Touloumi, Giota; Bakoyannis, Giorgos; Paparizos, Vassilios; Lazanas, Marios; Gargalianos, Panagiotis; Chryssos, Georgios; Antoniadou, Anastasia; Psichogiou, Mina; Panos, Georgios; Katsarou, Olga; Sambatakou, Helen; Kordossis, Theodoros; Hatzakis, Angelos

    2013-03-01

    Whether response to combination antiretroviral therapy (cART) differs between those infected with HIV-1 subtype A or B remains unclear. We compared virological and immunological response to cART in individuals infected with subtype A or B in an ethnically homogeneous population. Data derived from the Athens Multicenter AIDS Cohort Study (AMACS) and analysis were restricted to those of Greek origin. Time to virological response (confirmed HIV-RNA 500 copies/ml at any time or no response by month 6) were analyzed using survival models and CD4 changes after cART initiation using piecewise linear mixed effects models. Of the 571 subjects included in the analysis, 412 (72.2%) were infected with subtype B and 159 (27.8%) with subtype A. After adjusting for various prognostic factors, the rate of virological response was higher for those infected with subtype A versus B (adjusted HR: 1.35; 95% CI: 1.08-1.68; p=0.009). Subtype A was also marginally associated with a lower hazard of virological failure compared to subtype B (HR=0.73; 95% CI: 0.53-1.02; p=0.062). Further adjustment for treatment adherence did not substantially changed the main results. No significant differences were observed in the rates of CD4 increases by subtype. The overall median (95% CI) CD4 increase at 2 years of cART was 193 (175, 212) cells/μl. Our study, based on one of the largest homogeneous groups of subtype A and B infections in Europe, showed that individuals infected with subtype A had an improved virological but similar immunological response to cART compared to those infected with subtype B.

  11. Analysing long term discursive processes

    DEFF Research Database (Denmark)

    Horsbøl, Anders

    which extend beyond the single interaction, for instance negotiations or planning processes, seems to have played a less important role, with studies such as Iedema 2001 and Wodak 2000 as exceptions. These long term processes, however, are central to the constitution and workings of organizations......What do timescales - the notion that processes take place or can be viewed within a shorter or longer temporal range (Lemke 2005) - mean for the analysis of discourse? What are the methodological consequences of analyzing discourse at different timescales? It may be argued that discourse analysis...... in general has favored either the analysis of short term processes such as interviews, discussions, and lessons, or the analysis of non-processual entities such as (multimodal) texts, arguments, discursive repertoires, and discourses (in a Foucaultian sense). In contrast, analysis of long term processes...

  12. Comparing long term energy scenarios

    International Nuclear Information System (INIS)

    Cumo, M.; Simbolotti, G.

    2001-01-01

    Major projection studies by international organizations and senior analysts have been compared with reference to individual key parameters (population, energy demand/supply, resources, technology, emissions and global warming) to understand trends and implications of the different scenarios. Then, looking at the long term (i.e., 2050 and beyond), parameters and trends have been compared together to understand and quantify whether and when possible crisis or market turbulence might occur due to shortage of resources or environmental problems [it

  13. Long term radioactive waste management

    International Nuclear Information System (INIS)

    Lavie, J.M.

    1984-01-01

    In France, waste management, a sensitive issue in term of public opinion, is developing quickly, and due to twenty years of experience, is now reaching maturity. With the launching of the French nuclear programme, the use of radioactive sources in radiotherapy and industry, waste management has become an industrial activity. Waste management is an integrated system dealing with the wastes from their production to the long term disposal, including their identification, sortage, treatment, packaging, collection and transport. This system aims at guaranteing the protection of present and future populations with an available technology. In regard to their long term management, and the design of disposals, radioactive wastes are divided in three categories. This classification takes into account the different radioisotopes contained, their half life and their total activity. Presently short-lived wastes are stored in the shallowland disposal of the ''Centre de la Manche''. Set up within the French Atomic Energy Commission (CEA), the National Agency for waste management (ANDRA) is responsible within the framework of legislative and regulatory provisions for long term waste management in France [fr

  14. Predicting HIV RNA virologic outcome at 52-weeks follow-up in antiretroviral clinical trials. The INCAS and AVANTI Study Groups.

    Science.gov (United States)

    Raboud, J M; Rae, S; Montaner, J S

    2000-08-15

    To determine the ability of intermediate plasma viral load (pVL) measurements to predict virologic outcome at 52 weeks of follow-up in clinical trials of antiretroviral therapy. Individual patient data from three clinical trials (INCAS, AVANTI-2 and AVANTI-3) were combined into a single database. Virologic success was defined to be plasma viral load (pVL) <500 copies/ml at week 52. The sensitivity and specificity of intermediate pVL measurements below the limit of detection, 100, 500, 1000, and 5000 copies/ml to predict virologic success were calculated. The sensitivity, specificity, and positive and negative predictive values of a pVL measurement <1000 copies/ml at week 16 to predict virologic outcome at week 52 were 74%, 74%, 48%, and 90%, respectively, for patients on double therapy. For patients on triple therapy, the sensitivity, specificity, and positive and negative predictive values of a pVL measurement <50 copies/ml at week 16 to predict virologic outcome were 68%, 68%, 80%, and 47%, respectively. For patients receiving double therapy, a poor virologic result at an intermediate week of follow-up is a strong indicator of virologic failure at 52 weeks whereas intermediate virologic success is no guarantee of success at 1 year. For patients on triple therapy, disappointing intermediate results do not preclude virologic success at 1 year and intermediate successes are more likely to be sustained.

  15. A cross-sectional study to evaluate second line virological failure and elevated bilirubin as a surrogate for adherence to atazanavir/ritonavir in two urban HIV clinics in Lilongwe, Malawi.

    Science.gov (United States)

    Ongubo, Dennis Miyoge; Lim, Robertino; Tweya, Hannock; Stanley, Christopher Chikhosi; Tembo, Petros; Broadhurst, Richard; Gugsa, Salem; Ngongondo, McNeil; Speight, Colin; Heller, Tom; Phiri, Sam; Hosseinipour, Mina C

    2017-07-03

    Malawi's national antiretroviral therapy program provides atazanavir/ritonavir-based second line regimens which cause concentration-dependent rise in indirect bilirubin. We sought to determine if elevated bilirubin, as a surrogate of atazanavir/ritonavir adherence, can aid in the evaluation of second line virological failure in Malawi. We conducted a cross-sectional study of HIV-infected patients ≥15 years who were on boosted protease inhibitor-based second line antiretroviral therapy for at least 6 months in two urban HIV clinics in Lilongwe, Malawi. Antiretroviral therapy history and adherence data were extracted from the electronic medical records and blood was drawn for viral load, complete blood count, total bilirubin, and CD4 cell count at a clinic visit. Factors associated with virological failure were assessed using multivariate logistic regression model. Out of 376 patients on second line antiretroviral therapy evaluated, 372 (98.9%) were on atazanavir/ritonavir-based therapy and 142 (37.8%) were male. Mean age was 40.9 years (SD ± 10.1), mean duration on second line antiretroviral therapy was 41.9 months (SD ± 27.6) and 256 patients (68.1%) had elevated bilirubin >1.3 mg/dL. Overall, 35 (9.3%) patients had viral load >1000 copies/ml (virological failure). Among the virologically failing vs. non-failing patients, bilirubin was elevated in 34.3% vs. 72.0% respectively (p bilirubin levels (aOR 5.4, p bilirubin levels better predicted virological failure than pill count adherence. Therefore, strategic use of bilirubin and viral load testing to target adherence counseling and support may be cost-effective in monitoring second line antiretroviral therapy adherence and virological failure. Drug resistance testing targeted for patients with virological failure despite elevated bilirubin levels would facilitate timely switch to third line antiretroviral regimens whenever available.

  16. HIV-1 virological remission lasting more than 12 years after interruption of early antiretroviral therapy in a perinatally infected teenager enrolled in the French ANRS EPF-CO10 paediatric cohort: a case report.

    Science.gov (United States)

    Frange, Pierre; Faye, Albert; Avettand-Fenoël, Véronique; Bellaton, Erianna; Descamps, Diane; Angin, Mathieu; David, Annie; Caillat-Zucman, Sophie; Peytavin, Gilles; Dollfus, Catherine; Le Chenadec, Jerome; Warszawski, Josiane; Rouzioux, Christine; Sáez-Cirión, Asier

    2016-01-01

    Durable HIV-1 remission after interruption of combined antiretroviral therapy (ART) has been reported in some adults who started treatment during primary infection; however, whether long-term remission in vertically infected children is possible was unknown. We report a case of a young adult perinatally infected with HIV-1 with viral remission despite long-term treatment interruption. The patient was identified in the ANRS EPF-CO10 paediatric cohort among 100 children infected with HIV perinatally who started ART before 6 months of age. HIV RNA viral load and CD4 cell counts were monitored from birth. Ultrasensitive HIV RNA, peripheral blood mononuclear cell (PBMC)-associated HIV DNA, HIV-specific T-cell responses (ie, production of cytokines and capacity to suppress HIV infection), reactivation of the CD4 cell reservoir (measured by p24 ELISA and HIV RNA in supernatants upon phytohaemagglutinin activation of purified CD4 cells), and plasma concentrations of antiretroviral drugs were assessed after 10 years of documented control off therapy. The infant was born in 1996 to a woman with uncontrolled HIV-1 viraemia and received zidovudine-based prophylaxis for 6 weeks. HIV RNA and DNA were not detected 3 days and 14 days after birth. HIV DNA was detected at 4 weeks of age. HIV RNA reached 2·17× 10(6) copies per mL at 3 months of age and ART was started. HIV RNA was undetectable 1 month later. ART was discontinued by the family at some point between 5·8 and 6·8 years of age. HIV RNA was undetectable at 6·8 years of age and ART was not resumed. HIV RNA has remained below 50 copies per mL and CD4 cell counts stable through to 18·6 years of age. After 11·5 years of control off treatment, HIV RNA was below 4 copies per mL and HIV DNA was 2·2 log10 copies per 10(6) PBMCs. The HLA genotype showed homozygosity at several loci (A*2301-, B*1503/4101, C*0210/0802, DRB1*1101-, and DQB1*0602-). HIV-specific CD8 T-cell responses and T-cell activation were weak. Findings

  17. Calendar time trends in the incidence and prevalence of triple-class virologic failure in antiretroviral drug-experienced people with HIV in Europe

    DEFF Research Database (Denmark)

    Nakagawa, Fumiyo; Lodwick, Rebecca; Costagliola, Dominique

    2012-01-01

    Despite the increasing success of antiretroviral therapy (ART), virologic failure of the 3 original classes [triple-class virologic failure, (TCVF)] still develops in a small minority of patients who started therapy in the triple combination ART era. Trends in the incidence and prevalence of TCVF...

  18. Long-term biodosimetry Redux

    International Nuclear Information System (INIS)

    Simon, Steven L.; Bouville, Andre

    2016-01-01

    This paper revisits and reiterates the needs, purposes and requirements of bio-dosimetric assays for long-term dose and health risk assessments. While the most crucial need for bio-dosimetric assays is to guide medical response for radiation accidents, the value of such techniques for improving our understanding of radiation health risk by supporting epidemiological (long-term health risk) studies is significant. As new cohorts of exposed persons are identified and new health risk studies are undertaken with the hopes that studying the exposed will result in a deeper understanding of radiation risk, the value of reliable dose reconstruction is underscored. The ultimate application of biodosimetry in long-term health risk studies would be to completely replace model-based dose reconstruction-a complex suite of methods for retrospectively estimating dose that is commonly fraught with large uncertainties due to the absence of important exposure-related information, as well as imperfect models. While biodosimetry could potentially supplant model-based doses, there are numerous limitations of presently available techniques that constrain their widespread application in health risk research, including limited ability to assess doses received far in the past, high cost, great inter-individual variability, invasiveness, higher than preferred detection limits and the inability to assess internal dose (for the most part). These limitations prevent the extensive application of biodosimetry to large cohorts and should be considered a challenge to researchers to develop new and more flexible techniques that meet the demands of long-term health risk research. Events in recent years, e.g. the Fukushima reactor accident and the increased threat of nuclear terrorism, underscore that any event that results in significant radiation exposures of a group of people will also produce a much larger population, exposed at lower levels, but that likewise needs (or demands) an exposure

  19. Long term stability of power systems

    Energy Technology Data Exchange (ETDEWEB)

    Kundur, P; Gao, B [Powertech Labs. Inc., Surrey, BC (Canada)

    1994-12-31

    Power system long term stability is still a developing subject. In this paper we provide our perspectives and experiences related to long term stability. The paper begins with the description of the nature of the long term stability problem, followed by the discussion of issues related to the modeling and solution techniques of tools for long term stability analysis. Cases studies are presented to illustrate the voltage stability aspect and plant dynamics aspect of long term stability. (author) 20 refs., 11 figs.

  20. A Randomized Controlled Trial of a Text Messaging Intervention to Promote Virologic Suppression and Retention in Care in an Urban Safety-Net HIV Clinic: The Connect4Care (C4C) Trial.

    Science.gov (United States)

    Christopoulos, Katerina A; Riley, Elise D; Carrico, Adam W; Tulsky, Jacqueline; Moskowitz, Judith T; Dilworth, Samantha; Coffin, Lara S; Wilson, Leslie; Peretz, Jason Johnson; Hilton, Joan F

    2018-02-21

    Text messaging is a promising strategy to support HIV care engagement, but little is known about its efficacy in urban safety-net HIV clinic populations. We conducted a randomized controlled trial of a supportive and motivational text messaging intervention, Connect4Care (C4C), among viremic patients who had a history of poor retention or were new to clinic. Participants were randomized (stratified by new HIV diagnosis status) to receive one of the following for 12 months: 1) thrice-weekly intervention messages, plus texted primary care appointment reminders and a monthly text message requesting confirmation of study participation, or; 2) texted reminders and monthly messages alone. Viral load was assessed at 6 and 12 months. The primary outcome was virologic suppression (<200 copies/mL) at 12 months, estimated via repeated measures log-binomial regression, adjusted for new diagnosis status. The secondary outcome was retention in clinic care. Between August 2013-November 2015, 230 participants were randomized. Virologic suppression at 12 months was similar between intervention and control participants (48.8% vs. 45.8%), with negligible change from 6-month estimates, yielding RR 1.07 (95% CI: 0.82, 1.39). Suppression was higher in the newly diagnosed (78.3% vs. 45.3%). There were no intervention effects on the secondary outcome. Exploratory analyses suggested that patients with more responses to study text messages had better outcomes, regardless of arm. The C4C text messaging intervention did not significantly increase virologic suppression or retention in care. Response to text messages may be a useful way for providers to gauge risk for poor HIV outcomes. NCT01917994.

  1. Evaluation of the genotypic prediction of HIV-1 coreceptor use versus a phenotypic assay and correlation with the virological response to maraviroc: the ANRS GenoTropism study.

    Science.gov (United States)

    Recordon-Pinson, Patricia; Soulié, Cathia; Flandre, Philippe; Descamps, Diane; Lazrek, Mouna; Charpentier, Charlotte; Montes, Brigitte; Trabaud, Mary-Anne; Cottalorda, Jacqueline; Schneider, Véronique; Morand-Joubert, Laurence; Tamalet, Catherine; Desbois, Delphine; Macé, Muriel; Ferré, Virginie; Vabret, Astrid; Ruffault, Annick; Pallier, Coralie; Raymond, Stéphanie; Izopet, Jacques; Reynes, Jacques; Marcelin, Anne-Geneviève; Masquelier, Bernard

    2010-08-01

    Genotypic algorithms for prediction of HIV-1 coreceptor usage need to be evaluated in a clinical setting. We aimed at studying (i) the correlation of genotypic prediction of coreceptor use in comparison with a phenotypic assay and (ii) the relationship between genotypic prediction of coreceptor use at baseline and the virological response (VR) to a therapy including maraviroc (MVC). Antiretroviral-experienced patients were included in the MVC Expanded Access Program if they had an R5 screening result with Trofile (Monogram Biosciences). V3 loop sequences were determined at screening, and coreceptor use was predicted using 13 genotypic algorithms or combinations of algorithms. Genotypic predictions were compared to Trofile; dual or mixed (D/M) variants were considered as X4 variants. Both genotypic and phenotypic results were obtained for 189 patients at screening, with 54 isolates scored as X4 or D/M and 135 scored as R5 with Trofile. The highest sensitivity (59.3%) for detection of X4 was obtained with the Geno2pheno algorithm, with a false-positive rate set up at 10% (Geno2pheno10). In the 112 patients receiving MVC, a plasma viral RNA load of <50 copies/ml was obtained in 68% of cases at month 6. In multivariate analysis, the prediction of the X4 genotype at baseline with the Geno2pheno10 algorithm including baseline viral load and CD4 nadir was independently associated with a worse VR at months 1 and 3. The baseline weighted genotypic sensitivity score was associated with VR at month 6. There were strong arguments in favor of using genotypic coreceptor use assays for determining which patients would respond to CCR5 antagonist.

  2. Navigating Long-Term Care

    Directory of Open Access Journals (Sweden)

    James D. Holt MD

    2017-03-01

    Full Text Available Americans over age 65 constitute a larger percentage of the population each year: from 14% in 2010 (40 million elderly to possibly 20% in 2030 (70 million elderly. In 2015, an estimated 66 million people provided care to the ill, disabled, and elderly in the United States. In 2000, according to the Centers for Disease Control and Prevention (CDC, 15 million Americans used some form of long-term care: adult day care, home health, nursing home, or hospice. In all, 13% of people over 85 years old, compared with 1% of those ages 65 to 74, live in nursing homes in the United States. Transitions of care, among these various levels of care, are common: Nursing home to hospital transfer, one of the best-studied transitions, occurs in more than 25% of nursing home residents per year. This article follows one patient through several levels of care.

  3. Long term study of mechanical

    Directory of Open Access Journals (Sweden)

    Ahmed M. Diab

    2016-06-01

    Full Text Available In this study, properties of limestone cement concrete containing different replacement levels of limestone powder were examined. It includes 0%, 5%, 10%, 15%, 20% and 25% of limestone powder as a partial replacement of cement. Silica fume was added incorporated with limestone powder in some mixes to enhance the concrete properties. Compressive strength, splitting tensile strength and modulus of elasticity were determined. Also, durability of limestone cement concrete with different C3A contents was examined. The weight loss, length change and cube compressive strength loss were measured for concrete attacked by 5% sodium sulfate using an accelerated test up to 525 days age. The corrosion resistance was measured through accelerated corrosion test using first crack time, cracking width and steel reinforcement weight loss. Consequently, for short and long term, the use of limestone up to 10% had not a significant reduction in concrete properties. It is not recommended to use blended limestone cement in case of sulfate attack. The use of limestone cement containing up to 25% limestone has insignificant effect on corrosion resistance before cracking.

  4. Long-term competence restoration.

    Science.gov (United States)

    Morris, Douglas R; DeYoung, Nathaniel J

    2014-01-01

    While the United States Supreme Court's Jackson v. Indiana decision and most state statutes mandate determinations of incompetent defendants' restoration probabilities, courts and forensic clinicians continue to lack empirical evidence to guide these determinations and do not yet have a consensus regarding whether and under what circumstances incompetent defendants are restorable. The evidence base concerning the restoration likelihood of those defendants who fail initial restoration efforts is even further diminished and has largely gone unstudied. In this study, we examined the disposition of a cohort of defendants who underwent long-term competence restoration efforts (greater than six months) and identified factors related to whether these defendants were able to attain restoration and adjudicative success. Approximately two-thirds (n = 52) of the 81 individuals undergoing extended restoration efforts were eventually deemed restored to competence. Lengths of hospitalization until successful restoration are presented with implications for the reasonable length of time that restoration efforts should persist. Older individuals were less likely to be restored and successfully adjudicated, and individuals with more severe charges and greater factual legal understanding were more likely to be restored and adjudicated. The significance of these findings for courts and forensic clinicians is discussed.

  5. Uranium ... long-term confidence

    International Nuclear Information System (INIS)

    Anon.

    1983-01-01

    Half way through 1983 the outlook for the world's uranium producers was far from bright if one takes a short term view. The readily accessible facts present a gloomy picture. The spot prices of uranium over the past few years decreased from a high of $42-$43/lb to a low of $17 in 1982. It now hovers between $23 and $24. the contract prices negotiated between producers and consumers are not so accessible but they do not reflect the spot price. The reasons why contractual uranium prices do not follow the usual dictates of supply and demand are related to the position in which uranium and associated power industries find themselves. There is public reaction with strong emotional overtones as well as much reduced expectations about the electric power needs of the world. Furthermore the supply of uranium is not guaranteed despite present over production. However the people in the industry, taking the medium- and long-term view, are not despondent

  6. Long-term corrosion studies

    International Nuclear Information System (INIS)

    Gdowski, G.

    1998-01-01

    The scope of this activity is to assess the long-term corrosion properties of metallic materials under consideration for fabricating waste package containers. Three classes of metals are to be assessed: corrosion resistant, intermediate corrosion resistant, and corrosion allowance. Corrosion properties to be evaluated are general, pitting and crevice corrosion, stress-corrosion cracking, and galvanic corrosion. The performance of these materials will be investigated under conditions that are considered relevant to the potential emplacement site. Testing in four aqueous solutions, and vapor phases above them, and at two temperatures are planned for this activity. (The environmental conditions, test metals, and matrix are described in detail in Section 3.0.) The purpose and objective of this activity is to obtain the kinetic and mechanistic information on degradation of metallic alloys currently being considered for waste package containers. This information will be used to provide assistance to (1) waste package design (metal barrier selection) (E-20-90 to E-20-92), (2) waste package performance assessment activities (SIP-PA-2), (3) model development (E-20-75 to E-20-89). and (4) repository license application

  7. Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-week results of a randomized trial.

    Directory of Open Access Journals (Sweden)

    Barbara Rossetti

    Full Text Available Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption per protocol at week 48.Patients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm or continue current ART (continuation arm.In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm. The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005. The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030. At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm.Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therapy.

  8. Transmitted drug resistant HIV-1 and association with virologic and CD4 cell count response to combination antiretroviral therapy in the EuroSIDA Study

    DEFF Research Database (Denmark)

    Bannister, Wendy P; Cozzi-Lepri, Alessandro; Clotet, Bonaventura

    2008-01-01

    OBJECTIVES: To investigate prevalence of transmitted drug-resistant human immunodeficiency virus (TDR) and factors associated with TDR and to compare virological and CD4 count response to combination antiretroviral therapy. METHODS: In this study, 525 mostly chronically infected EuroSIDA patients...

  9. Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue based regimens in ART-naïve and experienced patients

    DEFF Research Database (Denmark)

    Silberstein, F; Cozzi-Lepri, A; Ruiz, L

    2007-01-01

    BACKGROUND: A negative association between the polymorphism F214L and type 1 thymidine analogue (TA) mutations (TAMs) has been observed. However, the virological response to TAs according to the detection of F214L has not been evaluated. METHODS: We studied 590 patients from EuroSIDA who started ...... were observed in patients with M41L/T215Y and mixed TAM profiles detected before the initiation of cART. CONCLUSIONS: This study provides evidence that the detection of polymorphism F214L is associated with a favorable virological response to TA-based cART.......BACKGROUND: A negative association between the polymorphism F214L and type 1 thymidine analogue (TA) mutations (TAMs) has been observed. However, the virological response to TAs according to the detection of F214L has not been evaluated. METHODS: We studied 590 patients from EuroSIDA who started TA...... therapy for the first time as part of potent combination antiretroviral therapy (cART) and who were tested for genotypic resistance within the past 6 months. End points were median reduction in the week 24 viral load and time to virological failure (2 consecutive VL measurements >400 copies/mL after...

  10. Financing long term liabilities (Germany)

    International Nuclear Information System (INIS)

    2003-01-01

    charges and fees levied from the waste producers. Altogether, financial resources for decommissioning are needed for the following steps: the post-operational phase in which the facility is prepared for dismantling after its final shut-down, dismantling of the radioactive part of the facility, management, storage and disposal of the radioactive waste, restoration of the site, licensing and regulatory supervision of all these steps. Additional means are necessary for the management, storage and disposal of the spent fuel. The way in which the availability of financial resources is secured differs between public owned installations and installations of the private power utilities. In Germany, past practices has resulted in singular contaminated sites of limited extent, mainly during the first half of the 20. century. Those contaminated sites have been or are being cleaned up and redeveloped. In large areas of Saxony and Thuringia, the geological formations permitted the surface and underground mining of Uranium ore. Facilities of the former Soviet-German WISMUT Ltd. where ore was mined and processed from 1946 until the early 1990's can be found at numerous sites. In the course of the re-unification of Germany, the soviet shares of the WISMUT were taken over by the Federal Republic of Germany and the closure of the WISMUT facilities was initiated. In that phase the extent of the damages to the environment and of the necessary remediation work became clear. All mining and milling sites are now closed and are under decommissioning. A comprehensive remediation concept covers all WISMUT sites. Heaps and mill-tailing ponds are transferred into a long-term stable condition. The area of the facilities to be remediated amounts to more than 30 km 2 . Heaps cover a total area of ca. 15,5 km 2 , tailing ponds in which the tailings resulting from the Uranium production are stored as sludges cover 6,3 km 2 ). In total, the remediation issues are very complex and without precedent. The

  11. Virologic outcomes in early antiretroviral treatment: HPTN 052.

    Science.gov (United States)

    Eshleman, Susan H; Wilson, Ethan A; Zhang, Xinyi C; Ou, San-San; Piwowar-Manning, Estelle; Eron, Joseph J; McCauley, Marybeth; Gamble, Theresa; Gallant, Joel E; Hosseinipour, Mina C; Kumarasamy, Nagalingeswaran; Hakim, James G; Kalonga, Ben; Pilotto, Jose H; Grinsztejn, Beatriz; Godbole, Sheela V; Chotirosniramit, Nuntisa; Santos, Breno Riegel; Shava, Emily; Mills, Lisa A; Panchia, Ravindre; Mwelase, Noluthando; Mayer, Kenneth H; Chen, Ying Q; Cohen, Myron S; Fogel, Jessica M

    2017-05-01

    The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350-550 cells/mm 3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4  1000 copies/mL > 24 weeks after ART initiation. Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention.

  12. A Long-term Plan for Kalk

    DEFF Research Database (Denmark)

    2017-01-01

    In this case, the author demonstrates together with the owner-manager of KALK A/S, Mr Rasmus Jorgensen, how to use the Family Business Map to frame a constructive discussion about long-term planning. The Family Business Map is a tool for long-term planning in family firms developed by Professor...

  13. Virtual Models of Long-Term Care

    Science.gov (United States)

    Phenice, Lillian A.; Griffore, Robert J.

    2012-01-01

    Nursing homes, assisted living facilities and home-care organizations, use web sites to describe their services to potential consumers. This virtual ethnographic study developed models representing how potential consumers may understand this information using data from web sites of 69 long-term-care providers. The content of long-term-care web…

  14. Extensive virologic and immunologic characterization in an HIV-infected individual following allogeneic stem cell transplant and analytic cessation of antiretroviral therapy: A case study.

    Science.gov (United States)

    Cummins, Nathan W; Rizza, Stacey; Litzow, Mark R; Hua, Stephane; Lee, Guinevere Q; Einkauf, Kevin; Chun, Tae-Wook; Rhame, Frank; Baker, Jason V; Busch, Michael P; Chomont, Nicolas; Dean, Patrick G; Fromentin, Rémi; Haase, Ashley T; Hampton, Dylan; Keating, Sheila M; Lada, Steven M; Lee, Tzong-Hae; Natesampillai, Sekar; Richman, Douglas D; Schacker, Timothy W; Wietgrefe, Stephen; Yu, Xu G; Yao, Joseph D; Zeuli, John; Lichterfeld, Mathias; Badley, Andrew D

    2017-11-01

    Notwithstanding 1 documented case of HIV-1 cure following allogeneic stem cell transplantation (allo-SCT), several subsequent cases of allo-SCT in HIV-1 positive individuals have failed to cure HIV-1 infection. The aim of our study was to describe changes in the HIV reservoir in a single chronically HIV-infected patient on suppressive antiretroviral therapy who underwent allo-SCT for treatment of acute lymphoblastic leukemia. We prospectively collected peripheral blood mononuclear cells (PBMCs) by leukapheresis from a 55-year-old man with chronic HIV infection before and after allo-SCT to measure the size of the HIV-1 reservoir and characterize viral phylogeny and phenotypic changes in immune cells. At day 784 post-transplant, when HIV-1 was undetectable by multiple measures-including PCR measurements of both total and integrated HIV-1 DNA, replication-competent virus measurement by large cell input quantitative viral outgrowth assay, and in situ hybridization of colon tissue-the patient consented to an analytic treatment interruption (ATI) with frequent clinical monitoring. He remained aviremic off antiretroviral therapy until ATI day 288, when a low-level virus rebound of 60 HIV-1 copies/ml occurred, which increased to 1,640 HIV-1 copies/ml 5 days later, prompting reinitiation of ART. Rebounding plasma HIV-1 sequences were phylogenetically distinct from proviral HIV-1 DNA detected in circulating PBMCs before transplantation. The main limitations of this study are the insensitivity of reservoir measurements, and the fact that it describes a single case. allo-SCT led to a significant reduction in the size of the HIV-1 reservoir and a >9-month-long ART-free remission from HIV-1 replication. Phylogenetic analyses suggest that the origin of rebound virus was distinct from the viruses identified pre-transplant in the PBMCs.

  15. Prevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children - a EuroCoord-CHAIN-EPPICC joint project

    DEFF Research Database (Denmark)

    Ngo-Giang-Huong, Nicole; Wittkop, Linda; Judd, Ali

    2016-01-01

    BACKGROUND: Few studies have evaluated the impact of pre-treatment drug resistance (PDR) on response to combination antiretroviral treatment (cART) in children. The objective of this joint EuroCoord-CHAIN-EPPICC/PENTA project was to assess the prevalence of PDR mutations and their association...... algorithm to infer resistance to prescribed drugs. Time to virological failure (VF) was defined as the first of two consecutive HIV-RNA > 500 copies/mL after 6 months cART and was assessed by Cox proportional hazards models. All models were adjusted for baseline demographic, clinical, immunology.......7-5.7). Of 37 children (7.8 %, 95 % confidence interval (CI), 5.5-10.6) harboring a virus with ≥1 PDR mutations, 30 children had a virus resistant to ≥1 of the prescribed drugs. Overall, the cumulative Kaplan-Meier estimate for virological failure was 19.8 % (95 %CI, 16.4-23.9). Cumulative risk for VF tended...

  16. Virologic response to tipranavir-ritonavir or darunavir-ritonavir based regimens in antiretroviral therapy experienced HIV-1 patients: a meta-analysis and meta-regression of randomized controlled clinical trials.

    Directory of Open Access Journals (Sweden)

    Asres Berhan

    Full Text Available The development of tipranavir and darunavir, second generation non-peptidic HIV protease inhibitors, with marked improved resistance profiles, has opened a new perspective on the treatment of antiretroviral therapy (ART experienced HIV patients with poor viral load control. The aim of this study was to determine the virologic response in ART experienced patients to tipranavir-ritonavir and darunavir-ritonavir based regimens.A computer based literature search was conducted in the databases of HINARI (Health InterNetwork Access to Research Initiative, Medline and Cochrane library. Meta-analysis was performed by including randomized controlled studies that were conducted in ART experienced patients with plasma viral load above 1,000 copies HIV RNA/ml. The odds ratios and 95% confidence intervals (CI for viral loads of <50 copies and <400 copies HIV RNA/ml at the end of the intervention were determined by the random effects model. Meta-regression, sensitivity analysis and funnel plots were done. The number of HIV-1 patients who were on either a tipranavir-ritonavir or darunavir-ritonavir based regimen and achieved viral load less than 50 copies HIV RNA/ml was significantly higher (overall OR = 3.4; 95% CI, 2.61-4.52 than the number of HIV-1 patients who were on investigator selected boosted comparator HIV-1 protease inhibitors (CPIs-ritonavir. Similarly, the number of patients with viral load less than 400 copies HIV RNA/ml was significantly higher in either the tipranavir-ritonavir or darunavir-ritonavir based regimen treated group (overall OR = 3.0; 95% CI, 2.15-4.11. Meta-regression showed that the viral load reduction was independent of baseline viral load, baseline CD4 count and duration of tipranavir-ritonavir or darunavir-ritonavir based regimen.Tipranavir and darunavir based regimens were more effective in patients who were ART experienced and had poor viral load control. Further studies are required to determine their consistent

  17. Improvement of Depression and Anxiety After Discontinuation of Long- Term Efavirenz Treatment

    NARCIS (Netherlands)

    Mothapo, K.M.; Schellekens, A.F.A.; Crevel, R. van; Keuter, M.; Grintjes-Huisman, K.; Koopmans, P.; Ven, A. van der

    2015-01-01

    Neuropsychiatric symptoms in human immunodeficiency virus (HIV)-infected patients may be a late complication of efavirenz treatment. This study: 1) assessed the level of neuropsychiatric symptoms in HIV-infected patients on long-term efavirenz therapy; 2) explored the effect of a switch to

  18. Application of supercritical fluid extraction (SFE) to predict bioremediation efficacy of long-term composting of PAH-contaminated soil

    Czech Academy of Sciences Publication Activity Database

    Cajthaml, Tomáš; Šašek, Václav

    2005-01-01

    Roč. 39, č. 21 (2005), s. 8448-8452 ISSN 0013-936X R&D Projects: GA ČR GP206/03/P078 Institutional research plan: CEZ:AV0Z50200510 Keywords : SFE * long-term composting * PAH Subject RIV: EE - Microbiology, Virology Impact factor: 4.054, year: 2005

  19. Long-term Maintenance of Fungal Cultures on Perlite in Cryovials – an Alternative for Agar Slants

    Czech Academy of Sciences Publication Activity Database

    Homolka, Ladislav; Lisá, Ludmila

    2008-01-01

    Roč. 53, č. 6 (2008), s. 534-536 ISSN 0015-5632 R&D Projects: GA MŠk LC06066 Institutional research plan: CEZ:AV0Z50200510 Keywords : basidiomycete * perlite * long-term maintenance Subject RIV: EE - Microbiology, Virology Impact factor: 1.172, year: 2008

  20. Long term wet spent nuclear fuel storage

    International Nuclear Information System (INIS)

    1987-04-01

    The meeting showed that there is continuing confidence in the use of wet storage for spent nuclear fuel and that long-term wet storage of fuel clad in zirconium alloys can be readily achieved. The importance of maintaining good water chemistry has been identified. The long-term wet storage behaviour of sensitized stainless steel clad fuel involves, as yet, some uncertainties. However, great reliance will be placed on long-term wet storage of spent fuel into the future. The following topics were treated to some extent: Oxidation of the external surface of fuel clad, rod consolidation, radiation protection, optimum methods of treating spent fuel storage water, physical radiation effects, and the behaviour of spent fuel assemblies of long-term wet storage conditions. A number of papers on national experience are included

  1. Industrial Foundations as Long-Term Owners

    DEFF Research Database (Denmark)

    Thomsen, Steen; Poulsen, Thomas; Børsting, Christa Winther

    Short-termism has become a serious concern for corporate governance, and this has inspired a search for institutional arrangements to promote long-term decision-making. In this paper, we call attention to long-term ownership by industrial foundations, which is common in Northern Europe but little...... known in the rest of the world. We use a unique Danish data set to document that industrial foundations are long-term owners that practice long-term governance. We show that foundation ownership is highly stable compared to other ownership structures. Foundation-owned companies replace managers less...... frequently. They have conservative capital structures with low financial leverage. They score higher on an index of long-termism in finance, investment, and employment. They survive longer. Overall, our paper supports the hypothesis that corporate time horizons are influenced by ownership structures...

  2. Coping with PH over the Long Term

    Science.gov (United States)

    ... a job, a volunteer commitment, or even a hobby can take a toll on long-term survivors ... people find solace in meditation, faith, humor, writing, hobbies and more. Find an outlet that you enjoy ...

  3. Long term effects of radiation in man

    International Nuclear Information System (INIS)

    Tso Chih Ping; Idris Besar

    1984-01-01

    An overview of the long term effects of radiation in man is presented, categorizing into somatic effects, genetic effects and teratogenic effects, and including an indication of the problems that arise in their determination. (author)

  4. Long term liquidity analysis of the firm

    Directory of Open Access Journals (Sweden)

    Jaroslav Gonos

    2009-09-01

    Full Text Available Liquidity control is a very difficult and important function. If the business is not liquid in the long term, it is under threatof bankruptcy, and on the other hand surplus of the cash in hand threaten its future efficiency, because the cash in hand is a sourceof only limited profitability. Long term liquidity is related to the ability of the short term and long term liabilities payment. Articleis trying to point out to the monitoring and analyzing of the long term liquidity in the concrete business, in this case the printing industrycompany. Hereby at the end of the article mentioned monitored and analyzed liquidity is evaluated in the five years time period.

  5. Long Term Care Minimum Data Set (MDS)

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Long-Term Care Minimum Data Set (MDS) is a standardized, primary screening and assessment tool of health status that forms the foundation of the comprehensive...

  6. Sleep facilitates long-term face adaptation

    OpenAIRE

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-01-01

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted imag...

  7. Liver Fibrosis Regression Measured by Transient Elastography in Human Immunodeficiency Virus (HIV)-Hepatitis B Virus (HBV)-Coinfected Individuals on Long-Term HBV-Active Combination Antiretroviral Therapy.

    Science.gov (United States)

    Audsley, Jennifer; Robson, Christopher; Aitchison, Stacey; Matthews, Gail V; Iser, David; Sasadeusz, Joe; Lewin, Sharon R

    2016-01-01

    Background.  Advanced fibrosis occurs more commonly in human immunodeficiency virus (HIV)-hepatitis B virus (HBV) coinfected individuals; therefore, fibrosis monitoring is important in this population. However, transient elastography (TE) data in HIV-HBV coinfection are lacking. We aimed to assess liver fibrosis using TE in a cross-sectional study of HIV-HBV coinfected individuals receiving combination HBV-active (lamivudine and/or tenofovir/tenofovir-emtricitabine) antiretroviral therapy, identify factors associated with advanced fibrosis, and examine change in fibrosis in those with >1 TE assessment. Methods.  We assessed liver fibrosis in 70 HIV-HBV coinfected individuals on HBV-active combination antiretroviral therapy (cART). Change in fibrosis over time was examined in a subset with more than 1 TE result (n = 49). Clinical and laboratory variables at the time of the first TE were collected, and associations with advanced fibrosis (≥F3, Metavir scoring system) and fibrosis regression (of least 1 stage) were examined. Results.  The majority of the cohort (64%) had mild to moderate fibrosis at the time of the first TE, and we identified alanine transaminase, platelets, and detectable HIV ribonucleic acid as associated with advanced liver fibrosis. Alanine transaminase and platelets remained independently advanced in multivariate modeling. More than 28% of those with >1 TE subsequently showed liver fibrosis regression, and higher baseline HBV deoxyribonucleic acid was associated with regression. Prevalence of advanced fibrosis (≥F3) decreased 12.3% (32.7%-20.4%) over a median of 31 months. Conclusions.  The observed fibrosis regression in this group supports the beneficial effects of cART on liver stiffness. It would be important to study a larger group of individuals with more advanced fibrosis to more definitively assess factors associated with liver fibrosis regression.

  8. Influence of Hepatitis C Virus Sustained Virological Response on Immunosuppressive Tryptophan Catabolism in ART-Treated HIV/HCV Coinfected Patients

    NARCIS (Netherlands)

    Jenabian, Mohammad-Ali; Mehraj, Vikram; Costiniuk, Cecilia T.; Vyboh, Kishanda; Kema, Ido; Rollet, Kathleen; Ramirez, Robert Paulino; Klein, Marina B.; Routy, Jean-Pierre

    2016-01-01

    Background: We previously reported an association between tryptophan (Trp) catabolism and immune dysfunction in HIV monoinfection. Coinfection with HIV is associated with more rapid evolution of hepatitis C virus (HCV)-associated liver disease despite antiretroviral therapy (ART), possibly due to

  9. Very long-term sequelae of craniopharyngioma.

    Science.gov (United States)

    Wijnen, Mark; van den Heuvel-Eibrink, Marry M; Janssen, Joseph A M J L; Catsman-Berrevoets, Coriene E; Michiels, Erna M C; van Veelen-Vincent, Marie-Lise C; Dallenga, Alof H G; van den Berge, J Herbert; van Rij, Carolien M; van der Lely, Aart-Jan; Neggers, Sebastian J C M M

    2017-06-01

    Studies investigating long-term health conditions in patients with craniopharyngioma are limited by short follow-up durations and generally do not compare long-term health effects according to initial craniopharyngioma treatment approach. In addition, studies comparing long-term health conditions between patients with childhood- and adult-onset craniopharyngioma report conflicting results. The objective of this study was to analyse a full spectrum of long-term health effects in patients with craniopharyngioma according to initial treatment approach and age group at craniopharyngioma presentation. Cross-sectional study based on retrospective data. We studied a single-centre cohort of 128 patients with craniopharyngioma treated from 1980 onwards (63 patients with childhood-onset disease). Median follow-up since craniopharyngioma presentation was 13 years (interquartile range: 5-23 years). Initial craniopharyngioma treatment approaches included gross total resection ( n  = 25), subtotal resection without radiotherapy ( n  = 44), subtotal resection with radiotherapy ( n  = 25), cyst aspiration without radiotherapy ( n  = 8), and 90 Yttrium brachytherapy ( n  = 21). Pituitary hormone deficiencies (98%), visual disturbances (75%) and obesity (56%) were the most common long-term health conditions observed. Different initial craniopharyngioma treatment approaches resulted in similar long-term health effects. Patients with childhood-onset craniopharyngioma experienced significantly more growth hormone deficiency, diabetes insipidus, panhypopituitarism, morbid obesity, epilepsy and psychiatric conditions compared with patients with adult-onset disease. Recurrence-/progression-free survival was significantly lower after initial craniopharyngioma treatment with cyst aspiration compared with other therapeutic approaches. Survival was similar between patients with childhood- and adult-onset craniopharyngioma. Long-term health conditions were comparable after

  10. Long-term prisoner in prison isolation

    Directory of Open Access Journals (Sweden)

    Karolina Grudzińska

    2013-06-01

    Full Text Available Long-term prisoner belongs to a particular category of people who are imprisoned in prisons. On the one hand in this group are often heavily demoralized people who committed the most serious crimes, on the other hand it is a group of prisoners, who should be well thought out and programmed the impact of rehabilitation. The situation of man trapped for years poses in a complicated situation not only the prisoners, but also the entire prison staff. They have to take care of the fact that the prison isolation did not cause the state in which convicts form itself in learned helplessness and lack of skills for self-planning and decision-making. In addition, planning the rehabilitation impact of long-term prisoners should not be forgotten that these prisoners in the short or the long term will return to the libertarian environment therefore, should prevent any negative effects of long-term imprisonment. This article presents the main issues related to the execution of imprisonment against long-term prisoners. It is an attempt to systematize the knowledge of this category of people living in prison isolation.

  11. Long-term follow-up study and long-term care of childhood cancer survivors

    Directory of Open Access Journals (Sweden)

    Hyeon Jin Park

    2010-04-01

    Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

  12. Tissue Pharmacologic and Virologic Determinants of Duodenal and Rectal Gastrointestinal-Associated Lymphoid Tissue Immune Reconstitution in HIV-Infected Patients Initiating Antiretroviral Therapy.

    Science.gov (United States)

    Asmuth, David M; Thompson, Corbin G; Chun, Tae-Wook; Ma, Zhong-Min; Mann, Surinder; Sainz, Talia; Serrano-Villar, Sergio; Utay, Netanya S; Garcia, Juan Carlos; Troia-Cancio, Paolo; Pollard, Richard B; Miller, Christopher J; Landay, Alan; Kashuba, Angela D

    2017-10-17

    Plasma, duodenal, and rectal tissue antiretroviral therapy (ART) drug concentrations, human immunodeficiency virus (HIV) RNA and HIV DNA copy numbers, and recovery of mucosal immunity were measured before and 9 months after initiation of 3 different ART regimens in 26 subjects. Plasma and tissue HIV RNA correlated at baseline and when 9-month declines were compared, suggesting that these compartments are tightly associated. Antiretroviral tissue:blood penetration ratios were above the 50% inhibitory concentration values in almost 100% of cases. There were no correlations between drug concentrations and HIV DNA/RNA. Importantly, no evidence was found for residual viral replication or deficient tissue drug penetration to account for delayed gastrointestinal-associated lymphoid tissue immune recovery. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  13. Persistent disparities in antiretroviral treatment (ART) coverage and virological suppression across Europe, 2004 to 2015

    DEFF Research Database (Denmark)

    Laut, Kamilla; Shepherd, Leah; Radoi, Roxana

    2018-01-01

    BACKGROUND: Direct comparisons between countries in core HIV care parameters are often hampered by differences in data collection. AIM: Within the EuroSIDA study, we compared levels of antiretroviral treatment (ART) coverage and virological suppression (HIV RNA ...-specific estimates of ART coverage and virological suppression. Underlying reasons for this variation warrant further analysis to identify a best practice and benchmark HIV care across EuroSIDA....

  14. Long-Term Prognosis of Plantar Fasciitis

    DEFF Research Database (Denmark)

    Hansen, Liselotte; Krogh, Thøger Persson; Ellingsen, Torkell

    2018-01-01

    , exercise-induced symptoms, bilateral heel pain, fascia thickness, and presence of a heel spur) could predict long-term outcomes, (3) to assess the long-term ultrasound (US) development in the fascia, and (4) to assess whether US-guided corticosteroid injections induce atrophy of the heel fat pad. Study....... The risk was significantly greater for women (P heel...... regardless of symptoms and had no impact on prognosis, and neither did the presence of a heel spur. Only 24% of asymptomatic patients had a normal fascia on US at long-term follow-up. A US-guided corticosteroid injection did not cause atrophy of the heel fat pad. Our observational study did not allow us...

  15. Long-term dependence in exchange rates

    Directory of Open Access Journals (Sweden)

    A. Karytinos

    2000-01-01

    Full Text Available The extent to which exchange rates of four major currencies against the Greek Drachma exhibit long-term dependence is investigated using a R/S analysis testing framework. We show that both classic R/S analysis and the modified R/S statistic if enhanced by bootstrapping techniques can be proven very reliable tools to this end. Our findings support persistence and long-term dependence with non-periodic cycles for the Deutsche Mark and the French Franc series. In addition a noisy chaos explanation is favored over fractional Brownian motion. On the contrary, the US Dollar and British Pound were found to exhibit a much more random behavior and lack of any long-term structure.

  16. Long-term trends in mortality and AIDS-defining events after combination ART initiation among children and adolescents with perinatal HIV infection in 17 middle- and high-income countries in Europe and Thailand: A cohort study.

    Directory of Open Access Journals (Sweden)

    Ali Judd

    2018-01-01

    Full Text Available Published estimates of mortality and progression to AIDS as children with HIV approach adulthood are limited. We describe rates and risk factors for death and AIDS-defining events in children and adolescents after initiation of combination antiretroviral therapy (cART in 17 middle- and high-income countries, including some in Western and Central Europe (W&CE, Eastern Europe (Russia and Ukraine, and Thailand.Children with perinatal HIV aged 6 months of cART death and progression to AIDS were assessed. Of 3,526 children included, 32% were from the United Kingdom or Ireland, 30% from elsewhere in W&CE, 18% from Russia or Ukraine, and 20% from Thailand. At cART initiation, median age was 5.2 (IQR 1.4-9.3 years; 35% of children aged 400 c/mL predicted late death. Predictors of early and late progression to AIDS were similar. Study limitations include incomplete recording of US Centers for Disease Control (CDC disease stage B events and serious adverse events in some countries; events that were distributed over a long time period, and that we lacked power to analyse trends in patterns and causes of death over time.In our study, 3,526 children and adolescents with perinatal HIV infection initiated antiretroviral therapy (ART in countries in Europe and Thailand. We observed that over 40% of deaths occurred ≤6 months after cART initiation. Greater early mortality risk in infants, as compared to older children, and in Russia, Ukraine, or Thailand as compared to W&CE, raises concern. Current severe immune suppression, being underweight, and unsuppressed viral load were associated with a higher risk of death at >6 months after initiation of cART.

  17. Long term planning for wind energy development

    International Nuclear Information System (INIS)

    Trinick, M.

    1995-01-01

    In a planning system intended to be governed primarily by policies in statutory plans a reasonable horizon for long term planning is 10 years or longer. Because of statutory requirements, developers have no option but to pay due regard to, and take a full part in, long term planning. The paper examines the type of policies which have emerged in the last few years to cater for wind energy development. It canvasses the merits of different types of policies. Finally, it discusses the policy framework which may emerge to cater for development outside NFFO. (Author)

  18. Long-term characteristics of nuclear emulsion

    International Nuclear Information System (INIS)

    Naganawa, N; Kuwabara, K

    2010-01-01

    Long-term characteristics of the nuclear emulsion so called 'OPERA film' used in the neutrino oscillation experiment, OPERA, has been studied for 8 years since its production or refreshing after it. In the results, it turned out to be excellent in sensitivity, amount of random noise, and refreshing characteristics. The retention capacity of latent image of tracks was also studied. The result will open the way to the recycling of 7,000,000 emulsion films which will remain not developed after 5 years of OPERA's run, and other long-term experiments with emulsion.

  19. Long-term characteristics of nuclear emulsion

    Science.gov (United States)

    Naganawa, N.; Kuwabara, K.

    2010-02-01

    Long-term characteristics of the nuclear emulsion so called ``OPERA film'' used in the neutrino oscillation experiment, OPERA, has been studied for 8 years since its production or refreshing after it. In the results, it turned out to be excellent in sensitivity, amount of random noise, and refreshing characteristics. The retention capacity of latent image of tracks was also studied. The result will open the way to the recycling of 7,000,000 emulsion films which will remain not developed after 5 years of OPERA's run, and other long-term experiments with emulsion.

  20. Long-term home care scheduling

    DEFF Research Database (Denmark)

    Gamst, Mette; Jensen, Thomas Sejr

    In several countries, home care is provided for certain citizens living at home. The long-term home care scheduling problem is to generate work plans spanning several days such that a high quality of service is maintained and the overall cost is kept as low as possible. A solution to the problem...... provides detailed information on visits and visit times for each employee on each of the covered days. We propose a branch-and-price algorithm for the long-term home care scheduling problem. The pricing problem generates one-day plans for an employee, and the master problem merges the plans with respect...

  1. Long term storage techniques for 85Kr

    International Nuclear Information System (INIS)

    Foster, B.A.; Pence, D.T.; Staples, B.A.

    1975-01-01

    As new nuclear fuel reprocessing plants go on stream, the collection of fission product 85 Kr will be required to avoid potential local release problems and long-term atmospheric buildup. Storage of the collected 85 Kr for a period of at least 100 years will be necessary to allow approximately 99.9 percent decay before it is released. A program designed to develop and evaluate proposed methods for long-term storage of 85 Kr is discussed, and the results of a preliminary evaluation of three methods, high pressure steel cylinders, zeolite encapsulation, and clathrate inclusion are presented. (U.S.)

  2. Marcadores virológicos no convencionales en pacientes infectados con el virus de la inmunodeficiencia humana: ADN HIV-T, ADN HIV- 2LTR y ARN de HIV Non conventional virological markers in HIV-infected patients: T-HIV DNA, 2LTR-HIV DNA and HIV RNA

    Directory of Open Access Journals (Sweden)

    Rosana Gariglio

    2004-10-01

    Full Text Available La terapia antirretroviral de alta eficacia (TAAE induce una reducción marcada y persistente de la viremia plasmática, contribuyendo a disminuir la mortalidad y morbilidad de los pacientes HIV-positivos. Así, la carga viral (CV es el método de referencia para evaluar la eficacia terapéutica. Sin embargo, aun en presencia de una TAAE eficiente no se ha logrado la erradicación viral. En este estudio analizamos la presencia del ADN total de HIV (ADN HIV-T, del ADN no integrado con 2LTR (ADN HIV-2LTR y del ARN de HIV, en un grupo de 55 pacientes HIV-positivos en distintos estadios clínicos, con y sin TAAE, mediante ensayos de PCR con revelado colorimétrico en microplaca, optimizados en nuestro laboratorio. La sensibilidad clínica del ARN del HIV fue evaluada con el bDNA, resultando del 74% y del 64%, respectivamente, con una concordancia del 85%. Este ensayo podría ser utilizado en el seguimiento de pacientes bajo TAAE. El ADN HIV-2LTR resultó positivo en el 54% aunque estuvo ausente en pacientes con elevada CV. Este marcador se consideraba un producto lábil y su presencia se asociaba a infección reciente. Sin embargo, actuales evidencias ponen en discusión su estabilidad por lo que su significado clínico debe ser reconsiderado. La ausencia del ADN HIV-2LTR en pacientes con CV detectable puede relacionarse con la heterogeneidad de la secuencia utilizada para su detección. El ADN HIV-T estuvo presente en el 100% de las muestras y resultaría relevante como marcador de remisión cuando se dispongan de terapias que efectivamente erradiquen la infección.Highly active antiretroviral therapy (HAART induces a persistent reduction of the plasmatic viremia, contributing to decrease mortality and morbidity of infected people with human immunodeficiency virus (HIV. Thus, viral load (VL is the reference method to evaluate therapy effectiveness. However, even in the presence of efficient HAART viral eradication was yet not achieved. In this

  3. Experiences of long-term tranquillizer use

    DEFF Research Database (Denmark)

    Skinhoj, K T; Larsson, S; Helweg-Joergensen, S

    2001-01-01

    , the psychodynamic perspective is integrated within a multi-dimensional model that considers biological, cognitive, identity, gender and social learning factors. The analysis reveals the possibility of achieving a detailed understanding of the dynamic processes involved in the development of long-term tranquillizer...

  4. Long-Term Orientation in Trade

    NARCIS (Netherlands)

    Hofstede, G.J.; Jonker, C.M.; Verwaart, D.

    2008-01-01

    Trust does not work in the same way across cultures. This paper presents an agent model of behavior in trade across Hofstedes cultural dimension of long-term vs. short-term orientation. The situation is based on a gaming simulation, the Trust and Tracing game. The paper investigates the

  5. Safety of long-term PPI therapy

    DEFF Research Database (Denmark)

    Reimer, Christina

    2013-01-01

    Proton pump inhibitors have become the mainstay of medical treatment of acid-related disorders. Long-term use is becoming increasingly common, in some cases without a proper indication. A large number of mainly observational studies on a very wide range of possible associations have been publishe...... to a careful evaluation of the indication for PPI treatment....

  6. Long term consequences of early childhood malnutrition

    NARCIS (Netherlands)

    Kinsey, B.H.; Hoddinott, J; Alderman, H.

    2006-01-01

    This paper examines the impact of pre-school malnutrition on subsequent human capital formation in rural Zimbabwe using a maternal fixed effects - instrumental variables (MFE-IV) estimator with a long term panel data set. Representations of civil war and drought shocks are used to identify

  7. Financial Incentives in Long-Term Care

    NARCIS (Netherlands)

    P.L.H. Bakx (Pieter)

    2015-01-01

    markdownabstract__Abstract__ Long-term care (ltc) aims to help individuals to cope with their impairments. In my thesis, I describe ltc financing alternatives and their consequences for the allocation of ltc. This thesis consists of two parts. In the first part, I investigate how alternative ways

  8. Long-term outcomes of patellofemoral arthroplasty.

    NARCIS (Netherlands)

    Jonbergen, J.P.W. van; Werkman, D.M.; Barnaart, L.F.; Kampen, A. van

    2010-01-01

    The purpose of this study was to correlate the long-term survival of patellofemoral arthroplasty with primary diagnosis, age, sex, and body mass index. One hundred eighty-five consecutive Richards type II patellofemoral arthroplasties were performed in 161 patients with isolated patellofemoral

  9. Long-Term Memory and Learning

    Science.gov (United States)

    Crossland, John

    2011-01-01

    The English National Curriculum Programmes of Study emphasise the importance of knowledge, understanding and skills, and teachers are well versed in structuring learning in those terms. Research outcomes into how long-term memory is stored and retrieved provide support for structuring learning in this way. Four further messages are added to the…

  10. The 2013 Long-Term Budget Outlook

    Science.gov (United States)

    2013-09-01

    number of years, leading to substantial additional federal spending. For example, the nation could experience a massive earthquake, a nuclear meltdown...budget surpluses remaining after paying down publicly held debt available for redemption . a. For comparison with the current long-term projections, CBO

  11. Long-term effects of ionizing radiation

    International Nuclear Information System (INIS)

    Kaul, Alexander; Burkart, Werner; Grosche, Bernd; Jung, Thomas; Martignoni, Klaus; Stephan, Guenther

    1997-01-01

    This paper approaches the long-term effects of ionizing radiation considering the common thought that killing of cells is the basis for deterministic effects and that the subtle changes in genetic information are important in the development of radiation-induced cancer, or genetic effects if these changes are induced in germ cells

  12. Pituitary diseases : long-term psychological consequences

    NARCIS (Netherlands)

    Tiemensma, Jitske

    2012-01-01

    Nowadays, pituitary adenomas can be appropriately treated, but patients continue to report impaired quality of life (QoL) despite long-term remission or cure. In patients with Cushing’s disease, Cushing’s syndrome or acromegaly, doctors should be aware of subtle cognitive impairments and the

  13. The long term stability of lidar calibrations

    DEFF Research Database (Denmark)

    Courtney, Michael; Gayle Nygaard, Nicolai

    Wind lidars are now used extensively for wind resource measurements. One of the requirements for the data to be accepted in support of project financing (so-called ‘banka-bility’) is to demonstrate the long-term stability of lidar cali-brations. Calibration results for six Leosphere WindCube li...

  14. Rebalancing for Long-Term Investors

    NARCIS (Netherlands)

    Driessen, Joost; Kuiper, Ivo

    2017-01-01

    In this study we show that the rebalance frequency of a multi-asset portfolio has only limited impact on the utility of a long-term passive investor. Although continuous rebalancing is optimal, the loss of a suboptimal strategy corresponds to up to only 30 basis points of the initial wealth of the

  15. HIV-1 Gag-specific exosome-targeted T cell-based vaccine stimulates effector CTL responses leading to therapeutic and long-term immunity against Gag/HLA-A2-expressing B16 melanoma in transgenic HLA-A2 mice

    Directory of Open Access Journals (Sweden)

    Rong Wang

    2014-01-01

    Full Text Available Human immunodeficiency virus type-1 (HIV-1-specific dendritic cell (DC vaccines have been applied to clinical trials that show only induction of some degree of immune responses, warranting the search of other more efficient vaccine strategies. Since HIV-1-specific CD8+ cytotoxic T lymphocytes (CTLs have been found to recognize some HIV-1 structural protein Gag conserved and cross-strain epitopes, Gag has become one of the most attractive target candidates for HIV-1 vaccine development. In this study, we generated HIV-1 Gag-specific Gag-Texo vaccine by using ConA-stimulated polyclonal CD8+ T-cells with uptake of Gag-expressing adenoviral vector AdVGag-transfected DC (DCGag-released exosomes (EXOs, and assessed its stimulation of Gag-specific CD8+ CTL responses and antitumor immunity. We demonstrate that Gag-Texo and DCGag vaccines comparably stimulate Gag-specific effector CD8+ CTL responses. Gag-Texo-stimulated CTL responses result in protective immunity against Gag-expressing BL6-10Gag melanoma in 8/8 wild-type C57BL/6 mice. In addition, we show that Gag-Texo vaccine also induces CTL responses leading to protective and long-term immunity against Gag/HLA-A2-expressing BL6-10Gag/A2 melanoma in 8/8 and 2/8 transgenic HLA-A2 mice, respectively. The average number of lung tumor colonies in mice with 30-days post-immunization is only 23, which is significantly less than that (>300 in control ConA-T-immunized HLA-A2 mice. Furthermore, Gag-Texo vaccine also induces some degree of therapeutic immunity. The average number (50 and size (0.23 mm in diameter of lung tumor colonies in Gag-Texo-immunized HLA-A2 mice bearing 6-day-established lung BL6-10Gag/A2 melanoma metastasis are significantly less than the average number (>300 and size (1.02 mm in diameter in control ConA-T-immunized HLA-A2 mice. Taken together, HIV-1 Gag-Texo vaccine capable of stimulating Gag-specific CTL responses and therapeutic immunity may be useful as a new immunotherapeutic

  16. Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): a European multicohort study

    DEFF Research Database (Denmark)

    Wittkop, Linda; Günthard, Huldrych F; de Wolf, Frank

    2011-01-01

    The effect of transmitted drug resistance (TDR) on first-line combination antiretroviral therapy (cART) for HIV-1 needs further study to inform choice of optimum drug regimens. We investigated the effect of TDR on outcome in the first year of cART within a large European collaboration....

  17. Increased virological failure in naive HIV-1-infected patients taking lamivudine compared with emtricitabine in combination with tenofovir and efavirenz or nevirapine in the Dutch nationwide ATHENA cohort

    NARCIS (Netherlands)

    Rokx, C.; Fibriani, A.; Vijver, D.A. van de; Verbon, A.; Schutten, M.; Gras, L.; Rijnders, B.J.; Koopmans †, P.P.; Keuter, M.; Ven, A.J.A.M. van der; Hofstede, H.J.M. ter; Dofferhoff, A.S.M.; Warris, A.; Crevel, R. van; et al.,

    2015-01-01

    BACKGROUND: Guidelines for treatment of human immunodeficiency virus type 1 (HIV-1) infection consider lamivudine and emtricitabine to be interchangeable components in first-line combination antiretroviral therapy (cART). The evidence for their clinical equivalence in cART is inconsistent. The

  18. Effect of abacavir on sustained virologic response to HCV treatment in HIV/HCV co-infected patients, Cohere in Eurocoord

    DEFF Research Database (Denmark)

    Smit, Colette; Arends, Joop; Peters, Lars

    2015-01-01

    BACKGROUND: Contradicting results on the effect of abacavir (ABC) on hepatitis C virus (HCV) treatment responses in HIV/HCV co-infected patients have been reported. We evaluated the influence of ABC on the response to pegylated interferon (pegIFN) and ribavirin (RBV)-containing HCV treatment in H...

  19. Performance of immunological response in predicting virological failure.

    Science.gov (United States)

    Ingole, Nayana; Mehta, Preeti; Pazare, Amar; Paranjpe, Supriya; Sarkate, Purva

    2013-03-01

    In HIV-infected individuals on antiretroviral therapy (ART), the decision on when to switch from first-line to second-line therapy is dictated by treatment failure, and this can be measured in three ways: clinically, immunologically, and virologically. While viral load (VL) decreases and CD4 cell increases typically occur together after starting ART, discordant responses may be seen. Hence the current study was designed to determine the immunological and virological response to ART and to evaluate the utility of immunological response to predict virological failure. All treatment-naive HIV-positive individuals aged >18 years who were eligible for ART were enrolled and assessed at baseline, 6 months, and 12 months clinically and by CD4 cell count and viral load estimations. The patients were categorized as showing concordant favorable (CF), immunological only (IO), virological only (VO), and concordant unfavorable responses (CU). The efficiency of immunological failure to predict virological failure was analyzed across various levels of virological failure (VL>50, >500, and >5,000 copies/ml). At 6 months, 87(79.81%), 7(5.5%), 13 (11.92%), and 2 (1.83%) patients and at 12 months 61(69.3%), 9(10.2%), 16 (18.2%), and 2 (2.3%) patients had CF, IO, VO, and CU responses, respectively. Immunological failure criteria had a very low sensitivity (11.1-40%) and positive predictive value (8.3-25%) to predict virological failure. Immunological criteria do not accurately predict virological failure resulting in significant misclassification of therapeutic responses. There is an urgent need for inclusion of viral load testing in the initiation and monitoring of ART.

  20. Long-term selenium status in humans

    International Nuclear Information System (INIS)

    Baskett, C.K.; Spate, V.L.; Mason, M.M.; Nichols, T.A.; Williams, A.; Dubman, I.M.; Gudino, A.; Denison, J.; Morris, J.S.

    2001-01-01

    The association of sub-optimal selenium status with increased risk factors for some cancers has been reported in two recent epidemiological studies. In both studies the same threshold in selenium status was observed, below which, cancer incidence increased. To assess the use of nails as a biologic monitor to measure the long-term selenium status, an eight-year longitudinal study was undertaken with a group of 11 adult subjects, 5 women and 6 men. Selenium has been measured by instrumental neutron activation analysis. Differences between fingernails and toenails with be discussed. In addition, the results will be discussed in the context of the long-term stability of the nail monitor to measure selenium status during those periods when selenium determinants are static; and the changes that occur as a result of selenium supplementation. (author)

  1. Influenza in long-term care facilities.

    Science.gov (United States)

    Lansbury, Louise E; Brown, Caroline S; Nguyen-Van-Tam, Jonathan S

    2017-09-01

    Long-term care facility environments and the vulnerability of their residents provide a setting conducive to the rapid spread of influenza virus and other respiratory pathogens. Infections may be introduced by staff, visitors or new or transferred residents, and outbreaks of influenza in such settings can have devastating consequences for individuals, as well as placing extra strain on health services. As the population ages over the coming decades, increased provision of such facilities seems likely. The need for robust infection prevention and control practices will therefore remain of paramount importance if the impact of outbreaks is to be minimised. In this review, we discuss the nature of the problem of influenza in long-term care facilities, and approaches to preventive and control measures, including vaccination of residents and staff, and the use of antiviral drugs for treatment and prophylaxis, based on currently available evidence. © 2017 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.

  2. Long-Term Ownership by Industrial Foundations

    DEFF Research Database (Denmark)

    Børsting, Christa Winther; Kuhn, Johan Moritz; Poulsen, Thomas

    2016-01-01

    in Denmark. Industrial foundations are independent legal entities without owners or members typically with the dual objective of preserving the company and using excess profits for charity. We use a unique Danish data set to examine the governance of foundation-owned companies. We show that they are long......-term in several respects. Foundations hold on to their shares for longer. Foundation-owned companies replace managers less frequently. They have more conservative capital structures with less leverage. Their companies survive longer. Their business decisions appear to be more long term. This paper supports...... the hypothesis that time horizons are influenced by ownership structures and particularly that industrial foundations promote longtermism. Policymakers which are interested in promoting longtermism should allow and perhaps even encourage the creation of industrial foundations. More generally they should consider...

  3. Analysis of long-term energy scenarios

    Energy Technology Data Exchange (ETDEWEB)

    Lemming, J.; Morthorst, P.E.

    1998-09-01

    When addressing the role of fusion energy in the 21. century, the evaluation of possible future structures in the electricity market and the energy sector as a whole, can be a useful tool. Because fusion energy still needs demonstration, commercialized fusion energy is not likely to be a reality within the next few decades. Therefore long-term scenarios are needed describing the energy markets, which fusion energy eventually will be part of. This report performs an analysis of two of the most detailed existing long-term scenarios describing possible futures of the energy system. The aim is to clarify the frames in which the future development of the global energy demand, as well as the structure of the energy system can be expected to develop towards the year 2100. (au) 19 refs.

  4. Long-term effects of radiation

    International Nuclear Information System (INIS)

    Smith, J.; Smith, T.

    1981-01-01

    It is pointed out that sources of long-term damage from radiation are two-fold. People who have been exposed to doses of radiation from initial early fallout but have recovered from the acute effects may still suffer long-term damage from their exposure. Those who have not been exposed to early fallout may be exposed to delayed fallout, the hazards from which are almost exclusively from ingesting strontium, caesium and carbon isotopes present in food; the damage caused is relatively unimportant compared with that caused by the brief doses from initial radiation and early fallout. A brief discussion is presented of the distribution of delayed long-lived isotope fallout, and an outline is sketched of late biological effects, such as malignant disease, cataracts, retarded development, infertility and genetic effects. (U.K.)

  5. Case Report: Stevens-Johnson syndrome following a single double dosing of nevirapine-containing regimen once in an HIV-infected woman on long-term antiretroviral therapy. [version 1; referees: 1 approved, 2 approved with reservations

    Directory of Open Access Journals (Sweden)

    Betty Kakande

    2015-06-01

    Full Text Available A 31-year old HIV-infected African woman on nevirapine, tenofovir and lamivudine for more than 4 years presented with an 8-day history of symptoms and signs of Stevens-Johnson syndrome. She was on no other medication. Her viral load was undetectable and she had maintained a CD4 count of between 356 and 387cells/mm3 in the preceding 2½ years. She missed her antiretrovirals 10 days before the onset of her symptoms and subsequently doubled her daily dose the following day. She had been on no other medication in the preceding 8 weeks. Her ARVs were stopped and she fully re-epithelialized with the exception of the lips, over the following 10 days. She was started on a daily single tablet of Odimune® (a fixed drug combination antiretroviral containing tenofovir, emtricitabine and efavirenz.   Nevirapine is the most common offender in cases of antiretroviral-associated SJS in published literature. Lamivudine is very rarely implicated while there are no similar reports with tenofovir.  We concluded that nevirapine was by far the most likely offender in this case. Nevirapine toxicity is associated with high CD4 counts, undetectable viral load and high drug plasma level. We postulate that the sudden increase of the plasma levels of nevirapine in a patient with a high CD4 count and undetectable viral load created a perfect storm for the development of SJS in our patient, who had been on the NVP-containing regimen for many years. Clinicians should be aware that severe adverse drug reactions are dynamic and can occur even when the drug has been in use for a long time.

  6. Case Report: Stevens-Johnson syndrome following a single double dosing of nevirapine-containing regimen once in an HIV-infected woman on long-term antiretroviral therapy.

    Science.gov (United States)

    Kakande, Betty; Isaacs, Thuraya; Muloiwa, Rudzani; Dlamini, Sipho; Lehloenya, Rannakoe

    2015-01-01

    A 31-year old HIV-infected African woman on nevirapine, tenofovir and lamivudine for more than 4 years presented with an 8-day history of symptoms and signs of Stevens-Johnson syndrome. She was on no other medication. Her viral load was undetectable and she had maintained a CD4 count of between 356 and 387cells/mm (3) in the preceding 2½ years. She missed her antiretrovirals 10 days before the onset of her symptoms and subsequently doubled her daily dose the following day. She had been on no other medication in the preceding 8 weeks. Her ARVs were stopped and she fully re-epithelialized with the exception of the lips, over the following 10 days. She was started on a daily single tablet of Odimune® (a fixed drug combination antiretroviral containing tenofovir, emtricitabine and efavirenz). Nevirapine is the most common offender in cases of antiretroviral-associated SJS in published literature. Lamivudine is very rarely implicated while there are no similar reports with tenofovir.  We concluded that nevirapine was by far the most likely offender in this case. Nevirapine toxicity is associated with high CD4 counts, undetectable viral load and high drug plasma level. We postulate that the sudden increase of the plasma levels of nevirapine in a patient with a high CD4 count and undetectable viral load created a perfect storm for the development of SJS in our patient, who had been on the NVP-containing regimen for many years. Clinicians should be aware that severe adverse drug reactions are dynamic and can occur even when the drug has been in use for a long time.

  7. Long term economic relationships from cointegration maps

    Science.gov (United States)

    Vicente, Renato; Pereira, Carlos de B.; Leite, Vitor B. P.; Caticha, Nestor

    2007-07-01

    We employ the Bayesian framework to define a cointegration measure aimed to represent long term relationships between time series. For visualization of these relationships we introduce a dissimilarity matrix and a map based on the sorting points into neighborhoods (SPIN) technique, which has been previously used to analyze large data sets from DNA arrays. We exemplify the technique in three data sets: US interest rates (USIR), monthly inflation rates and gross domestic product (GDP) growth rates.

  8. Murine model of long term obstructive jaundice

    Science.gov (United States)

    Aoki, Hiroaki; Aoki, Masayo; Yang, Jing; Katsuta, Eriko; Mukhopadhyay, Partha; Ramanathan, Rajesh; Woelfel, Ingrid A.; Wang, Xuan; Spiegel, Sarah; Zhou, Huiping; Takabe, Kazuaki

    2016-01-01

    Background With the recent emergence of conjugated bile acids as signaling molecules in cancer, a murine model of obstructive jaundice by cholestasis with long-term survival is in need. Here, we investigated the characteristics of 3 murine models of obstructive jaundice. Methods C57BL/6J mice were used for total ligation of the common bile duct (tCL), partial common bile duct ligation (pCL), and ligation of left and median hepatic bile duct with gallbladder removal (LMHL) models. Survival was assessed by Kaplan-Meier method. Fibrotic change was determined by Masson-Trichrome staining and Collagen expression. Results 70% (7/10) of tCL mice died by Day 7, whereas majority 67% (10/15) of pCL mice survived with loss of jaundice. 19% (3/16) of LMHL mice died; however, jaundice continued beyond Day 14, with survival of more than a month. Compensatory enlargement of the right lobe was observed in both pCL and LMHL models. The pCL model demonstrated acute inflammation due to obstructive jaundice 3 days after ligation but jaundice rapidly decreased by Day 7. The LHML group developed portal hypertension as well as severe fibrosis by Day 14 in addition to prolonged jaundice. Conclusion The standard tCL model is too unstable with high mortality for long-term studies. pCL may be an appropriate model for acute inflammation with obstructive jaundice but long term survivors are no longer jaundiced. The LHML model was identified to be the most feasible model to study the effect of long-term obstructive jaundice. PMID:27916350

  9. Long-term course of opioid addiction.

    Science.gov (United States)

    Hser, Yih-Ing; Evans, Elizabeth; Grella, Christine; Ling, Walter; Anglin, Douglas

    2015-01-01

    Opioid addiction is associated with excess mortality, morbidities, and other adverse conditions. Guided by a life-course framework, we review the literature on the long-term course of opioid addiction in terms of use trajectories, transitions, and turning points, as well as other factors that facilitate recovery from addiction. Most long-term follow-up studies are based on heroin addicts recruited from treatment settings (mostly methadone maintenance treatment), many of whom are referred by the criminal justice system. Cumulative evidence indicates that opioid addiction is a chronic disorder with frequent relapses. Longer treatment retention is associated with a greater likelihood of abstinence, whereas incarceration is negatively related to subsequent abstinence. Over the long term, the mortality rate of opioid addicts (overdose being the most common cause) is about 6 to 20 times greater than that of the general population; among those who remain alive, the prevalence of stable abstinence from opioid use is low (less than 30% after 10-30 years of observation), and many continue to use alcohol and other drugs after ceasing to use opioids. Histories of sexual or physical abuse and comorbid mental disorders are associated with the persistence of opioid use, whereas family and social support, as well as employment, facilitates recovery. Maintaining opioid abstinence for at least five years substantially increases the likelihood of future stable abstinence. Recent advances in pharmacological treatment options (buprenorphine and naltrexone) include depot formulations offering longer duration of medication; their impact on the long-term course of opioid addiction remains to be assessed.

  10. Long-term economic outlook. Annual review

    Energy Technology Data Exchange (ETDEWEB)

    1988-01-01

    This review provides economic growth forecast tables for Ontario, Canada, the US, Western Europe, and Japan. Economic growth, government policy, the long-term prospects for inflation, interest rates and foreign exchange rates, trends in the Canadian dollar, and energy markets and prices are also reviewed. Data generally cover 1965-2025. Appendices give a summary of historical and forecast data. 18 figs., 16 tabs.

  11. Long-term data storage in diamond

    OpenAIRE

    Dhomkar, Siddharth; Henshaw, Jacob; Jayakumar, Harishankar; Meriles, Carlos A.

    2016-01-01

    The negatively charged nitrogen vacancy (NV?) center in diamond is the focus of widespread attention for applications ranging from quantum information processing to nanoscale metrology. Although most work so far has focused on the NV? optical and spin properties, control of the charge state promises complementary opportunities. One intriguing possibility is the long-term storage of information, a notion we hereby introduce using NV-rich, type 1b diamond. As a proof of principle, we use multic...

  12. French Approach for Long Term Storage Safety

    International Nuclear Information System (INIS)

    Marciano, Jacob; Carreton, Jean-Pierre; Lizot, Marie Therese; Lhomme, Veronique

    2014-01-01

    IRSN presents its statement regarding long-term storage facilities; in France, the regulatory documents do not define the long term duration. The storage facility lifetime can only be appreciated according to the needs and materials stored therein. However, the magnitude of the long-term can be estimated at a few hundred years compared to a few decades for current storage. Usually, in France, construction of storage facilities is driven from the necessity various necessities, linked to the management of radioactive material (eg spent fuel) and to the management of radioactive waste. Because of the variety of 'stored materials and objects' (fission product solutions, plutonium oxide powders, activated solids, drums containing technological waste, spent fuel...), a great number of storage facility design solutions have been developed (surface, subsurface areas, dry or wet conditions...) in the World. After describing the main functions of a storage facility, IRSN displays the safety principles and the associated design principles. The specific design principles applied to particular storage (dry or wet spent fuel storage, depleted uranium or reprocessed uranium storage, plutonium storage, waste containing tritium storage, HLW and ILLW storage...) are also presented. Finally, the concerns due to the long-term duration storage and related safety assessment are developed. After discussing these issues, IRSN displays its statement. The authorization procedures governing the facility lifetime are similar to those of any basic nuclear installation, the continuation of the facility operation remaining subject to periodic safety reviews (in France, every 10 years). The applicant safety cases have to show, that the safety requirements are always met; this requires, at minimum, to take into account at the design stage, comfortable design margins. (author)

  13. Accounting of Long-Term Biological Assets

    OpenAIRE

    Valeriy Mossakovskyy; Vasyl Korytnyy

    2015-01-01

    The article is devoted to generalization of experience in valuation of long-term biological assets of plant-growing and animal-breeding, and preparation of suggestions concerning improvement of accounting in this field. Recommendations concerning accounting of such assets are given based on the study of accounting practice at specific agricultural company during long period of time. Authors believe that fair value is applicable only if price level for agricultural products is fixed by the gov...

  14. Optimal long-term contracting with learning

    OpenAIRE

    He, Zhiguo; Wei, Bin; Yu, Jianfeng; Gao, Feng

    2016-01-01

    We introduce uncertainty into Holmstrom and Milgrom (1987) to study optimal long-term contracting with learning. In a dynamic relationship, the agent's shirking not only reduces current performance but also increases the agent's information rent due to the persistent belief manipulation effect. We characterize the optimal contract using the dynamic programming technique in which information rent is the unique state variable. In the optimal contract, the optimal effort is front-loaded and decr...

  15. Timber joints under long-term loading

    DEFF Research Database (Denmark)

    Feldborg, T.; Johansen, M.

    This report describes tests and results from stiffness and strength testing of splice joints under long-term loading. During two years of loading the spicimens were exposed to cyclically changing relative humidity. After the loading period the specimens were short-term tested. The connectors were...... integral nail-plates and nailed steel and plywood gussets. The report is intended for designers and researchers in timber engineering....

  16. Inflation Hedging for Long-Term Investors

    OpenAIRE

    Shaun K. Roache; Alexander P. Attie

    2009-01-01

    Long-term investors face a common problem-how to maintain the purchasing power of their assets over time and achieve a level of real returns consistent with their investment objectives. While inflation-linked bonds and derivatives have been developed to hedge the effects of inflation, their limited supply and liquidity lead many investors to continue to rely on the indirect hedging properties of traditional asset classes. In this paper, we assess these properties over different time horizons,...

  17. Long term evolution 4G and beyond

    CERN Document Server

    Yacoub, Michel; Figueiredo, Fabrício; Tronco, Tania

    2016-01-01

    This book focus on Long Term Evolution (LTE) and beyond. The chapters describe different aspects of research and development in LTE, LTE-Advanced (4G systems) and LTE-450 MHz such as telecommunications regulatory framework, voice over LTE, link adaptation, power control, interference mitigation mechanisms, performance evaluation for different types of antennas, cognitive mesh network, integration of LTE network and satellite, test environment, power amplifiers and so on. It is useful for researchers in the field of mobile communications.

  18. Long-Term Care Services for Veterans

    Science.gov (United States)

    2017-02-14

    includes but is not limited to home physical , occupational, or speech therapy ; wound care; and intravenous (IV) care. A VA physician determines that a...restoring/rehabilitating the veteran’s health, such as skilled nursing care, physical therapy , occupational therapy , and IV therapy Same as HBPC... geriatric evaluation,  palliative care,  adult day health care,  homemaker/home health aide care,  respite care, Long-Term Care Services for

  19. Long term adequacy of uranium resources

    International Nuclear Information System (INIS)

    Steyn, J.

    1990-01-01

    This paper examines the adequacy of world economic uranium resources to meet requirements in the very long term, that is until at least 2025 and beyond. It does so by analysing current requirements forecasts, existing and potential production centre supply capability schedules and national resource estimates. It takes into account lead times from resource discovery to production and production rate limitations. The institutional and political issues surrounding the question of adequacy are reviewed. (author)

  20. Sexuality and Physical Intimacy in Long Term Care: Sexuality, long term care, capacity assessment

    OpenAIRE

    Lichtenberg, Peter A.

    2014-01-01

    Sexuality and sexual needs in older adults remains a neglected area of clinical intervention, particularly so in long term care settings. Because older adults in medical rehabilitation and long term care beds present with significant frailties, and often significant neurocognitive disorders it makes it difficult for occupational therapists and other staff to evaluate the capacity of an older adult resident to participate in sexual relationships. The current paper reviews the current literatur...

  1. The long-term effectiveness of generic adult fixed-dose combination ...

    African Journals Online (AJOL)

    Background: Access to pediatric antiretroviral formulations is increasing in resource-limited countries, however adult FDCs are still commonly used by antiretroviral therapy (ART) programs. Objective: To describe long-term effectiveness of using adult FDC of d4T+3TC+NVP (Triomune) in children for HIV treatment. Methods: ...

  2. LONG-TERM OUTCOME IN PEDIATRIC TRICHOTILLOMANIA.

    Science.gov (United States)

    Schumer, Maya C; Panza, Kaitlyn E; Mulqueen, Jilian M; Jakubovski, Ewgeni; Bloch, Michael H

    2015-10-01

    To examine long-term outcome in children with trichotillomania. We conducted follow-up clinical assessments an average of 2.8 ± 0.8 years after baseline evaluation in 30 of 39 children who previously participated in a randomized, double-blind, placebo-controlled trial of N-acetylcysteine (NAC) for pediatric trichotillomania. Our primary outcome was change in hairpulling severity on the Massachusetts General Hospital Hairpulling Hospital Hairpulling Scale (MGH-HPS) between the end of the acute phase and follow-up evaluation. We also obtained secondary measures examining styles of hairpulling, comorbid anxiety and depressive symptoms, as well as continued treatment utilization. We examined both correlates and predictors of outcome (change in MGH-HPS score) using linear regression. None of the participants continued to take NAC at the time of follow-up assessment. No significant changes in hairpulling severity were reported over the follow-up period. Subjects reported significantly increased anxiety and depressive symptoms but improvement in automatic pulling symptoms. Increased hairpulling symptoms during the follow-up period were associated with increased depression and anxiety symptoms and increased focused pulling. Older age and greater focused pulling at baseline assessment were associated with poor long-term prognosis. Our findings suggest that few children with trichotillomania experience a significant improvement in trichotillomania symptoms if behavioral treatments are inaccessible or have failed to produce adequate symptom relief. Our findings also confirm results of previous cross-sectional studies that suggest an increased risk of depression and anxiety symptoms with age in pediatric trichotillomania. Increased focused pulling and older age among children with trichotillomania symptoms may be associated with poorer long-term prognosis. © 2015 Wiley Periodicals, Inc.

  3. Long-term EEG in children.

    Science.gov (United States)

    Montavont, A; Kaminska, A; Soufflet, C; Taussig, D

    2015-03-01

    Long-term video-EEG corresponds to a recording ranging from 1 to 24 h or even longer. It is indicated in the following situations: diagnosis of epileptic syndromes or unclassified epilepsy, pre-surgical evaluation for drug-resistant epilepsy, follow-up of epilepsy or in cases of paroxysmal symptoms whose etiology remains uncertain. There are some specificities related to paediatric care: a dedicated pediatric unit; continuous monitoring covering at least a full 24-hour period, especially in the context of pre-surgical evaluation; the requirement of presence by the parents, technician or nurse; and stronger attachment of electrodes (cup electrodes), the number of which is adapted to the age of the child. The chosen duration of the monitoring also depends on the frequency of seizures or paroxysmal events. The polygraphy must be adapted to the type and topography of movements. It is essential to have at least an electrocardiography (ECG) channel, respiratory sensor and electromyography (EMG) on both deltoids. There is no age limit for performing long-term video-EEG even in newborns and infants; nevertheless because of scalp fragility, strict surveillance of the baby's skin condition is required. In the specific context of pre-surgical evaluation, long-term video-EEG must record all types of seizures observed in the child. This monitoring is essential in order to develop hypotheses regarding the seizure onset zone, based on electroclinical correlations, which should be adapted to the child's age and the psychomotor development. Copyright © 2015. Published by Elsevier SAS.

  4. Long-term governance for sustainability

    International Nuclear Information System (INIS)

    Martell, M.

    2007-01-01

    Meritxell Martell spoke of the long-term aspects of radioactive waste management. She pointed out that decision-making processes need to be framed within the context of sustainability, which means that a balance should be sought between scientific considerations, economic aspects and structural conditions. Focusing on structural aspects, Working Group 3 of COWAM-Spain came to the conclusion that the activity of the regulator is a key factor of long-term management. Another finding is that from a sustainability perspective multi-level governance is more effective for coping with the challenges of radioactive waste management than one tier of government-making decisions. The working group also felt that the current Local Information Committees need to evolve towards more institutionalized and legitimized mechanisms for long-term involvement. Ms. Martell introduced a study comparing the efficiency of economic instruments to advance sustainable development in nuclear communities vs. municipalities in mining areas. The study found that funds transferred to nuclear zones had become a means to facilitate local acceptance of nuclear facilities rather than a means to promote socio-economic development. Another finding is that economic instruments are not sufficient guarantees of sustainable development by themselves; additional preconditions include leadership, vision and entrepreneur-ship on the part of community leaders, private or public investments, among others. Finally, Ms. Martell summarised the challenges faced by the Spanish radioactive waste management programme, which include the need for strategic thinking, designing the future in a participatory fashion, and working with local and regional governments and citizens to devise mechanisms for social learning, economic development and environmental protection. (author)

  5. Is sustained virological response a marker of treatment efficacy in patients with chronic hepatitis C viral infection with no response or relapse to previous antiviral intervention?

    DEFF Research Database (Denmark)

    Gurusamy, Kurinchi S; Wilson, Edward; Koretz, Ronald L

    2013-01-01

    Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs.......Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs....

  6. Long term aspects of uranium tailings management

    International Nuclear Information System (INIS)

    Bragg, K.

    1980-05-01

    This paper sets out the background issues which lead to the development of interim close-out criteria for uranium mill tailings. It places the current state-of-the-art for tailings management into both a national and international perspective and shows why such interim criteria are needed now. There are seven specific criteria proposed dealing with the need to have: passive barriers, limits on surface water recharge, durable systems, long term performance guarantees, limits to access, controls on water and airborne releases and finally to have a knowledge of exposure pathways. This paper is intended to serve as a focus for subsequent discussions with all concerned parties. (auth)

  7. Human Behaviour in Long-Term Missions

    Science.gov (United States)

    1997-01-01

    In this session, Session WP1, the discussion focuses on the following topics: Psychological Support for International Space Station Mission; Psycho-social Training for Man in Space; Study of the Physiological Adaptation of the Crew During A 135-Day Space Simulation; Interpersonal Relationships in Space Simulation, The Long-Term Bed Rest in Head-Down Tilt Position; Psychological Adaptation in Groups of Varying Sizes and Environments; Deviance Among Expeditioners, Defining the Off-Nominal Act in Space and Polar Field Analogs; Getting Effective Sleep in the Space-Station Environment; Human Sleep and Circadian Rhythms are Altered During Spaceflight; and Methodological Approach to Study of Cosmonauts Errors and Its Instrumental Support.

  8. Optimal Long-Term Financial Contracting

    OpenAIRE

    Peter M. DeMarzo; Michael J. Fishman

    2007-01-01

    We develop an agency model of financial contracting. We derive long-term debt, a line of credit, and equity as optimal securities, capturing the debt coupon and maturity; the interest rate and limits on the credit line; inside versus outside equity; dividend policy; and capital structure dynamics. The optimal debt-equity ratio is history dependent, but debt and credit line terms are independent of the amount financed and, in some cases, the severity of the agency problem. In our model, the ag...

  9. Novel use of surveillance data to detect HIV-infected persons with sustained high viral load and durable virologic suppression in New York City.

    Directory of Open Access Journals (Sweden)

    Arpi S Terzian

    Full Text Available Monitoring of the uptake and efficacy of ART in a population often relies on cross-sectional data, providing limited information that could be used to design specific targeted intervention programs. Using repeated measures of viral load (VL surveillance data, we aimed to estimate and characterize the proportion of persons living with HIV/AIDS (PLWHA in New York City (NYC with sustained high VL (SHVL and durably suppressed VL (DSVL.Retrospective cohort study of all persons reported to the NYC HIV Surveillance Registry who were alive and ≥12 years old by the end of 2005 and who had ≥2 VL tests in 2006 and 2007. SHVL and DSVL were defined as PLWHA with 2 consecutive VLs ≥100,000 copies/mL and PLWHA with all VLs ≤400 copies/mL, respectively. Logistic regression models using generalized estimating equations were used to model the association between SHVL and covariates. There were 56,836 PLWHA, of whom 7% had SHVL and 38% had DSVL. Compared to those without SHVL, persons with SHVL were more likely to be younger, black and have injection drug use (IDU risk. PLWHA with SHVL were more likely to die by 2007 and be younger by nearly ten years, on average.Nearly 60% of PLWHA in 2005 had multiple VLs, of whom almost 40% had DSVL, suggesting successful ART uptake. A small proportion had SHVL, representing groups known to have suboptimal engagement in care. This group should be targeted for additional outreach to reduce morbidity and secondary transmission. Measures based on longitudinal analyses of surveillance data in conjunction with cross-sectional measures such as community viral load represent more precise and powerful tools for monitoring ART effectiveness and potential impact on disease transmission than cross-sectional measures alone.

  10. Long-term environmental behaviour of radionuclides

    International Nuclear Information System (INIS)

    Brechignac, F.; Moberg, L.; Suomela, M.

    2000-04-01

    The radioactive pollution of the environment results from the atmospheric nuclear weapons testing (during the mid-years of twentieth century), from the development of the civilian nuclear industry and from accidents such as Chernobyl. Assessing the resulting radiation that humans might receive requires a good understanding of the long-term behaviour of radionuclides in the environment. This document reports on a joint European effort to advance this understanding, 3 multinational projects have been coordinated: PEACE, EPORA and LANDSCAPE. This report proposes an overview of the results obtained and they are presented in 6 different themes: i) redistribution in the soil-plant system, ii) modelling, iii) countermeasures, iv) runoff v) spatial variations, and vi) dose assessment. The long term behaviour of the radionuclides 137 Cs, 90 Sr and 239-240 Pu is studied through various approaches, these approaches range from in-situ experiments designed to exploit past contamination events to laboratory simulations. A broad scope of different ecosystems ranging from arctic and boreal regions down to mediterranean ones has been considered. (A.C.)

  11. Craniopharyngioma in Children: Long-term Outcomes

    Science.gov (United States)

    STEINBOK, Paul

    2015-01-01

    The survival rate for childhood craniopharyngioma has been improving, with more long-term survivors. Unfortunately it is rare for the patient to be normal, either from the disease itself or from the effects of treatment. Long-term survivors of childhood craniopharyngioma suffer a number of impairments, which include visual loss, endocrinopathy, hypothalamic dysfunction, cerebrovascular problems, neurologic and neurocognitive dysfunction. Pituitary insufficiency is present in almost 100%. Visual and hypothalamic dysfunction is common. There is a high risk of metabolic syndrome and increased risk of cerebrovascular disease, including stroke and Moyamoya syndrome. Cognitive, psychosocial, and emotional problems are prevalent. Finally, there is a higher risk of premature death among survivors of craniopharyngioma, and often this is not from tumor recurrence. It is important to consider craniopharyngioma as a chronic disease. There is no perfect treatment. The treatment has to be tailored to the individual patient to minimize dysfunction caused by tumor and treatments. So “cure” of the tumor does not mean a normal patient. The management of the patient and family needs multidisciplinary evaluation and should involve ophthalmology, endocrinology, neurosurgery, oncology, and psychology. Furthermore, it is also important to address emotional issues and social integration. PMID:26345668

  12. Institutionalization and Organizational Long-term Success

    Directory of Open Access Journals (Sweden)

    Denise L. Fleck

    2007-05-01

    Full Text Available Institutionalization processes have an ambivalent effect on organizational long-term success. Even though they foster organizational stability and permanence, they also bring about rigidity and resistance to change. As a result, successful organizations are likely to lose their competitive advantage over time. The paper addresses this issue through the investigation of the institutionalization processes of two long-lived companies: General Electric, a firm that has been a long-term success and its rival, Westinghouse, which was broken up after eleven decades of existence. The longitudinal, multilevel analysis of firms and industry has identified two different modes of organizational institutionalization. The reactive mode gives rise to rigidity and change resistance, much like institutional theory predicts; the proactive mode, on the other hand, neutralizes those negative effects of institutionalization processes. In the reactive mode, structure predominates. In the proactive mode, agency plays a major role in organizational institutionalization, and in managing the organization’s relations with the environment, clearly contributing to environmental institutionalization.

  13. Long term testing of PSI-membranes

    Energy Technology Data Exchange (ETDEWEB)

    Huslage, J; Brack, H P; Geiger, F; Buechi, F N; Tsukada, A; Scherer, G G [Paul Scherrer Inst. (PSI), Villigen (Switzerland)

    1999-08-01

    Long term tests of PSI membranes based on radiation-grafted FEP and ETFE films were carried out and FEP-based membranes were evaluated by monitoring the in-situ membrane area resistance measured by a current pulse method. By modifying our irradiation procedure and using the double crosslinking concept we obtain reproducible membrane cell lifetimes (in term of in-situ membrane resistance) of greater than 5000 hours at 60-65{sup o}C. Preliminary tests at 80-85{sup o}C with lifetimes of greater than 2500 demonstrate the potential long term stability of PSI proton exchange membranes based on FEP over the whole operating temperature range of low-temperature polymer electrolyte fuel cells. Radiation grafted PSI membranes based on ETFE have better mechanical properties than those of the FEP membranes. Mechanical properties are particularly important in large area cells and fuel cell stacks. ETFE membranes have been tested successfully for approximately 1000 h in a 2-cell stack (100 cm{sup 2} active area each cell). (author) 4 figs., 4 refs.

  14. Neo bladder long term follow-up

    International Nuclear Information System (INIS)

    Fakhr, I.; Mohamed, A. M.; Moustafa, A.; Al-Sherbiny, M.; Salama, M.

    2013-01-01

    One of the commonest forms of orthotopic bladder substitution for bladder cancer surivors, used in our institute, is the use of ileocecal segment. Sometimes, the need for Indiana pouch heterotropic continent diversion arises. Aim: To compare the long-term effect of orthotopic ileocecal bladder and heterotropic Indiana pouch following radical cystectomy in bladder cancer patients. Patients and methods: Between January 2008 and December 2011, 91 patients underwent radical cystectomy/anterior pelvic exentration and ortho topic ileocecal bladder reconstruction (61 patients) and Indiana pouch (30 patients), when orthotopic diversion could not be technically or oncologically feasible. Results: Convalescence was uneventful in most patients. All minor and major urinary leakage cases, in both diversions groups, where successfully conservatively treated. Only one patient in the ileocecal group with major urinary leak required re-exploration with successful revision of uretro-colonic anastomosis. Only one patient in the Indiana pouch group had accidentally discovered sub-centimetric stone, which was simply expelled. The overall survival proportion of ileocecal group was 100% compared to 80% in the Indiana pouch group (p < 0.001). The disease free survival proportion of ileocecal group was 90.8% compared to 80% in the Indiana pouch group (p = 0.076). Effective comparative daytime and nighttime urinary continence as well as renal function deterioration were not statistically significant between both reconstruction types. Conclusion: Both ileocecal bladder and Indiana pouch are safe procedures in regard to long-term effects over kidney function following radical cystectomy

  15. Toward a comprehensive long term nicotine policy.

    Science.gov (United States)

    Gray, N; Henningfield, J E; Benowitz, N L; Connolly, G N; Dresler, C; Fagerstrom, K; Jarvis, M J; Boyle, P

    2005-06-01

    Global tobacco deaths are high and rising. Tobacco use is primarily driven by nicotine addiction. Overall tobacco control policy is relatively well agreed upon but a long term nicotine policy has been less well considered and requires further debate. Reaching consensus is important because a nicotine policy is integral to the target of reducing tobacco caused disease, and the contentious issues need to be resolved before the necessary political changes can be sought. A long term and comprehensive nicotine policy is proposed here. It envisages both reducing the attractiveness and addictiveness of existing tobacco based nicotine delivery systems as well as providing alternative sources of acceptable clean nicotine as competition for tobacco. Clean nicotine is defined as nicotine free enough of tobacco toxicants to pass regulatory approval. A three phase policy is proposed. The initial phase requires regulatory capture of cigarette and smoke constituents liberalising the market for clean nicotine; regulating all nicotine sources from the same agency; and research into nicotine absorption and the role of tobacco additives in this process. The second phase anticipates clean nicotine overtaking tobacco as the primary source of the drug (facilitated by use of regulatory and taxation measures); simplification of tobacco products by limitation of additives which make tobacco attractive and easier to smoke (but tobacco would still be able to provide a satisfying dose of nicotine). The third phase includes a progressive reduction in the nicotine content of cigarettes, with clean nicotine freely available to take the place of tobacco as society's main nicotine source.

  16. Long term ground movement of TRISTAN synchrotron

    International Nuclear Information System (INIS)

    Endo, K.; Ohsawa, Y.; Miyahara, M.

    1989-01-01

    The long term ground movement is estimated through the geological survey before a big accelerator is planned. For the case of TRISTAN-MR (main ring), its site was surveyed to reflect the underground information to the building prior to the construction. The movement of the synchrotron magnet mainly results from the structure of the tunnel. If an individual movement of the magnet exceeds a certain threshold limit, it gives a significant effect on the particle behavior in a synchrotron. Height of the quadrupole magnets were observed periodically during past two years at the TRISTAN-MR and their height differences along the 3 km circumference of the accelerator ring were decomposed into the Fourier components depicting the causes of the movements. Results shows the movement of the tunnel foundation which was also observed by the simultaneous measurement of both magnets and fiducial marks on the tunnel wall. The long term movement of the magnets is summarized with the geological survey prior to construction. 1 ref., 6 figs., 1 tab

  17. Long-term environmental behaviour of radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Brechignac, F.; Moberg, L.; Suomela, M

    2000-04-01

    The radioactive pollution of the environment results from the atmospheric nuclear weapons testing (during the mid-years of twentieth century), from the development of the civilian nuclear industry and from accidents such as Chernobyl. Assessing the resulting radiation that humans might receive requires a good understanding of the long-term behaviour of radionuclides in the environment. This document reports on a joint European effort to advance this understanding, 3 multinational projects have been coordinated: PEACE, EPORA and LANDSCAPE. This report proposes an overview of the results obtained and they are presented in 6 different themes: (i) redistribution in the soil-plant system, (ii) modelling, (iii) countermeasures, (iv) runoff (v) spatial variations, and (vi) dose assessment. The long term behaviour of the radionuclides {sup 137}Cs, {sup 90}Sr and {sup 239-240}Pu is studied through various approaches, these approaches range from in-situ experiments designed to exploit past contamination events to laboratory simulations. A broad scope of different ecosystems ranging from arctic and boreal regions down to mediterranean ones has been considered. (A.C.)

  18. Long-term preservation of anammox bacteria.

    Science.gov (United States)

    Rothrock, Michael J; Vanotti, Matias B; Szögi, Ariel A; Gonzalez, Maria Cruz Garcia; Fujii, Takao

    2011-10-01

    Deposit of useful microorganisms in culture collections requires long-term preservation and successful reactivation techniques. The goal of this study was to develop a simple preservation protocol for the long-term storage and reactivation of the anammox biomass. To achieve this, anammox biomass was frozen or lyophilized at two different freezing temperatures (-60°C and in liquid nitrogen (-200°C)) in skim milk media (with and without glycerol), and the reactivation of anammox activity was monitored after a 4-month storage period. Of the different preservation treatments tested, only anammox biomass preserved via freezing in liquid nitrogen followed by lyophilization in skim milk media without glycerol achieved stoichiometric ratios for the anammox reaction similar to the biomass in both the parent bioreactor and in the freshly harvested control treatment. A freezing temperature of -60°C alone, or in conjunction with lyophilization, resulted in the partial recovery of the anammox bacteria, with an equal mixture of anammox and nitrifying bacteria in the reactivated biomass. To our knowledge, this is the first report of the successful reactivation of anammox biomass preserved via sub-zero freezing and/or lyophilization. The simple preservation protocol developed from this study could be beneficial to accelerate the integration of anammox-based processes into current treatment systems through a highly efficient starting anammox biomass.

  19. Andra long term memory project - 59277

    International Nuclear Information System (INIS)

    Charton, Patrick; Boissier, Fabrice; Martin, Guillaume

    2012-01-01

    Document available in abstract form only. Full text of publication follows: Long term memory of repositories is required by safety, reversibility and social expectations. Thus Andra has implemented since 2010 a long-term memory project to reinforce and diversify its current arrangements in this field, as well as to explore opportunities to extend memory keeping over thousands years. The project includes opportunity studies of dedicated facilities. The 'Ecotheque' and 'Geotheque' projects contribute to memory respectively through environmental and geological samples preservation. The options of creating (i) an archive centre for Andra's interim and permanent archives, (ii) an artist center to study the contribution of arts to memory preservation, (iii) a museum of radioactive waste disposal history and technology (radium industry..., sea disposal, current solutions...) are considered. Other studies provided by the project examine our heritage. This includes the continuity of languages and symbolic systems, the continuity of writing and engraving methods, the archaeology of landscapes (memory of the earths evolution, multi-century memory of industrial and agricultural landscapes), the archaeology practices (how might a future archaeologist be interested in our current activity?), the preservation of historical sites and industrial memory, the continuity of institutional organizations, the memory and history of science evolution as well as broad history

  20. Long term creep behavior of concrete

    International Nuclear Information System (INIS)

    Kennedy, T.W.

    1975-01-01

    This report presents the findings of an experimental investigation to evaluate the long term creep behavior of concrete subjected to sustained uniaxial loads for an extended period of time at 75 0 F. The factors investigated were (1) curing time (90, 183, and 365 days); (2) curing history (as-cast and air-dried); and (3) uniaxial stress (600 and 2400 psi). The experimental investigation applied uniaxial compressive loads to cylindrical concrete specimens and measured strains with vibrating wire strain gages that were cast in the concrete specimen along the axial and radial axes. Specimens cured for 90 days prior to loading were subjected to a sustained load for a period of one year, at which time the loads were removed; the specimens which were cured for 183 or 365 days, however, were not unloaded and have been under load for 5 and 4.5 years, respectively. The effect of each of the above factors on the instantaneous and creep behavior is discussed and the long term creep behavior of the specimens cured for 183 or 365 days is evaluated. The findings of these evaluations are summarized. (17 figures, 10 tables) (U.S.)

  1. Sleep facilitates long-term face adaptation.

    Science.gov (United States)

    Ditye, Thomas; Javadi, Amir Homayoun; Carbon, Claus-Christian; Walsh, Vincent

    2013-10-22

    Adaptation is an automatic neural mechanism supporting the optimization of visual processing on the basis of previous experiences. While the short-term effects of adaptation on behaviour and physiology have been studied extensively, perceptual long-term changes associated with adaptation are still poorly understood. Here, we show that the integration of adaptation-dependent long-term shifts in neural function is facilitated by sleep. Perceptual shifts induced by adaptation to a distorted image of a famous person were larger in a group of participants who had slept (experiment 1) or merely napped for 90 min (experiment 2) during the interval between adaptation and test compared with controls who stayed awake. Participants' individual rapid eye movement sleep duration predicted the size of post-sleep behavioural adaptation effects. Our data suggest that sleep prevented decay of adaptation in a way that is qualitatively different from the effects of reduced visual interference known as 'storage'. In the light of the well-established link between sleep and memory consolidation, our findings link the perceptual mechanisms of sensory adaptation--which are usually not considered to play a relevant role in mnemonic processes--with learning and memory, and at the same time reveal a new function of sleep in cognition.

  2. Accumulation of long-term transcriptionally active integrated retroviral vectors in active promoters and enhancers

    Czech Academy of Sciences Publication Activity Database

    Šenigl, Filip; Miklík, Dalibor; Auxt, Miroslav; Hejnar, Jiří

    2017-01-01

    Roč. 45, č. 22 (2017), s. 12752-12765 ISSN 0305-1048 R&D Projects: GA ČR(CZ) GA14-34873S; GA MŠk LO1419 Institutional support: RVO:68378050 Keywords : human-immunodeficiency-virus * dna methylation * site selection * human genome * avian-sarcoma * morphological reversion * hiv-1 integration * mlv integration * gene-expression * leukosis virus Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Virology Impact factor: 10.162, year: 2016

  3. [HIV-1 genetic variability in non Spaniard infected children].

    Science.gov (United States)

    Piñeiro Pérez, R; Mellado Peña, M J; Holguín, A; Cilleruelo, M J; García Hortelano, M; Villota, J; Martín Fontelos, P

    2009-01-01

    The prevalence of HIV-1 non-B subtypes (HIV-NBS) is increasing in Europe, because of emigration from countries where genetic variants are endemic. Although HIV-NBS could have a different clinical evolution and could respond differently to antiretrovirals (AR) than B-subtypes, these variant's response remain undocumented. To identify HIV-1 genetic variants and to determine clinical evolution in a non-Spaniard children infected with HIV-1. Children with HIV-1 infection from endemic countries were tested for HIV-1 subtypes between 1-1-1988 and 31-12-2006. Twelve children less than 18 years old and born abroad were selected. HIV-NBS were isolated in 5 children (42%): CRF2_AG recombinant in 3 cases (Equatorial Guinea), Subtype C in one (Equatorial Guinea) and CRF13_cpx in last one (India). Because of the increasing frequency of patients with HIV-NBS and their unknown long-term evolution, all children from endemic countries should be tested for HIV subtypes. We believe new studies with more patients during longer times could reveal differences in these patient's clinical, immunological and virological evolution.

  4. HIV and pregnancy

    OpenAIRE

    Lindgren, Susanne

    1996-01-01

    From the Department of Clinical Science, Divisions of Obstetrics and Gynaecology and Paediatrics and the Department of Immumology, Microbiology, Pathology and Infectious Diseases, Division of Clinical Virology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden HIV and Pregnancy An Epidemiological, Clinical and Virological Study of HIV-infected Pregnant Women amd T...

  5. Long-term stability of salivary cortisol

    DEFF Research Database (Denmark)

    Garde, A H; Hansen, Åse Marie

    2005-01-01

    either stored in small vials or spiked to polyester Salivette tampons before analysis for cortisol using Spectria RIA kits. The effects of storage were evaluated by a linear regression model (mixed procedure) on a logarithmic scale. No effects on cortisol concentrations were found after storage of saliva......The measurement of salivary cortisol provides a simple, non-invasive, and stress-free measure frequently used in studies of the hypothalamic-pituitary-adrenal axis activity. In research projects, samples are often required to be stored for longer periods of time either because of the protocol...... of the project or because of lack of funding for analysis. The aim of the present study was to explore the effects of long-term storage of samples on the amounts of measurable cortisol. Ten pools of saliva were collected on polyester Salivette tampons from five subjects. After centrifugation the samples were...

  6. Long-term cryogenic space storage system

    Science.gov (United States)

    Hopkins, R. A.; Chronic, W. L.

    1973-01-01

    Discussion of the design, fabrication and testing of a 225-cu ft spherical cryogenic storage system for long-term subcritical applications under zero-g conditions in storing subcritical cryogens for space vehicle propulsion systems. The insulation system design, the analytical methods used, and the correlation between the performance test results and analytical predictions are described. The best available multilayer insulation materials and state-of-the-art thermal protection concepts were applied in the design, providing a boiloff rate of 0.152 lb/hr, or 0.032% per day, and an overall heat flux of 0.066 Btu/sq ft hr based on a 200 sq ft surface area. A six to eighteen month cryogenic storage is provided by this system for space applications.

  7. Long-term control of root growth

    Science.gov (United States)

    Burton, Frederick G.; Cataldo, Dominic A.; Cline, John F.; Skiens, W. Eugene

    1992-05-26

    A method and system for long-term control of root growth without killing the plants bearing those roots involves incorporating a 2,6-dinitroaniline in a polymer and disposing the polymer in an area in which root control is desired. This results in controlled release of the substituted aniline herbicide over a period of many years. Herbicides of this class have the property of preventing root elongation without translocating into other parts of the plant. The herbicide may be encapsulated in the polymer or mixed with it. The polymer-herbicide mixture may be formed into pellets, sheets, pipe gaskets, pipes for carrying water, or various other forms. The invention may be applied to other protection of buried hazardous wastes, protection of underground pipes, prevention of root intrusion beneath slabs, the dwarfing of trees or shrubs and other applications. The preferred herbicide is 4-difluoromethyl-N,N-dipropyl-2,6-dinitro-aniline, commonly known as trifluralin.

  8. Long term performance of radon mitigation systems

    International Nuclear Information System (INIS)

    Prill, R.; Fisk, W.J.

    2002-01-01

    Researchers installed radon mitigation systems in 12 houses in Spokane, Washington and Coeur d'Alene, Idaho during the heating season 1985--1986 and continued to monitor indoor radon quarterly and annually for ten years. The mitigation systems included active sub-slab ventilation, basement over-pressurization, and crawlspace isolation and ventilation. The occupants reported various operational problems with these early mitigation systems. The long-term radon measurements were essential to track the effectiveness of the mitigation systems over time. All 12 homes were visited during the second year of the study, while a second set 5 homes was visited during the fifth year to determine the cause(s) of increased radon in the homes. During these visits, the mitigation systems were inspected and measurements of system performance were made. Maintenance and modifications were performed to improve system performance in these homes

  9. Rising Long-term Interest Rates

    DEFF Research Database (Denmark)

    Hallett, Andrew Hughes

    Rather than chronicle recent developments in European long-term interest rates as such, this paper assesses the impact of increases in those interest rates on economic performance and inflation. That puts us in a position to evaluate the economic pressures for further rises in those rates......, the first question posed in this assignment, and the scope for overshooting (the second question), and then make some illustrative predictions of future interest rates in the euro area. We find a wide range of effects from rising interest rates, mostly small and mostly negative, focused on investment...... till the emerging European recovery is on a firmer basis and capable of overcoming increases in the cost of borrowing and shrinking fiscal space. There is also an implication that worries about rising/overshooting interest rates often reflect the fact that inflation risks are unequally distributed...

  10. Prediction of long-term creep curves

    International Nuclear Information System (INIS)

    Oikawa, Hiroshi; Maruyama, Kouichi

    1992-01-01

    This paper aims at discussing how to predict long-term irradiation enhanced creep properties from short-term tests. The predictive method based on the θ concept was examined by using creep data of ferritic steels. The method was successful in predicting creep curves including the tertiary creep stage as well as rupture lifetimes. Some material constants involved in the method are insensitive to the irradiation environment, and their values obtained in thermal creep are applicable to irradiation enhanced creep. The creep mechanisms of most engineering materials definitely change at the athermal yield stress in the non-creep regime. One should be aware that short-term tests must be carried out at stresses lower than the athermal yield stress in order to predict the creep behavior of structural components correctly. (orig.)

  11. Hanford grout: predicting long-term performance

    International Nuclear Information System (INIS)

    Sewart, G.H.; Mitchell, D.H.; Treat, R.L.; McMakin, A.H.

    1987-01-01

    Grouted disposal is being planned for the low-level portion of liquid radioactive wastes at the Hanford site in Washington state. The performance of the disposal system must be such that it will protect people and the environment for thousands of years after disposal. To predict whether a specific grout disposal system will comply with existing and foreseen regulations, a performance assessment (PA) is performed. Long-term PAs are conducted for a range of performance conditions. Performance assessment is an inexact science. Quantifying projected impacts is especially difficult when only scant data exist on the behavior of certain components of the disposal system over thousands of years. To develop defensible results, we are honing the models and obtaining experimental data. The combination of engineered features and PA refinements is being used to ensure that Hanford grout will meet its principal goal: to protect people and the environment in the future

  12. The discovery of long-term potentiation.

    Science.gov (United States)

    Lømo, Terje

    2003-04-29

    This paper describes circumstances around the discovery of long-term potentiation (LTP). In 1966, I had just begun independent work for the degree of Dr medicinae (PhD) in Per Andersen's laboratory in Oslo after an eighteen-month apprenticeship with him. Studying the effects of activating the perforant path to dentate granule cells in the hippocampus of anaesthetized rabbits, I observed that brief trains of stimuli resulted in increased efficiency of transmission at the perforant path-granule cell synapses that could last for hours. In 1968, Tim Bliss came to Per Andersen's laboratory to learn about the hippocampus and field potential recording for studies of possible memory mechanisms. The two of us then followed up my preliminary results from 1966 and did the experiments that resulted in a paper that is now properly considered to be the basic reference for the discovery of LTP.

  13. Long-term opioid therapy in Denmark

    DEFF Research Database (Denmark)

    Birke, H; Ekholm, Ola; Sjøgren, P

    2017-01-01

    significantly associated with initiation of L-TOT in individuals with CNCP at baseline. During follow-up, L-TOT in CNCP patients increased the likelihood of negative changes in pain interference with work (OR 9.2; 95% CI 1.9-43.6) and in moderate activities (OR 3.7; 95% CI 1.1-12.6). The analysis of all......,145). A nationally representative subsample of individuals (n = 2015) completed the self-administered questionnaire in both 2000 and 2013. Collected information included chronic pain (≥6 months), health behaviour, self-rated health, pain interference with work activities and physical activities. Long-term users were...... individuals indicated a dose-response relationship between longer treatment duration and the risk of experiencing negative changes. CONCLUSIONS: Individuals on L-TOT seemed not to achieve the key goals of opioid therapy: pain relief, improved quality of life and functional capacity. SIGNIFICANCE: Long...

  14. Long Term Planning at IQ Metal

    DEFF Research Database (Denmark)

    2017-01-01

    This is a Danish version. This case about long term planning at the owner-managed manufacturing firm IQ Metal shows how the future management and ownership may be organized to utilize owner assets and minimize roadblocks. Initially, the owner-manager Bo Fischer Larsen explains how he acquired...... a stake in 2007 in the company which at that time was named Braendstrup Maskinfabrik. He furthermore expalins how he has developed the company based on a strategic plan focusing on professionalization and outsourcing. Next, the video shows how to type Bo Fischer Larsen's replies to the questions...... in The Owner Strategy Map into the questionnaire available on www.ejerstrategi-kortet.dk. Lastly, the Owner Strategy Map's recommendation of how to organize the future management and ownership of IQ Metal is explained....

  15. Long-term Consequences of Early Parenthood

    DEFF Research Database (Denmark)

    Johansen, Eva Rye; Nielsen, Helena Skyt; Verner, Mette

    (and to lesser extent employment), as fathers appear to support the family, especially when early parenthood is combined with cohabitation with the mother and the child. Heterogeneous effects reveal that individuals with a more favorable socioeconomic background are affected more severely than......Having children at an early age is known to be associated with unfavorable economic outcomes, such as lower education, employment and earnings. In this paper, we study the long-term consequences of early parenthood for mothers and fathers. Our study is based on rich register-based data that......, importantly, merges all childbirths to the children’s mothers and fathers, allowing us to study the consequences of early parenthood for both parents. We perform a sibling fixed effects analysis in order to account for unobserved family attributes that are possibly correlated with early parenthood...

  16. Long term radiological impact of thorium extraction

    International Nuclear Information System (INIS)

    Menard, S.; Schapira, J.P.

    1995-01-01

    Thorium extraction produces a certain amount of radioactive wastes. Potential long term radiological impact of these residues has been calculated using the recent ICRP-68 ingestion dose factors in connection with the computing code DECAY, developed at Orsay and described in this work. This code solves the well known Bateman's equations which govern the time dependence of a set of coupled radioactive nuclei. Monazites will be very likely the minerals to be exploited first, in case of an extensive use of thorium as nuclear fuel. Because monazites contain uranium as well, mining residues will contain not only the descendants of 232 Th and a certain proportion of non-extracted thorium (taken here to be 5%), but also this uranium, if left in the wastes for economical reasons. If no uranium would be present at all in the mineral, the potential radiotoxicity would strongly decrease in approximately 60 years, at the pace of the 5.8 years period of 228 Ra, which becomes the longest-lived radionuclide of the 4n radioactive family in the residues. Moreover, there is no risk due to radon exhalation, because of the very short period of 220 Rn. These significant differences between uranium and thorium mining have to be considered in view of some estimated long term real radiological impacts due to uranium residues, which could reach a value of the order of 1 mSv/year, the dose limit recommended for the public by the recent ICRP-60. (authors). 15 refs., 4 figs., 3 tabs., 43 appendices

  17. Managing Records for the Long Term - 12363

    Energy Technology Data Exchange (ETDEWEB)

    Montgomery, John V. [U.S. Department of Energy, Office of Legacy Management, Morgantown, West Virginia (United States); Gueretta, Jeanie [U.S. Department of Energy, Office of Legacy Management, Grand Junction, Colorado (United States)

    2012-07-01

    The U.S. Department of Energy (DOE) is responsible for managing vast amounts of information documenting historical and current operations. This information is critical to the operations of the DOE Office of Legacy Management. Managing legacy records and information is challenging in terms of accessibility and changing technology. The Office of Legacy Management is meeting these challenges by making records and information management an organizational priority. The Office of Legacy Management mission is to manage DOE post-closure responsibilities at former Cold War weapons sites to ensure the future protection of human health and the environment. These responsibilities include environmental stewardship and long-term preservation and management of operational and environmental cleanup records associated with each site. A primary organizational goal for the Office of Legacy Management is to 'Preserve, Protect, and Share Records and Information'. Managing records for long-term preservation is an important responsibility. Adequate and dedicated resources and management support are required to perform this responsibility successfully. Records tell the story of an organization and may be required to defend an organization in court, provide historical information, identify lessons learned, or provide valuable information for researchers. Loss of records or the inability to retrieve records because of poor records management processes can have serious consequences and even lead to an organisation's downfall. Organizations must invest time and resources to establish a good records management program because of its significance to the organization as a whole. The Office of Legacy Management will continue to research and apply innovative ways of doing business to ensure that the organization stays at the forefront of effective records and information management. DOE is committed to preserving records that document our nation's Cold War legacy, and the

  18. Long-term potentiation and long-term depression: a clinical perspective

    Directory of Open Access Journals (Sweden)

    Timothy V.P. Bliss

    2011-01-01

    Full Text Available Long-term potentiation and long-term depression are enduring changes in synaptic strength, induced by specific patterns of synaptic activity, that have received much attention as cellular models of information storage in the central nervous system. Work in a number of brain regions, from the spinal cord to the cerebral cortex, and in many animal species, ranging from invertebrates to humans, has demonstrated a reliable capacity for chemical synapses to undergo lasting changes in efficacy in response to a variety of induction protocols. In addition to their physiological relevance, long-term potentiation and depression may have important clinical applications. A growing insight into the molecular mechanisms underlying these processes, and technological advances in non-invasive manipulation of brain activity, now puts us at the threshold of harnessing long-term potentiation and depression and other forms of synaptic, cellular and circuit plasticity to manipulate synaptic strength in the human nervous system. Drugs may be used to erase or treat pathological synaptic states and non-invasive stimulation devices may be used to artificially induce synaptic plasticity to ameliorate conditions arising from disrupted synaptic drive. These approaches hold promise for the treatment of a variety of neurological conditions, including neuropathic pain, epilepsy, depression, amblyopia, tinnitus and stroke.

  19. Robotics for Long-Term Monitoring

    International Nuclear Information System (INIS)

    Shahin, Sarkis; Duran, Celso

    2002-01-01

    While long-term monitoring and stewardship means many things to many people, DOE has defined it as The physical controls, institutions, information, and other mechanisms needed to ensure protection of people and the environment at sites where DOE has completed or plans to complete cleanup (e.g., landfill closures, remedial actions, and facility stabilization). Across the United States, there are thousands of contaminated sites with multiple contaminants released from multiple sources where contaminants have transported and commingled. The U.S. government and U.S. industry are responsible for most of the contamination and are landowners of many of these contaminated properties. These sites must be surveyed periodically for various criteria including structural deterioration, water intrusion, integrity of storage containers, atmospheric conditions, and hazardous substance release. The surveys, however, are intrusive, time-consuming, and expensive and expose survey personnel to radioactive contamination. In long-term monitoring, there's a need for an automated system that will gather and report data from sensors without costly human labor. In most cases, a SCADA (Supervisory Control and Data Acquisition) unit is used to collect and report data from a remote location. A SCADA unit consists of an embedded computer with data acquisition capabilities. The unit can be configured with various sensors placed in different areas of the site to be monitored. A system of this type is static, i.e., the sensors, once placed, cannot be moved to other locations within the site. For those applications where the number of sampling locations would require too many sensors, or where exact location of future problems is unknown, a mobile sensing platform is an ideal solution. In many facilities that undergo regular inspections, the number of video cameras and air monitors required to eliminate the need for human inspections is very large and far too costly. HCET's remote harsh

  20. Long-Term Clock Behavior of GPS IIR Satellites

    National Research Council Canada - National Science Library

    Epstein, Marvin; Dass, Todd; Rajan, John; Gilmour, Paul

    2007-01-01

    .... Rubidium clocks, as opposed to cesium clocks, have significant long-term drift. The current literature describes an initial model of drift aging for rubidium atomic clocks followed by a long-term characteristic...

  1. Elevated rheumatoid factor and long term risk of rheumatoid arthritis

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Schnohr, Peter

    2012-01-01

    To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis.......To test whether elevated concentration of rheumatoid factor is associated with long term development of rheumatoid arthritis....

  2. Impact of HIV-1 reverse transcriptase polymorphism F214L on virological response to thymidine analogue-based regimens in antiretroviral therapy (ART)-naive and ART-experienced patients

    DEFF Research Database (Denmark)

    Ceccherini-Silberstein, Francesca; Cozzi-Lepri, Alessandro; Ruiz, Lidia

    2007-01-01

    A negative association between the polymorphism F214L and type 1 thymidine analogue (TA) mutations (TAMs) has been observed. However, the virological response to TAs according to the detection of F214L has not been evaluated....

  3. Long term results of mandibular distraction

    Directory of Open Access Journals (Sweden)

    Batra Puneet

    2006-03-01

    Full Text Available Mandibular distraction osteogenesis has become a popular surgical modality due to its many advantages over conventional orthognathic surgical procedures. However, in spite of the technique having been used for over 15 years, no concrete long term results are available regarding the stability of results. We discuss the various studies which have reported either in favour or against the stablility of results after distraction. We report a series of 6 cases (3 unilateral and 3 bilateral distraction where distraction was carried out before puberty and followed them up to seven years after removal of distractors. This case series shows that results achieved by distraction osteogenesis are unstable or best unpredictable with respect to producing a permanent size increase in the mandible. The role of the distraction osteogenesis in overcoming the pterygomassetric sling is questionable. We suggest a multicenter study with adequate patient numbers treated with a similar protocol and documented after growth cessation to have meaningful conclusions on the debate of distraction osteogenesis versus orthognathic surgery.

  4. [Perioperative management of long-term medication].

    Science.gov (United States)

    Vogel Kahmann, I; Ruppen, W; Lurati Buse, G; Tsakiris, D A; Bruggisser, M

    2011-01-01

    Anesthesiologists and surgeons are increasingly faced with patients who are under long-term medication. Some of these drugs can interact with anaesthetics or anaesthesia and/or surgical interventions. As a result, patients may experience complications such as bleeding, ischemia, infection or severe circulatory reactions. On the other hand, perioperative discontinuation of medication is often more dangerous. The proportion of outpatient operations has increased dramatically in recent years and will probably continue to increase. Since the implementation of DRGs (pending in Switzerland, introduced in Germany for some time), the patient enters the hospital the day before operation. This means that the referring physician as well as anesthesiologists and surgeons at an early stage must deal with issues of perioperative pharmacotherapy. This review article is about the management of the major drug classes during the perioperative period. In addition to cardiac and centrally acting drugs and drugs that act on hemostasis and the endocrine system, special cases such as immunosuppressants and herbal remedies are mentioned.

  5. Long term agreements energy efficiency. Progress 1999

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2000-11-01

    Long Term Agreements (LTAs) on energy efficiency have been contracted with various business sectors since 1992, as part of energy conservation policy: industrial sectors, commercial services, agrarian sectors and non-profit services. LTAs are voluntary agreements between a specific sector and the Minister of Economic Affairs. In some cases, the Minister of Agriculture, Nature Management and Fisheries is also involved. The sector commits to an effort to improve energy efficiency by a particular percentage within an agreed period. As at 31 December 1999, a total of 29 LTAs had been contracted with industrial sectors and 14 with non-industrial ones. This report describes the progress of the LTAs in 1999. It reviews the energy efficiency improvements realised through the LTAs, both overall and in each individual sector. The aim is to make the efforts and results in the various sectors accessible to the general public. Appendix 1 describes the positioning of the LTA instrument. This Appendix provides and insight into the position of the LTAs within the overall set of policy instruments. It also covers the subsidy schemes and fiscal instruments that support the LTAs, the relationships between LTAs and environmental policy and new developments relating to the LTAs in the years ahead. Appendices 2 to 6 contain the reports on the LTAs and a list of abbreviations (Appendix 7)

  6. Long-term outcome of neuroparacoccidioidomycosis treatment

    Directory of Open Access Journals (Sweden)

    Fabio Francesconi

    2011-02-01

    Full Text Available INTRODUCTION: Neuroparacoccidioidomycosis (NPCM is a term used to describe the invasion of the central nervous system by the pathogenic fungus Paracoccidioides brasiliensis. NPCM has been described sporadically in some case reports and small case series, with little or no focus on treatment outcome and long-term follow-up. METHODS: All patients with NPCM from January 1991 to December 2006 were analyzed and were followed until December 2009. RESULTS: Fourteen (3.8% cases of NPCM were identified out of 367 patients with paracoccidioidomycosis (PCM. A combination of oral fluconazole and sulfamethoxazole/trimethoprim (SMZ/TMP was the regimen of choice, with no documented death due to Paracoccidioides brasiliensis infection. Residual neurological deficits were observed in 8 patients. Residual calcification was a common finding in neuroimaging follow-up. CONCLUSIONS: All the patients in this study responded positively to the association of oral fluconazole and sulfamethoxazole/trimethoprim, a regimen that should be considered a treatment option in cases of NPCM. Neurological sequela was a relatively common finding. For proper management of these patients, anticonvulsant treatment and physical therapy support were also needed.

  7. Long term prospects for world gas trade

    International Nuclear Information System (INIS)

    Linder, P.T.

    1991-01-01

    Results are presented from a world gas trade model used to forecast long term gas markets. Assumptions that went into the model are described, including the extent of current proven gas reserves, production ratios, total energy and gas demand, gas supply cost curves for each producing country, available gas liquefaction and transportation facilities, and liquefied natural gas (LNG) shipping costs. The results indicate that even with generally very low supply costs for most gas producing basins, gas trade will continue to be restricted by the relatively high cost of transportation, whether by pipeline or tanker. As a consequence, future gas trade will tend to be regionally oriented. United States gas imports will come mostly from Canada, Venezuela, and Mexico; Western Europe will largely be supplied by the Soviet Union and Africa, and Japan's requirements will generally be met by Pacific Rim producers. Although the Middle East has vast quantities of gas reserves, its export growth will continue to be hampered by its remote location from major markets. 16 figs

  8. Long term results of childhood dysphonia treatment.

    Science.gov (United States)

    Mackiewicz-Nartowicz, Hanna; Sinkiewicz, Anna; Bielecka, Arleta; Owczarzak, Hanna; Mackiewicz-Milewska, Magdalena; Winiarski, Piotr

    2014-05-01

    The aim of this study was to assess the long term results of treatment and rehabilitation of childhood dysphonia. This study included a group of adolescents (n=29) aged from 15 to 20 who were treated due to pediatric hyperfunctional dysphonia and soft vocal fold nodules during their pre-mutational period (i.e. between 5 and 12 years of age). The pre-mutational therapy was comprised of proper breathing pattern training, voice exercises and psychological counseling. Laryngostroboscopic examination and perceptual analysis of voice were performed in each patient before treatment and one to four years after mutation was complete. The laryngostroboscopic findings, i.e. symmetry, amplitude, mucosal wave and vocal fold closure, were graded with NAPZ scale, and the GRBAS scale was used for the perceptual voice analysis. Complete regression of the childhood dysphonia was observed in all male patients (n=14). Voice disorders regressed completely also in 8 out of 15 girls, but symptoms of dysphonia documented on perceptual scale persisted in the remaining seven patients. Complex voice therapy implemented in adolescence should be considered as either the treatment or preventive measure of persistent voice strain, especially in girls. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Long-term data storage in diamond

    Science.gov (United States)

    Dhomkar, Siddharth; Henshaw, Jacob; Jayakumar, Harishankar; Meriles, Carlos A.

    2016-01-01

    The negatively charged nitrogen vacancy (NV−) center in diamond is the focus of widespread attention for applications ranging from quantum information processing to nanoscale metrology. Although most work so far has focused on the NV− optical and spin properties, control of the charge state promises complementary opportunities. One intriguing possibility is the long-term storage of information, a notion we hereby introduce using NV-rich, type 1b diamond. As a proof of principle, we use multicolor optical microscopy to read, write, and reset arbitrary data sets with two-dimensional (2D) binary bit density comparable to present digital-video-disk (DVD) technology. Leveraging on the singular dynamics of NV− ionization, we encode information on different planes of the diamond crystal with no cross-talk, hence extending the storage capacity to three dimensions. Furthermore, we correlate the center’s charge state and the nuclear spin polarization of the nitrogen host and show that the latter is robust to a cycle of NV− ionization and recharge. In combination with super-resolution microscopy techniques, these observations provide a route toward subdiffraction NV charge control, a regime where the storage capacity could exceed present technologies. PMID:27819045

  10. Long-term data storage in diamond.

    Science.gov (United States)

    Dhomkar, Siddharth; Henshaw, Jacob; Jayakumar, Harishankar; Meriles, Carlos A

    2016-10-01

    The negatively charged nitrogen vacancy (NV - ) center in diamond is the focus of widespread attention for applications ranging from quantum information processing to nanoscale metrology. Although most work so far has focused on the NV - optical and spin properties, control of the charge state promises complementary opportunities. One intriguing possibility is the long-term storage of information, a notion we hereby introduce using NV-rich, type 1b diamond. As a proof of principle, we use multicolor optical microscopy to read, write, and reset arbitrary data sets with two-dimensional (2D) binary bit density comparable to present digital-video-disk (DVD) technology. Leveraging on the singular dynamics of NV - ionization, we encode information on different planes of the diamond crystal with no cross-talk, hence extending the storage capacity to three dimensions. Furthermore, we correlate the center's charge state and the nuclear spin polarization of the nitrogen host and show that the latter is robust to a cycle of NV - ionization and recharge. In combination with super-resolution microscopy techniques, these observations provide a route toward subdiffraction NV charge control, a regime where the storage capacity could exceed present technologies.

  11. Long-term predictions using natural analogues

    International Nuclear Information System (INIS)

    Ewing, R.C.

    1995-01-01

    One of the unique and scientifically most challenging aspects of nuclear waste isolation is the extrapolation of short-term laboratory data (hours to years) to the long time periods (10 3 -10 5 years) required by regulatory agencies for performance assessment. The direct validation of these extrapolations is not possible, but methods must be developed to demonstrate compliance with government regulations and to satisfy the lay public that there is a demonstrable and reasonable basis for accepting the long-term extrapolations. Natural systems (e.g., open-quotes natural analoguesclose quotes) provide perhaps the only means of partial open-quotes validation,close quotes as well as data that may be used directly in the models that are used in the extrapolation. Natural systems provide data on very large spatial (nm to km) and temporal (10 3 -10 8 years) scales and in highly complex terranes in which unknown synergisms may affect radionuclide migration. This paper reviews the application (and most importantly, the limitations) of data from natural analogue systems to the open-quotes validationclose quotes of performance assessments

  12. Long-term effects of islet transplantation.

    Science.gov (United States)

    Holmes-Walker, D Jane; Kay, Thomas W H

    2016-10-01

    Islet transplantation has made great progress in recent years. This is a remarkable technical feat but raises the question of what the long-term benefits and risks are for type I diabetes recipients. Graft survival continues to improve, and recent multicenter studies show that islet transplantation is particularly effective to prevent hypoglycemic events even in those who do not become insulin-independent and to achieve excellent glycemic control. Concerns include histocompatability leucocyte antigen (HLA) sensitization and other risks including from immunosuppression that islet transplantation shares with other forms of allotransplantation. Reversal of hypoglycemia unawareness and protection from severe hypoglycemia events are two of the main benefits of islet transplantation and they persist for the duration of graft function. Islet transplantation compares favorably with other therapies for those with hypoglycemia unawareness, although new technologies have not been tested head-to-head with transplantation. HLA sensitization increases with time after transplantation especially if immunosuppression is ceased and is a risk for those who may require future transplantation as well as being associated with loss of graft function.

  13. CERN Services for Long Term Data Preservation

    CERN Document Server

    Shiers, Jamie; Blomer, Jakob; Ganis, Gerardo; Dallmeier-Tiessen, Sunje; Simko, Tibor; Cancio Melia, German; CERN. Geneva. IT Department

    2016-01-01

    In this paper we describe the services that are offered by CERN for Long Term preservation of High Energy Physics (HEP) data, with the Large Hadron Collider (LHC) as a key use case. Data preservation is a strategic goal for European High Energy Physics (HEP), as well as for the HEP community worldwide and we position our work in this global content. Specifically, we target the preservation of the scientific data, together with the software, documentation and computing environment needed to process, (re-)analyse or otherwise (re-)use the data. The target data volumes range from hundreds of petabytes (PB – 10^15 bytes) to hundreds of exabytes (EB – 10^18 bytes) for a target duration of several decades. The Use Cases driving data preservation are presented together with metrics that allow us to measure how close we are to meeting our goals, including the possibility for formal certification for at least part of this work. Almost all of the services that we describe are fully generic – the exception being A...

  14. Containment long-term operational integrity

    International Nuclear Information System (INIS)

    Sammataro, R.F.

    1990-01-01

    Periodic integrated leak rate tests are required to assure that containments continue to meet allowable leakage limits. Although overall performance has been quite good to date, several major containment aging and degradation mechanisms have been identified. Two pilot plant life extension (PLEX) studies serve as models for extending the operational integrity of present containments for light-water cooled nuclear power plants in the United States. One study is for a Boiling-Water Reactor (BWR) and the second is for a Pressurized-Water Reactor (PWR). Research and testing programs for determining the ultimate pressure capacity and failure mechanisms for containments under severe loading conditions and studies for extending the life of current plants beyond the present 40-year licensed lifetime are under way. This paper presents an overview of containment designs in the United States. Also presented are a discussion of the American Society of Mechanical Engineers Boiler and Pressure Vessel Code (ASME Code) and regulatory authority requirements for the design, construction, inservice inspection, leakage testing and repair of steel and concrete containments. Findings for containments from the pilot PLEX studies and continuing containment integrity research and testing programs are discussed. The ASME Code and regulatory requirements together with recommendations from the PLEX studies and containment integrity research and testing provide a basis for continued containment long-term operational integrity. (orig./GL)

  15. Long term results of compression sclerotherapy.

    Science.gov (United States)

    Labas, P; Ohradka, B; Cambal, M; Reis, R; Fillo, J

    2003-01-01

    To compare the short and long term results of different techniques of compression sclerotherapy. In the past 10 years the authors treated 1622 pts due to chronic venous insufficiency. There were 3 groups of patients: 1) Pts treated by Sigg's technique using Aethoxysclerol, 2) Pts treated by Fegan's technique with Fibrovein, and 3) Pts treated by Fegan's procedure, but using a combination of both sclerosants. In all cases, the techniques of empty vein, bubble air, uninterrupted 6-week compression and forced mobilisation were used. In the group of pats. treated by Sigg's procedure, the average cure rate was 67.47% after 6 months, 60.3% after 5 years of follow-up. In Fegan's group this rate was 83.6% after 6 months and 78.54% after 5 year assessment. Statistically, significant differences were found only by the disappearance of varices and reduction of pain in favour of Fegan's technique. In the group of pts treated by Fegan's (Aethoxysclerol + Fibrovein) this rate after 5 years was 86%. The only statistically significant difference was found by the disappearance of varices in favour of Fegan's technique using a combination of 2 detergent sclerosants. Sclerotherapy is effective when properly executed in any length of vein no matter how dilated it has become. The recurrences are attributed more to inadequate technique than to the shortcoming of the procedure. Sclerotherapy is miniinvasive, with few complications, and can be repeated on out-patient basis. (Tab. 1, Ref. 22.).

  16. Transuranic waste: long-term planning

    International Nuclear Information System (INIS)

    Young, K.C.

    1985-07-01

    Societal concerns for the safe handling and disposal of toxic waste are behind many of the regulations and the control measures in effect today. Transuranic waste, a specific category of toxic (radioactive) waste, serves as a good example of how regulations and controls impact changes in waste processing - and vice versa. As problems would arise with waste processing, changes would be instituted. These changes improved techniques for handling and disposal of transuranic waste, reduced the risk of breached containment, and were usually linked with regulatory changes. Today, however, we face a greater public awareness of and concern for toxic waste control; thus, we must anticipate potential problems and work on resolving them before they can become real problems. System safety analyses are valuable aids in long-term planning for operations involving transuranic as well as other toxic materials. Examples of specific system safety analytical methods demonstrate how problems can be anticipated and resolution initiated in a timely manner having minimal impacts upon allocation of resource and operational goals. 7 refs., 1 fig

  17. Long-term plutonium storage: Design concepts

    International Nuclear Information System (INIS)

    Wilkey, D.D.; Wood, W.T.; Guenther, C.D.

    1994-01-01

    An important part of the Department of Energy (DOE) Weapons Complex Reconfiguration (WCR) Program is the development of facilities for long-term storage of plutonium. The WCR design goals are to provide storage for metals, oxides, pits, and fuel-grade plutonium, including material being held as part of the Strategic Reserve and excess material. Major activities associated with plutonium storage are sorting the plutonium inventory, material handling and storage support, shipping and receiving, and surveillance of material in storage for both safety evaluations and safeguards and security. A variety of methods for plutonium storage have been used, both within the DOE weapons complex and by external organizations. This paper discusses the advantages and disadvantages of proposed storage concepts based upon functional criteria. The concepts discussed include floor wells, vertical and horizontal sleeves, warehouse storage on vertical racks, and modular storage units. Issues/factors considered in determining a preferred design include operational efficiency, maintenance and repair, environmental impact, radiation and criticality safety, safeguards and security, heat removal, waste minimization, international inspection requirements, and construction and operational costs

  18. Essays on long-term mortality and interest rate risk

    NARCIS (Netherlands)

    de Kort, J.P.

    2017-01-01

    This dissertation comprises a study of long-term risks which play a major role in actuarial science. In Part I we analyse long-term mortality risk and its impact on consumption and investment decisions of economic agents, while Part II focuses on the mathematical modelling of long-term interest

  19. Scientific Understanding from Long Term Observations: Insights from the Long Term Ecological Research (LTER) Program

    Science.gov (United States)

    Gosz, J.

    2001-12-01

    The network dedicated to Long Term Ecological Research (LTER) in the United States has grown to 24 sites since it was formed in 1980. Long-term research and monitoring are performed on parameters thatare basic to all ecosystems and are required to understand patterns, processes, and relationship to change. Collectively, the sites in the LTER Network provide opportunities to contrast marine, coastal, and continental regions, the full range of climatic gradients existing in North America, and aquatic and terrestrial habitats in a range of ecosystem types. The combination of common core areas and long-term research and monitoring in many habitats have allowed unprecedented abilities to understand and compare complex temporal and spatial dynamics associated with issues like climate change, effects of pollution, biodiversity and landuse. For example, McMurdo Dry Valley in the Antarctic has demonstrated an increase in glacier mass since 1993 which coincides with a period of cooler than normal summers and more than average snowfall. In contrast, the Bonanza Creek and Toolik Lake sites in Alaska have recorded a warming period unprecedented in the past 200 years. Nitrogen deposition effects have been identified through long-term watershed studies on biogeochemical cycles, especially at Coweeta Hydrological Lab, Harvard Forest, and the Hubbard Brook Experimental Forest. In aquatic systems, such as the Northern Temperate Lakes site, long-term data revealed time lags in effects of invaders and disturbance on lake communities. Biological recovery from an effect such as lake acidification was shown to lag behind chemical recovery. The long-term changes documented over 2 decades have been instrumental in influencing management practices in many of the LTER areas. In Puerto Rico, the Luquillo LTER demonstrated that dams obstruct migrations of fish and freshwater shrimp and water abstraction at low flows can completely obliterate downstream migration of juveniles and damage

  20. Energy in 2010 - 2020. Long term challenges; Energie 2010-2020. Les defis du long terme

    Energy Technology Data Exchange (ETDEWEB)

    Dessus, Benjamin [ed.] [Centre National de la Recherche Scientifique (CNRS), 75 - Paris (France)

    2000-02-02

    This report presents the results of a workshop intending to anticipate the long term challenges, to guide better the short term power options, to understand the available political, economical and technical assumptions for the prospective world situation, to give some strategic hints on the necessary transition. Indeed, the difficult issue which the workshop tried to tackle was how should we prepare to reveal the energetic challenge of the development of the eight to ten billion inhabitants of our Planet in the next century without jeopardizing its existence. The energetic problems, a hardcore of the international preoccupation of both growth and environment, as it was recently evidenced by the climatic conference in Kyoto, have ever been the object of a particular attention on the part of General Commissariat of Plan. Thus, the commission 'Energy in 2010 - 2020' has been instituted in April 1996 in order to update the works done in 1990 - 1991 by the commission 'Energy 2010'. Soon it occurred to this new commission the task of illuminating its works by a long term (2050 - 2100) world prospective analysis of the challenges and problems linked to energy, growth and environment. In conclusion, this document tried to find answers to questions like: - which are the risks the energy consumption augmentation entail? - can we control them by appropriate urbanism and transport policies or technological innovation?. Four options for immediate action are suggested: - the energy efficiency should become a priority objective of policies; -coping with the long term challenges requires acting at present; - building the transition between governmental leadership and market; - taking profit of all the possible synergies between short and long term planning.

  1. Monitoring long-term oral corticosteroids.

    Science.gov (United States)

    Mundell, Lewis; Lindemann, Roberta; Douglas, James

    2017-01-01

    Corticosteroids are synthetic analogues of human hormones normally produced by the adrenal cortex. They have both glucocorticoid and mineralocorticoid properties. The glucocortoid components are anti-inflammatory, immunosuppressive, anti-proliferative and vasoconstrictive. They influence the metabolism of carbohydrate and protein, in addition to playing a key role in the body's stress response. Mineralocorticoid's main significance is in the balance of salt and water concentrations. Due to the combination of these effects, corticosteroids can cause many adverse effects. Oral corticosteroids are absorbed systemically and are therefore more likely to cause adverse effects than topical or inhaled corticosteroids. Furthermore, it is assumed that greater duration of treatment will lead to a greater number of adverse effects, and therefore the most at risk group are those taking high dose, long-term oral corticosteroids (LTOC). High dose is defined as a prescription of >5 mg oral prednisolone and long term as duration of treatment >1 month (based on National Institute for Health and Care Excellence guidance for patient's 'at risk' of systemic side effects). Parameters to be monitored in primary care include weight, blood pressure, triglycerides, glucose and urea and electrolytes. From clinical experience within the general practice setting, the authors propose that these patients do not receive adequate baseline monitoring before starting corticosteroids nor are these markers monitored consistently thereafter. This project intended to evidence this claim, evaluate the adverse effect profile and improve monitoring in this patient group. The initial audit of 22 patients, within a single general practice, detected at least one documented adverse effect in 64% of patients, while 41% reported more than one adverse effect. 45% had recorded weight gain, 18% had recorded osteoporosis, 18% had at least one recorded cataract, 14% had recorded Hypertension, 14% had recorded

  2. A security/safety survey of long term care facilities.

    Science.gov (United States)

    Acorn, Jonathan R

    2010-01-01

    What are the major security/safety problems of long term care facilities? What steps are being taken by some facilities to mitigate such problems? Answers to these questions can be found in a survey of IAHSS members involved in long term care security conducted for the IAHSS Long Term Care Security Task Force. The survey, the author points out, focuses primarily on long term care facilities operated by hospitals and health systems. However, he believes, it does accurately reflect the security problems most long term facilities face, and presents valuable information on security systems and practices which should be also considered by independent and chain operated facilities.

  3. HLW Long-term Management Technology Development

    International Nuclear Information System (INIS)

    Choi, Jong Won; Kang, C. H.; Ko, Y. K.

    2010-02-01

    Permanent disposal of spent nuclear fuels from the power generation is considered to be the unique method for the conservation of human being and nature in the present and future. In spite of spent nuclear fuels produced from power generation, based on the recent trends on the gap between supply and demand of energy, the advance on energy price and reduction of carbon dioxide, nuclear energy is expected to play a role continuously in Korea. It means that a new concept of nuclear fuel cycle is needed to solve problems on spent nuclear fuels. The concept of the advanced nuclear fuel cycle including PYRO processing and SFR was presented at the 255th meeting of the Atomic Energy Commission. According to the concept of the advanced nuclear fuel cycle, actinides and long-term fissile nuclides may go out of existence in SFR. And then it is possible to dispose of short term decay wastes without a great risk bearing. Many efforts had been made to develop the KRS for the direct disposal of spent nuclear fuels in the representative geology of Korea. But in the case of the adoption of Advanced nuclear fuel cycle, the disposal of PYRO wastes should be considered. For this, we carried out the Safety Analysis on HLW Disposal Project with 5 sub-projects such as Development of HLW Disposal System, Radwaste Disposal Safety Analysis, Feasibility study on the deep repository condition, A study on the Nuclide Migration and Retardation Using Natural Barrier, and In-situ Study on the Performance of Engineered Barriers

  4. The long-term nuclear explosives predicament

    International Nuclear Information System (INIS)

    Swahn, J.

    1992-01-01

    A scenario is described, where the production of new military fissile materials is halted and where civil nuclear power is phased out in a 'no-new orders' case. It is found that approximately 1100 tonnes of weapons-grade uranium, 233 tonnes of weapons-grade plutonium and 3795 tonnes of reactor-grade plutonium have to be finally disposed of as nuclear waste. This material could be used for the construction of over 1 million nuclear explosives. Reactor-grade plutonium is found to be easier to extract from spent nuclear fuel with time and some physical characteristics important for the construction of nuclear explosives are improved. Alternative methods for disposal of the fissile material that will avoid the long-term nuclear explosives predicament are examined. Among these methods are dilution, denaturing or transmutation of the fissile material and options for practicably irrecoverable disposal in deep boreholes, on the sea-bed, and in space. It is found that the deep boreholes method for disposal should be the primary alternative to be examined further. This method can be combined with an effort to 'forget' where the material was put. Included in the thesis is also an evaluation of the possibilities of controlling the limited civil nuclear activities in a post-nuclear world. Some surveillance technologies for a post-nuclear world are described, including satellite surveillance. In a review part of the thesis, methods for the production of fissile material for nuclear explosives are described, the technological basis for the construction of nuclear weapons is examined, including use of reactor-grade plutonium for such purposes; also plans for the disposal of spent fuel from civil nuclear power reactors and for the handling of the fissile material from dismantled warheads is described. The Swedish plan for the handling and disposal of spent nuclear fuel is described in detail. (490 refs., 66 figs., 27 tabs.)

  5. Long term results of pyeloplasty in adults

    International Nuclear Information System (INIS)

    Tayib, Abdul Malik

    2004-01-01

    To determine the presenting systems, complications, stone coincidence in adult patients with primary ureteropelvic junction (UPJ) obstruction seen at King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia. We are also reporting the success rate and long term results of adult pyeloplasty. We reviewed the records of 34 patients who underwent 37 pyeloplasty operations during the period January 1992 through to June 2002. The preoperative radiological diagnosis made by intravenous urogram or renal isotopes scan. We excluded from our study patients with previous history of passage of stones, renal or ureteral surgeries, large renal pelvis stone that may cause UPJ obstruction or abnormalities that may lead to secondry UPJ obstruction such as vesicoureteral reflux. There were 28 male patients and 8 females, their age varied between 16 and 51-years, the mean age was 36.1 years, and 18 (52.9%) patients had concomitant renal stones. Ispsilateral split renal function improved by 3-7% post pyeloplasty in 23 patients, while in one patient the function stayed the same, and in another patient the split function reduced by 4%. T1/2 renal isotopes washout time became less than 15 minutes in 19 patients and less than 20 minutes in 6 patients. Intravenous urogram revealed disappearence of the obstruction at UPJ in 7 patients while in 2 patients it became poorly functioning. Anderson Hynes pyeloplasty is an excellent procedure for treating UPJ obstruction in adults. Our success rate is comparable to the international repoted rates, while our study revealed a higher incidence of concomitant renal stones than the international studies. (author)

  6. Nutritional deficit and Long Term Potentiation alterations

    Directory of Open Access Journals (Sweden)

    M. Petrosino

    2009-01-01

    Full Text Available In the present work we examined the ability of prenatally malnourished offspring to produce and maintain long-term potentiation (LTP of the perforant path/dentate granule cell synapse in freely moving rats at 15,30, and 90 days of age. Population spike amplitude (PSA was calculated from dentate field potential recordings prior to and at 15, 30, 60 min. and 3, 5, 18 and 24 h following tetanization of the perforant pathway. All animals of both malnourished and well-nourished diet groups at 15 days of age showed potentiation of PSA measures but the measures obtained from 15-day-old prenatally malnourished animals were significantly less than that of age-matched, well-nourished controls. At 30 days of age, remarkable effect of tetanization was likely observed from PSA measures for this age group followed much the same pattern. At 90 days of age, PSA measures obtained from malnourished animals decreased from pretetanization levels immediately following tetanization. At this age, however, at three hours time recordings, this measure growing up to a level which did not differ significantly from that of the control group. These results indicate that the width of tetanization induced enhancement of dentate granule cell response in preweanling rats (15-day-old animals is signifacantly affected fromgestational protein malnutrition and this trend is kept in animals tested at 30 and 90 days of age. The fact, however, that considerable limitation in LTP generation was gained from prenatally malnourished animals at 90 days of age, implying that dietary rehabilitation starting at birth is an intervention strategy not capable to imbrove the effects of the gestational stress.

  7. Perinatal respiratory infections and long term consequences

    Directory of Open Access Journals (Sweden)

    Luciana Indinnimeo

    2015-10-01

    Full Text Available Respiratory syncytial virus (RSV is the most important pathogen in the etiology of respiratory infections in early life. 50% of children are affected by RSV within the first year of age, and almost all children become infected within two years. Numerous retrospective and prospective studies linking RSV and chronic respiratory morbidity show that RSV bronchiolitis in infancy is followed by recurrent wheezing after the acute episod. According to some authors a greater risk of wheezing in children with a history of RSV bronchiolitis would be limited to childhood, while according to others this risk would be extended into adolescence and adulthood. To explain the relationship between RSV infection and the development of bronchial asthma or the clinical pathogenetic patterns related to a state of bronchial hyperreactivity, it has been suggested that RSV may cause alterations in the response of the immune system (immunogenic hypothesis, activating directly mast cells and basophils and changing the pattern of differentiation of immune cells present in the bronchial tree as receptors and inflammatory cytokines. It was also suggested that RSV infection can cause bronchial hyperreactivity altering nervous airway modulation, acting on nerve fibers present in the airways (neurogenic hypothesis.The benefits of passive immunoprophylaxis with palivizumab, which seems to represent an effective approach in reducing the sequelae of RSV infection in the short- and long-term period, strengthen the implementation of prevention programs with this drug, as recommended by the national guidelines of the Italian Society of Neonatology. Proceedings of the 11th International Workshop on Neonatology and Satellite Meetings · Cagliari (Italy · October 26th-31st, 2015 · From the womb to the adultGuest Editors: Vassilios Fanos (Cagliari, Italy, Michele Mussap (Genoa, Italy, Antonio Del Vecchio (Bari, Italy, Bo Sun (Shanghai, China, Dorret I. Boomsma (Amsterdam, the

  8. Long term results of trabeculectomy surgery

    Directory of Open Access Journals (Sweden)

    Ferhat Evliyaoğlu

    2015-09-01

    Full Text Available Objective: Evaluation of long-term results of primary trabeculectomy operation Methods: The cases that are followed up with diagnosis of glaucoma in Okmeydanı Training and Research Hospital Eye Clinic between January 2000 and December 2001 were evaluated retrospectively. All of the cases, despite maximum therapy, have high intraocular pressure (IOP, undergone primary trabeculectomy operation, are followed at least 6 months and regularly followed through 10 years were included in this study. IOP with or without medical treatment 18mmg or less than 18 mmHg accepted as successful. IOL pressure measured with applanation tonometry. Results: 89 eyes of 70 cases were included in this study. The cases included in the study, 42 male (60%, and 28 (40% were female. The mean age was 63.65±12.18 years. Preoperative intraocular pressure determined as 30.36 ± 3.2 mmHg. In the follow up examination mean intra ocular pressure was 15.31 ± 1.2 mmHg at 1st month, 15.47± 1.1mmHg at 3rd month, 15.02±1.8 mmHg at 6th month, 15.34± 2.1 mmHg at 1st year, 15.82 ± 2.1mmHg at 2nd year, 17.06 ± 2.3mmHg at 5th year and 18.02 ± 2.2 mmHg at 10th year. Statistical analysis of these data showed significant decreased of intra ocular pressure in the post operative period in compare to the preoperative period, 1st month, 3rd month, 6th month, 1st year, 2nd year, 5th year an 10th year (p < 0.01. The follow-up period in the study was 91.10 ± 40.15 months (6-120 months. Conclusion: Primary trabeculectomy can be considered as an alternative treatment procedure especially in patients who does not use drugs regularly and unable to attend regular medical examination. J Clin Exp Invest 2015; 6 (3: 263-268

  9. Northern European long term climate archives

    Energy Technology Data Exchange (ETDEWEB)

    Hohl, Veronica [Stockholm Univ. (Sweden)

    2005-01-01

    The Swedish Nuclear Fuel and Waste Management Company is responsible for the management and disposal of Sweden's radioactive waste. It is intended to deposit the spent nuclear fuel in a deep geological repository. This repository shall keep the radiotoxic material separated from humans and the environment for extended periods, from decades to millennia and possibly to geological timescales. During this time perspective climate induced changes such as shore-level displacement and evolution of permafrost and ice sheets are expected to occur which may affect the repository. The possible occurrence, extent and duration of these long-term changes, are therefore of interest when considering the assessment of repository performance and safety. The main climate parameters determining both surface and subsurface conditions are temperature and precipitation. As a result of the last advance of the Weichselian ice sheet only few geological archives exist, which contain information on past climatic conditions in Sweden before c 16,000 years BP. The purpose of this literature review is to compile and evaluate available information from Scandinavian, Northern and Central European geological archives, which record climatic conditions during the Weichselian time period. The compilation provides paleotemperature data sets, which may be used to explore the possible evolution of periglacial permafrost in Sweden. This report is a synopsis of 22 publications detailing climatic and environmental changes during the Weichselian time period in Northwestern Europe based on quantified paleotemperature records. Some of the data is presented as temperature curves which were digitised specifically for this report. The time range covered by the different publications varies considerably. Only few authors dealt with the whole Weichselian period and the majority cover only a few thousand years. This however is not considered to influence the reliability of the archives. The reason for the

  10. Northern European long term climate archives

    International Nuclear Information System (INIS)

    Hohl, Veronica

    2005-01-01

    The Swedish Nuclear Fuel and Waste Management Company is responsible for the management and disposal of Sweden's radioactive waste. It is intended to deposit the spent nuclear fuel in a deep geological repository. This repository shall keep the radiotoxic material separated from humans and the environment for extended periods, from decades to millennia and possibly to geological timescales. During this time perspective climate induced changes such as shore-level displacement and evolution of permafrost and ice sheets are expected to occur which may affect the repository. The possible occurrence, extent and duration of these long-term changes, are therefore of interest when considering the assessment of repository performance and safety. The main climate parameters determining both surface and subsurface conditions are temperature and precipitation. As a result of the last advance of the Weichselian ice sheet only few geological archives exist, which contain information on past climatic conditions in Sweden before c 16,000 years BP. The purpose of this literature review is to compile and evaluate available information from Scandinavian, Northern and Central European geological archives, which record climatic conditions during the Weichselian time period. The compilation provides paleotemperature data sets, which may be used to explore the possible evolution of periglacial permafrost in Sweden. This report is a synopsis of 22 publications detailing climatic and environmental changes during the Weichselian time period in Northwestern Europe based on quantified paleotemperature records. Some of the data is presented as temperature curves which were digitised specifically for this report. The time range covered by the different publications varies considerably. Only few authors dealt with the whole Weichselian period and the majority cover only a few thousand years. This however is not considered to influence the reliability of the archives. The reason for the varying

  11. Hot functional test chemistry - long term experience

    International Nuclear Information System (INIS)

    Vonkova, K.; Kysela, J.; Marcinsky, M.; Martykan, M.

    2010-01-01

    Primary circuit materials undergo general corrosion in high temperature, deoxygenated, neutral or mildly alkaline solutions to form thin oxide films. These oxide layers (films) serve as protective film and mitigate the further corrosion of primary materials. Inner chromium-rich oxide layer has low cation diffusion coefficients and thus control iron and nickel transport from the metal surface to the outer layer and their dissolution into the coolant. Much less corrosion products are generated by the compact, integral and stable oxide (passivation) layer. For the latest Czech and Slovak stations commissioned (Temelin and Mochovce) a modified Hot Functional Test (HFT) chemistry was developed in the NRI Rez. Chromium rich surface layer formatted due to modified HTF chemistry ensures lower corrosion rates and radiation field formation and thus also mitigates crud formation during operation. This procedure was also designed to prepare the commissioned unit for the further proper water chemistry practise. Mochovce 1 (SK) was the first station commissioned using these recommendations in 1998. Mochovce 2 (1999) and Temelin 1 and 2 (CZ - 2000 and 2002) were subsequently commissioned using these guidelines too. The main principles of the controlled primary water chemistry applied during the hot functional tests are reviewed and importance of the water chemistry, technological and other relevant parameters is stressed regarding to the quality of the passive layer formed on the primary system surfaces. Samples from Mochovce indicated that duplex oxide layers up to 20 μm thick were produced, which were mainly magnetite substituted with nickel and chromium (e.g. 60-65% Fe, 18-28% Cr, 9-12% Ni, <1% Mn and 1-2% Si on a stainless steel primary circuit sample). Long term operation experience from both nuclear power plants are discussed in this paper. Radiation field, occupational radiation exposure and corrosion layers evolution during the first c. ten years of operation are

  12. History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change

    DEFF Research Database (Denmark)

    Reekie, J; Mocroft, A; Ledergerber, B

    2010-01-01

    OBJECTIVES: HIV-infected persons experience different patterns of viral suppression after initiating combination antiretroviral therapy (cART). The relationship between such differences and risk of virological failure after starting a new antiretroviral could help with patient monitoring strategi...

  13. Long-Term Patency of Lymphovenous Anastomoses: A Systematic Review.

    Science.gov (United States)

    Tourani, Saam S; Taylor, G Ian; Ashton, Mark W

    2016-08-01

    With advancements in technology and microsurgical techniques, lymphovenous anastomosis has become a popular reconstructive procedure in the treatment of chronic lymphedema. However, the long-term patency of these anastomoses is not clear in the literature. A systematic review of the MEDLINE and EMBASE databases was performed to assess the reported long-term patency of lymphovenous anastomoses. A total of eight studies satisfied the inclusion criteria. Pooled data from four similar experiments in normal dogs showed an average long-term (≥5 months) patency of 52 percent. The only experiment in dogs with chronic lymphedema failed to show any long-term patency. The creation of peripheral lymphovenous anastomoses with a moderate long-term patency rate has become technically possible. However, the long-term results in chronic lymphedema are limited.

  14. Reforming Long-Term Care Funding in Alberta.

    Science.gov (United States)

    Crump, R Trafford; Repin, Nadya; Sutherland, Jason M

    2015-01-01

    Like many provinces across Canada, Alberta is facing growing demand for long-term care. Issues with the mixed funding model used to pay long-term care providers had Alberta Health Services concerned that it was not efficiently meeting the demand for long-term care. Consequently, in 2010, Alberta Health Services introduced the patient/care-based funding (PCBF) model. PCBF is similar to activity-based funding in that it directly ties the complexity and care needs of long-term care residents to the payment received by long-term care providers. This review describes PCBF and discusses some of its strengths and weaknesses. In doing so, this review is intended to inform other provinces faced with similar long-term care challenges and contemplating their own funding reforms.

  15. A cost of long-term memory in Drosophila

    OpenAIRE

    Mery, Frederic; Kawecki, Tadeusz J.

    2005-01-01

    Two distinct forms of consolidated associative memory are known in Drosophila: long-term memory and so-called anesthesia-resistant memory. Long-term memory is more stable, but unlike anesthesia-resistant memory, its formation requires protein synthesis. We show that flies induced to form long-term memory become more susceptible to extreme stress (such as desiccation). In contrast, induction of anesthesia-resistant memory had no detectable effect on desiccation resistance. This finding may hel...

  16. Private long-term care insurance and state tax incentives.

    Science.gov (United States)

    Stevenson, David G; Frank, Richard G; Tau, Jocelyn

    2009-01-01

    To increase the role of private insurance in financing long-term care, tax incentives for long-term care insurance have been implemented at both the federal and state levels. To date, there has been surprisingly little study of these initiatives. Using a panel of national data, we find that market take-up for long-term care insurance increased over the last decade, but state tax incentives were responsible for only a small portion of this growth. Ultimately, the modest ability of state tax incentives to lower premiums implies that they should be viewed as a small piece of the long-term care financing puzzle.

  17. [Reproductive options for people living with HIV: 2013 guidelines from the French expert working group].

    Science.gov (United States)

    Mandelbrot, L; Berrebi, A; Rouzioux, C; Partisani, M; Faucher, P; Tubiana, R; Matheron, S; Bujan, L; Morlat, P

    2014-01-01

    The desire for children is a legitimate aspiration that should be part of multidisciplinary care for all men, women or couples living with HIV. The use of effective antiretroviral therapy has revolutionized the prevention of sexual, as well as mother-to-child HIV transmission. When the HIV plasma viral load is undetectable on long-term antiretroviral therapy, the risk of mother-to-child transmission is <1% and the risk of heterosexual HIV transmission without condom use in a stable relationship is very low (estimated at less than 1/10,000) in the absence of inflammation of the genital tract. In a man with a long-term undetectable viral load, viral shedding in semen is uncommon, but may occur persistently or intermittently. The same appears true of viral shedding in the vaginal tract of women. Reproductive options are: natural conception, self-insemination when the woman is HIV-infected, assisted reproduction. Natural conception is now considered to be an acceptable option when the conditions are met, after exploring four aspects: (1) virological (viral load undetectable sustained for at least 6 months on therapy), (2) genital (absence of genital infections or lesions), (3) fertility (after appropriate evaluation) and (4) detecting the ovulation period to limit intercourse without condoms. Assisted reproduction has two objectives in the context of HIV, to allow the couple to conceive without abandoning condom use and/or to treat infertility. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  18. A new image for long-term care.

    Science.gov (United States)

    Wager, Richard; Creelman, William

    2004-04-01

    To counter widely held negative images of long-term care, managers in the industry should implement quality-improvement initiatives that include six key strategies: Manage the expectations of residents and their families. Address customers' concerns early. Build long-term customer satisfaction. Allocate resources to achieve exceptional outcomes in key areas. Respond to adverse events with compassion. Reinforce the facility's credibility.

  19. Setting the stage for long-term reproductive health.

    Science.gov (United States)

    Payne, Craig A; Vander Ley, Brian; Poock, Scott E

    2013-11-01

    This article discusses some of the aspects of heifer development that contribute to long-term health and productivity, such as disease prevention and control. Nutrition is also an important component of long-term health, and body condition score is discussed as a way to determine whether the nutrient demands of heifers are being met. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Long-term effects of a preoperative smoking cessation programme

    DEFF Research Database (Denmark)

    Villebro, Nete Munk; Pedersen, Tom; Møller, Ann M

    2008-01-01

    Preoperative smoking intervention programmes reduce post-operative complications in smokers. Little is known about the long-term effect upon smoking cessation.......Preoperative smoking intervention programmes reduce post-operative complications in smokers. Little is known about the long-term effect upon smoking cessation....

  1. Pediatric polytrauma : Short-term and long-term outcomes

    NARCIS (Netherlands)

    vanderSluis, CK; Kingma, J; Eisma, WH; tenDuis, HJ

    Objective: To assess the short-term and long-term outcomes of pediatric polytrauma patients and to analyze the extent to which short-term outcomes can predict long-term outcomes. Materials and Methods: Ail pediatric polytrauma patients (Injury Severity Score of greater than or equal to 16, less than

  2. Inflammatory markers in relation to long-term air pollution

    NARCIS (Netherlands)

    Mostafavi Montazeri, Nahid|info:eu-repo/dai/nl/375290575; Vlaanderen, Jelle|info:eu-repo/dai/nl/31403160X; Chadeau-Hyam, Marc; Beelen, Rob|info:eu-repo/dai/nl/30483100X; Modig, Lars; Palli, Domenico; Bergdahl, Ingvar A; Vineis, Paolo; Hoek, Gerard|info:eu-repo/dai/nl/069553475; Kyrtopoulos, Soterios Α; Vermeulen, Roel|info:eu-repo/dai/nl/216532620

    Long-term exposure to ambient air pollution can lead to chronic health effects such as cancer, cardiovascular and respiratory disease. Systemic inflammation has been hypothesized as a putative biological mechanism contributing to these adverse health effects. We evaluated the effect of long-term

  3. Factors associated with long-term mortality in acute pancreatitis

    DEFF Research Database (Denmark)

    Nøjgaard, Camilla; Matzen, Peter; Bendtsen, Flemming

    2011-01-01

    Knowledge of the long-term prognosis of acute pancreatitis (AP) is limited. The aims were to investigate: (1) prognostic factors associated with long-term mortality in patients with AP; (2) whether or not the level of serum (S-)amylase at admission had an impact on the prognosis; (3) causes...

  4. Sacrococcygeal teratoma: Clinical characteristics and long-term ...

    African Journals Online (AJOL)

    Background/Purpose : The excision of sacrococcygeal teratoma (SCT) may be associated with significant long-term morbidity for the child. We reviewed our experience with SCT in a tertiary health care facility in a developing country with particular interest on the long-term sequelae. Methods : Between January 1990 and ...

  5. Albumin: Creatinine Ratio during long term Diabetes Mellitus in the ...

    African Journals Online (AJOL)

    Albumin: Creatinine Ratio during long term Diabetes Mellitus in the Assessment of early Nephropathy in Sudanese Population. ... Further studies with 24 hour urine sample are recommended for assessment of Microalbuminuria in long term Diabetic patients, provided that the patients are on a normal diet with regular ...

  6. Developmental Dyslexia and Explicit Long-Term Memory

    Science.gov (United States)

    Menghini, Deny; Carlesimo, Giovanni Augusto; Marotta, Luigi; Finzi, Alessandra; Vicari, Stefano

    2010-01-01

    The reduced verbal long-term memory capacities often reported in dyslexics are generally interpreted as a consequence of their deficit in phonological coding. The present study was aimed at evaluating whether the learning deficit exhibited by dyslexics was restricted only to the verbal component of the long-term memory abilities or also involved…

  7. Long term physical and chemical stability of polyelectrolyte multilayer membranes

    NARCIS (Netherlands)

    de Grooth, Joris; Haakmeester, Brian; Wever, Carlos; Potreck, Jens; de Vos, Wiebe Matthijs; Nijmeijer, Dorothea C.

    2015-01-01

    This work presents a detailed investigation into the long term stability of polyelectrolyte multilayer (PEM) modified membranes, a key factor for the application of these membranes in water purification processes. Although PEM modified membranes have been frequently investigated, their long term

  8. Long-term hearing preservation in vestibular schwannoma

    DEFF Research Database (Denmark)

    Stangerup, Sven-Eric; Thomsen, Jens; Tos, Mirko

    2010-01-01

    The aim of the present study was to evaluate the long-term hearing during "wait and scan" management of vestibular schwannomas.......The aim of the present study was to evaluate the long-term hearing during "wait and scan" management of vestibular schwannomas....

  9. Quantification of long term emission potential from landfills

    NARCIS (Netherlands)

    Heimovaara, T.J.

    2011-01-01

    Novel approaches for the after-care of Municipal Solid Waste (MSW) landfills are based on technological measures to reduce the long term emission potential in a short time period. Biological degradation in landfills is a means to significantly reduce the long term emission potential. Leachate

  10. Long-term effects of childbirth in MS

    NARCIS (Netherlands)

    D'hooghe, M.B.; Nagels, G.; Uitdehaag, B.M.J.

    2010-01-01

    Background: The uncertainty about long-term effects of childbirth presents MS patients with dilemmas. Methods: Based on clinical data of 330 female MS patients, the long-term effects of childbirth were analysed, using a cross-sectional study design. Four groups of patients were distinguished: (1)

  11. Long-Term Orientation and Educational Performance. Working Paper 174

    Science.gov (United States)

    Figlio, David; Giuliano, Paola; Özek, Umut; Sapienza, Paola

    2017-01-01

    We use remarkable population-level administrative education and birth records from Florida to study the role of Long-Term Orientation on the educational attainment of immigrant students living in the US. Controlling for the quality of schools and individual characteristics, students from countries with long-term oriented attitudes perform better…

  12. Long-Term Dynamics of Autonomous Fractional Differential Equations

    Science.gov (United States)

    Liu, Tao; Xu, Wei; Xu, Yong; Han, Qun

    This paper aims to investigate long-term dynamic behaviors of autonomous fractional differential equations with effective numerical method. The long-term dynamic behaviors predict where systems are heading after long-term evolution. We make some modification and transplant cell mapping methods to autonomous fractional differential equations. The mapping time duration of cell mapping is enlarged to deal with the long memory effect. Three illustrative examples, i.e. fractional Lotka-Volterra equation, fractional van der Pol oscillator and fractional Duffing equation, are studied with our revised generalized cell mapping method. We obtain long-term dynamics, such as attractors, basins of attraction, and saddles. Compared with some existing stability and numerical results, the validity of our method is verified. Furthermore, we find that the fractional order has its effect on the long-term dynamics of autonomous fractional differential equations.

  13. Experimental Researches on Long-Term Strength of Granite Gneiss

    Directory of Open Access Journals (Sweden)

    Lin Liu

    2015-01-01

    Full Text Available It is important to confirm the long-term strength of rock materials for the purpose of evaluating the long-term stability of rock engineering. In this study, a series of triaxial creep tests were conducted on granite gneiss under different pore pressures. Based on the test data, we proposed two new quantitative methods, tangent method and intersection method, to confirm the long-term strength of rock. Meanwhile, the isochronous stress-strain curve method was adopted to make sure of the accuracy and operability of the two new methods. It is concluded that the new methods are suitable for the study of the long-term strength of rock. The effect of pore pressure on the long-term strength of rock in triaxial creep tests is also discussed.

  14. Long-Term Memory Performance in Adult ADHD.

    Science.gov (United States)

    Skodzik, Timo; Holling, Heinz; Pedersen, Anya

    2017-02-01

    Memory problems are a frequently reported symptom in adult ADHD, and it is well-documented that adults with ADHD perform poorly on long-term memory tests. However, the cause of this effect is still controversial. The present meta-analysis examined underlying mechanisms that may lead to long-term memory impairments in adult ADHD. We performed separate meta-analyses of measures of memory acquisition and long-term memory using both verbal and visual memory tests. In addition, the influence of potential moderator variables was examined. Adults with ADHD performed significantly worse than controls on verbal but not on visual long-term memory and memory acquisition subtests. The long-term memory deficit was strongly statistically related to the memory acquisition deficit. In contrast, no retrieval problems were observable. Our results suggest that memory deficits in adult ADHD reflect a learning deficit induced at the stage of encoding. Implications for clinical and research settings are presented.

  15. The Womanly World of Long Term Care: The Plight of the Long Term Care Worker. Gray Paper.

    Science.gov (United States)

    Older Women's League, Washington, DC.

    Long-term care workers (those who are paid to provide custodial care for long-term patients in nursing homes or at home) must care for a growing number of increasingly disabled or dependent persons. They are working for agencies and institutions under growing pressure to increase productivity. They face new training and competency requirements,…

  16. Differences in Virological and Immunological Risk Factors for Non-Hodgkin and Hodgkin Lymphoma

    DEFF Research Database (Denmark)

    Shepherd, Leah; Ryom, Lene; Law, Matthew

    2018-01-01

    Background: Non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL) are increased in populations with immune dysfunction, including people living with HIV; however, there is little evidence for to what degree immunological and virological factors differently affect NHL and HL risk. Methods: Data from...... the Data Collection on Adverse events of Anti-HIV Drugs Study cohort were analyzed to identify independent risk factors for NHL and HL using hazard ratios (HRs), focusing on current and cumulative area under the curve (AUC) measures of immunological and virological status. Variables with different...

  17. Audit of long-term and short-term liabilities

    Directory of Open Access Journals (Sweden)

    Korinko M.D.

    2017-03-01

    Full Text Available The article determines the importance of long-term and short-term liabilities for the management of financial and material resources of an enterprise. It reviews the aim, objects and information generators for realization of audit of short-term and long-term obligations. The organizing and methodical providing of audit of long-term and short-term liabilities of an enterprise are generalized. The authors distinguish the stages of realization of audit of long-term and short-term liabilities, the aim of audit on each of the presented stages, and recommend methodical techniques. It is fixed that it is necessary to conduct the estimation of the systems of internal control and record-keeping of an enterprise by implementation of public accountant procedures for determination of volume and maintenance of selection realization. After estimating the indicated systems, a public accountant determines the methodology for realization of public accountant verification of long-term and short-term liabilities. The analytical procedures that public accountants are expedient to use for realization of audit of short-term and long-term obligations are determined. The authors suggest the classification of the educed defects on the results of the conducted public accountant verification of short-term and long-term obligations.

  18. Modeling long-term dynamics of electricity markets

    International Nuclear Information System (INIS)

    Olsina, Fernando; Garces, Francisco; Haubrich, H.-J.

    2006-01-01

    In the last decade, many countries have restructured their electricity industries by introducing competition in their power generation sectors. Although some restructuring has been regarded as successful, the short experience accumulated with liberalized power markets does not allow making any founded assertion about their long-term behavior. Long-term prices and long-term supply reliability are now center of interest. This concerns firms considering investments in generation capacity and regulatory authorities interested in assuring the long-term supply adequacy and the stability of power markets. In order to gain significant insight into the long-term behavior of liberalized power markets, in this paper, a simulation model based on system dynamics is proposed and the underlying mathematical formulations extensively discussed. Unlike classical market models based on the assumption that market outcomes replicate the results of a centrally made optimization, the approach presented here focuses on replicating the system structure of power markets and the logic of relationships among system components in order to derive its dynamical response. The simulations suggest that there might be serious problems to adjust early enough the generation capacity necessary to maintain stable reserve margins, and consequently, stable long-term price levels. Because of feedback loops embedded in the structure of power markets and the existence of some time lags, the long-term market development might exhibit a quite volatile behavior. By varying some exogenous inputs, a sensitivity analysis is carried out to assess the influence of these factors on the long-run market dynamics

  19. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial.

    Science.gov (United States)

    Orkin, Chloe; Molina, Jean-Michel; Negredo, Eugenia; Arribas, José R; Gathe, Joseph; Eron, Joseph J; Van Landuyt, Erika; Lathouwers, Erkki; Hufkens, Veerle; Petrovic, Romana; Vanveggel, Simon; Opsomer, Magda

    2018-01-01

    Simplified regimens with reduced pill burden and fewer side-effects are desirable for people living with HIV. We investigated the efficacy and safety of switching to a single-tablet regimen of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide versus continuing a regimen of boosted protease inhibitor, emtricitabine, and tenofovir disoproxil fumarate. EMERALD was a phase-3, randomised, active-controlled, open-label, international, multicentre trial, done at 106 sites across nine countries in North America and Europe. HIV-1-infected adults were eligible to participate if they were treatment-experienced and virologically suppressed (viral load <50 copies per mL for ≥2 months; one viral load of 50-200 copies per mL was allowed within 12 months before screening), and patients with a history of virological failure on non-darunavir regimens were allowed. Randomisation was by computer-generated interactive web-response system and stratified by boosted protease inhibitor use at baseline. Patients were randomly assigned (2:1) to switch to the open-label study regimen or continue the control regimen. The study regimen consisted of a fixed-dose tablet containing darunavir 800 mg, cobicistat 150 mg, emtricitabine 200 mg, and tenofovir alafenamide 10 mg, which was taken once per day for 48 weeks. The primary outcome was the proportion of participants with virological rebound (confirmed viral load ≥50 copies per mL or premature discontinuations, with last viral load ≥50 copies per mL) cumulative through week 48; we tested non-inferiority (4% margin) of the study regimen versus the control regimen in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT02269917. The study began on April 1, 2015, and the cutoff date for the week 48 primary analysis was Feb 24, 2017. Of 1141 patients (763 in the study group and 378 in the control group), 664 (58%) had previously received five or more antiretrovirals, including screening

  20. Long-Term Resource Adequacy, Long-Term Flexibility Requirements, and Revenue Sufficiency

    Energy Technology Data Exchange (ETDEWEB)

    Milligan, Michael [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Bloom, Aaron P [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Townsend, Aaron [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Ela, Erik [Electric Power Research Institute; Botterud, Audun [Argonne National Laboratory; Levin, Todd [Argonne National Laboratory

    2018-02-15

    Variable generation (VG) can reduce market prices over time and also the energy that other suppliers can sell in the market. The suppliers that are needed to provide capacity and flexibility to meet the long-term reliability requirements may, therefore, earn less revenue. This chapter discusses the topics of resource adequacy and revenue sufficiency - that is, determining and acquiring the quantity of capacity that will be needed at some future date and ensuring that those suppliers that offer the capacity receive sufficient revenue to recover their costs. The focus is on the investment time horizon and the installation of sufficient generation capability. First, the chapter discusses resource adequacy, including newer methods of determining adequacy metrics. The chapter then focuses on revenue sufficiency and how suppliers have sufficient opportunity to recover their total costs. The chapter closes with a description of the mechanisms traditionally adopted by electricity markets to mitigate the issues of resource adequacy and revenue sufficiency and discusses the most recent market design changes to address these issues.

  1. Long-Term Stewardship Baseline Report and Transition Guidance

    Energy Technology Data Exchange (ETDEWEB)

    Kristofferson, Keith

    2001-11-01

    Long-term stewardship consists of those actions necessary to maintain and demonstrate continued protection of human health and the environment after facility cleanup is complete. As the Department of Energy’s (DOE) lead laboratory for environmental management programs, the Idaho National Engineering and Environmental Laboratory (INEEL) administers DOE’s long-term stewardship science and technology efforts. The INEEL provides DOE with technical, and scientific expertise needed to oversee its long-term environmental management obligations complexwide. Long-term stewardship is administered and overseen by the Environmental Management Office of Science and Technology. The INEEL Long-Term Stewardship Program is currently developing the management structures and plans to complete INEEL-specific, long-term stewardship obligations. This guidance document (1) assists in ensuring that the program leads transition planning for the INEEL with respect to facility and site areas and (2) describes the classes and types of criteria and data required to initiate transition for areas and sites where the facility mission has ended and cleanup is complete. Additionally, this document summarizes current information on INEEL facilities, structures, and release sites likely to enter long-term stewardship at the completion of DOE’s cleanup mission. This document is not intended to function as a discrete checklist or local procedure to determine readiness to transition. It is an overarching document meant as guidance in implementing specific transition procedures. Several documents formed the foundation upon which this guidance was developed. Principal among these documents was the Long-Term Stewardship Draft Technical Baseline; A Report to Congress on Long-Term Stewardship, Volumes I and II; Infrastructure Long-Range Plan; Comprehensive Facility Land Use Plan; INEEL End-State Plan; and INEEL Institutional Plan.

  2. The long-term power purchase: Recovery of capacity costs

    International Nuclear Information System (INIS)

    Cross, P.S.

    1990-01-01

    As electric utilities increase their reliance on the long-term power purchase as an alternative to utility-owned generation, the appropriate rate treatment of the costs established in the purchase agreement assumes growing importance. In the November 9, 1989, issue, the authors examined the recent trend among state regulators to treat the long-term purchase in a manner similar to the addition by a utility of a new plant, including a full-scale prudence review. This installment will review recent rulings on the related issue of rate recovery of long-term capacity costs through the fuel cost adjustment clause

  3. Space ventures and society long-term perspectives

    Science.gov (United States)

    Brown, W. M.

    1985-01-01

    A futuristic evaluation of mankind's potential long term future in space is presented. Progress in space will not be inhibited by shortages of the Earth's physical resources, since long term economic growth will be focused on ways to constrain industrial productivity by changing social values, management styles, or government competence. Future technological progress is likely to accelerate with an emphasis on international cooperation, making possible such large joint projects as lunar colonies or space stations on Mars. The long term future in space looks exceedingly bright even in relatively pessimistic scenarios. The principal driving forces will be technological progress, commercial and public-oriented satellites, space industrialization, space travel, and eventually space colonization.

  4. Long-term care financing through Federal tax incentives.

    Science.gov (United States)

    Moran, D W; Weingart, J M

    1988-12-01

    Congress and the Administration are currently exploring various methods of promoting access to long-term care. In this article, an inventory of recent legislative proposals for using the Federal tax code to expand access to long-term care services is provided. Proposals are arrayed along a functional typology that includes tax mechanisms to encourage accumulation of funds, promote purchase of long-term care insurance, or induce the diversion of funds accumulated for another purpose (such as individual retirement accounts). The proposals are evaluated against the public policy objective of encouraging risk pooling to minimize social cost.

  5. Evaluation of long term leaching of borosilicate glasses

    International Nuclear Information System (INIS)

    Lanza, F.; Parnisari, E.

    1978-01-01

    For the evaluation of long term hazard of glass, data on long term glass leaching are needed. Moreover for long term leaching a model of homogeneous dissolution seems reasonable and ask for confirmation. Tests were performed at 30 0 , 80 0 , 100 0 , using an apparatus of the Soxhlet type, to 3.600 hours. Results were obtained as a weight loss and analysed following a relation with time composed by a parabolic and a linear part. Analysis of the surface layer using energy dispersion X ray spectrometry were performed. A critical analysis of the results and of the apparatus is presented

  6. Managerial Long-Term Responsibility in Family-Controlled Firms

    Directory of Open Access Journals (Sweden)

    Dietmar Sternad

    2013-01-01

    Full Text Available Evidence suggests that long-term orientation (LTO as a dominantstrategic logic contributes to the sustainable performance offamily-controlled firms (FCFS. Combining a review of the literatureon lto with stewardship theory and upper echelons theoryreasoning, this article presents a typology of managerial responsibilityand introduces the concept of long-term responsibility as amanagerial characteristic constituting a major driving force behindcreating lto. The antecedents of long-term responsibilityunder family firm-specific conditions (stemming from the familysystem, the governance system, and family-firm managers’ personalcharacteristics are also identified and presented in an integratedmodel. The paper contributes to a more comprehensiveunderstanding of intertemporal choice in fcfs and explains whythey tend to be more long-term oriented than other types of firms.

  7. Long-term bridge performance high priority bridge performance issues.

    Science.gov (United States)

    2014-10-01

    Bridge performance is a multifaceted issue involving performance of materials and protective systems, : performance of individual components of the bridge, and performance of the structural system as a whole. The : Long-Term Bridge Performance (LTBP)...

  8. Long-Term Visual Prognosis of Peripheral Multifocal Chorioretinitis

    NARCIS (Netherlands)

    Ossewaarde-van Norel, J; ten Dam-van Loon, NH; de Boer, JH; Rothova, A.

    2015-01-01

    Purpose To report on the clinical manifestations, complications, and long-term visual prognosis of patients with peripheral multifocal chorioretinitis and to search for predictors for a lower visual outcome. Design Retrospective consecutive observational case series. Methods setting: Institutional.

  9. In search of the elusive long-term price

    International Nuclear Information System (INIS)

    Connor, M.J.; Combs, J.

    1989-01-01

    The Uranium Institute, WNFM, and past USCEA sessions described and compared existing price reporting systems. The McGraw-Hill conference led to a rather heated discussion as to the propriety of spot prices having the influence they do on amounts paid in long-term contracts. The Ux representative proposed a future's market as a way that producers could hedge against some of the uncertainty of volatile spot market. In discussing the search for the elusive long-term price, there are two interrelated issues. The first is obvious-the search for a starting or initializing price that is representative of recently-signed or pending long-term contracts. The second is less obvious, but perhaps more important-the search for a successful mechanism for determining later delivery values in long-term contracts. This paper addresses the question of pricing mechanisms first

  10. Long-Term Stewardship Science and Technology Requirements

    International Nuclear Information System (INIS)

    McDonald, J.K.; Nickelson, R.A.

    2002-01-01

    To ensure technology developed for long-term stewardship will meet existing requirements, a review of requirements was performed. In addition to identifying existing science and technology related requirements, gaps and conflicts of requirements were identified

  11. Advancing an ethical framework for long-term care.

    Science.gov (United States)

    Carter, Mary Whelan

    2002-02-01

    This article represents an effort to formulate an ethical framework for long-term care with the explicit purpose of providing a catalyst to promote further discourse and expand consideration of what an ethic of long-term care might entail. Grounding the discussion, an introduction to traditional ethical philosophy is presented, focusing mainly on the fundamentals of deontological and teleological ethical theories. Attention then shifts to a review of the more frequently cited principles found in the long-term care ethics literature, followed by a critique of the current reliance upon principlism to resolve ethical dilemmas in long-term care. In response to this criticism, an agent-driven ethical framework stressing dignity and respect for personhood, drawn from the philosophy of Immanuel Kant, is advanced.

  12. Vulnerable long-term psychiatric in- patients need screening for ...

    African Journals Online (AJOL)

    as prominent medical issues in long-term care and provide guidelines for their ..... described in the literature.7,28 These patients might benefit from a renewed emphasis on ..... costs associated with marijuana comorbidity. Drug & Alcohol.

  13. Long-term performance potential of concentrated photovoltaic (CPV) systems

    KAUST Repository

    Burhan, Muhammad; Shahzad, Muhammad Wakil; Ng, Kim Choon

    2017-01-01

    estimation of a large PV field, the long term performance as electrical output is a more rational approach over the conventional testing methods, such as at Standard Testing Conditions (STC) and at the Nominal Operating Cell Temperature (NOCT) available

  14. Strategies to meet the need for long-term data.

    Science.gov (United States)

    Chalmers, John; Woodward, Mark; Borghi, Claudio; Manolis, Athanasios; Mancia, Giuseppe

    2016-08-01

    Chronic diseases afflict patients for many years, often to the end of life, and there is increasing need for estimating lifelong risk and for evaluating the effects of treatment in the long term. Yet recommendations for lifelong treatment are most frequently based on findings from randomized clinical trials lasting only a few years. There is therefore a clear need for much longer term data, and here we present the advantages and disadvantages of many strategies, including the use of long-term posttrial follow-up, of long-term prospective cohort studies, registry databases, and of administrative databases. We also emphasize the need for long-term cost-effectiveness studies. One of the most promising strategies comes from linkage of data gathered through the ever-expanding pool of administrative databases worldwide with data from other sources, including randomized trials and the many forms of observational study.

  15. Long-Term Ecological Monitoring Field Sampling Plan for 2007

    International Nuclear Information System (INIS)

    T. Haney R. VanHorn

    2007-01-01

    This field sampling plan describes the field investigations planned for the Long-Term Ecological Monitoring Project at the Idaho National Laboratory Site in 2007. This plan and the Quality Assurance Project Plan for Waste Area Groups 1, 2, 3, 4, 5, 6, 7, 10, and Removal Actions constitute the sampling and analysis plan supporting long-term ecological monitoring sampling in 2007. The data collected under this plan will become part of the long-term ecological monitoring data set that is being collected annually. The data will be used to determine the requirements for the subsequent long-term ecological monitoring. This plan guides the 2007 investigations, including sampling, quality assurance, quality control, analytical procedures, and data management. As such, this plan will help to ensure that the resulting monitoring data will be scientifically valid, defensible, and of known and acceptable quality

  16. Long-term memory, sleep, and the spacing effect.

    Science.gov (United States)

    Bell, Matthew C; Kawadri, Nader; Simone, Patricia M; Wiseheart, Melody

    2014-01-01

    Many studies have shown that memory is enhanced when study sessions are spaced apart rather than massed. This spacing effect has been shown to have a lasting benefit to long-term memory when the study phase session follows the encoding session by 24 hours. Using a spacing paradigm we examined the impact of sleep and spacing gaps on long-term declarative memory for Swahili-English word pairs by including four spacing delay gaps (massed, 12 hours same-day, 12 hours overnight, and 24 hours). Results showed that a 12-hour spacing gap that includes sleep promotes long-term memory retention similar to the 24-hour gap. The findings support the importance of sleep to the long-term benefit of the spacing effect.

  17. The Long-Term Retention of Knowledge and Skills

    National Research Council Canada - National Science Library

    Healy, Alice

    1998-01-01

    .... The second class of guidelines concerned ways to optimize the strategies used. We found that in tasks that require deliberate retrieval from memory, training that promotes efficient encoding strategies maximizes long-term retention...

  18. Radiation effects after low dose chronic long-term exposure

    International Nuclear Information System (INIS)

    Fliedner, T.M.; Friesecke, I.

    1997-01-01

    This document approaches the radiation effects after low dose chronic long-term exposure, presenting examples occurred, the pathophysiologic mechanisms for cell system tolerance in elevated radiation fields, and the diagnostic and therapeutic possibilities

  19. Statistical analysis of long term spatial and temporal trends of ...

    Indian Academy of Sciences (India)

    Statistical analysis of long term spatial and temporal trends of temperature ... CGCM3; HadCM3; modified Mann–Kendall test; statistical analysis; Sutlej basin. ... Water Resources Systems Division, National Institute of Hydrology, Roorkee 247 ...

  20. Modelled long term trends of surface ozone over South Africa

    CSIR Research Space (South Africa)

    Naidoo, M

    2011-10-01

    Full Text Available timescale seeks to provide a spatially comprehensive view of trends while also creating a baseline for comparisons with future projections of air quality through the forcing of air quality models with modelled predicted long term meteorology. Previous...

  1. Long-term risks of kidney living donation

    DEFF Research Database (Denmark)

    Maggiore, Umberto; Budde, Klemens; Heemann, Uwe

    2017-01-01

    Two recent matched cohort studies from the USA and Norway published in 2014 have raised some concerns related to the long-term safety of kidney living donation. Further studies on the long-term risks of living donation have since been published. In this position paper, Developing Education Science...... and Care for Renal Transplantation in European States (DESCARTES) board members critically review the literature in an effort to summarize the current knowledge concerning long-term risks of kidney living donation to help physicians for decision-making purposes and for providing information...... to the prospective live donors. Long-term risk of end-stage renal disease (ESRD) can be partially foreseen by trying to identify donors at risk of developing ‘de novo’ kidney diseases during life post-donation and by predicting lifetime ESRD risk. However, lifetime risk may be difficult to assess in young donors...

  2. Long-Term Ecological Monitoring Field Sampling Plan for 2007

    Energy Technology Data Exchange (ETDEWEB)

    T. Haney

    2007-07-31

    This field sampling plan describes the field investigations planned for the Long-Term Ecological Monitoring Project at the Idaho National Laboratory Site in 2007. This plan and the Quality Assurance Project Plan for Waste Area Groups 1, 2, 3, 4, 5, 6, 7, 10, and Removal Actions constitute the sampling and analysis plan supporting long-term ecological monitoring sampling in 2007. The data collected under this plan will become part of the long-term ecological monitoring data set that is being collected annually. The data will be used t determine the requirements for the subsequent long-term ecological monitoring. This plan guides the 2007 investigations, including sampling, quality assurance, quality control, analytical procedures, and data management. As such, this plan will help to ensure that the resulting monitoring data will be scientifically valid, defensible, and of known and acceptable quality.

  3. Long-term Consequences of Childhood ADHD on Criminal Activities*

    OpenAIRE

    Fletcher, Jason; Wolfe, Barbara

    2009-01-01

    The question of whether childhood mental illness has long term consequences in terms of criminal behavior has been little studied, yet it could have major consequences for both the individual and society more generally. In this paper, we focus on Attention-Deficit/Hyperactivity Disorder (ADHD), one of the most prevalent mental conditions in school-age children, to examine the long-term effects of childhood mental illness on criminal activities, controlling for a rich set of individual, family...

  4. Long-term patient survival in ANCA-associated vasculitis

    DEFF Research Database (Denmark)

    Flossmann, Oliver; Berden, Annelies; de Groot, Kirsten

    2011-01-01

    Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain.......Wegener's granulomatosis and microscopic polyangiitis are antineutrophil cytoplasm antibodies (ANCA)-associated vasculitides with significant morbidity and mortality. The long-term survival of patients with ANCA associated vasculitis treated with current regimens is uncertain....

  5. Aspects of long-term variability in sun and stars

    International Nuclear Information System (INIS)

    Skumanich, A.; Eddy, J.A.

    1981-01-01

    Evidence of long-term solar variability is reviewed, including historical data and the tree-ring record of radiocarbon. Epochs of suppressed activity like the Maunder Minimum are shown to be frequent occurences of the last several thousand years, but without no obvious period of recurrence. Weak evidence exists for the 11-year cycle as early as Medieval times, although with insufficient accuracy to establish long-term phase stability. (orig.)

  6. Rapid internationalization and long-term performance: The knowledge link

    OpenAIRE

    García-García, Raquel; García-Canal, Esteban; Guillén, Mauro F.

    2017-01-01

    Drawing on the knowledge-based view and organizational learning theory, we develop and test a set of hypotheses to provide a first attempt at analyzing the effect of speed of internationalization on long-term performance. Using a panel-data sample of Spanish listed firms (1986-2010), we find that there is an inverted U-shaped relationship between speed of internationalization and long-term performance. We also find that whereas technological knowledge steepens this relationship, the diversity...

  7. Preclinical rodent toxicity studies for long term use of ceftriaxone

    Directory of Open Access Journals (Sweden)

    Elena Ratti

    2015-01-01

    Ceftriaxone showed rapid absorption with half-life values ranging between 1 and 1.5 h. Additionally, there was no evidence of accumulation and a virtually complete elimination by 16 h after the last dose. Overall there were no toxicologically meaningful drug-related animal findings associated with the long-term administration (6 months of ceftriaxone. These results support safety of long-term use of ceftriaxone in human clinical trials.

  8. Long-term outcome of craniopharyngioma in children. A review

    International Nuclear Information System (INIS)

    Tamiya, Takashi; Okada, Masaki; Miyake, Keisuke; Kawai, Nobuyuki

    2011-01-01

    The treatment for pediatric craniopharyngioma remains challenging and controversial. Although this tumor is histologically benign, the treatments include radical surgery, conservative surgery, radiotherapy, intracystic chemotherapy and multimodality approaches. In addition, the long-term functional outcomes including visual function, endocrine function, cognitive function, hypothalamic function, and quality of life are complex and major problems among survivors. In this paper, we reviewed the recent treatments for pediatric craniopharyngioma and the long-term outcomes after treatment in literatures. (author)

  9. Long-term care: a substantive factor in financial planning.

    Science.gov (United States)

    Willis, D A

    2000-01-01

    More than 50 percent of women will enter a nursing home at some point in their lives. About one-third of men living to age 65 will also need nursing home care. Planning for long-term care is even more important since Medicare covers very little of the cost of such care. The Indiana Partnership Plan is one program designed to help fund the long-term care costs while allowing individuals protect other financial assets.

  10. The Myth That Insulating Boards Serves Long-Term Value

    OpenAIRE

    Bebchuk, Lucian Arye

    2013-01-01

    According to an influential view in corporate law writings and debates, pressure from shareholders leads companies to take myopic actions that are costly in the long term, and insulating boards from such pressure serves the long-term interests of companies as well as their shareholders. This board insulation claim has been regularly invoked in a wide range of contexts to support existing or tighter limits on shareholder rights and involvement. This paper subjects this view to a comprehensive ...

  11. Long-Term Prognosis of Ischemic Stroke in Young Adults

    OpenAIRE

    Varona, Jose F.

    2010-01-01

    There is limited information about long-term prognosis of ischemic stroke in young adults. Giving the potentially negative impact in physical, social, and emotional aspects of an ischemic stroke in young people, providing early accurate long-term prognostic information is very important in this clinical setting. Moreover, detection of factors associated with bad outcomes (death, recurrence, moderate-to-severe disability) help physicians in optimizing secondary prevention strategies. The prese...

  12. Long-term stability of sodium caseinate-stabilized nanoemulsions.

    Science.gov (United States)

    Yerramilli, Manispuritha; Ghosh, Supratim

    2017-01-01

    Oil-in-water (5 wt%) nanoemulsions were prepared with different concentration (2.5-10 wt%) of sodium caseinate as a sole emulsifier and their long-term storage stability was investigated for 6 months. Previous studies associated with sodium caseinate looked only into nanoemulsion formation; hence the challenges with long-term stability were not addressed. All nanoemulsions displayed an average droplet size sodium caseinate-stabilized nanoemulsions.

  13. Introduction of long term cycle of reactor operation

    International Nuclear Information System (INIS)

    Aoyati, M.; Tanaka, T.

    2004-01-01

    Introduction of long term cycle of LWR reactor operation at NPP in Japan is considered, and problems of technical, legislative and economical character, increase of power coefficient are discussed. More long term operation period provides decreasing frequency of periodic inspections and reduction of personnel radiation doses. Reliability of fuel, energetic equipment, mechanisms and devices must be taken into account for the decision of technical problems. Consumptions for electric power generation are studied [ru

  14. Long term acroecosystem research in the Southern Plains

    Science.gov (United States)

    Jean L. Steiner; Patrick J. Starks; Jurgen Garbrecht; Daniel Moriasi; Paul Bartholomew; Jim Neel; Kenneth E. Turner; Brian Northup

    2016-01-01

    The Southern Plains (SP) site of the Long Term Agroecosystem Research (LTAR) network is headquartered at the USDA-ARS Grazinglands Research Laboratory (GRL) in El Reno, Oklahoma. The GRL was established in 1948. A long-term watershed and climate research program was established in the Little Washita River Experimental Watershed (LWREW) in 1961 and in the Fort Cobb...

  15. Adverse event reporting in Czech long-term care facilities.

    Science.gov (United States)

    Hěib, Zdenřk; Vychytil, Pavel; Marx, David

    2013-04-01

    To describe adverse event reporting processes in long-term care facilities in the Czech Republic. Prospective cohort study involving a written questionnaire followed by in-person structured interviews with selected respondents. Long-term care facilities located in the Czech Republic. Staff of 111 long-term care facilities (87% of long-term care facilities in the Czech Republic). None. Sixty-three percent of long-term health-care facilities in the Czech Republic have adverse event-reporting processes already established, but these were frequently very immature programs sometimes consisting only of paper recording of incidents. Compared to questionnaire responses, in-person interview responses only partially tended to confirm the results of the written survey. Twenty-one facilities (33%) had at most 1 unconfirmed response, 31 facilities (49%) had 2 or 3 unconfirmed responses and the remaining 11 facilities (17%) had 4 or more unconfirmed responses. In-person interviews suggest that use of a written questionnaire to assess the adverse event-reporting process may have limited validity. Staff of the facilities we studied expressed an understanding of the importance of adverse event reporting and prevention, but interviews also suggested a lack of knowledge necessary for establishing a good institutional reporting system in long-term care.

  16. Changing incentives for long-term gas contracts

    International Nuclear Information System (INIS)

    Bohi, D.R.

    1992-01-01

    There is much concern about the absence of long-term gas contracts with fixed price and quantity conditions, which until recent years was the standard way of doing business in the gas industry. These types of contracts performed a valuable service in the development of the gas industry, and there comparative absence today is sometimes thought to be one reason for the current malaise in the industry. One hears the argument that there must be some kind of 'market failure' that prevents buyers and sellers from entering into these long term arrangements, and recent changes in state and federal regulations are often cited as the cause of the problem. The purpose of the author's remarks is to argue that what is taken as a breakdown in the market may be simply a reaction to a decline in economic incentives to enter into long-term contracts with rigid price and quantity terms. This is, in other words, simply one more aspect of change in the gas business that Frank Heintz referred to in his opening remarks this morning. The author starts by giving a brief description of the motives for engaging in long-term contracts, and then describes how incentives to use long-term contracts have declined for both gas buyers and gas sellers. He concludes that the decline in the use of long-term contracts is not cause for regulatory concern, but a result of the continuing transformation of the gas business to one that more closely resembles other commodity markets

  17. Long-term nitrite inhalant exposure and cancer risk in MSM

    Science.gov (United States)

    Dutta, Anupriya; Uno, Hajime; Holman, Alex; Lorenz, David R.; Wolinsky, Steven M.; Gabuzda, Dana

    2017-01-01

    Objectives: Nitrite inhalants (poppers) are commonly used recreational drugs among MSM and were previously associated with elevated rates of high-risk sexual behavior, HIV and human herpesvirus type 8 (HHV-8) seroconversion, and transient immunosuppressive effects in experimental models. Whether long-term popper use is associated with cancer risk among MSM in the HAART era is unclear. Design: Prospective cohort study of cancer risk in 3223 HIV-infected and uninfected MSM in the Multicenter AIDS Cohort Study from 1996–2010. Methods: Poisson regression models were used to examine the association between heavy popper use (defined as daily or weekly use for at least 1 year) and risk of individual cancers or composite category of virus-associated cancers. Results: Among all participants, heavy popper use was not associated with increased risk of any individual cancers. Among HIV-uninfected men aged 50–70, heavy popper use was associated with increased risk of virus-associated cancer with causes linked to human papillomavirus, HHV-8, and Epstein–Barr virus in models adjusted for demographics, number of sexual partners, immunological parameters (CD4+ cell counts or CD4+/CD8+ ratios), and hepatitis B and C viruses [incidence rate ratio (IRR), 95% confidence interval (CI) 3.24, 1.05–9.96], or sexually transmitted infections (IRR 3.03, 95% CI, 1.01–9.09), as was cumulative use over a 5-year period (IRR 1.012, 95% CI 1.003–1.021; P = 0.007). There was no significant association between heavy popper use and virus-associated cancer in HIV-infected men. Conclusions: Long-term heavy popper use is associated with elevated risk of some virus-associated cancers with causes related to human papillomavirus, HHV-8, and Epstein–Barr virus infections in older HIV-uninfected MSM independent of sexual behavior and immunological parameters. PMID:28441176

  18. Benchmarking HIV health care: from individual patient care to health care evaluation. An example from the EuroSIDA study

    Directory of Open Access Journals (Sweden)

    Podlekareva Daria N

    2012-09-01

    Full Text Available Abstract Background State-of-the-art care involving the utilisation of multiple health care interventions is the basis for an optimal long-term clinical prognosis for HIV-patients. We evaluated health care for HIV patients based on four key indicators. Methods Four indicators of health care were assessed: Compliance with current guidelines on initiation of: 1 combination antiretroviral therapy (cART; 2 chemoprophylaxis; 3 frequency of laboratory monitoring; and 4 virological response to cART (proportion of patients with HIV-RNA 90% of time on cART. Results 7097 EuroSIDA patients were included from Northern (n = 923, Southern (n = 1059, West Central (n = 1290 East Central (n = 1366, Eastern (n = 1964 Europe, and Argentina (n = 495. Patients in Eastern Europe with a CD4 3 were less likely to initiate cART and Pneumocystis jiroveci-chemoprophylaxis compared to patients from all other regions, and less frequently had a laboratory assessment of their disease status. The proportion of patients with virological response was highest in Northern, 89% vs. 84%, 78%, 78%, 61%, 55% in West Central, Southern, East Central Europe, Argentina and Eastern Europe, respectively (p Conclusions This assessment of HIV health care utilization revealed pronounced regional differences in adherence to guidelines and can help to identify gaps and direct target interventions. It may serve as a tool for the assessment and benchmarking of the clinical management of HIV patients in any setting worldwide.

  19. Molecular virology of feline calicivirus.

    Science.gov (United States)

    Pesavento, Patricia A; Chang, Kyeong-Ok; Parker, John S L

    2008-07-01

    Caliciviridae are small, nonenveloped, positive-stranded RNA viruses. Much of our understanding of the molecular biology of the caliciviruses has come from the study of the naturally occurring animal caliciviruses. In particular, many studies have focused on the molecular virology of feline calicivirus (FCV), which reflects its importance as a natural pathogen of cats. FCVs demonstrate a remarkable capacity for high genetic, antigenic, and clinical diversity; "outbreak" vaccine resistant strains occur frequently. This article updates the reader on the current status of clinical behavior and pathogenesis of FCV.

  20. Follow-up on long-term antiretroviral therapy for cats infected with feline immunodeficiency virus.

    Science.gov (United States)

    Medeiros, Sheila de Oliveira; Abreu, Celina Monteiro; Delvecchio, Rodrigo; Ribeiro, Anísia Praxedes; Vasconcelos, Zilton; Brindeiro, Rodrigo de Moraes; Tanuri, Amilcar

    2016-04-01

    Feline immunodeficiency virus (FIV) is a lentivirus that induces AIDS-like disease in cats. Some of the antiretroviral drugs available to treat patients with HIV type 1 are used to treat FIV-infected cats; however, antiretroviral therapy (ART) is not used in cats as a long-term treatment. In this study, the effects of long-term ART were evaluated in domestic cats treated initially with the nucleoside transcriptase reverse inhibitor (NTRI) zidovudine (AZT) over a period ranging from 5-6 years, followed by a regimen of the NTRI lamivudine (3TC) plus AZT over 3 years. Viral load, sequencing of pol (reverse transcriptase [RT]) region and CD4:CD8 lymphocyte ratio were evaluated during and after treatment. Untreated cats were evaluated as a control group. CD4:CD8 ratios were lower, and uncharacterized resistance mutations were found in the RT region in the group of treated cats. A slight increase in viral load was observed in some cats after discontinuing treatment. The data strongly suggest that treated cats were resistant to therapy, and uncharacterized resistance mutations in the RT gene of FIV were selected for by AZT. Few studies have been conducted to evaluate the effect of long-term antiretroviral therapy in cats. To date, resistance mutations have not been described in vivo. © ISFM and AAFP 2015.

  1. Risk assessment for long-term post-accident sequences

    International Nuclear Information System (INIS)

    Ellia-Hervy, A.; Ducamp, F.

    1987-11-01

    Probabilistic risk analysis, currently conducted by the CEA (French Atomic Energy Commission) for the French replicate series of 900 MWe power plants, has identified accident sequences requiring long-term operation of some systems after the initiating event. They have been named long-term sequences. Quantification of probabilities of such sequences cannot rely exclusively on equipment failure-on-demand data: it must also take into account operating failures, the probability of which increase with time. Specific studies have therefore been conducted for a number of plant systems actuated during these long-term sequences. This has required: - Definition of the most realistic equipment utilization strategies based on existing emergency procedures for 900 MWe French plants. - Evaluation of the potential to repair failed equipment, given accessibility, repair time, and specific radiation conditions for the given sequence. - Definition of the event bringing the long-term sequence to an end. - Establishment of an appropriate quantification method, capable of taking into account the evolution of assumptions concerning equipment utilization strategies or repair conditions over time. The accident sequence quantification method based on realistic scenarios has been used in the risk assessment of the initiating event loss of reactor coolant accident occurring at power and at shutdown. Compared with the results obtained from conventional methods, this method redistributes the relative weight of accident sequences and also demonstrates that the long term can be a significant contribution to the probability of core melt

  2. Long-term psychosocial consequences of surgical congenital malformations.

    Science.gov (United States)

    Diseth, Trond H; Emblem, Ragnhild

    2017-10-01

    Surgical congenital malformations often represent years of treatment, large number of hospital stays, treatment procedures, and long-term functional sequels affecting patients' psychosocial functioning. Both functional defects and psychosocial difficulties that occur commonly in childhood may pass through adolescence on to adulthood. This overview presents reports published over the past 3 decades to elucidate the long-term psychosocial consequences of surgical congenital malformations. Literature searches conducted on PubMed database revealed that less than 1% of all the records of surgical congenital malformations described long-term psychosocial consequences, but with diverse findings. This inconsistency may be due to methodological differences or deficiencies; especially in study design, patient sampling, and methods. Most of the studies revealed that the functional deficits may have great impact on patients' mental health, psychosocial functioning, and QoL; both short- and long-term negative consequences. Factors other than functional problems, e.g., repeated anesthesia, multiple hospitalization, traumatic treatment procedures, and parental dysfunctioning, may also predict long-term mental health and psychosocial functioning. Through multidisciplinary approach, pediatric surgeons should also be aware of deficits in emotional and psychosocial functioning. To achieve overall optimal psychosocial functioning, the challenge is to find a compromise between physically optimal treatment procedures and procedures that are not psychologically detrimental. Copyright © 2017. Published by Elsevier Inc.

  3. ERDA's long-term waste management goals and programs

    International Nuclear Information System (INIS)

    Perge, A.F.; Trice, V.G. Jr.; Walton, R.D. Jr.

    1976-01-01

    This paper presents an overview of the ERDA's major program for the long-term waste management of radioactive waste and provides a perspective for symposium participants with regard to the interrelationship of specific components of the program that are discussed in detail in other ERDA-sponsored papers. Needs, goals, and plans are reviewed for ERDA's management of the commercially generated wastes which are expected to be delivered to ERDA in accordance with Federal regulations. At present, ERDA responsibilities include long-term management of commercial-level wastes. Possible future regulations may give ERDA responsibility for the long-term management of commercial low-level solid wastes contaminated with transuranic nuclides. Primary planning goals and programs for the development of terminal storage facilities and waste processing technology to produce acceptable waste forms for long-term management are reviewed for each of the waste types identified above. The status of development programs for the long-term management of airborne radionuclides, which may be required at some time in the future, is also reviewed. (author)

  4. Child maltreatment: pathway to chronic and long-term conditions?

    Science.gov (United States)

    Taylor, Julie; Bradbury-Jones, Caroline; Lazenbatt, Anne; Soliman, Francesca

    2016-09-01

    The manifesto Start Well, Live Better by the UK Faculty of Public Health (Start Well, Live Better-A Manifesto for the Public's Health. London: UK Faculty of Public Health, 2014) sets out 12 compelling priorities for the protection of people's health. The focus of this document is preventative, calling for a comprehensive strategy to target a wide-ranging set of challenges to public health; however, it fails to mention child maltreatment and its negative impact on long-term health outcomes. In this article, we explore the long-term negative consequences of child maltreatment and how these can be conceptually aligned with four different characteristics of long-term health conditions. We suggest that situating child maltreatment within a long-term conditions framework could have significant advantages and implications for practice, policy and research, by strengthening a commitment across disciplines to apply evidence-based principles linked with policy and evaluation and recognizing the chronic effects of maltreatment to concentrate public, professional and government awareness of the extent and impact of the issue. We argue that a public health approach is the most effective way of focusing preventative efforts on the long-term sequelae of child maltreatment and to foster cooperation in promoting children's rights to grow and develop in a safe and caring environment free from violence and abuse. © The Author 2015. Published by Oxford University Press on behalf of Faculty of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Long-Term Retardation of Uranium in the KURT Environment

    International Nuclear Information System (INIS)

    Baik, Min Hoon; Shin, Joo Do; Park, Tae Jin

    2016-01-01

    One of possibilities resolving this issue is to study the migration and retardation processes of radionuclides in the subsurface environments by using naturally occurring radionuclides as analogues of radioactive waste. To date, however, the long-term behavior of radionuclides in a granitic groundwater system is not yet fully understood. The ubiquitous presence of uranium (U) in rocks makes it an ideal natural analogue for studying the behaviors of radionuclides in a deep geological repository for the final disposal of HLW. In this study, long-term retardation behavior of natural uranium was investigated using granite rock samples taken from the KURT (KAERI Underground Research Tunnel), located in Daejeon city. The distribution of uranium and its binding mechanism in granite samples were investigated using the sequential chemical extraction (SCE) technique combined with X-ray diffraction (XRD) and ICP-MS methods. In this study, the long-term retardation of uranium in the KURT environment was investigated using SCE and EPMA techniques combined with ICP-MS and XRD. Results showed that long-term interaction of rock with groundwater can change U species and mineralize dissolved U, which can consequently contribute to the retardation of U in the fractured granitic rock environment. This study will help us to understand the long-term behavior of radionuclides migrating through the fractured granite rock and then enhance the reliability of the safety assessment for a HLW repository

  6. Long-Term Stewardship Program Science and Technology Requirements

    Energy Technology Data Exchange (ETDEWEB)

    Joan McDonald

    2002-09-01

    Many of the United States’ hazardous and radioactively contaminated waste sites will not be sufficiently remediated to allow unrestricted land use because funding and technology limitations preclude cleanup to pristine conditions. This means that after cleanup is completed, the Department of Energy will have long-term stewardship responsibilities to monitor and safeguard more than 100 sites that still contain residual contamination. Long-term stewardship encompasses all physical and institutional controls, institutions, information, and other mechanisms required to protect human health and the environment from the hazards remaining. The Department of Energy Long-Term Stewardship National Program is in the early stages of development, so considerable planning is still required to identify all the specific roles and responsibilities, policies, and activities needed over the next few years to support the program’s mission. The Idaho National Engineering and Environmental Laboratory was tasked with leading the development of Science and Technology within the Long-Term Stewardship National Program. As part of that role, a task was undertaken to identify the existing science and technology related requirements, identify gaps and conflicts that exist, and make recommendations to the Department of Energy for future requirements related to science and technology requirements for long-term stewardship. This work is summarized in this document.

  7. Rates of sustained virological response 12 weeks after the scheduled end of direct-acting antiviral (DAA)-based hepatitis C virus (HCV) therapy from the National German HCV registry: does HIV coinfection impair the response to DAA combination therapy?

    Science.gov (United States)

    Bischoff, J; Mauss, S; Cordes, C; Lutz, T; Scholten, S; Moll, A; Jäger, H; Cornberg, M; Manns, M P; Baumgarten, A; Rockstroh, J K

    2018-04-01

    The European Association for the Study of the Liver (EASL) treatment recommendations for hepatitis C no longer discriminate between HIV/hepatitis C virus (HCV)-coinfected and HCV-monoinfected patients. However, recent data from Spain are questioning these recommendations on the basis of the findings of higher relapse rates and lower cure rates in HIV/HCV-infected subjects. The aim of our study was to compare HCV cure rates in monoinfected and coinfected patients from Germany. Data acquired from the Deutsches Hepatitis C-Registry were analysed. A total of 5657 HCV-monoinfected subjects and 488 HIV/HCV-coinfected patients were included in the study. Rates of sustained virological response 12 weeks after the scheduled end of therapy (SVR12) were collected in both subgroups and in cirrhotic and noncirrhotic patients. HIV/HCV-coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P  350 cells/μL in 63.1% of HIV-positive subjects and 88.7% were on antiretroviral therapy. SVR12 rates were 90.3% (5111 of 5657) in our HCV-monoinfected cohort and 91.2% (445 of 488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657 (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected patients. SVR12 rates did not differ between HCV-monoinfected and HIV/HCV-coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P = 0.864). A treatment duration of 8 weeks did not reduce the percentage of patients with SVR12 in either subgroup (93.7% in both groups). We found high SVR12 rates in monoinfected as well as coinfected individuals. No differences were detected between the two subgroups regardless of whether there was accompanying liver cirrhosis or a shortened treatment duration. © 2018 British HIV Association.

  8. The long-term benefits of director stock ownership

    Directory of Open Access Journals (Sweden)

    Brian Bolton

    2009-11-01

    Full Text Available In October 2009, the United States Treasury Department and Congress considered new regulations requiring executives and directors to receive much of their compensation in the form of long-term stock. One concern with this is that it may have negative consequences by entrenching managers and directors over the long term. This study compares the potential benefits of long-term director ownership with the potential costs of entrenchment. Using the dollar amount of stock owned by independent directors, the results suggest that the incentive effect dominates any costs related to entrenchment: firms with greater stock ownership outperform other firms, regardless of the degree of managerial entrenchment that may be present. The implication for policy-makers is that providing directors with incentives through stock ownership can be a very effective corporate governance mechanism.

  9. Long-term visual associations affect attentional guidance.

    Science.gov (United States)

    Olivers, Christian N L

    2011-06-01

    When observers perform a visual search task, they are assumed to adopt an attentional set for what they are looking for. The present experiment investigates the influence of long-term visual memory associations on this attentional set. On each trial, observers were asked to search a display for a grayscale version of a known traffic sign. On each trial, a distractor sign was drawn in full color. This color could either be related or unrelated to the target sign. Distractors interfered more with search when their color was related (e.g. red when the target was a stop sign), implying that long-term color associations resulted in inadvertent attentional guidance, even though color was irrelevant to the task. The results add to the growing body of evidence that long-term memory representations automatically affect attentional orienting. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Sexuality and physical intimacy in long-term care.

    Science.gov (United States)

    Lichtenberg, Peter A

    2014-01-01

    Sexuality and sexual needs in older adults remains a neglected area of clinical intervention, particularly so in long-term care settings. Because older adults in medical rehabilitation and long-term care beds present with significant frailties, and often significant neurocognitive disorders, it makes it difficult for occupational therapists and other staff to evaluate the capacity of an older adult resident to participate in sexual relationships. The current paper reviews the current literature on sexuality and aging, examines some of the clinical practices and guidelines regarding sexual expression in long-term care, and presents two case examples. A semistructured interview and decision tree is presented to assist therapists in making careful and informed decisions and thereby balancing the needs for protection with the needs for autonomy.

  11. Winning market positioning strategies for long term care facilities.

    Science.gov (United States)

    Higgins, L F; Weinstein, K; Arndt, K

    1997-01-01

    The decision to develop an aggressive marketing strategy for its long term care facility has become a priority for the management of a one-hundred bed facility in the Rocky Mountain West. Financial success and lasting competitiveness require that the facility in question (Deer Haven) establish itself as the preferred provider of long term care for its target market. By performing a marketing communications audit, Deer Haven evaluated its present market position and created a strategy for solidifying and dramatizing this position. After an overview of present conditions in the industry, we offer a seven step process that provides practical guidance for positioning a long term care facility. We conclude by providing an example application.

  12. Long-term properties of bituminized waste products

    International Nuclear Information System (INIS)

    Snellman, M.; Valkiainen, M.

    1985-10-01

    This study is a survey of the factors of importance for the long term behaviour of bituminized ion exchange resins. Phenomena occurring in bituminized waste products affected by the treatment, storage and disposal are identified. Test methods have been developed for characterizing product properties, which are important for the long-term behaviour. The long-term properties of bituminized ion-exchange resins are studied in a repository environment with access of water equilibrated with concrete. In these circumstances the most important properties are related to the interactions of bituminized waste with the surrounding barriers. The most important phenomena are water uptake due to rehydration of the resins and subsequent swelling of the product

  13. Long-term properties of bituminized waste products

    International Nuclear Information System (INIS)

    Snellman, M.; Valkiainen, M.

    1985-10-01

    This study is a survey of the factors of importance for long term behaviour of bituminized ion exchange resins. Phenomena occurring in bituminized waste products affected by the treatment, storage and disposal are identified. Test methods have been developed for characterizing product properties, which are important for the long-term behaviour. The long-term properties of bituminized ion-exchange resins are studied in a repository environment with access of water equilibrated with concrete. In these circumstances the most important properties are ralated to the interactions of bituminized waste with the surrounding barriers. The most important phenomena are water uptake due to rehydration of the resins and subsequent swelling of the product. (author)

  14. On the relationship between short- and long-term memory

    DEFF Research Database (Denmark)

    Sørensen, Thomas Alrik

    James (1890) divided memory into separate stores; primary and secondary – or short-term and long-term memory. The interaction between the two stores often assumes that information initially is represented in volatile short-term store before entering and consolidating in the more durable long-term......, accepted). Counter to popular beliefs this suggest that long-term memory precedes short-term memory and not vice versa....... memory system (e.g. Atkinson & Shiffrin, 1968). Short-term memory seems to provide a surprising processing bottleneck where only a very limited amount of information can be represented at any given moment (Miller, 1956; Cowan, 2001). A number of studies have investigated the nature of this processing...

  15. Ethics and Intimate Sexual Activity in Long-Term Care.

    Science.gov (United States)

    Metzger, Eran

    2017-07-01

    A case is presented in which the staff of a long-term care facility discovers that the husband of a resident with dementia is engaged in sexual activity with her. The case illustrates a dilemma for long-term care facilities that create a home-like environment with a goal of maximizing residents' autonomy while ensuring their safety. An approach to assessing capacity to consent to intimate sexual activity is described, followed by guidelines that nursing homes can implement to support residents who wish to engage in sexual activity. Recommendations are also offered for supporting long-term care staff and family members of residents who are interested in intimate sexual activity. © 2017 American Medical Association. All Rights Reserved.

  16. Marijuana effects on long-term memory assessment and retrieval.

    Science.gov (United States)

    Darley, C F; Tinklenberg, J R; Roth, W T; Vernon, S; Kopell, B S

    1977-05-09

    The ability of 16 college-educated male subjects to recall from long-term memory a series of common facts was tested during intoxication with marijuana extract calibrated to 0.3 mg/kg delta-9-tetrahydrocannabinol and during placebo conditions. The subjects' ability to assess their memory capabilities was then determined by measuring how certain they were about the accuracy of their recall performance and by having them predict their performance on a subsequent recognition test involving the same recall items. Marijuana had no effect on recall or recognition performance. These results do not support the view that marijuana provides access to facts in long-term storage which are inaccessible during non-intoxication. During both marijuana and placebo conditions, subjects could accurately predict their recognition memory performance. Hence, marijuana did not alter the subjects' ability to accurately assess what information resides in long-term memory even though they did not have complete access to that information.

  17. Long-term impact of sales promotion on brand image

    Directory of Open Access Journals (Sweden)

    Danijela Mandić

    2009-12-01

    Full Text Available Sales promotion (SP is an inevitable tool in the marketing communications mix, especially in the FMCG markets, due to pressures such as retailers’ growing demands and increasing competition. This has proven to be an issue for many companies, especially those with a premium brand positioning and those concerned about the impact that SP might have on the long-term image of the company. Despite the fact that literature is replete with research on SP, it seems to be vastly generalized and mostly focused on price reductions. Thus, this paper aims to analyze and discuss the issue of the long-term impact that SP has on companies, especially on premium brands in the FMCG markets. It concludes that, when used properly and strategically, SP may have a positive long-term impact on brands.

  18. Long-term multipactor discharge in multicarrier systems

    International Nuclear Information System (INIS)

    Anza, S.; Vicente, C.; Gimeno, B.; Boria, V. E.; Armendariz, J.

    2007-01-01

    A new mechanism of long-term multipactor in multicarrier systems is studied employing both analytical and numerical methods. In particular, the investigation is focused on the impact that a realistic secondary emission yield at low energies produces on the development of long term multipactor. A novel analytical model for this interperiod charge accumulation is presented using the traditional multipactor theory for parallel plates, and approximating the multicarrier signal as a single-carrier signal modulated by a pulsed signal envelope. The analytical predictions are verified by numerical simulations for a typical rectangular waveguide. The analytical and numerical results demonstrate that the susceptibility of the system to develop a long-term multipactor discharge increases with higher values of low-energy secondary emission yield

  19. Long-term Internship through Cooperative Education with Regional Industries

    Science.gov (United States)

    Takahashi, Kenzo; Hase, Hiroyuki

    The long term internship is one of special educational programs for graduate students of Graduate School of Engineering in University of Fukui. This is a collaborative program between university and industries where selected post-graduate students are dispatched to companies for a long term and educated in real business environments. It is the final goal of the program to develop sophisticated specialists who would be able to catch the business strategy in industries and solve any problems by themselves. The program is managed in a semester (6 months) and contains 1.5 month prior education of preliminary special knowledge, ethics and secrecy, about 3 month dispatch with long-term internship, and 1.5 month post-education for complementary education and presentation. This paper presents the effect of this program which has been evolving since 2005.

  20. A basic strategy for financing long term care.

    Science.gov (United States)

    Greenberg, J A; Leutz, W N

    1984-02-01

    As pressure mounts to contain Medicaid long term care spending, short-range "quick fixes" must be avoided. Three such false solutions in particular have shortcomings that may actually exacerbate long term care's financial dilemma because they are based on inadequate definitions of the problem. Two of these proposals--legislation to broaden family responsibility toward institutionalized elders on Medicaid and expanded state power to put liens on such elders' real property--err by trying to mandate "caring" and are predicated on a misunderstanding of the "spend-down" problem. The other proposal--to provide tax incentives to family members who care for elders--requires a large administrative apparatus, assumes an elasticity of supply that may not exist, and could disrupt the "gift relationship" on which family exchanges are often based. What is needed is a strategy with short term, intermediate, and long term objectives that move toward an insurance approach. The short term plan should lay the groundwork for intermediate strategy and control costs by changing rate-setting methods and putting limits on facility construction. The intermediate plan should change the problem's definition from one of merely controlling Medicaid long term care expenditures to one of efficiently managing state resources for the elderly through the development of state financing and local delivery systems that target older persons in greatest need. An effective means of doing this is through the creation of social/HMOs, which have five key features: integration of service responsibility and authority; flexibility in organizational design; balanced clientele; pooled prepaid funding; and financial risk for the provider organization. Finally, the long term strategy should transfer much of the long term care financial burden from individuals and state Medicaid agencies to insurance mechanisms. Many individuals would thus avoid impoverishment caused by health care spending and Medicaid would