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S Perrin J Cremer P Roll O Faucher A Ménard J Reynes P Dellamonica A Naqvi J Micallef E Jouve C Tamalet C Solas C Pissier I Arnoux C Nicolino-Brunet L Espinosa N Lévy E Kaspi A Robaglia-Schlupp I Poizot-Martin P Cau 《PloS one》2012,7(7):e41129
Background
The ANRS EP45 “Aging” study investigates the cellular mechanisms involved in the accelerated aging of HIV-1 infected and treated patients. The data reported focus on mitochondria, organelles known to be involved in cell senescence.Methods
49 HIV-1 infected patients untreated with antiretroviral therapy, together with 49 seronegative age- and sex-matched control subjects and 81 HIV-1 infected and treated patients, were recruited by 3 AIDS centres (Marseille, Montpellier, Nice; France; http://clinicaltrials.gov/, ). In more than 88% of treated patients, the viral load was <40 copies/ml and the CD4+ cell count was >500/mm3. ROS (reactive oxygen species) production and ΔΨm (inner membrane potential) were measured by flow cytometry in blood lymphocytes and monocytes (functional parameters). Three mitochondrial network quantitative morphological parameters were computed using confocal microscopy and image analysis. Three PBMC mitochondrial proteins (porin and subunits 2 and 4 of cytochrome C oxidase encoded by mtDNA or nuclear DNA, respectively) were analysed by western blotting. NCT01038999Results
Quantitative changes in PBMC mitochondrial proteins were not induced by either HIV-1 infection or ART. Discriminant analysis integrating functional (ROS production and ΔΨm) or morphological (network volume density, fragmentation and branching) parameters revealed HIV-1 infection and ART differential effects according to cell type. First line ART tended to rescue lymphocyte mitochondrial parameters altered by viral infection, but induced slight changes in monocytes. No statistical difference was found between the effects of three ART regimens on mitochondrial parameters. Correlations between functional parameters and viral load confirmed the damaging effects of HIV-1 in lymphocyte mitochondria.Conclusions
In patients considered to be clinically stable, mitochondria exhibited functional and morphological modifications in PBMCs resulting from either direct or indirect effects of HIV-1 infection (lymphocytes), or from first line ART (monocytes). Together with other tissue impairments, these changes may contribute to global aging.Trial Registration
ClinicalTrials.gov NCT01038999 NCT01038999相似文献3.
Drake AL Roxby AC Kiarie J Richardson BA Wald A John-Stewart G Farquhar C 《PloS one》2012,7(4):e34635
Background
Maternal administration of the acyclovir prodrug valacyclovir is compatible with pregnancy and breastfeeding. However, the safety profile of prolonged infant and maternal exposure to acyclovir in the context of antiretrovirals (ARVs) for prevention of mother-to-child HIV-1 transmission (PMTCT) has not been described.Methods
Pregnant Kenyan women co-infected with HIV-1/HSV-2 with CD4 counts > 250 cells/mm3 were enrolled at 34 weeks gestation and randomized to twice daily 500 mg valacyclovir or placebo until 12 months postpartum. Women received zidovudine from 28 weeks gestation and single dose nevirapine was given to women and infants at the time of delivery for PMTCT. Infant blood was collected at 6 weeks for creatinine and ALT. Breast milk specimens were collected at 2 weeks postpartum from 71 women in the valacyclovir arm; acyclovir levels were determined for a random sample of 44 (62%) specimens. Fisher’s Exact and Wilcoxon rank-sum tests were used for analysis.Results
One hundred forty-eight women were randomized and 146 mother-infant pairs were followed postpartum. PMTCT ARVs were administered to 98% of infants and all mothers. Valacyclovir was not associated with infant or maternal toxicities or adverse events, and no congenital malformations were observed. Infant creatinine levels were all normal (< 0.83 mg/dl) and median creatinine (median 0.50 mg/dl) and infant growth did not differ between study arms. Acyclovir was detected in 35 (80%) of 44 breast milk samples collected at 2 weeks postpartum. Median and maximum acyclovir levels were 2.62 and 10.15 mg/ml, respectively (interquartile range 0.6–4.19).Conclusions
Exposure to PMTCT ARVs and acyclovir after maternal administration of valacyclovir during pregnancy and postpartum to women co-infected with HIV-1/HSV-2 was not associated with an increase in infant or maternal toxicities or adverse events.Trial Registration
ClinicalTrials.gov NCT00530777相似文献4.
Firnhaber C Azzoni L Foulkes AS Gross R Yin X Van Amsterdam D Schulze D Glencross DK Stevens W Hunt G Morris L Fox L Sanne I Montaner LJ 《PloS one》2011,6(6):e21450
Background
The clinical outcomes of short interruptions of PI-based ART regimens remains undefined.Methods
A 2-arm non-inferiority trial was conducted on 53 HIV-1 infected South African participants with viral load <50 copies/ml and CD4 T cell count >450 cells/µl on stavudine (or zidovudine), lamivudine and lopinavir/ritonavir. Subjects were randomized to a) sequential 2, 4 and 8-week ART interruptions or b) continuous ART (cART). Primary analysis was based on the proportion of CD4 count >350 cells(c)/ml over 72 weeks. Adherence, HIV-1 drug resistance, and CD4 count rise over time were analyzed as secondary endpoints.Results
The proportions of CD4 counts >350 cells/µl were 82.12% for the intermittent arm and 93.73 for the cART arm; the difference of 11.95% was above the defined 10% threshold for non-inferiority (upper limit of 97.5% CI, 24.1%; 2-sided CI: −0.16, 23.1). No clinically significant differences in opportunistic infections, adverse events, adherence or viral resistance were noted; after randomization, long-term CD4 rise was observed only in the cART arm.Conclusion
We are unable to conclude that short PI-based ART interruptions are non-inferior to cART in retention of immune reconstitution; however, short interruptions did not lead to a greater rate of resistance mutations or adverse events than cART suggesting that this regimen may be more forgiving than NNRTIs if interruptions in therapy occur.Trial Registration
ClinicalTrials.gov NCT00100646相似文献5.
Tebas P Henry WK Matining R Weng-Cherng D Schmitz J Valdez H Jahed N Myers L Powderly WG Katzenstein D 《PloS one》2008,3(4):e2021
Background
Concern about costs and antiretroviral therapy (ART)-associated toxicities led to the consideration of CD4 driven strategies for the management of HIV. That approach was evaluated in the SMART trial that reported an unexpected increase of cardiovascular events after treatment interruption (TI). Our goal was to evaluate fasting metabolic changes associated with interruption of antiretroviral therapy and relate them to changes of immune activation markers and cardiovascular risk.Methodology
ACTG 5102 enrolled 47 HIV-1-infected subjects on stable ART, with <200 HIV RNA copies/mL and CD4 cell count ≥500 cells/µL. Subjects were randomly assigned to continue ART for 18 weeks with or without 3 cycles of interleukin-2 (IL-2) (cycle = 4.5 million IU sc BID x 5 days every 8 weeks). After 18 weeks ART was discontinued in all subjects until the CD4 cell count dropped below 350 cells/µL. Glucose and lipid parameters were evaluated every 8 weeks initially and at weeks 2, 4, 8 and every 8 weeks after TI. Immune activation was evaluated by flow-cytometry and soluble TNFR2 levels.Principal Findings
By week 8 of TI, levels of total cholesterol (TC) (median (Q1, Q3) (−0.73 (−1.19, −0.18) mmol/L, p<0.0001), LDL, HDL cholesterol (−0.36(−0.73,−0.03)mmol/L, p = 0.0007 and −0.05(−0.26,0.03), p = 0.0033, respectively) and triglycerides decreased (−0.40 (−0.84, 0.07) mmol/L, p = 0.005). However the TC/HDL ratio remained unchanged (−0.09 (−1.2, 0.5), p = 0.2). Glucose and insulin levels did not change (p = 0.6 and 0.8, respectively). After TI there was marked increase in immune activation (CD8+/HLA-DR+/CD38+ cells, 34% (13, 43), p<0.0001) and soluble TNFR2 (1089 ng/L (−189, 1655), p = 0.0008) coinciding with the rebound of HIV viremia.Conclusions
Our data suggests that interrupting antiretroviral therapy does not reduce cardiovascular disease (CVD) risk, as the improvements in lipid parameters are modest and overshadowed by the decreased HDL levels. Increased immune cell activation and systemic inflammatory responses associated with recrudescent HIV viremia may provide a more cogent explanation for the increased cardiovascular risk associated with treatment interruption and HIV infection.Trial Registration
ClinicalTrials.gov NCT00015704相似文献6.
Ledwaba L Tavel JA Khabo P Maja P Qin J Sangweni P Liu X Follmann D Metcalf JA Orsega S Baseler B Neaton JD Lane HC;Project Phidisa Biomarkers Team 《PloS one》2012,7(3):e24243
Background
Levels of high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and D-dimer predict mortality in HIV patients on antiretroviral therapy (ART) with relatively preserved CD4+ T cell counts. We hypothesized that elevated pre-ART levels of these markers among patients with advanced HIV would be associated with an increased risk of death following the initiation of ART.Methods
Pre-ART plasma from patients with advanced HIV in South Africa was used to measure hsCRP, IL-6 and D-dimer. Using a nested case-control study design, the biomarkers were measured for 187 deaths and two controls matched on age, sex, clinical site, follow-up time and CD4+ cell counts. Odds ratios were estimated using conditional logistic regression. In addition, for a random sample of 100 patients, biomarkers were measured at baseline and 6 months following randomization to determine whether ART altered their levels.Results
Median baseline biomarkers levels for cases and controls, respectively, were 11.25 vs. 3.6 mg/L for hsCRP, 1.41 vs. 0.98 mg/L for D-dimer, and 9.02 vs. 4.20 pg/mL for IL-6 (all p<0.0001). Adjusted odds ratios for the highest versus lowest quartile of baseline biomarker levels were 3.5 (95% CI: 1.9–6.7) for hsCRP, 2.6 (95%CI 1.4–4.9) for D-dimer, and 3.8 (95% CI: 1.8–7.8) for IL-6. These associations were stronger for deaths that occurred more proximal to the biomarker measurements. Levels of D-dimer and IL-6, but not hsCRP, were significantly lower at month 6 after commencing ART compared to baseline (p<0.0001).Conclusions
Among patients with advanced HIV disease, elevated pre-ART levels of hsCRP, IL-6 and D-dimer are strongly associated with early mortality after commencing ART. Elevated levels of inflammatory and coagulation biomarkers may identify patients who may benefit from aggressive clinical monitoring after commencing ART. Further investigation of strategies to reduce biomarkers of inflammation and coagulation in patients with advanced HIV disease is warranted.Trial Registration
Parent Study: ClinicalTrials.gov NCT00342355相似文献7.
John R. Koethe Andrew O. Westfall Dora K. Luhanga Gina M. Clark Jason D. Goldman Priscilla L. Mulenga Ronald A. Cantrell Benjamin H. Chi Isaac Zulu Michael S. Saag Jeffrey S. A. Stringer 《PloS one》2010,5(3)
Background
The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree).Methodology
Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation) to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months.Principal Findings
From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites.Conclusions
A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings.Trial Registration
Clinicaltrials.gov NCT00929604相似文献8.
Koenig SP Bang H Severe P Jean Juste MA Ambroise A Edwards A Hippolyte J Fitzgerald DW McGreevy J Riviere C Marcelin S Secours R Johnson WD Pape JW Schackman BR 《PLoS medicine》2011,8(9):e1001095
Background
In a randomized clinical trial of early versus standard antiretroviral therapy (ART) in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial.Methods and Findings
Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS), including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART) and US$979 (standard ART). Early ART patients had higher mean costs for ART (US$398 versus US$81) but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384). The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS–US$9,979/YLS) including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS–US$5,537/YLS).Conclusions
Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita) after a maximum of 3 years, after excluding research-related laboratory tests.Trial registration
ClinicalTrials.gov Please see later in the article for the Editors'' Summary NCT00120510相似文献9.
Steven J. Reynolds Cissy Kityo Claire W. Hallahan Geoffrey Kabuye Diana Atwiine Frank Mbamanya Francis Ssali Robin Dewar Marybeth Daucher Richard T. Davey Jr Peter Mugyenyi Anthony S. Fauci Thomas C. Quinn Mark R. Dybul 《PloS one》2010,5(4)
Background
Short cycle treatment interruption could reduce toxicity and drug costs and contribute to further expansion of antiretroviral therapy (ART) programs.Methods
A 72 week, non-inferiority trial enrolled one hundred forty six HIV positive persons receiving ART (CD4+ cell count ≥125 cells/mm3 and HIV RNA plasma levels <50 copies/ml) in one of three arms: continuous, 7 days on/7 days off and 5 days on/2 days off treatment. Primary endpoint was ART treatment failure determined by plasma HIV RNA level, CD4+ cell count decrease, death attributed to study participation, or opportunistic infection.Results
Following enrollment of 32 participants, the 7 days on/7 days off arm was closed because of a failure rate of 31%. Six of 52 (11.5%) participants in the 5 days on/2 days off arm failed. Five had virologic failure and one participant had immunologic failure. Eleven of 51 (21.6%) participants in the continuous treatment arm failed. Nine had virologic failure with 1 death (lactic acidosis) and 1 clinical failure (extra-pulmonary TB). The upper 97.5% confidence boundary for the difference between the percent of non-failures in the 5 days on/2 days off arm (88.5% non-failure) compared to continuous treatment (78.4% non failure) was 4.8% which is well within the preset non-inferiority margin of 15%. No significant difference was found in time to failure in the 2 study arms (p = 0.39).Conclusions
Short cycle 5 days on/2 days off intermittent ART was at least as effective as continuous therapy.Trial Registration
ClinicalTrials.gov NCT00339456相似文献10.
Ciaranello AL Perez F Maruva M Chu J Engelsmann B Keatinge J Walensky RP Mushavi A Mugwagwa R Dabis F Freedberg KA;CEPAC-International Investigators 《PloS one》2011,6(6):e20224
Background
The Zimbabwean national prevention of mother-to-child HIV transmission (PMTCT) program provided primarily single-dose nevirapine (sdNVP) from 2002–2009 and is currently replacing sdNVP with more effective antiretroviral (ARV) regimens.Methods
Published HIV and PMTCT models, with local trial and programmatic data, were used to simulate a cohort of HIV-infected, pregnant/breastfeeding women in Zimbabwe (mean age 24.0 years, mean CD4 451 cells/µL). We compared five PMTCT regimens at a fixed level of PMTCT medication uptake: 1) no antenatal ARVs (comparator); 2) sdNVP; 3) WHO 2010 guidelines using “Option A” (zidovudine during pregnancy/infant NVP during breastfeeding for women without advanced HIV disease; lifelong 3-drug antiretroviral therapy (ART) for women with advanced disease); 4) WHO “Option B” (ART during pregnancy/breastfeeding without advanced disease; lifelong ART with advanced disease); and 5) “Option B+:” lifelong ART for all pregnant/breastfeeding, HIV-infected women. Pediatric (4–6 week and 18-month infection risk, 2-year survival) and maternal (2- and 5-year survival, life expectancy from delivery) outcomes were projected.Results
Eighteen-month pediatric infection risks ranged from 25.8% (no antenatal ARVs) to 10.9% (Options B/B+). Although maternal short-term outcomes (2- and 5-year survival) varied only slightly by regimen, maternal life expectancy was reduced after receipt of sdNVP (13.8 years) or Option B (13.9 years) compared to no antenatal ARVs (14.0 years), Option A (14.0 years), or Option B+ (14.5 years).Conclusions
Replacement of sdNVP with currently recommended regimens for PMTCT (WHO Options A, B, or B+) is necessary to reduce infant HIV infection risk in Zimbabwe. The planned transition to Option A may also improve both pediatric and maternal outcomes. 相似文献11.
Christine Danel Mathieu Kabran André Inwoley Anani Badje Jean Louis Herrmann Raoul Moh Jér?me Lecarrou Delphine Gabillard Jean Baptiste Ntakpe Nina Deschamps Eric Ouattara Christian Perronne Serge Eholie Xavier Anglaret 《PloS one》2014,9(10)
Objective
To assess the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) test for active tuberculosis (TB) in HIV adults, and its variation over time in patients on antiretroviral therapy (ART) and/or isoniazide preventive therapy (IPT).Methods
Transversal study and cohort nested in the Temprano ANRS 12136 randomized controlled trial assessing benefits of initiating ART earlier than currently recommended by World Health Organization, with or without a 6-month IPT. Performance of QFT-GIT for detecting active TB at baseline in the first 50% participants, and 12-month incidence of conversion/reversion in the first 25% participants were assessed. QFT-GIT threshold for positivity was 0.35 IU/ml.Results
Among the 975 first participants (median baseline CD4 count 383/mm3, positive QFT-GIT test 35%), 2.7% had active TB at baseline. QFT-GIT sensitivity, specificity, positive and negative predictive value for active TB were 88.0%, 66.6%, 6.5% and 99.5%. For the 444 patients with a second test at 12 months, rates for conversion and reversion were 9.3% and 14%. Reversion was more frequent in patients without ART and younger patients. IPT and early ART were not associated with reversion/conversion.Conclusion
A negative QFT-GIT could rule out active TB in HIV-infected adults not severely immunosuppressed, thus avoiding repeated TB testing and accelerating diagnosis and care for other diseases.Trial Registration
ClinicalTrials.gov . NCT00495651相似文献12.
Li JZ Brumme CJ Lederman MM Brumme ZL Wang H Spritzler J Carrington M Medvik K Walker BD Schooley RT Kuritzkes DR;AIDS Clinical Trials Group A Study Team 《PloS one》2012,7(3):e34134
Background
In the placebo-controlled trial ACTG A5197, a trend favoring viral suppression was seen in the HIV-1-infected subjects who received a recombinant Ad5 HIV-1 gag vaccine.Objective
To identify individuals with initial viral suppression (plasma HIV-1 RNA set point <3.0 log10 copies/ml) during the analytic treatment interruption (ATI) and evaluate the durability and correlates of virologic control and characteristics of HIV sequence evolution.Methods
HIV-1 gag and pol RNA were amplified and sequenced from plasma obtained during the ATI. Immune responses were measured by flow cytometric analysis and intracellular cytokine expression assays. Characteristics of those with and without initial viral suppression were compared using the Wilcoxon rank sum and Fisher''s exact tests.Results
Eleven out of 104 participants (10.6%) were classified as initial virologic suppressors, nine of whom had received the vaccine. Initial virologic suppressors had significantly less CD4+ cell decline by ATI week 16 as compared to non-suppressors (median 7 CD4+ cell gain vs. 247 CD4+ cell loss, P = 0.04). However, of the ten initial virologic suppressors with a pVL at ATI week 49, only three maintained pVL <3.0 log10 copies/ml. HIV-1 Gag-specific CD4+ interferon-γ responses were not associated with initial virologic suppression and no evidence of vaccine-driven HIV sequence evolution was detected. Participants with initial virologic suppression were found to have a lower percentage of CD4+ CTLA-4+ cells prior to treatment interruption, but a greater proportion of HIV-1 Gag-reactive CD4+ TNF-α+ cells expressing either CTLA-4 or PD-1.Conclusions
Among individuals participating in a rAd5 therapeutic HIV-1 gag vaccine trial, initial viral suppression was found in a subset of patients, but this response was not sustained. The association between CTLA-4 and PD-1 expression on CD4+ T cells and virologic outcome warrants further study in trials of other therapeutic vaccines in development.Trial Registration
ClinicalTrials.gov NCT00080106相似文献13.
Patkar A Gilmer W Pae CU Vöhringer PA Ziffra M Pirok E Mulligan M Filkowski MM Whitham EA Holtzman NS Thommi SB Logvinenko T Loebel A Masand P Ghaemi SN 《PloS one》2012,7(4):e34757
Objective
To examine the efficacy of ziprasidone vs. placebo for the depressive mixed state in patients with bipolar disorder type II or major depressive disorder (MDD).Methods
73 patients were randomized in a double-blinded, placebo-controlled study to ziprasidone (40-160 mg/d) or placebo for 6 weeks. They met DSM-IV criteria for a major depressive episode (MDE), while also meeting 2 or 3 (but not more nor less) DSM-IV manic criteria. They did not meet DSM-IV criteria for a mixed or manic episode. Baseline psychotropic drugs were continued unchanged. The primary endpoint measured was Montgomery- Åsberg Depression Rating Scale (MADRS) scores over time. The mean dose of ziprasidone was 129.7±45.3 mg/day and 126.1±47.1 mg/day for placebo.Results
The primary outcome analysis indicated efficacy of ziprasidone versus placebo (p = 0.0038). Efficacy was more pronounced in type II bipolar disorder than in MDD (p = 0.036). Overall ziprasidone was well tolerated, without notable worsening of weight or extrapyramidal symptoms.Conclusions
There was a statistically significant benefit with ziprasidone versus placebo in this first RCT of any medication for the provisional diagnostic concept of the depressive mixed state.Trial Registration
Clinicaltrials.gov NCT00490542相似文献14.
Gregory M. Lucas Bernadette Anna Mullen Noya Galai Richard D. Moore Katie Cook Mary E. McCaul Sheldon Glass Krisann K. Oursler Cynthia Rand 《PloS one》2013,8(7)
Background
Data regarding the efficacy of directly administered antiretroviral therapy (DAART) are mixed. Opioid treatment programs (OTPs) provide a convenient framework for DAART. In a randomized controlled trial, we compared DAART and self-administered therapy (SAT) among HIV-infected subjects attending five OTPs in Baltimore, MD.Methods
HIV-infected individuals attending OTPs were eligible if they were not taking antiretroviral therapy (ART) or were virologically failing ART at last clinical assessment. In subjects assigned to DAART, we observed one ART dose per weekday at the OTP for up to 12 months. SAT subjects administered ART at home. The primary efficacy comparison was the between-arm difference in the average proportions with HIV RNA <50 copies/mL during the intervention phase (3-, 6-, and 12-month study visits), using a logistic regression model accounting for intra-person correlation due to repeated observations. Adherence was measured with electronic monitors in both arms.Results
We randomized 55 and 52 subjects from five Baltimore OTPs to DAART and SAT, respectively. The average proportions with HIV RNA <50 copies/mL during the intervention phase were 0.51 in DAART and 0.40 in SAT (difference 0.11, 95% CI: −0.020 to 0.24). There were no significant differences between arms in electronically-measured adherence, average CD4 cell increase from baseline, average change in log10 HIV RNA from baseline, opportunistic conditions, hospitalizations, mortality, or the development of new drug resistance mutations.Conclusions
In this randomized trial, we found little evidence that DAART provided clinical benefits compared to SAT among HIV-infected subjects attending OTPs.Trial Registration
ClinicalTrails.gov NCT00279110?term =  NCT00279110&rank = 1 NCT00279110相似文献15.
Introduction
Iodine is essential for normal fetal and neonatal development. We studied the prevalence and impact on fetal thyroid development of iodine deficiency in pregnant women in the northern part of the Paris conurbation.Materials and Methods
110 patients underwent several determinations of urinary iodine excretion (UIE) and of serum FT4, FT3, and TSH. Fetal thyroid gland size was assessed using ultrasonography.Results
We found evidence of widespread iodine deficiency (mean UIE, 49.8 µg/L [standard deviation, 2.11]). Iodine deficiency did not correlate significantly with maternal thyroid parameters but showed a significant negative correlation with fetal thyroid gland size (rho = 0.25, P = 0.02).Conclusion
Iodine deficiency during pregnancy is still a problem in our geographical area and affects the fetal thyroid gland.Clinical Trials.gov NCT00162539相似文献16.
Török ME Nguyen DB Tran TH Nguyen TB Thwaites GE Hoang TQ Nguyen HD Tran TH Nguyen TC Hoang HT Wolbers M Farrar JJ 《PloS one》2011,6(12):e27821
Background
Dexamethasone has been shown to reduce mortality in patients with tuberculous meningitis but the long-term outcome of the disease is unknown.Methods
Vietnamese adults and adolescents with tuberculous meningitis recruited to a randomised, double-blind, placebo-controlled trial of adjunctive dexamethasone were followed-up at five years, to determine the effect of dexamethasone on long-term survival and neurological disability.Results
545 patients were randomised to receive either dexamethasone (274 patients) or placebo (271 patients). 50 patients (9.2%) were lost to follow-up at five years. In all patients two-year survival, probabilities tended to be higher in the dexamethasone arm (0.63 versus 0.55; p = 0.07) but five-year survival rates were similar (0.54 versus 0.51, p = 0.51) in both groups. In patients with grade 1 TBM, but not with grade 2 or grade 3 TBM, the benefit of dexamethasone treatment tended to persist over time (five-year survival probabilities 0.69 versus 0.55, p = 0.07) but there was no conclusive evidence of treatment effect heterogeneity by TBM grade (p = 0.36). The dexamethasone group had a similar proportion of severely disabled patients among survivors at five years as the placebo group (17/128, 13.2% vs. 17/116, 14.7%) and there was no significant association between dexamethasone treatment and disability status at five years (p = 0.32).Conclusions
Adjunctive dexamethasone appears to improve the probability of survival in patients with TBM, until at least two years of follow-up. We could not demonstrate a five-year survival benefit of dexamethasone treatment which may be confined to patients with grade 1 TBM.Trial Registration
ClinicalTrials.gov NCT01317654?term = tuberculous+meningitis&rank = 3 NCT01317654相似文献17.
Background
The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4+ counts compared to no therapy.Methodology
Participants not on continuous ART with ≥300 CD4+ cells/mm3 were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2 cycle. CD4+ counts, HIV RNA, and HIV progression events were collected monthly.Principal Findings
A total of 267 participants were randomized. At week 32, the mean CD4+ count was 134 cells greater in the IL-2 alone group (p<0.001), and 133 cells greater in the IL-2 plus ART group (p<0.001) compared to the no therapy group. Twelve participants in the IL-2 groups compared to 1 participant in the group assigned to no therapy experienced an opportunistic event or died (HR 5.84, CI: 0.59 to 43.57; p = 0.009).Conclusions
IL-2 alone or with peri-cycle HAART increases CD4+ counts but was associated with a greater number of opportunistic events or deaths compared to no therapy. These results call into question the immunoprotective significance of IL-2-induced CD4+ cells.Trial Registration
ClinicalTrials.gov NCT00110812相似文献18.
A Alkhalaf N Kleefstra KH Groenier HJ Bilo RO Gans P Heeringa JL Scheijen CG Schalkwijk GJ Navis SJ Bakker 《PloS one》2012,7(7):e40427
Background
Formation of advanced glycation endproducts (AGEs), endothelial dysfunction, and low-grade inflammation are intermediate pathways of hyperglycemia-induced vascular complications. We investigated the effect of benfotiamine on markers of these pathways in patients with type 2 diabetes and nephropathy.Methods
Patients with type 2 diabetes and urinary albumin excretion in the high-normal and microalbuminuric range (15–300 mg/24h) were randomized to receive benfotiamine (n = 39) or placebo (n = 43). Plasma and urinary AGEs (N ε-(carboxymethyl) lysine [CML], N ε-(Carboxyethyl) lysine [CEL], and 5-hydro-5-methylimidazolone [MG-H1]) and plasma markers of endothelial dysfunction (soluble vascular cell adhesion molecule-1 [sVCAM-1], soluble intercellular adhesion molecule-1 [sICAM-1], soluble E-selectin) and low-grade inflammation (high-sensitivity C-reactive protein [hs-CRP], serum amyloid-A [SAA], myeloperoxidase [MPO]) were measured at baseline and after 6 and 12 weeks.Results
Compared to placebo, benfotiamine did not result in significant reductions in plasma or urinary AGEs or plasma markers of endothelial dysfunction and low-grade inflammation.Conclusions
Benfotiamine for 12 weeks did not significantly affect intermediate pathways of hyperglycemia-induced vascular complications.Trial Regristration
ClinicalTrials.gov NCT00565318相似文献19.
Sachdeva KS Satyanarayana S Dewan PK Nair SA Reddy R Kundu D Chadha SS Venkatachalaiah AK Parmar M Chauhan LS 《PloS one》2011,6(7):e22061
Background
In 2009, nearly half (289,756) of global re-treatment TB notifications are from India; no nationally-representative data on the source of previous treatment was available to inform strategies for improvement of initial TB treatment outcome.Objectives
To assess the source of previous treatment for re-treatment TB patients registered under India''s Revised National TB control Programme (RNTCP).Methodology
A nationally-representative cross sectional study was conducted in a sample of 36 randomly-selected districts. All consecutively registered retreatment TB patients during a defined 15-day period in these 36 districts were contacted and the information on the source of previous treatment sought.Results
Data was collected from all 1712 retreatment TB patients registered in the identified districts during the study period. The data includes information on 595 ‘relapse’ cases, 105 ‘failure’ cases, 437 ‘treatment after default (TAD)’ cases and 575 ‘re-treatment others’ cases. The source of most recent previous anti-tuberculosis therapy for 754 [44% (95% CI, 38.2%–49.9%)] of the re-treatment TB patients was from providers outside the TB control programme. A higher proportion of patients registered as TAD (64%) and ‘retreatment others’ (59%) were likely to be treated outside the National Programme, when compared to the proportion among ‘relapse’ (22%) or ‘failure’ (6%). Extrapolated to national registration, of the 292,972 re-treatment registrations in 2010, 128,907 patients would have been most recently treated outside the national programme.Conclusions
Nearly half of the re-treatment cases registered with the national programme were most recently treated outside the programme setting. Enhanced efforts towards extending treatment support and supervision to patients treated by private sector treatment providers are urgently required to improve the quality of treatment and reduce the numbers of patients with recurrent disease. In addition, reasons for the large number of recurrent TB cases from those already treated by the national programme require urgent detailed investigation. 相似文献20.
van Damme P Kafeja F Anemona A Basile V Hilbert AK De Coster I Rondini S Micoli F Qasim Khan RM Marchetti E Di Cioccio V Saul A Martin LB Podda A 《PloS one》2011,6(9):e25398