共查询到20条相似文献,搜索用时 15 毫秒
1.
Beck EJ Mandalia S Sangha R Sharott P Youle M Baily G Brettle R Gompels M Johnson M McCarron B Ong E Pozniak A Schwenk A Taylor S Walsh J Wilkins E Williams I Gazzard B;NPMS-HHC Steering Group 《PloS one》2011,6(12):e27830
Aim
To calculate use, cost and cost-effectiveness of people living with HIV (PLHIV) starting routine treatment and care before starting combination antiretroviral therapy (cART) and PLHIV starting first-line 2NRTIs+NNRTI or 2NRTIs+PIboosted, comparing PLHIV with CD4≤200 cells/mm3 and CD4>200 cells/mm3. Few studies have calculated the use, cost and cost-effectiveness of routine treatment and care before starting cART and starting cART above and below CD4 200 cells/mm3.Methods
Use, costs and cost-effectiveness were calculated for PLHIV in routine pre-cART and starting first-line cART, comparing CD4≤200 cells/mm3 with CD4>200 cells/mm3 (2008 UK prices).Results
cART naïve patients CD4≤200 cells/mm3 had an annual cost of £6,407 (95%CI £6,382 to £6,425) PPY compared with £2,758 (95%CI £2,752 to £2,761) PPY for those with CD4>200 cells/mm3; cost per life year gained of pre-cART treatment and care for those with CD4>200 cells/mm3 was £1,776 (cost-saving to £2,752). Annual cost for starting 2NRTIs+NNRTI or 2NRTIs+PIboosted with CD4≤200 cells/mm3 was £12,812 (95%CI £12,685–£12,937) compared with £10,478 (95%CI £10,376–£10,581) for PLHIV with CD4>200 cells/mm3. Cost per additional life-year gained on first-line therapy for those with CD4>200 cells/mm3 was £4639 (£3,967 to £2,960).Conclusion
PLHIV starting to use HIV services before CD4≤200 cells/mm3 is cost-effective and enables them to be monitored so they start cART with a CD4>200 cells/mm3, which results in better outcomes and is cost-effective. However, 25% of PLHIV accessing services continue to present with CD4≤200 cells/mm3. This highlights the need to investigate the cost-effectiveness of testing and early treatment programs for key populations in the UK. 相似文献2.
Joseph N. Jarvis Thomas S. Harrison Stephen D. Lawn Graeme Meintjes Robin Wood Susan Cleary 《PloS one》2013,8(7)
Objectives
Cryptococcal meningitis (CM)-related mortality may be prevented by screening patients for sub-clinical cryptococcal antigenaemia (CRAG) at antiretroviral-therapy (ART) initiation and pre-emptively treating those testing positive. Prior to programmatic implementation in South Africa we performed a cost-effectiveness analysis of alternative preventive strategies for CM.Design
Cost-effectiveness analysis.Methods
Using South African data we modelled the cost-effectiveness of four strategies for patients with CD4 cell-counts <100 cells/µl starting ART 1) no screening or prophylaxis (standard of care), 2) universal primary fluconazole prophylaxis, 3) CRAG screening with fluconazole treatment if antigen-positive, 4) CRAG screening with lumbar puncture if antigen-positive and either amphotericin-B for those with CNS disease or fluconazole for those without. Analysis was limited to the first year of ART.Results
The least costly strategy was CRAG screening followed by high-dose fluconazole treatment of all CRAG-positive individuals. This strategy dominated the standard of care at CRAG prevalence ≥0.6%. Although CRAG screening followed by lumbar puncture in all antigen-positive individuals was the most effective strategy clinically, the incremental benefit of LPs and amphotericin therapy for those with CNS disease was small and additional costs were large (US$158 versus US$51per person year; incremental cost effectiveness ratio(ICER) US$889,267 per life year gained). Both CRAG screening strategies are less costly and more clinically effective than current practice. Primary prophylaxis is more effective than current practice, but relatively cost-ineffective (ICER US$20,495).Conclusions
CRAG screening would be a cost-effective strategy to prevent CM-related mortality among patients initiating ART in South Africa. These findings provide further justification for programmatic implementation of CRAG screening. 相似文献3.
4.
Beck EJ Mandalia S Lo G Sharott P Youle M Anderson J Baily G Brettle R Fisher M Gompels M Kinghorn G Johnson M McCarron B Pozniak A Tang A Walsh J White D Williams I Gazzard B;NPMS-HHC Steering Group 《PloS one》2011,6(5):e20200
Aim
Calculate time to first-line treatment failure, annual cost and cost-effectiveness of NNRTI versus PIboosted first-line HAART regimens in the UK, 1996–2006.Background
Population costs for HIV services are increasing in the UK and interventions need to be effective and efficient to reduce or stabilize costs. 2NRTIs + NNRTI regimens are cost-effective regimens for first-line HAART, but these regimens have not been compared with first-line PIboosted regimens.Methods
Times to first-line treatment failure and annual costs were calculated for first-line HAART regimens by CD4 count when starting HAART (2006 UK prices). Cost-effectiveness of 2NRTIs+NNRTI versus 2NRTIs+PIboosted regimens was calculated for four CD4 strata.Results
55% of 5,541 people living with HIV (PLHIV) started HAART with CD4 count ≤200 cells/mm3, many of whom were Black Africans. Annual treatment cost decreased as CD4 count increased; most marked differences were observed between starting HAART with CD4 ≤200 cells/mm3 compared with CD4 count >200 cells/mm3. 2NRTI+PIboosted and 2NRTI+NNRTI regimens were the most effective regimens across the four CD4 strata; 2NRTI+NNRTI was cost-saving or cost-effective compared with 2NRTI + PIboosted regimens.Conclusion
To ensure more effective and efficient provision of HIV services, 2NRTI+NNRTI should be started as first-line HAART regimen at CD4 counts ≤350 cell/mm3, unless specific contra-indications exist. This will increase the number of PLHIV receiving HAART and will initially increase population costs of providing HIV services. However, starting PLHIV earlier on cost-effective regimens will maintain them in better health and use fewer health or social services, thereby generating fewer treatment and care costs, enabling them to remain socially and economically active members of society. This does raise a number of ethical issues, which will have to be acknowledged and addressed, especially in countries with limited resources. 相似文献5.
Background
People living with HIV/AIDS (PLWHA) frequently have abnormal blood counts including anemia, leucopenia and thrombocytopenia. The role of infection with plasmodia on these hematological parameters in PLWHA is not well known. In this study we compared selected hematological parameters between malaria positive and negative PLWHA.Methods
We conducted a cross-sectional study of PLWHA attending the Douala Laquintinie hospital. After obtaining consent, demographic and clinical data were obtained via a standardized questionnaire. Blood samples collected for hematological assays were run using an automated full blood counter. Malaria parasitaemia was determined by blood smear microscopy.Results
A total of 238 adult PLWHA were enrolled, 48.3% of who were on antiretroviral therapy and 24.8% of whom had malaria parasitaemia. The respective mean (±SD) of hemoglobin level, RBC count, WBC count, platelet count, lymphocyte count and CD4+ T cell counts in malaria co-infected patients versus non-infected patients were: 10.8(±1.9) g/dl versus 11.4(±2.0)g/dl; 3,745,254(±793,353) cells/µl versus 3,888,966(±648,195) cells/µl; 4,403(±1,534) cells/µl versus 4,920(±1,922) cells/µl; 216,051(±93,884) cells/µl versus 226,792(±98,664) cells/µl; 1,846(±711) cells/µl versus 2,052(±845) cells/µl and 245(±195) cells/µl versus 301(±211) cells/µl. All these means were not statistically significantly different from each other.Conclusion
There was no significant difference in studied hematological parameters between malaria positive and negative PLWHA. These data suggest little or no impact of malaria infection. Hematological anomalies in PLWHA in this area need not be necessarily attributed to malaria. These need to be further investigated to identify and treat other potential causes. 相似文献6.
Walensky RP Wood R Ciaranello AL Paltiel AD Lorenzana SB Anglaret X Stoler AW Freedberg KA;CEPAC-International Investigators 《PLoS medicine》2010,7(12):e1000382
Background
The new 2010 World Health Organization (WHO) HIV treatment guidelines recommend earlier antiretroviral therapy (ART) initiation (CD4<350 cells/µl instead of CD4<200 cells/µl), multiple sequential ART regimens, and replacement of first-line stavudine with tenofovir. This paper considers what to do first in resource-limited settings where immediate implementation of all of the WHO recommendations is not feasible.Methods and Findings
We use a mathematical model and local input data to project clinical and economic outcomes in a South African HIV-infected cohort (mean age = 32.8 y, mean CD4 = 375/µl). For the reference strategy, we assume that all patients initiate stavudine-based ART with WHO stage III/IV disease and receive one line of ART (stavudine/WHO/one-line). We rank—in survival, cost-effectiveness, and equity terms—all 12 possible combinations of the following: (1) stavudine replacement with tenofovir, (2) ART initiation (by WHO stage, CD4<200 cells/µl, or CD4<350 cells/µl), and (3) one or two regimens, or lines, of available ART. Projected life expectancy for the reference strategy is 99.0 mo. Considering each of the guideline components separately, 5-y survival is maximized with ART initiation at CD4<350 cells/µl (stavudine/<350/µl/one-line, 87% survival) compared with stavudine/WHO/two-lines (66%) and tenofovir/WHO/one-line (66%). The greatest life expectancies are achieved via the following stepwise programmatic additions: stavudine/<350/µl/one-line (124.3 mo), stavudine/<350/µl/two-lines (177.6 mo), and tenofovir/<350/µl/two-lines (193.6 mo). Three program combinations are economically efficient: stavudine/<350/µl/one-line (cost-effectiveness ratio, US$610/years of life saved [YLS]), tenofovir/<350/µl/one-line (US$1,140/YLS), and tenofovir/<350/µl/two-lines (US$2,370/YLS).Conclusions
In settings where immediate implementation of all of the new WHO treatment guidelines is not feasible, ART initiation at CD4<350 cells/µl provides the greatest short- and long-term survival advantage and is highly cost-effective. Please see later in the article for the Editors'' Summary 相似文献7.
Sharp ER Willberg CB Kuebler PJ Abadi J Fennelly GJ Dobroszycki J Wiznia AA Rosenberg MG Nixon DF 《PloS one》2012,7(1):e29154
Background
In the USA, most HIV-1 infected children are on antiretroviral drug regimens, with many individuals surviving through adolescence and into adulthood. The course of HIV-1 infection in these children is variable, and understudied.Methodology/Principal Findings
We determined whether qualitative differences in immune cell subsets could explain a slower disease course in long term survivors with no evidence of immune suppression (LTS-NS; CD4%≥25%) compared to those with severe immune suppression (LTS-SS; CD4%≤15%). Subjects in the LTS-NS group had significantly higher frequencies of naïve (CCR7+CD45RA+) and central memory (CCR7+CD45RA−) CD4+ T cells compared to LTS-SS subjects (p = 0.0005 and <0.0001, respectively). Subjects in the rapid progressing group had significantly higher levels of CD4+ TEMRA (CCR7−CD45RA+) cells compared to slow progressing subjects (p<0.0001).Conclusions/Significance
Rapid disease progression in vertical infection is associated with significantly higher levels of CD4+ TEMRA (CCR7−CD45RA+) cells. 相似文献8.
Background
Accurate, inexpensive point-of-care CD4+ T cell testing technologies are needed that can deliver CD4+ T cell results at lower level health centers or community outreach voluntary counseling and testing. We sought to evaluate a point-of-care CD4+ T cell counter, the Pima CD4 Test System, a portable, battery-operated bench-top instrument that is designed to use finger stick blood samples suitable for field use in conjunction with rapid HIV testing.Methods
Duplicate measurements were performed on both capillary and venous samples using Pima CD4 analyzers, compared to the BD FACSCalibur (reference method). The mean bias was estimated by paired Student''s t-test. Bland Altman plots were used to assess agreement.Results
206 participants were enrolled with a median CD4 count of 396 (range; 18–1500). The finger stick PIMA had a mean bias of −66.3 cells/µL (95%CI −83.4−49.2, P<0.001) compared to the FACSCalibur; the bias was smaller at lower CD4 counts (0–250 cells/µL) with a mean bias of −10.8 (95%CI −27.3−+5.6, P = 0.198), and much greater at higher CD4 cell counts (>500 cells/µL) with a mean bias of −120.6 (95%CI −162.8, −78.4, P<0.001). The sensitivity (95%CI) of the Pima CD4 analyzer was 96.3% (79.1–99.8%) for a <250 cells/ul cut-off with a negative predictive value of 99.2% (95.1–99.9%).Conclusions
The Pima CD4 finger stick test is an easy-to-use, portable, relatively fast device to test CD4+ T cell counts in the field. Issues of negatively-biased CD4 cell counts especially at higher absolute numbers will limit its utility for longitudinal immunologic response to ART. The high sensitivity and negative predictive value of the test makes it an attractive option for field use to identify patients eligible for ART, thus potentially reducing delays in linkage to care and ART initiation. 相似文献9.
Bellistrì GM Casabianca A Merlini E Orlandi C Ferrario G Meroni L Galli M Magnani M Monforte Ad Marchetti G 《PloS one》2010,5(12):e15663
Background
The bone marrow (BM) cytokine milieu might substantially affect T-lymphocyte homeostasis in HIV-positive individuals. Interleukin-7 (IL-7) is a bone marrow-derived cytokine regulating T-cell homeostasis through a CD4+-driven feedback loop. CD4+ T-lymphopenia is associated with increased free IL-7 levels and reduced IL-7R expression/function, which are only partially reverted by highly active antiretroviral therapy (HAART). We investigated the BM production, peripheral expression and signaling (pStat5+ and Bcl-2+ CD4+/CD8+ T cells) of IL-7/IL-7Rα in 30 HAART-treated HIV-positive patients who did not experience CD4+ recovery (CD4+ ≤200/µl) and who had different levels of HIV viremia; these patients included 18 immunological nonresponders (INRs; HIV-RNA≤50), 12 complete failures (CFs; HIV-RNA>1000), and 23 HIV-seronegative subjects.Methods
We studied plasma IL-7 levels, IL-7Rα+CD4+/CD8+ T-cell proportions, IL-7Rα mRNA expression in PBMCs, spontaneous IL-7 production by BM mononuclear cells (BMMCs), and IL-7 mRNA/IL-7Rα mRNA in BMMC-derived stromal cells (SCs). We also studied T-cell responsiveness to IL-7 by measuring the proportions of pStat5+ and Bcl-2+ CD4+/CD8+ T cells.Results
Compared to HIV-seronegative controls, CFs and INRs presented elevated plasma IL-7 levels and lower IL-7Rα CD4+/CD8+ cell-surface expression and peripheral blood production, confirming the most relevant IL-7/IL-7R disruption. Interestingly, BM investigation revealed a trend of higher spontaneous IL-7 production in INRs (p = .09 vs. CFs) with a nonsignificant trend toward higher IL-7-Rα mRNA levels in BMMC-derived stromal cells. However, upon IL-7 stimulation, the proportion of pStat5+CD4+ T cells did not increase in INRs despite higher constitutive levels (p = .06); INRs also displayed lower Bcl-2+CD8+ T-cell proportions than controls (p = .04).Conclusions
Despite severe CD4+ T-lymphopenia and a disrupted IL-7/IL-7R profile in the periphery, INRs display elevated BM IL-7/IL-7Rα expression but impaired T-cell responsiveness to IL-7, suggesting the activity of a central compensatory pathway targeted to replenish the CD4+ compartment, which is nevertheless inappropriate to compensate the dysfunctional signaling through IL-7 receptor. 相似文献10.
Introduction
The objectives of this study are to address if and how albumin can be used as an indication of malnutrition in HIV infected and uninfected Africans.Methods
In 2005, 710 HIV-infected and 226 HIV-uninfected women enrolled in a cohort study. Clinical/demographic parameters, CD4 count, albumin, liver transaminases; anthropometric measurements and Bioelectrical Impedance Analysis (BIA) were performed. Malnutrition outcomes were defined as body mass index (BMI), Fat-free mass index (FFMI) and Fat mass index (FMI). Separate linear predictive models including albumin were fit to these outcomes in HIV negative and HIV positive women by CD4 strata (CD4>350,200–350 and <200 cells/µl).Results
In unadjusted models for each outcome in HIV-negative and HIV positive women with CD4>350 cells/µl, serum albumin was not significantly associated with BMI, FFMI or FMI. Albumin was significantly associated with all three outcomes (p<0.05) in HIV+ women with CD4 200–350 cells/µl, and highly significant in HIV+ women with CD4<200 cells/µl (P<0.001). In multivariable linear regression, albumin remained associated with FFMI in women with CD4 count<200 cells/µl (p<0.01) but not in HIV+ women with CD4>200.Discussion
While serum albumin is widely used to indicate nutritional status it did not consistently predict malnutrition outcomes in HIV- women or HIV+ women with higher CD4. This result suggests that albumin may measure end stage disease as well as malnutrition and should not be used as a proxy for nutritional status without further study of its association with validated measures. 相似文献11.
The immune cell composition in Barrett's metaplastic tissue resembles that in normal duodenal tissue
Background and Objective
Barrett''s esophagus (BE) is characterized by the transition of squamous epithelium into columnar epithelium with intestinal metaplasia. The increased number and types of immune cells in BE have been indicated to be due to a Th2-type inflammatory process. We tested the alternative hypothesis that the abundance of T-cells in BE is caused by a homing mechanism that is found in the duodenum.Patients and Methods
Biopsies from BE and duodenal tissue from 30 BE patients and duodenal tissue from 18 controls were characterized by immmunohistochemistry for the presence of T-cells and eosinophils(eos). Ex vivo expanded T-cells were further phenotyped by multicolor analysis using flowcytometry.Results
The high percentage of CD4+-T cells (69±3% (mean±SEM/n = 17, by flowcytometry)), measured by flowcytometry and immunohistochemistry, and the presence of non-activated eosinophils found in BE by immunohistochemical staining, were not different from that found in duodenal tissue. Expanded lymphocytes from these tissues had a similar phenotype, characterized by a comparable but low percentage of αE(CD103) positive CD4+cells (44±5% in BE, 43±4% in duodenum of BE and 34±7% in duodenum of controls) and a similar percentage of granzyme-B+CD8+ cells(44±5% in BE, 33±6% in duodenum of BE and 36±7% in duodenum of controls). In addition, a similar percentage of α4β7+ T-lymphocytes (63±5% in BE, 58±5% in duodenum of BE and 62±8% in duodenum of controls) was found. Finally, mRNA expression of the ligand for α4β7, MAdCAM-1, was also similar in BE and duodenal tissue. No evidence for a Th2-response was found as almost no IL-4+-T-cells were seen.Conclusion
The immune cell composition (lymphocytes and eosinophils) and expression of intestinal adhesion molecule MAdCAM-1 is similar in BE and duodenum. This supports the hypothesis that homing of lymphocytes to BE tissue is mainly caused by intestinal homing signals rather than to an active inflammatory response. 相似文献12.
Di Marco GS Rustemeyer P Brand M Koch R Kentrup D Grabner A Greve B Wittkowski W Pavenstädt H Hausberg M Reuter S Lang D 《PloS one》2011,6(9):e24046
Background
Kidney transplantation (RTx) leads to amelioration of endothelial function in patients with advanced renal failure. Endothelial progenitor cells (EPCs) may play a key role in this repair process. The aim of this study was to determine the impact of RTx and immunosuppressive therapy on the number of circulating EPCs.Methods
We analyzed 52 RTx patients (58±13 years; 33 males, mean ± SD) and 16 age- and gender-matched subjects with normal kidney function (57±17; 10 males). RTx patients received a calcineurin inhibitor (CNI)-based (65%) or a CNI-free therapy (35%) and steroids. EPC number was determined by double positive staining for CD133/VEGFR2 and CD34/VEGFR2 by flow cytometry. Stromal cell-derived factor 1 alpha (SDF-1) levels were assessed by ELISA. Experimentally, to dissociate the impact of RTx from the impact of immunosuppressants, we used the 5/6 nephrectomy model. The animals were treated with a CNI-based or a CNI-free therapy, and EPCs (Sca+cKit+) and CD26+ cells were determined by flow cytometry.Results
Compared to controls, circulating number of CD34+/VEGFR2+ and CD133+/VEGFR2+ EPCs increased in RTx patients. There were no correlations between EPC levels and statin, erythropoietin or use of renin angiotensin system blockers in our study. Indeed, multivariate analysis showed that SDF-1 – a cytokine responsible for EPC mobilization – is independently associated with the EPC number. 5/6 rats presented decreased EPC counts in comparison to control animals. Immunosuppressive therapy was able to restore normal EPC values in 5/6 rats. These effects on EPC number were associated with reduced number of CD26+ cells, which might be related to consequent accumulation of SDF-1.Conclusions
We conclude that kidney transplantation and its associated use of immunosuppressive drugs increases the number of circulating EPCs via the manipulation of the CD26/SDF-1 axis. Increased EPC count may be associated to endothelial repair and function in these patients. 相似文献13.
Livio Azzoni Andrea S. Foulkes Yan Liu Xiaohong Li Margaret Johnson Collette Smith Adeeba bte Kamarulzaman Julio Montaner Karam Mounzer Michael Saag Pedro Cahn Carina Cesar Alejandro Krolewiecki Ian Sanne Luis J. Montaner 《PLoS medicine》2012,9(4)
Background
Global programs of anti-HIV treatment depend on sustained laboratory capacity to assess treatment initiation thresholds and treatment response over time. Currently, there is no valid alternative to CD4 count testing for monitoring immunologic responses to treatment, but laboratory cost and capacity limit access to CD4 testing in resource-constrained settings. Thus, methods to prioritize patients for CD4 count testing could improve treatment monitoring by optimizing resource allocation.Methods and Findings
Using a prospective cohort of HIV-infected patients (n = 1,956) monitored upon antiretroviral therapy initiation in seven clinical sites with distinct geographical and socio-economic settings, we retrospectively apply a novel prediction-based classification (PBC) modeling method. The model uses repeatedly measured biomarkers (white blood cell count and lymphocyte percent) to predict CD4+ T cell outcome through first-stage modeling and subsequent classification based on clinically relevant thresholds (CD4+ T cell count of 200 or 350 cells/µl). The algorithm correctly classified 90% (cross-validation estimate = 91.5%, standard deviation [SD] = 4.5%) of CD4 count measurements <200 cells/µl in the first year of follow-up; if laboratory testing is applied only to patients predicted to be below the 200-cells/µl threshold, we estimate a potential savings of 54.3% (SD = 4.2%) in CD4 testing capacity. A capacity savings of 34% (SD = 3.9%) is predicted using a CD4 threshold of 350 cells/µl. Similar results were obtained over the 3 y of follow-up available (n = 619). Limitations include a need for future economic healthcare outcome analysis, a need for assessment of extensibility beyond the 3-y observation time, and the need to assign a false positive threshold.Conclusions
Our results support the use of PBC modeling as a triage point at the laboratory, lessening the need for laboratory-based CD4+ T cell count testing; implementation of this tool could help optimize the use of laboratory resources, directing CD4 testing towards higher-risk patients. However, further prospective studies and economic analyses are needed to demonstrate that the PBC model can be effectively applied in clinical settings. Please see later in the article for the Editors'' Summary 相似文献14.
Maman D Pujades-Rodriguez M Subtil F Pinoges L McGuire M Ecochard R Etard JF 《PloS one》2012,7(2):e31078
Background
In sub-Saharan Africa, men living with HIV often start ART at more advanced stages of disease and have higher early mortality than women. We investigated gender difference in long-term immune reconstitution.Methods/Principal Findings
Antiretroviral-naïve adults who received ART for at least 9 months in four HIV programs in sub-Saharan Africa were included. Multivariate mixed linear models were used to examine gender differences in immune reconstitution on first line ART.A total of 21,708 patients (68% women) contributed to 61,912 person-years of follow-up. At ART start,. Median CD4 at ART were 149 [IQR 85–206] for women and 125 cells/µL [IQR 63–187] for men. After the first year on ART, immune recovery was higher in women than in men, and gender-based differences increased by 20 CD4 cells/µL per year on average (95% CI 16–23; P<0.001). Up to 6 years after ART start, patients with low initial CD4 levels experienced similar gains compared to patients with high initial levels, including those with CD4>250cells/µL (difference between patients with <50 cells/µL and those with >250 was 284 cells/µL; 95% CI 272–296; LR test for interaction with time p = 0.63). Among patients with initial CD4 count of 150–200 cells/µL, women reached 500 CD4 cells after 2.4 years on ART (95% CI 2.4–2.5) and men after 4.5 years (95% CI 4.1–4.8) of ART use.Conclusion
Women achieved better long-term immune response to ART, reaching CD4 level associated with lower risks of AIDS related morbidity and mortality quicker than men. 相似文献15.
Background/Objective
The diagnosis of tuberculous meningitis (TBM) in resource poor TB endemic environments is challenging. The accuracy of current tools for the rapid diagnosis of TBM is suboptimal. We sought to develop a clinical-prediction rule for the diagnosis of TBM in a high HIV prevalence setting, and to compare performance outcomes to conventional diagnostic modalities and a novel lipoarabinomannan (LAM) antigen detection test (Clearview-TB®) using cerebrospinal fluid (CSF).Methods
Patients with suspected TBM were classified as definite-TBM (CSF culture or PCR positive), probable-TBM and non-TBM.Results
Of the 150 patients, 84% were HIV-infected (median [IQR] CD4 count = 132 [54; 241] cells/µl). There were 39, 55 and 54 patients in the definite, probable and non-TBM groups, respectively. The LAM sensitivity and specificity (95%CI) was 31% (17;48) and 94% (85;99), respectively (cut-point ≥0.18). By contrast, smear-microscopy was 100% specific but detected none of the definite-TBM cases. LAM positivity was associated with HIV co-infection and low CD4 T cell count (CD4<200 vs. >200 cells/µl; p = 0.03). The sensitivity and specificity in those with a CD4<100 cells/µl was 50% (27;73) and 95% (74;99), respectively. A clinical-prediction rule ≥6 derived from multivariate analysis had a sensitivity and specificity (95%CI) of 47% (31;64) and 98% (90;100), respectively. When LAM was combined with the clinical-prediction-rule, the sensitivity increased significantly (p<0.001) to 63% (47;68) and specificity remained high at 93% (82;98).Conclusions
Despite its modest sensitivity the LAM ELISA is an accurate rapid rule-in test for TBM that has incremental value over smear-microscopy. The rule-in value of LAM can be further increased by combination with a clinical-prediction rule, thus enhancing the rapid diagnosis of TBM in HIV-infected persons with advanced immunosuppression. 相似文献16.
17.
Granich R Kahn JG Bennett R Holmes CB Garg N Serenata C Sabin ML Makhlouf-Obermeyer C De Filippo Mack C Williams P Jones L Smyth C Kutch KA Ying-Ru L Vitoria M Souteyrand Y Crowley S Korenromp EL Williams BG 《PloS one》2012,7(2):e30216
Background
Antiretroviral Treatment (ART) significantly reduces HIV transmission. We conducted a cost-effectiveness analysis of the impact of expanded ART in South Africa.Methods
We model a best case scenario of 90% annual HIV testing coverage in adults 15–49 years old and four ART eligibility scenarios: CD4 count <200 cells/mm3 (current practice), CD4 count <350, CD4 count <500, all CD4 levels. 2011–2050 outcomes include deaths, disability adjusted life years (DALYs), HIV infections, cost, and cost per DALY averted. Service and ART costs reflect South African data and international generic prices. ART reduces transmission by 92%. We conducted sensitivity analyses.Results
Expanding ART to CD4 count <350 cells/mm3 prevents an estimated 265,000 (17%) and 1.3 million (15%) new HIV infections over 5 and 40 years, respectively. Cumulative deaths decline 15%, from 12.5 to 10.6 million; DALYs by 14% from 109 to 93 million over 40 years. Costs drop $504 million over 5 years and $3.9 billion over 40 years with breakeven by 2013. Compared with the current scenario, expanding to <500 prevents an additional 585,000 and 3 million new HIV infections over 5 and 40 years, respectively. Expanding to all CD4 levels decreases HIV infections by 3.3 million (45%) and costs by $10 billion over 40 years, with breakeven by 2023. By 2050, using higher ART and monitoring costs, all CD4 levels saves $0.6 billion versus current; other ART scenarios cost $9–194 per DALY averted. If ART reduces transmission by 99%, savings from all CD4 levels reach $17.5 billion. Sensitivity analyses suggest that poor retention and predominant acute phase transmission reduce DALYs averted by 26% and savings by 7%.Conclusion
Increasing the provision of ART to <350 cells/mm3 may significantly reduce costs while reducing the HIV burden. Feasibility including HIV testing and ART uptake, retention, and adherence should be evaluated. 相似文献18.
Sbiera S Dexneit T Reichardt SD Michel KD van den Brandt J Schmull S Kraus L Beyer M Mlynski R Wortmann S Allolio B Reichardt HM Fassnacht M 《PloS one》2011,6(9):e24345
Background
Pre- and early clinical studies on patients with autoimmune diseases suggested that induction of regulatory T(Treg) cells may contribute to the immunosuppressive effects of glucocorticoids(GCs).Objective
We readdressed the influence of GC therapy on Treg cells in immunocompetent human subjects and naïve mice.Methods
Mice were treated with increasing doses of intravenous dexamethasone followed by oral taper, and Treg cells in spleen and blood were analyzed by FACS. Sixteen patients with sudden hearing loss but without an inflammatory disease received high-dose intravenous prednisolone followed by stepwise dose reduction to low oral prednisolone. Peripheral blood Treg cells were analyzed prior and after a 14 day GC therapy based on different markers.Results
Repeated GC administration to mice for three days dose-dependently decreased the absolute numbers of Treg cells in blood (100 mg dexamethasone/kg body weight: 2.8±1.8×104 cells/ml vs. 33±11×104 in control mice) and spleen (dexamethasone: 2.8±1.9×105/spleen vs. 95±22×105/spleen in control mice), which slowly recovered after 14 days taper in spleen but not in blood. The relative frequency of FOXP3+ Treg cells amongst the CD4+ T cells also decreased in a dose dependent manner with the effect being more pronounced in blood than in spleen. The suppressive capacity of Treg cells was unaltered by GC treatment in vitro. In immunocompetent humans, GCs induced mild T cell lymphocytosis. However, it did not change the relative frequency of circulating Treg cells in a relevant manner, although there was some variation depending on the definition of the Treg cells (FOXP3+: 4.0±1.5% vs 3.4±1.5%*; AITR+: 0.6±0.4 vs 0.5±0.3%, CD127low: 4.0±1.3 vs 5.0±3.0%* and CTLA4+: 13.8±11.5 vs 15.6±12.5%; * p<0.05).Conclusion
Short-term GC therapy does not induce the hitherto supposed increase in circulating Treg cell frequency, neither in immunocompetent humans nor in mice. Thus, it is questionable that the clinical efficacy of GCs is achieved by modulating Treg cell numbers. 相似文献19.
Schöni-Affolter F Keiser O Mwango A Stringer J Ledergerber B Mulenga L Bucher HC Westfall AO Calmy A Boulle A Chintu N Egger M Chi BH;Swiss HIV Cohort Study;IeDEA Southern Africa 《PloS one》2011,6(12):e27919
Background
Loss to follow-up (LTFU) is common in antiretroviral therapy (ART) programmes. Mortality is a competing risk (CR) for LTFU; however, it is often overlooked in cohort analyses. We examined how the CR of death affected LTFU estimates in Zambia and Switzerland.Methods and Findings
HIV-infected patients aged ≥18 years who started ART 2004–2008 in observational cohorts in Zambia and Switzerland were included. We compared standard Kaplan-Meier curves with CR cumulative incidence. We calculated hazard ratios for LTFU across CD4 cell count strata using cause-specific Cox models, or Fine and Gray subdistribution models, adjusting for age, gender, body mass index and clinical stage. 89,339 patients from Zambia and 1,860 patients from Switzerland were included. 12,237 patients (13.7%) in Zambia and 129 patients (6.9%) in Switzerland were LTFU and 8,498 (9.5%) and 29 patients (1.6%), respectively, died. In Zambia, the probability of LTFU was overestimated in Kaplan-Meier curves: estimates at 3.5 years were 29.3% for patients starting ART with CD4 cells <100 cells/µl and 15.4% among patients starting with ≥350 cells/µL. The estimates from CR cumulative incidence were 22.9% and 13.6%, respectively. Little difference was found between naïve and CR analyses in Switzerland since only few patients died. The results from Cox and Fine and Gray models were similar: in Zambia the risk of loss to follow-up and death increased with decreasing CD4 counts at the start of ART, whereas in Switzerland there was a trend in the opposite direction, with patients with higher CD4 cell counts more likely to be lost to follow-up.Conclusions
In ART programmes in low-income settings the competing risk of death can substantially bias standard analyses of LTFU. The CD4 cell count and other prognostic factors may be differentially associated with LTFU in low-income and high-income settings. 相似文献20.
Crabtree-Ramírez B Caro-Vega Y Shepherd BE Wehbe F Cesar C Cortés C Padgett D Koenig S Gotuzzo E Cahn P McGowan C Masys D Sierra-Madero J;CCASAnet Team 《PloS one》2011,6(5):e20272