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1.
Kate Shearer Matthew P. Fox Mhairi Maskew Rebecca Berhanu Lawrence Long Ian Sanne 《PloS one》2013,8(8)
Introduction
Recent WHO guidelines for resource-limited settings recommend tenofovir in first-line antiretroviral therapy (ART) yet there are suggestions that patients receiving nevirapine with tenofovir have worse outcomes than those receiving efavirenz. We sought to compare outcomes among those taking nevirapine vs. efavirenz with tenofovir and lamivudine.Methods
We analyzed data on ART naïve, non-pregnant patients, ≥18 years old without tuberculosis co-infection, initiating tenofovir with lamivudine and either nevirapine or efavirenz between April 1, 2010 and July 31, 2011 (when South Africa’s public-sector use of tenofovir began) at Themba Lethu Clinic in South Africa. We measured virologic suppression (viral load <400 copies/ml), virologic failure (2 consecutive viral loads >1000 copies/ml), and attrition (death/loss to follow-up) all at 12 months after ART initiation. Modified Poisson regression with robust error estimation was used to estimate risk ratios (RR) and 95% confidence intervals (CI) for predictors of each outcome.Results
2,254 patients were prescribed efavirenz, 131 nevirapine. Patients were followed a median (range) of 12.0 (0.1–12.0) person-months. 62.2% were female and median (IQR) age was 37.7 years (31.5–44.1). Patients prescribed efavirenz had similar initiating CD4 counts (median 132 for both regimens) but were somewhat more likely to be WHO Stage III or IV (39.6% vs. 33.6%) than those prescribed nevirapine. No difference in attrition was found (aRR: 0.83; 95% CI: 0.49–1.41). Among patients with ≥1 viral load within 1 year on ART, those prescribed nevirapine were as likely to reach virologic suppression (aRR: 0.97; 95% CI: 0.88–1.07) but more likely to experience virologic failure (aRR: 1.84; 95% CI: 1.02–3.31) than those prescribed efavirenz.Conclusions
Our results support the notion that, among patients prescribed tenofovir and lamivudine, virologic failure is more common among those taking nevirapine than among those taking efavirenz. Longer-term follow up and larger studies will be needed to confirm this finding. 相似文献2.
Background
In children and adolescents with fever in neutropenia (FN) during chemotherapy for cancer, hemoglobin ≥90 g/L at presentation with FN had been associated with adverse events (AE). This analysis explored three hypothetical pathophysiological mechanisms potentially explaining this counterintuitive finding, and further analyzed the statistical association between hemoglobin and AE.Methods
Two of 8 centers, reporting on 311 of 421 FN episodes in 138 of 215 patients participated in this retrospective analysis based on prospectively collected data from three databases (SPOG 2003 FN, transfusion and hematology laboratories). Associations with AE were analyzed using mixed logistic regression.Results
Hemoglobin was ≥90 g/L in 141 (45%) of 311 FN episodes, specifically in 59/103 (57%) episodes with AE, and in 82/208 (39%) without (OR, 2.3; 99%CI, 1.1–4.9; P = 0.004). In FN with AE, hemoglobin was bimodally distributed with a dip around 85 g/L. There were no significant interactions for center, age and sex. In multivariate mixed logistic regression, AE was significantly and independently associated with leukopenia (leukocytes <0.3 G/L; OR, 3.3; 99%CI, 1.1–99; P = 0.004), dehydration (hemoglobinPresentation/hemoglobin8–72 hours ≥1.10 in untransfused patients; OR, 3.5; 99%CI, 1.1–11.4; P = 0.006) and non-moderate anemia (difference from 85 g/L; 1.6 per 10 g/L; 1.0–2.6; P = 0.005), but not with recent transfusion of packed red blood cells (pRBC), very recent transfusion of pRBC or platelets, or with hemoglobin ≥90 g/L as such.Conclusions
Non-moderate anemia and dehydration were significantly and relevantly associated with the risk of AE in children with cancer and FN. These results need validation in prospective cohorts before clinical implementation. 相似文献3.
Anitha Moorthy Amita Gupta Ramesh Bhosale Srikanth Tripathy Jayagowri Sastry Smita Kulkarni Madhuri Thakar Renu Bharadwaj Anju Kagal Arvind V. Bhore Sandesh Patil Vandana Kulkarni Varadharajan Venkataramani Usha Balasubramaniam Nishi Suryavanshi Carrie Ziemniak Nikhil Gupte Robert Bollinger Deborah Persaud for the India SWEN Study Team 《PloS one》2009,4(1)
Background
Daily nevirapine (NVP) prophylaxis to HIV-exposed infants significantly reduces breast-milk HIV transmission. We assessed NVP-resistance in Indian infants enrolled in the “six-week extended-dose nevirapine” (SWEN) trial who received single-dose NVP (SD-NVP) or SWEN for prevention of breast-milk HIV transmission but who also acquired subtype C HIV infection during the first year of life.Methods/Findings
Standard population sequencing and cloning for viral subpopulations present at ≥5% frequency were used to determine HIV genotypes from 94% of the 79 infected Indian infants studied. Timing of infection was defined based on when an infant''s blood sample first tested positive for HIV DNA. SWEN-exposed infants diagnosed with HIV by six weeks of age had a significantly higher prevalence of NVP-resistance than those who received SD-NVP, by both standard population sequencing (92% of 12 vs. 38% of 29; p = 0.002) and low frequency clonal analysis (92% of 12 vs. 59% of 29; p = 0.06). Likelihood of infection with NVP-resistant HIV through breast-milk among infants infected after age six weeks was substantial, but prevalence of NVP-resistance did not differ among SWEN or SD-NVP exposed infants by standard population sequencing (15% of 13 vs. 15% of 20; p = 1.00) and clonal analysis (31% of 13 vs. 40% of 20; p = 0.72). Types of NVP-resistance mutations and patterns of persistence at one year of age were similar between the two groups. NVP-resistance mutations did differ by timing of HIV infection; the Y181C variant was predominant among infants diagnosed in the first six weeks of life, compared to Y188C/H during late breast-milk transmission.Conclusions/Significance
Use of SWEN to prevent breast-milk HIV transmission carries a high likelihood of resistance if infection occurs in the first six weeks of life. Moreover, there was a continued risk of transmission of NVP-resistant HIV through breastfeeding during the first year of life, but did not differ between SD-NVP and SWEN groups. As with SD-NVP, the value of preventing HIV infection in a large number of infants should be considered alongside the high risk of resistance associated with extended NVP prophylaxis.Trial Registration
ClinicalTrials.gov NCT00061321相似文献4.
Wen-Chi Chen Jin-Shiung Cheng Po-Hung Chiang Feng-Woei Tsay Hoi-Hung Chan Hsueh-Wen Chang Hsien-Chung Yu Wei-Lun Tsai Kwok-Hung Lai Ping-I Hsu 《PloS one》2015,10(6)
Background
Nucleos(t)ide analogues reduce the incidence of hepatitis B virus (HBV) reactivation in cancer patients undergoing systemic cytotoxic chemotherapy but the experience of solid tumors remains limited. Aims. The aim of this study was to compare the efficacy of entecavir and lamivudine in the prophylaxis of HBV reactivation in solid tumor patients undergoing systemic cytotoxic chemotherapy.Methods
HBsAg seropositive patients undergoing systemic cytotoxic chemotherapy for solid tumors with prophylactic entecavir and lamivudine between January 2006 and June 2013 were retrospectively investigated. The incidence of HBV reactivation and outcome of the patients were analyzed. The risk factors of HBV reactivation were examined.Results
A total of 213 patients (entecavir group, 70 patients; lamivudine group, 143 patients) were evaluated. Less incidence of HBV reactivation was noticed in entecavir group than in lamivudine group (0% vs. 7.0%, P = 0.02). No HBV reactivation was noticed in the patients with a baseline HBV DNA level < 2000 IU/mL. A baseline HBV DNA level ≥ 2000 IU/mL, HBeAg, and lamivudine were significantly associated with HBV reactivation. Subgroup analysis of the patients with a baseline HBV DNA level ≥ 2000 IU/mL found that lamivudine was significantly associated with HBV reactivation. Most of the reactivation events were properly managed by using tenofovir disoproxil fumarate. The incidence of hepatitis during chemotherapy and disruption of chemotherapy was similar between patients using entecavir and lamivudine with a baseline HBV DNA level ≥ or < 2000 IU/mL.Conclusions
A baseline HBV DNA level ≥ 2000 IU/mL, HBeAg, and lamivudine were the risk factors of HBV reactivation during systemic cytotoxic chemotherapy in solid tumor patients. Entecavir was superior to lamivudine in terms of less incidence of reactivation in the patients with a baseline HBV DNA level ≥ 2000 IU/mL. Both agents were equally efficacious in the patients with HBV DNA levels < 2000 IU/mL. 相似文献5.
Patrice Tchendjou Chantal Same-Ekobo Annie Nga Mathurin Tejiokem Anfumbom Kfutwah Anne Njom Nlend Landry Tsague Anne Cécile Bissek Daniel Ekoa Joanna Orne-Gliemann Dominique Rousset Régis Pouillot Fran?ois Dabis 《PloS one》2010,5(4)
Background
Multidrug antiretroviral (ARV) regimens including HAART and short-course dual antiretroviral (sc-dARV) regimens were introduced in 2004 to improve Prevention of Mother-to-Child Transmission (PMTCT) in Cameroon. We assessed the effectiveness of these regimens from 6–10 weeks and 12 months of age, respectively.Methodology/Findings
We conducted a retrospective cohort study covering the period from October 2004 to March 2008 in a reference hospital in Cameroon. HIV-positive pregnant women with CD4 ≤350 cells/mm3 received first-line HAART [regimen 1] while the others received ARV prophylaxis including sc-dARV or single dose nevirapine (sd-NVP). Sc-dARV included at least two drugs according to different gestational ages: zidovudine (ZDV) from 28–32 weeks plus sd-NVP [regimen 2], ZDV and lamuvidine (3TC) from 33–36 weeks plus sd-NVP [regimen 3]. When gestational age was ≥37 weeks, women received sd-NVP during labour [regimen 4]. Infants received sd-NVP plus ZDV and 3TC for 7 days or 30 days. Early diagnosis (6–10 weeks) was done, using b-DNA and subsequently RT-PCR. We determined early MTCT rate and associated risk factors using logistic regression. The 12-month HIV-free survival was assessed using Cox regression. Among 418 mothers, 335 (80%) received multidrug ARV regimens (1, 2, and 3) and MTCT rate with multidrug regimens was 6.6% [95%CI: 4.3–9.6] at 6 weeks, without any significant difference between regimens. Duration of mother''s ARV regimen <4 weeks [OR = 4.7, 95%CI: 1.3–17.6], mother''s CD4 <350 cells/mm3 [OR = 6.4, 95%CI: 1.8–22.5] and low birth weight [OR = 4.0, 95%CI: 1.4–11.3] were associated with early MTCT. By 12 months, mixed feeding [HR = 8.7, 95%CI: 3.6–20.6], prematurity [HR = 2.3, 95%CI: 1.2–4.3] and low birth weight were associated with children''s risk of progressing to infection or death.Conclusions
Multidrug ARV regimens for PMTCT are feasible and effective in routine reference hospital. Early initiation of ARV during pregnancy and proper obstetrical care are essential to improve PMTCT. 相似文献6.
Erna Morden Karl-Günter Technau Janet Giddy Nicola Maxwell Olivia Keiser Mary-Ann Davies 《PloS one》2016,11(4)
BackgroundHIV-exposed uninfected (HEU) infants are a growing population in sub-Saharan Africa especially with the increasing coverage of more effective prevention of mother-to-child transmission (PMTCT) antiretroviral therapy regimens. This study describes the characteristics of South African HEU infants, investigates factors impacting birth weight and assesses their growth within the first 28 weeks of life.MethodsThis is a retrospective cohort based on routine clinical data from two South African PMTCT programmes. Data were collected between 2007 and 2013. Linear regression assessed factors affecting birth weight-for-age z-scores (WAZ) while growth (longitudinal WAZ) was assessed using mixed effects models.ResultsWe assessed the growth of 2621 HEU infants (median birth WAZ was -0.65 (IQR -1.46; 0.0) and 51% were male). The feeding modalities practised were as follows: 0.5% exclusive breastfeeding, 7.9% breastfeeding with unknown exclusivity, 0.08% mixed breastfeeding and 89.2% formula feeding. Mothers with CD4 <200 cells/μl delivered infants with a lower birth WAZ (adjusted ß -0.253 [95% CI -0.043; -0.072], p = 0.006) compared to mothers with aCD4 ≥500 cells/μl. Similarly, mothers who did not receive antiretroviral drugs delivered infants with a lower birth WAZ (adjusted ß -0.39 [95% CI -0.67; -0.11], p = 0.007) compared to mothers who received antenatal antiretrovirals. Infants with a birth weight <2 500g (ß 0.070 [95% CI 0.061; 0.078], p <0.0001) experienced faster growth within the first 28 weeks of life compared to infants with a birth weight ≥2 500g. Infants with any breastfeeding exposure experienced slower longitudinal growth compared to formula fed infants (adjusted ß -0.012 [95% CI 0.021; -0.003], p = 0.011).ConclusionLess severe maternal disease and the use of antiretrovirals positively impacts birth weight in this cohort of South African HEU infants. Formula feeding was common with breastfed infants experiencing marginally slower longitudinal growth. 相似文献
7.
Kirsten Salado-Rasmussen Zahra P. Theilgaard Mercy G. Chiduo Ib C. Bygbjerg Jan Gerstoft Margrethe Lüneborg-Nielsen Martha Lemnge Terese L. Katzenstein 《PloS one》2015,10(3)
Introduction
Risk factors for breast milk transmission of HIV-1 from mother to child include high plasma and breast milk viral load, low maternal CD4 count and breast pathology such as mastitis.Objective
To determine the impact of nevirapine and subclinical mastitis on HIV-1 RNA in maternal plasma and breast milk after intrapartum single-dose nevirapine combined with either 1-week tail of Combivir (zidovudine/lamivudine) or single-dose Truvada (tenofovir/emtricitabine).Methods
Maternal plasma and bilateral breast milk samples were collected between April 2008 and April 2011 at 1, 4 and 6 weeks postpartum from HIV-infected Tanzanian women. Moreover, plasma samples were collected at delivery from mother and infant.Results
HIV-1 RNA was quantified in 1,212 breast milk samples from 273 women. At delivery, 96% of the women and 99% of the infants had detectable nevirapine in plasma with a median (interquartile range, IQR) of 1.5 μg/mL (0.75–2.20 μg/mL) and 1.04 μg/mL (0.39–1.71 μg/mL), respectively (P < 0.001). At 1 week postpartum, 93% and 98% of the women had detectable nevirapine in plasma and breast milk, with a median (IQR) of 0.13 μg/mL (0.13–0.39 μg/mL) and 0.22 μg/mL (0.13–0.34 μg/mL), respectively. Maternal plasma and breast milk HIV-1 RNA correlated at all visits (R = 0.48, R = 0.7, R = 0.59; all P = 0.01). Subclinical mastitis was detected in 67% of the women at some time during 6 weeks, and in 38% of the breast milk samples. Breast milk samples with subclinical mastitis had significantly higher HIV-1 RNA at 1, 4 and 6 weeks (all P < 0.05).Conclusion
After short-course antiretroviral prophylaxis, nevirapine was detectable in most infant cord blood samples and the concentration in maternal plasma and breast milk was high through week 1 accompanied by suppressed HIV-1 RNA in plasma and breast milk. 相似文献8.
Carmen J Marsit Sean S Brummel Deborah Kacanek George R Seage III Stephen A Spector David A Armstrong Barry M Lester Kenneth Rich for the Pediatric HIV/AIDS Cohort Studies Network 《Epigenetics》2015,10(8):708-716
The use of combination antiretroviral therapy (cART) to prevent HIV mother-to-child transmission during pregnancy and delivery is generally considered safe. However, vigilant assessment of potential risks of these agents remains warranted. Epigenetic changes including DNA methylation are considered potential mechanisms linking the in utero environment with long-term health outcomes. Few studies have examined the epigenetic effects of prenatal exposure to pharmaceutical agents, including antiretroviral therapies, on children. In this study, we examined the methylation status of the LINE-1 and ALU-Yb8 repetitive elements as markers of global DNA methylation alteration in peripheral blood mononuclear cells obtained from newborns participating in the Pediatric HIV/AIDS Cohort Study SMARTT cohort of HIV-exposed, cART-exposed uninfected infants compared to a historical cohort of HIV-exposed, antiretroviral-unexposed infants from the Women and Infants Transmission Study Cohort. In linear regression models controlling for potential confounders, we found the adjusted mean difference of AluYb8 methylation of the cART-exposed compared to the -unexposed was −0.568 (95% CI: −1.023, −0.149) and for LINE-1 methylation was −1.359 (95% CI: −1.860, −0.857). Among those exposed to cART, subjects treated with atazanavir (ATV), compared to those on other treatments, had less AluYb8 methylation (−0.524, 95% CI: −0.025, −1.024). Overall, these results suggest a small but statistically significant reduction in the methylation of these repetitive elements in an HIV-exposed, cART-exposed cohort compared to an HIV-exposed, cART-unexposed historic cohort. The potential long-term implications of these differences are worthy of further examination. 相似文献
9.
Judith Ziske Andrea Kunz Julius Sewangi Inga Lau Festo Dugange Andrea Hauser Wolf Kirschner Gundel Harms Stefanie Theuring 《PloS one》2013,8(2)
Introduction
Tanzanian guidelines for prevention of mother-to-child-transmission of HIV (PMTCT) recommend an antiretroviral combination regimen involving zidovudine (AZT) during pregnancy, single-dosed nevirapine at labor onset, AZT plus Lamivudine (3TC) during delivery, and AZT/3TC for 1–4 weeks postpartum. As drug toxicities are a relevant concern, we assessed hematological alterations in AZT-exposed women and their infants.Methods and Materials
A cohort of HIV-positive women, either with AZT intake (n = 82, group 1) or without AZT intake (n = 62, group 2) for PMTCT during pregnancy, was established at Kyela District Hospital, Tanzania. The cohort also included the infants of group 1 with an in-utero AZT exposure ≥4 weeks, receiving AZT for 1 week postpartum (n = 41), and infants of group 2 without in-utero AZT exposure, receiving a prolonged 4-week AZT tail (n = 58). Complete blood counts were evaluated during pregnancy, birth, weeks 4–6 and 12.Results
For women of group 1 with antenatal AZT intake, we found a statistically significant decrease in hemoglobin level, red blood cells, white blood cells, granulocytes, as well as an increase in red cell distribution width and platelet count. At delivery, the median red blood cell count was significantly lower and the median platelet count was significantly higher in women of group 1 compared to group 2. At birth, infants from group 1 showed a lower median hemoglobin level and granulocyte count and a higher frequency of anemia and granulocytopenia. At 4–6 weeks postpartum, the mean neutrophil granulocyte count was significantly lower and neutropenia was significantly more frequent in infants of group 2.Conclusions
AZT exposure during pregnancy as well as after birth resulted in significant hematological alterations for women and their newborns, although these changes were mostly mild and transient in nature. Research involving larger cohorts is needed to further analyze the impact of AZT-containing regimens on maternal and infant health. 相似文献10.
V von Wyl V Cambiano MR Jordan S Bertagnolio A Miners D Pillay J Lundgren AN Phillips 《PloS one》2012,7(8):e42834
Background
The most recent World Health Organization (WHO) antiretroviral treatment guidelines recommend the inclusion of zidovudine (ZDV) or tenofovir (TDF) in first-line therapy. We conducted a cost-effectiveness analysis with emphasis on emerging patterns of drug resistance upon treatment failure and their impact on second-line therapy.Methods
We used a stochastic simulation of a generalized HIV-1 epidemic in sub-Saharan Africa to compare two strategies for first-line combination antiretroviral treatment including lamivudine, nevirapine and either ZDV or TDF. Model input parameters were derived from literature and, for the simulation of resistance pathways, estimated from drug resistance data obtained after first-line treatment failure in settings without virological monitoring. Treatment failure and cost effectiveness were determined based on WHO definitions. Two scenarios with optimistic (no emergence; base) and pessimistic (extensive emergence) assumptions regarding occurrence of multidrug resistance patterns were tested.Results
In the base scenario, cumulative proportions of treatment failure according to WHO criteria were higher among first-line ZDV users (median after six years 36% [95% simulation interval 32%; 39%]) compared with first-line TDF users (31% [29%; 33%]). Consequently, a higher proportion initiated second-line therapy (including lamivudine, boosted protease inhibitors and either ZDV or TDF) in the first-line ZDV user group 34% [31%; 37%] relative to first-line TDF users (30% [27%; 32%]). At the time of second-line initiation, a higher proportion (16%) of first-line ZDV users harboured TDF-resistant HIV compared with ZDV-resistant viruses among first-line TDF users (0% and 6% in base and pessimistic scenarios, respectively). In the base scenario, the incremental cost effectiveness ratio with respect to quality adjusted life years (QALY) was US$83 when TDF instead of ZDV was used in first-line therapy (pessimistic scenario: US$ 315), which was below the WHO threshold for high cost effectiveness (US$ 2154).Conclusions
Using TDF instead of ZDV in first-line treatment in resource-limited settings is very cost-effective and likely to better preserve future treatment options in absence of virological monitoring. 相似文献11.
Catherine Adler Edwige Haelterman Patricia Barlow Arnaud Marchant Jack Levy Tessa Goetghebuer 《PloS one》2015,10(8)
Background
Several studies indicate that HIV-exposed uninfected (HEU) children have a high infectious morbidity. We previously reported an increased incidence of group B streptococcus (GBS) infections in HEU infants born in Belgium.Methods
This study was undertaken to evaluate the incidence and risk factors of all cause severe infections in HEU infants born in Belgium between 1985 and 2006, including the pre-antiretroviral (ARV) prophylaxis era (1985 to 1994). The medical charts of 537 HEU infants followed in a single center were reviewed.Results
The incidence rate of severe infections during the first year of life was 16.8/100 HEU infant-years. The rates of invasive S. pneumoniae (0.62/100 infant-years) and GBS infections (1.05/100 infant-years) were, respectively, 4 and 13-fold higher in HEU infants than in the general infant population. Preterm birth was a risk factor for severe infections in the neonatal period (aOR = 21.34, 95%CI:7.12–63.93) and post-neonatal period (aHR = 3.00, 95%CI:1.53–5.88). As compared to the pre-ARV prophylaxis era, infants born in the ARV prophylaxis era (i.e., after April 1994) had a greater risk of severe infections (aHR = 2.93; 95%CI:1.07–8.05). This risk excess was present in those who received ARV prophylaxis (aHR 2.01, 95%CI 0.72–5.65) and also in those born in the ARV prophylaxis era who did not benefit from ARV prophylaxis as a result of poor access to antenatal care or lack of compliance (aHR 3.06, 95%CI 0.88–10.66).Conclusions
In HEU infants born in an industrialized country, preterm birth and being born during the ARV prophylaxis era were risk factors of severe infections throughout the first year of life. These observations have important implications for the clinical management of HIV-infected mothers and their infants. 相似文献12.
Jiri Minarik Petr Pavlicek Ludek Pour Tomas Pika Vladimir Maisnar Ivan Spicka Jiri Jarkovsky Marta Krejci Jaroslav Bacovsky Jakub Radocha Jan Straub Petr Kessler Marek Wrobel Lenka Walterova Michal Sykora Jarmila Obernauerova Lucie Brozova Evzen Gregora Dagmar Adamova Jaromir Gumulec Zdenek Adam Vlastimil Scudla Roman Hajek for the Czech Myeloma Group 《PloS one》2015,10(4)
Objective
Subcutaneous (SC) application of bortezomib has been recently introduced as a new application route in multiple myeloma (MM) patients. We performed an analysis to compare the outcomes of bortezomib-based therapy in multiple myeloma (MM) patients treated using either intravenous (IV) or subcutaneous (SC) route of administration.Patients and methods
During January 2012 through December 2013, we performed a retrospective analysis of 446 patients with MM treated with bortezomib-based regimens (either once weekly – 63% or twice weekly – 27%) in both, the first line setting, and in relapse, with separate analysis of patients undergoing autologous stem cell transplantation. We assessed the response rates and toxicity profiles in both, IV and SC route of bortezomib administration.Results
The response rates in both IV and SC arm were similar with overall response rate 71.7% vs 70.7%, complete remissions in 13.9% vs 8.6%, very good partial remissions in 30.8% vs 34.5% and partial remissions in 27% vs 27.6%. The most frequent grade ≥3 toxicities were anemia, thrombocytopenia and neutropenia, with no significant differences between IV and SC group. There were no significant differences in the rate of peripheral neuropathy (PN). PN of any grade was present in 48% in the IV arm and in 41% in the SC arm. PN grade ≥2 was present in 20% vs 18% and PN grade ≥3 was present in 6% vs 4%.Conclusions
We conclude that subcutaneous application of bortezomib has similar therapeutic outcomes and toxicity profile as intravenous route of application. In our cohort there was no difference in the incidence of PN, suggesting that PN is dose dependent and might be reduced by lower intensity schemes rather than by the route of administration. 相似文献13.
Barassi C De Santis C Pastori C Marraccini P Ciuffreda D Capiluppi B Bressi C Siccardi AG Lazzarin A Tambussi G Lopalco L 《Journal of biological regulators and homeostatic agents》2000,14(1):68-74
We investigate the effects of highly active antiretroviral therapy (HAART) on humoral immune responses during a 24-month follow up of 15 HIV patients with acute primary HIV infection. The patients were divided into three groups on the basis of the therapeutic protocol they were following at the time of entry: a) five naive patients (untreated or treated with only ZDV or AZT); b) five patients following a triple combination of ZDV+ lamivudine (3TC)+ saquinovir (SQV); and c) five patients on a four-drug combination of ZDV+3TC+SQV+ ritonavir (RTV). The results show that the early introduction of HAART greatly reduces plasma viremia levels and restores the number of CD4 cells. A significant correlation was found between anti HIV neutralising activity and the four-drug, but not the three-drug combination. The reduction in infectivity was directed against viruses of different clades and associated with immunoglobulin fractions. Moreover, the neutralising antibodies in the HAART-treated patients appeared after two weeks of treatment and remained stable throughout the 24 months of follow up. The early appearance of neutralising antibodies represent an important component of immune responses during primary HIV infection, may contribute towards immune reconstitution in patients on HAART, and give further information that may be useful in developing new strategies designed to eradicate the disease. 相似文献
14.
Background
The combination of chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) currently has become the hotspot issue in the treatment of non-small lung cancer (NSCLC). This systematic review was conducted to compare the efficacy and safety of the synchronous combination of these two treatments with EGFR TKIs or chemotherapy alone in advanced NSCLC.Methods
EMBASE, PubMed, the Central Registry of Controlled Trials in the Cochrane Library (CENTRAL), Chinese biomedical literature database (CNKI) and meeting summaries were searched. The Phase II/III randomized controlled trials were selected by which patients with advanced NSCLC were randomized to receive a combination of EGFR TKIs and chemotherapy by synchronous mode vs. EGFR TKIs or chemotherapy alone.Results
A total of six randomized controlled trials (RCTs) including 4675 patients were enrolled in the systematic review. The meta-analysis demonstrated that the synchronous combination group of chemotherapy and EGFR TKIs did not reach satisfactory results; there was no significant difference in overall survival (OS), time to progression (TTP) and objective response rate (ORR), compared with monotherapy (OS: HR = 1.05, 95%CI = 0.98–1.12; TTP: HR = 0.94, 95%CI = 0.89–1.00; ORR: RR = 1.07, 95%CI = 0.98–1.17), and no significant difference in OS and progression-free survival (PFS), compared with EGFR TKIs alone (OS: HR = 1.10, 95% CI = 0.83–1.46; PFS: HR = 0.86, 95% CI = 0.67–1.10). The patients who received synchronous combined therapy presented with increased incidences of grade 3/4 anemia (RR = 1.40, 95% CI = 1.10–1.79) and rash (RR = 7.43, 95% CI = 4.56–12.09), compared with chemotherapy, grade 3/4 anemia (RR = 6.71, 95% CI = 1.25–35.93) and fatigue (RR = 9.60, 95% CI = 2.28–40.86) compared with EGFR TKI monotherapy.Conclusions
The synchronous combination of chemotherapy and TKIs is not superior to chemotherapy or EGFR TKIs alone for the first-line treatment of NSCLC. 相似文献15.
Roland Morley Alison Cardenas Peter Hawkins Yasuyo Suzuki Virginia Paton See-Chun Phan Mark Merchant Jessie Hsu Wei Yu Qi Xia Daniel Koralek Patricia Luhn Wassim Aldairy 《PloS one》2015,10(10)
Background
Onartuzumab, a recombinant humanized monovalent monoclonal antibody directed against MET, the receptor for the hepatocyte growth factor, has been investigated for the treatment of solid tumors. This publication describes the safety profile of onartuzumab in patients with solid tumors using data from the global onartuzumab clinical development program.Methods
Adverse event (AE) and laboratory data from onartuzumab phase II/III studies were analyzed and coded into standardized terms according to industry standards. The severity of AEs was assessed using the NCI Common Toxicity Criteria, Version 4. Medical Dictionary for Regulatory Activities (MedDRA) AEs were grouped using the standardized MedDRA queries (SMQs) “gastrointestinal (GI) perforation”, “embolic and thrombotic events, venous (VTE)”, and “embolic and thrombotic events, arterial (ATE)”, and the Adverse Event Group Term (AEGT) “edema.” The safety evaluable populations (patients who received at least one dose of study treatment) for each study were included in this analysis.Results
A total of 773 onartuzumab-treated patients from seven studies (phase II, n = 6; phase III, n = 1) were included. Edema and VTEs were reported in onartuzumab-treated patients in all seven studies. Edema events in onartuzumab arms were generally grade 1–2 in severity, observed more frequently than in control arms and at incidences ranging from 25.4−65.7% for all grades and from 1.2−14.1% for grade 3. Hypoalbuminemia was also more frequent in onartuzumab arms and observed at frequencies between 77.8% and 98.3%. The highest frequencies of all grade and grade ≥3 VTE events were 30.3% and 17.2%, respectively in onartuzumab arms. The cumulative incidence of all grade ATE events ranged from 0−5.6% (grade ≥3, 0−5.1%) in onartuzumab arms. The frequency of GI perforation was below 10% in all studies; the highest estimates were observed in studies with onartuzumab plus bevacizumab for all grades (0−6.2%) and grade ≥3 (0−6.2%).Conclusions
The frequencies of VTE, ATE, GI perforation, hypoalbuminemia, and edema in clinical studies were higher in patients receiving onartuzumab than in control arms; these are considered to be expected events in patients receiving onartuzumab. 相似文献16.
Marisa R. Young Robert C. Bailey Elijah Odoyo-June Tracy E. Irwin Walter Obiero Dedan O. Ongong'a Jacinta A. Badia Kawango Agot Sherry K. Nordstrom 《PloS one》2012,7(10)
Background
Several sub-Saharan African countries plan to scale-up infant male circumcision (IMC) for cost-efficient HIV prevention. Little data exist about the safety of IMC in East and southern Africa. We calculated adverse event (AE) rate and risks for AEs associated with introduction of IMC services at five government health facilities in western Kenya.Methods
AE data were analyzed for IMC procedures performed between September, 2009 and November, 2011. Healthy infants aged ≤2 months and weighing ≥2.5 kg were eligible for IMC. Following parental consent, trained clinicians provided IMC services free of charge under local anesthesia using the Mogen clamp. Odds ratios and 95% confidence intervals were used to explore AE risk factors.Findings
A total of 1,239 IMC procedures were performed. Median age of infants was 4 days (IQR = 1, 16). The overall AE rate among infants reviewed post-operatively was 2.7% (18/678; 95%CI: 1.4, 3.9). There was one severe AE involving excision of a small piece of the lateral aspect of the glans penis. Other AEs were mild or moderate and were treated conservatively. Babies one month of age or older were more likely to have an AE (OR 3.20; 95%CI: 1.23, 8.36). AE rate did not differ by nurse versus clinical officer or number of previous procedures performed.Conclusion
IMC services provided in Kenyan Government hospitals in the context of routine IMC programming have AE rates comparable to those in developed countries. The optimal time for IMC is within the first month of life. 相似文献17.
Kathryn M. Chu Andrew M. Boulle Nathan Ford Eric Goemaere Valerie Asselman Gilles Van Cutsem 《PloS one》2010,5(2)
Background
The majority of antiretroviral treatment programmes in sub-Saharan Africa are scaling up antiretroviral treatment using a fixed dose first-line antiretroviral regimen containing stavudine, lamivudine, and nevirapine. One of the primary concerns with the use of this regimen is nevirapine-associated hepatotoxicity.Methodology/Principal Findings
Study participants were 1809 HIV-infected, antiretroviral naïve adults initiating nevirapine-based antiretroviral therapy between November 2002 and December 2006. The primary outcome was early hepatotoxicity. Secondary outcomes were associations with hepatotoxicity and mortality at six months. The cumulative proportion of early hepatotoxicity ranged from 1.0–2.0% giving an incidence-rate at 102 days of 3.6–7.6 per 100 person-years. Median time to hepatotoxicity was 32 (IQR 28–58) days. At 12 weeks, only 8% of patients had alanine aminotransferase monitoring at all the time-points recommended by national guidelines. No association was found between age, gender, baseline CD4 count, concurrent tuberculosis infection, prior participation in a prevention of mother-to-child-transmission program, or baseline weight and early hepatotoxicity. There was no association between early hepatotoxicity and mortality.Conclusions
The cumulative proportion of early hepatotoxicity in nevirapine based antiretroviral therapy was low in this resource-constrained setting. Hepatotoxicity was not associated with mortality. Frequent routine monitoring of alanine aminotransferase proved difficult to implement in this public sector primary care programme. Focused monitoring in the first month may be a more cost-effective and pragmatic option in settings with limited resources. Correlation with clinical signs and symptoms may allow future alanine aminotransferase testing to be dictated by clinical criteria. 相似文献18.
Ira J. Dunkel Weiji Shi Kim Salvaggio Brian P. Marr Scott E. Brodie Y. Pierre Gobin David H. Abramson 《PloS one》2014,9(10)
Purpose
Intra-arterial chemotherapy is a promising strategy for intra-ocular retinoblastoma. Neutropenia is the most commonly encountered systemic toxicity and in this study we aimed to determine the risk factors associated with the development of severe (≥grade 3) neutropenia.Methods
Retrospective review of 187 evaluable cycles of melphalan-containing intra-arterial chemotherapy from the first three cycles administered to 106 patients with intra-ocular retinoblastoma from May 2006 to June 2011. Cycles were considered to be evaluable if (1) blood count results were available in the 7 to 14 days post-treatment interval and (2) concurrent intravenous chemotherapy was not administered. Toxicity was assessed via the Common Terminology Criteria for Adverse Events version 4.0.Results
54 cycles (29%) were associated with grade 3 (n = 43) or grade 4 (n = 11) neutropenia. Multivariate stepwise logistic regression revealed that a higher melphalan dose (>0.40 mg/kg) was significantly associated with severe neutropenia during all 3 cycles (odds ratio during cycle one 4.11, 95% confidence interval 1.33–12.73, p = 0.01), but the addition of topotecan and/or carboplatin were not. Prior treatment with systemic chemotherapy was not associated with severe neutropenia risk in any analysis.Conclusions
Intra-arterial melphalan-based chemotherapy can cause severe neutropenia, especially when a dose of greater than 0.40 mg/kg is administered. Further study with a larger sample may be warranted. 相似文献19.
Jayne Byakika-Tusiime Leslie W. Chinn Jessica H. Oyugi Celestino Obua David R. Bangsberg Deanna L. Kroetz 《PloS one》2008,3(12)
Background
Generic antiretroviral therapy is the mainstay of HIV treatment in resource-limited settings, yet there is little evidence confirming the bioequivalence of generic and brand name formulations. We compared the steady-state pharmacokinetics of lamivudine, stavudine and nevirapine in HIV-infected subjects who were receiving a generic formulation (Triomune®) or the corresponding brand formulations (Epivir®, Zerit®, and Viramune®).Methodology/Principal Findings
An open-label, randomized, crossover study was carried out in 18 HIV-infected Ugandan subjects stabilized on Triomune-40. Subjects received lamivudine (150 mg), stavudine (40 mg), and nevirapine (200 mg) in either the generic or brand formulation twice a day for 30 days, before switching to the other formulation. At the end of each treatment period, blood samples were collected over 12 h for pharmacokinetic analysis. The main outcome measures were the mean AUC0–12h and Cmax. Bioequivalence was defined as a geometric mean ratio between the generic and brand name within the 90% confidence interval of 0.8–1.25. The geometric mean ratios and the 90% confidence intervals were: stavudine Cmax, 1.3 (0.99–1.71) and AUC0–12h, 1.1 (0.87–1.38); lamivudine Cmax, 0.8 (0.63–0.98) and AUC0–12h, 0.8 (0.65–0.99); and nevirapine Cmax, 1.1 (0.95–1.23) and AUC0–12h, 1.1 (0.95–1.31). The generic formulation was not statistically bioequivalent to the brand formulations during steady state, although exposures were comparable. A mixed random effects model identified about 50% intersubject variability in the pharmacokinetic parameters.Conclusions/Significant Findings
These findings provide support for the use of Triomune in resource-limited settings, although identification of the sources of intersubject variability in these populations is critical. 相似文献20.
Raluca Buzdugan Sandra I. McCoy Constancia Watadzaushe Mi-Suk Kang Dufour Maya Petersen Jeffrey Dirawo Angela Mushavi Hilda Angela Mujuru Agnes Mahomva Reuben Musarandega Anna Hakobyan Owen Mugurungi Frances M. Cowan Nancy S. Padian 《PloS one》2015,10(8)