43例血友病/艾滋病患者经高效抗逆转录病毒治疗三年后免疫功能的观察

研究对43例血友病/艾滋病患者用高效抗逆转录病毒治疗三年,定期采用流式细胞仪检测CD4、CD3、CD8和NK细胞;病毒载量仪(bDNA)检测血浆病毒载量;同时检测血清免疫球蛋白及白细胞介素。结果表明,43例血友病/艾滋病患者在治疗三年后CD4+平均上升257/mm3(P<0.001),HIV RNA下降,治疗后平均降至(2.26±1.10)log/ml(P<0.0001),同时伴有IgA下降(P<0.05)IL-10,sIL-2R上升(P<0.05)。HAART能快速抑制HIV RNA的复制,纠正机体免疫功能紊乱和重建免疫功能。     

HAART对人类免疫缺陷病毒感染者淋巴细胞亚群的影响

应用流式细胞分析法通过分析检测41例AIDS患者与30例健康对照之间,以及21例AIDS患者在接受HAART治疗前后外周血淋巴细胞亚群的表达情况,研究感染HIV病毒以及HAART治疗对淋巴细胞亚群的影响。结果显示AIDS患者与健康对照相比,外周血CD4~+CD45RA~+、CD4~+CD28~+、CD4~+CD45RO~+、CD4~+CD95~+细胞比例明显低于正常对照,CD8~+CD95~+、CD8~+CD38~+、CD56~+细胞比例明显高于正常对照;经HAART治疗后,CD4~+CD45RA~+,CD4~+CD28~+细胞比例比治疗前升高,CD56~+细胞比例比治疗前显著下降。结果表明CD4~+T淋巴细胞表面CD45RA、CD28表达,以及CD56~+细胞能够预测AIDS患者HAART治疗效果。     

艾滋病HAART治疗免疫重建炎性综合征的免疫机制初步研究

目的 为探讨我国艾滋病病人(AIDS)启动高效抗反转录病毒治疗(HAART)后,发生免疫重建炎性综合征(IRIS)的免疫学发病机制,在前瞻性研究队列中对启动HAART的AIDS病人部分淋巴细胞亚群、调节性T细胞和部分Th1和Th2细胞因子等进行追踪分析.方法 将接受HAART初始治疗的238例AIDS病人建立前瞻性研究队列,分为在24周内发生IRIS的47例病人(IRIS组)和未发生IRIS的191例病人(非IRIS组).在HAART的0周、12周和24周采集两组血标本,对47例IRIS病例及随机选择的50例非IRIS病例进行免疫机制的研究分析,检测HIV病毒载量和CD4+细胞计数;使用流式细胞术检测部分淋巴细胞亚群和调节性T细胞(CD4+CD25+Foxp3+).在HAART的0周、4周、12周、24周及发生IRIS时分别采集全部238例患者的血标本,使用ELISA法测定血浆细胞因子IL-2、IFN-γ、IL-4、IL-10以及IL-7水平.结果 两组感染者的CD4+、CD8+纯真细胞和记忆细胞比例在0周、12周、24周及发生IRIS时比较差异均无统计学意义,但CD4+记忆细胞和CD8+记忆细胞比例在启动HAART后均明显上升.两组感染者CD4+CD38+活化细胞和CD8+CD38+活化细胞比例在基线时均较正常值明显升高,治疗后均有下降趋势.在0周、12周、24周及发生IRIS时CD4+CD25+Foxp3+调节性T细胞在IRIS组中均较非IRIS组要低.两组IL-2及IFN-γ在HAART后均呈上升趋势,且IRIS组在4周及发生IRIS时更明显高于非IRIS组;两组IL-4及IL-10在HAART后均呈下降趋势,IRIS组中IL-10在4周及发生IRIS时更明显低于非IRIS组.IL-7在两组中基线时均较正常值升高,并随HAART进程逐渐降低,其中IRIS组在各随访点IL-7均要高于非IRIS组.结论 接受HAART治疗者早期即出现记忆T细胞快速上升,在IRIS炎症反应中可能起重要作用.IL-2、IL-10和IFN-γ在发生IRIS时的水平差别,提示IRIS的发生与炎性细胞因子大量增加,炎性抑制因子相对不足有一定关系.IL-7也可能参与到IRIS的发病机制中.

Abstract：

Objective To investigate the immunological pathogenesis of immune reconstitution inflammatory syndrome (IRIS) during highly active antiretroviral therapy( HAART), in this prospective cohort study we analyzed the lymphocyte subsets, lymphocyte activation, changes in regulatory T cells, and levels of Th1 and Th2 cytokines in both IRIS and non-IRIS groups. Methods Two hundred and thirty-eight AIDS patients received HAART and participated prospective research cohort for 24 weeks follow-up. Forty-seven IRIS cases and 191 non-IRIS cases were enrolled in the IRIS group or non-IRIS group respectively. Blood samples were collected in both groups at pre- and post-HAART 12 weeks, 24 weeks. Using flow cytometer to detect the immunophenotypes of lymphocyte subsets (CD4 + CD45RA+ CD62L+, CD8+ CD45RA+ CD62L+naive T cells; CD4+ CD45RO+, CD8+ CD45RO+ memory T cells), activated T lymphocytes (CD4+CD38 +, CD8 + CD38 + cells), and regulatory T cell ( CD4 + CD25 + Foxp3 + ). Blood samples collected at pre-and post-HAART4 weeks, 12 weeks, 24 weeks and used ELISA to detect IL-2, IFN-γ, IL-4, IL-10and IL-7 cytokine serum levels. Results The percentages of CD4 + and CD8 + naive T cells and mlemory T cells exhibited no significant differences at the baseline, 12 weeks, 24 weeks of HAART initiation between both groups, but CD4 + and CD8 + memory T cells were demonstrated a trend towards to increase while compared to baseline during HAART. The percentages of CD4 + and CD8 + activated T cells are significantly higher at the baseline while compared to normal control and demonstrated a downward trend, but between both groups showed no significant difference. The percentages of CD4 + regulatory T cell was lower in IRIS group than non-IRIS group at the baseline, 12 weeks, 24 weeks and the onset of IRIS. Th1 cytokines, IL-2 and IFN-γshowed an upward trend during HAART at the levels of IRIS group had significantly increased at 4 weeks and the onset of IRIS. Th2 cytokines, IL-4 and IL-10 showed a downward trend during HAART,and the levels of IL-10 in IRIS group had significantly decreased at 4 weeks and the onset of IRIS. IL-7 was higher than normal control at the baseline in two groups and showed a downward trend during HAART. The level of IL-7 was higher than non-IRIS group at all follow-up points. Conclusion Memory T cells appear rapid increase in the early stage of HAART and may play a significant role in the inflammatory response of IRIS. CD4 + and CD8 + naive T cells, memory T cells and activated T cells showed no significant difference between IRIS and non-IRIS group within 24 weeks after HAART started. There was a significant reduction in the frequency of regulatory T cells in IRIS group without obvious upward trend during HAART, suggesting that the immune suppression function of regulatory T cells in IRIS was impaired. IL-2 and IFN-γ significantly increased while IL-10 significantly decreased at 4 weeks post-HAART initiation and onset of IRIS in IRISgroup than non-IRIS group, suggested that IRIS was related to cytokines environment disorder. That is, a significant increase in inflammatory cytokines, while the relative lack of non-inflammatory cytokines. The level of IL-7 decreased gradually after HAART started, and it was higher in IRIS group when compared to non-IRIS group in the first 24 weeks after HAART started. Also IL-7 may play a role in the pathogenesis of IRIS.     

306例艾滋病患者的血脂异常情况及相关因素分析

目的 分析艾滋病(AIDS)患者的血脂异常情况及相关因素。方法 纳入分析了2017年4月至2018年1月在北京协和医院感染科就诊的306例AIDS患者,对患者的一般资料、一般自我效能感量表、社会支持评定量表、国际体力活动短问卷和高脂血症患者膳食评价4个量表进行调查。结果 306例患者中血脂异常179名(58.50%),单因素分析结果为非核苷类逆转录酶抑制剂较其他抗病毒药物对血脂的影响更小(χ2＝10.710,P＝0.001),蛋白酶抑制剂较其他药物对血脂的影响更大(χ2＝12.559,P<0.001);血脂异常组的患者较正常组患者年龄、BMI更大。已婚者血脂水平存在差异。多因素分析结果为饮食习惯与女性性别、活动等级与BMI、年龄与病程在血脂异常中存在交互作用。结论 AIDS患者的血脂异常更多程度是由疾病本身及治疗造成的。医护人员在随访过程中尤其应关注使用蛋白酶抑制剂者、病程超过两年者、中年以上患者、初治时CD4计数高的特殊患者。     

艾滋病患者外周血淋巴细胞计数取代CD4~+T细胞计数监测HAART疗效

评价血友病合并人类免疫缺陷病毒(HIV)和丙型肝炎病毒(HCV)感染的患者接受高效抗逆转录病毒治疗(highly ac-tive anti-retroviral therapy,HAART)时总淋巴细胞计数(total lymphocyte count,TLC)与CD4+T淋巴细胞计数间的相关性。回顾性分析了61例接受HAART的血友病合并HIV和HCV感染的患者共885对TLC与CD4+T淋巴细胞计数间的相关性。TLC用于预测CD4+T淋巴细胞计数的敏感性、特异性和阳性预侧值分别在不同的TLC范围对应于CD4+T淋巴细胞计数<200个/mm3时和CD4+T淋巴细胞计数<350个/mm3时获得。结果885对TLC与CD4+T淋巴细胞计数间存在相关性(r=0.511,P<001)。TLC<1 600个/mm3对应CD4+T淋巴细胞计数<200个/mm3有62.8%的敏感性、68.1%的特异性、43.1%的阳性预测值;TLC<1 800个/mm3对应CD4+T淋巴细胞计数<350个/mm3有79.1%的敏感性、78.0%的特异性、72.5%的阳性预测值。TLC可以作为一种低廉的监测手段在AIDS患者接受HAART时用于估测CD4+T淋巴细胞计数,其敏感性、特异性和阳性预侧值在TLC<1 800个/mm3对应CD4+T淋巴细胞计数<350个/mm3时最为明显。     

抗艾滋病药物设计的新战略：逆转录病毒整合酶抑制因子

近年来 ,随着 HIV病毒分子生物学研究的不断深入以及多种治疗途径的综合运用 ,已使艾滋病人的预后得到了明显的改善。虽然目前的治疗可使病人 HIV的滴度明显降低 ,但 HIV仍然存在于病人的外周血单核细胞、静止 T淋巴细胞等细胞中。针对 HIV的逆转录酶和蛋白酶抑制因子已设计、筛选了多种药物并投入临床应用 ,但同时也导致抗药性病毒的产生 ,由于存在上述这些问题 ,有必要寻找新的病毒分子组份以便针对其设计、筛选新的特异、高效的抗HIV药物。HIV-1整合梅 ( HIV-1 intergrase)即是理想的该类靶分子。本文就 HIV整合酶抑制因子类药…     

黄芪加美乐心治疗病毒性心肌炎疗效观察

目的 :病毒性心肌炎是青壮年较常见的心肌疾病 ,近年来其发病率有上升趋势。自 1997年以来 ,我们在抗病毒等综合治疗的基础上 ,用黄芪加美乐心静脉点滴治疗心肌炎 ,取得良好的疗效 ,现将结果报告如下。方法 :6 5例病毒性心肌炎患者均符合“1987年心肌炎心肌病座谈会”制订的病毒性心肌炎诊断标准 ,治疗组 34例 ,其中男 2 1例 ,女 13例 ,年龄 16 - 5 6岁 ,平均年龄 36岁 ,对照组 31例 ,其中男 2 2例 ,女 9例 ,年龄 18- 5 2岁 ,平均 35岁 ,治疗组与对照组在年龄、症状、心电图及心肌酶学、心功能等方面均无明显差异。 6 5例病毒性心肌炎患者随…     

参麦注射液联合黄芪注射液治疗慢性心衰的疗效观察

目的 探讨参麦注射液联合黄芪注射液治疗慢性心衰的临床疗效.方法 将80例心衰患者随机分为两组,对照组采用常规治疗;治疗组在常规治疗基础上加参麦与黄芪注射液.结果 治疗组总有效率90.0%,对照组总有效率72.5%,治疗组优于对照组(P<0.05).结论 参麦注射液联合黄芪注射液治疗慢性心衰,既能减低心脏前后负荷,又能逆转心肌重构,优于常规治疗.     

湖南艾滋病患者Th17和Tr细胞及IL-17在抗病毒治疗过程中的变化

目的 观察HIV感染者和AIDS患者血IL-17、CD3+CD4+IL-17+细胞(Th17细胞)和CD4+CD25+Foxp3+T细胞(Tr细胞)的平衡状态及其在1年高效抗反转录病毒治疗(HAART)中的变化.方法 选取经HAART治疗的HIV/AIDS患者33例,同时选取33例健康志愿者为对照,分别于治疗0、6、12个月采集静脉血,检测血清IL-17水平、Th17细胞及Tr细胞百分比,并对比分析其相互关系.结果 HIV/AIDS在HAART治疗前、治疗6个月、12个月及健康对照外周血的Th17细胞在CD4+T细胞中的比例分别为(1.20±0.37)%、(2.50±1.03)%、(3.70±1.56)%和(4.70±1.43)%;Tr细胞在CD4+T细胞中的比例分别为(9.16±3.33)%、(7.19±2.91)%、(5.53±1.88)%和(4.43±0.97)%;血清IL-17水平分别为(5.3±2.5) pg/ml、(7.7±2.4) pg/ml、(10.4±3.1) pg/ml和(17.7±6.6) pg/ml.Th17细胞水平与CD4+T细胞计数正相关,与病毒载量负相关;Tr细胞水平与CD4+T细胞计数负相关,与病毒载量正相关.结论 HIV感染导致IL-17、Th17细胞和Tr细胞的失平衡,而HAART治疗可能逐渐恢复二者的免疫平衡状态.提示三者可能在艾滋病发病机制中起作用,并有可能成为观察艾滋病进展和HAART治疗效果的有效指标.

Abstract：

Objective To observe the Th17, IL-17 and Tr cells equilibrium state as well as their changes of HIV infected or AIDS suffered patients in one-year HAART treatment. Methods Select 33 HIV/AIDS patients received HAART treatment while 33 healthy volunteers as controls. Flow cytometry was used to analyze Th17 and Tr cells in venous blood at the time of pre-therapy, 6th, 12th month when IL-17 levels in serum are tested by ELISA. Results The ratio of Th17 cells in CD4 cells in HIV/AIDS patients and volunteers were (1.20±0.37)%, (2.50±1.03)%, (3.70±1.56)%, (4.70±1.43)%, respectively; The ratio of Tr cells were (9.16±3.33)%, (7.19±2.91)%, (5.53±1.88)%, (4.43±0.97)%, respectively; The levels of IL-17 in serum were (5.3±2.5) pg/ml, (7.7±2.4) pg/ml, (10.4±3.1) pg/ml, (17.7±6.6) pg/ml respectively. The Th17 cells' level was positively correlative with the amount of CD4 cells, negatively correlate with the count of viral load. However, the Tr cells level is positively correlative with the count of viral load, negatively relate to the quantity of CD4 cells. Conclusion HIV could make IL-17, Th17 cells and Tr cells lost their balance, but the immune equilibrium state may gradually recover after HAART treatment. Which indicates the IL-17, Th17 cells and Treg cells may play an important role in the pathogenesis of AIDS, and they are likely to be the effective indexes to observe the progress of AIDS and the treatment effect of highly active antiretroviral therapy(HAART).     

祛毒增宁胶囊治疗艾滋病的疗效观察

目的 临床观察中药祛毒增宁(ZL-1)胶囊治疗艾滋病(AIDS)的效果。方法 应用经河南省药品监督管理局批准的ZL-1胶囊治疗1000例AIDS患者。剂量为每次4粒，一日3次，共治疗一年，对其中60例患者进行仔细的临床观察及实验检查。结果 AIDS患者服中药后症状有较好的改善，绝大多数患者可以继续进行日常工作，CD4细胞数显著上升，治疗1个月后CD4数量增加了112．3％，6个月增加了156．7％，其中增加50．0％、100．0％和200．0％的分别为治疗者的79．6％、63．3％和46．9％。共检查了10例患者病毒载量的变化，3例患者的病毒载量明显下降(0．931-2．696对数)，4例稳定，二者占7／10。结论 ZL-1胶囊治疗AIDS有效，无副作用。     

Clinical and virological characteristics of hepatitis B or C virus co-infection with HIV in Indonesian patients

Hepatitis virus-related liver disease increases substantially the mortality rate of patients with HIV on highly active antiretroviral therapy (HAART). Therefore, early diagnosis of hepatitis B virus (HBV) and hepatitis C virus (HCV) is important. However, the prevalence of HBV and HCV infection in Indonesian patients infected with HIV is unknown. Therefore, this study examined the molecular and clinical characteristics of HBV and HCV in 126 patients infected with HIV, mostly on HAART, at Dr. Sardjito Hospital, Yogyakarta, Indonesia. The rates of triple infection, HIV/HCV co-infection, HIV/HBV co-infection, and mono-infection were 4.8%, 34.1%, 3.2%, and 57.9%, respectively. Seven HCV genotypes were detected, with genotypes 1a, 1b, 1c, 3a, 3k, 4a, and 6n found in 23 (52%), 1 (2%), 4 (9%), 5 (11%), 7 (16%), 3 (6%), and 1 (2%) patients, respectively, indicating multiple modes of transmission. HBV-DNA was detected in 2/10 patients with hepatitis B surface antigen; both patients were HAART naive. Univariate analysis revealed that male sex, higher education level, injection drug use, sexual contact, alanine aminotransferase ≥40 IU/L, and aspartate aminotransferase-to-platelet ratio index > 0.5 were associated with HCV co-infection. In multivariate analysis, injection drug use (OR: 26.52; 95% CI: 3.52-199.54) and alanine aminotransferase ≥40 IU/L (OR: 6.36; 95% CI: 1.23-32.89) were independently associated with HCV co-infection. HCV co-infection was common among Indonesian patients infected with HIV, particularly among injecting drug users, and was a risk factor for disease progression of HIV.     

Influence of hepatitis C and hepatitis G virus co-infection on viral and cellular dynamics in patients infected with human immunodeficiency virus following interruption of highly active anti-retroviral therapy

This study describes the influence of hepatitis C virus (HCV) and hepatitis G virus (HGV) co-infection on CD4 cell count decline and plasma human immunodeficiency virus (HIV) viral load in HIV-infected patients during a 1-year period following interruption of highly active anti-retroviral therapy (HAART) guided by CD4 count. CD4 cell count decline and plasma HIV viral load did not differ between HIV mono-infected patients and those patients co-infected with HCV and HGV. HCV genotype 1 had no apparent influence on the cellular and viral dynamics in HIV-infected patients compared with other HCV genotypes, although the unbalanced groups make larger studies desirable.     

Cellular immune responses in human immunodeficiency virus (HIV)-1-infected children: is immune restoration by highly active anti-retroviral therapy comparable to non-progression?

The objective of this study was to investigate whether the restored immune functions of vertically human immunodeficiency virus (HIV)-infected children who were severely immunodeficient before the initiation of highly active anti-retroviral therapy (HAART) are comparable to those of untreated slow progressors. We therefore assessed T cell proliferation and cytokine [interferon (IFN)-γ, interleukin (IL)-5 and IL-13] secretions after mitogen, recall antigens and HIV-1-specific stimulation in 12 untreated slow progressors, 16 untreated progressors and 18 treated patients. Treated children were profoundly immunodeficient before the initiation of HAART and had long-lasting suppression of viral replication on treatment. We demonstrated that slow progressors are characterized not only by the preservation of HIV-1-specific lymphoproliferative responses but also by the fact that these responses are clearly T helper type 1 (Th1)-polarized. Children on HAART had proliferative responses to HIV-1 p24 antigen, purified protein derivative (PPD) and tetanus antigen similar to slow progressors and higher than those of progressors. However, in contrast to slow progressors, most treated children exhibited a release of Th2 cytokines accompanying the IFN-γ secretion in response to the HIV-1 p24 antigen. Moreover, despite higher proliferative responses to phytohaemagglutinin (PHA) than the two groups of untreated children, treated children had lower levels of IFN-γ secretion in response to PHA than slow progressors. These data show that in severely immunodeficient vertically HIV-infected children, a long-lasting HAART allows recovering lymphoproliferative responses similar to untreated slow progressors. However, alterations in IFN-γ secretion in response to the mitogen PHA persisted, and their cytokine release after HIV-specific stimulation was biased towards a Th2 response.     

Endemic fungal infections caused by Cryptococcus neoformans and Penicillium marneffei in patients infected with human immunodeficiency virus and treated with highly active anti-retroviral therapy

This study compared the clinical presentations of 58 episodes of cryptococcosis in 50 patients and 26 episodes of penicillosis in 25 patients infected with human immunodeficiency virus (HIV) between June 1994 and June 2004, and assessed the safety of discontinuation of secondary prophylaxis for endemic fungal infections in those patients responding to highly active anti-retroviral therapy (HAART). Neurological symptoms were seen more commonly in patients with cryptococcosis, whereas respiratory symptoms, lymphadenopathy, hepatomegaly and/or splenomegaly, and non-thrush-related oral presentations were seen more commonly in patients with penicillosis. Patients with penicillosis were more likely to have abnormal chest radiography results and radiographic presentations of interstitial lesions, cavitations, fibrotic lesions and mass lesions. At the end of the study, maintenance antifungal therapy had been discontinued in 27 patients with cryptococcosis and in 18 patients with penicillosis in whom the median CD4 count had increased to 186 cells/microL (range, 9-523 cells/microL) and 95 cells/microL (range, 15-359 cells/microL), respectively, after HAART. Only one episode of penicillosis recurred (a relapse rate of 1.72/100 person-years; 95% CI, 1.44-2.10/100 person-years) after a median follow-up duration of 35.3 months (range, 2.6-91.6 months). No relapses occurred in patients with cryptococcosis after a median follow-up duration of 22.3 months (range, 1-83.4 months). These findings suggest that there are differences in the clinical presentations between endemic cryptococcosis and penicillosis in patients with HIV infection, and that it is safe to discontinue secondary antifungal prophylaxis for cryptococcosis and penicillosis in patients responding to HAART.     

A correlation analysis of HHV infection and its predictive factors in an HIV-seropositive population in Yunnan,China

Human herpesviruses (HHVs) have a particularly high prevalence in certain high-risk populations and cause increased morbidity and mortality in patients with acquired immunodeficiency syndrome (AIDS). Screening and treating subclinical HHV infections reduce human immunodeficiency virus (HIV) infection incidence, disease progression, and transmission. However, there are few studies on HHVs, HIV coinfection rates, and their related risk factors. We aimed to clarify the prevalence of all eight HHVs in peripheral blood samples collected from HIV-positive patients, and explore the association of HHV infection in HIV-positive patients in an HIV-seropositive population in Yunnan. We recruited 121 HIV-positive patients with highly active antiretroviral therapy (HAART) and 45 healthy individuals. All the eight HHVs were detected using polymerase chain reaction and their epidemiological information and clinical data were collected and statistically analyzed. A high prevalence of HHVs (89.3%) was observed in individuals with HIV infections and with herpes simplex virus (HSV)-2 (65.3%), and HSV-1 (59.5%) being the most common. Coinfection with more than two different HHVs was more common in patients with HIV infections receiving HAART (72.7%) than in healthy controls. Older age, being married, higher HIV-1 plasma viral loads, and use of antiviral protease inhibitors were independently correlated with an increased frequency of HHVs, but we found no association with CD4 count, WHO HIV clinical stage, and HIV infection duration. Our findings are of great significance for the prevention of HHV opportunistic infection in patients with AIDS and their clinical treatment.     

Non-acquired immunodeficiency syndrome definings malignancies among human immunodeficiency virus-positive subjects: Epidemiology and outcome after two decades of HAART era

Highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV) infection has been widely available in industrialized countries since 1996; its widespread use determined a dramatic decline in acquired immunodeficiency syndrome (AIDS)-related mortality, and consequently, a significant decrease of AIDS-defining cancers. However the increased mean age of HIV-infected patients, prolonged exposure to environmental and lifestyle cancer risk factors, and coinfection with oncogenic viruses contributed to the emergence of other malignancies that are considered non-AIDS-defining cancers (NADCs) as a relevant fraction of morbidity and mortality among HIV-infected people twenty years after HAART introduction. The role of immunosuppression in the pathogenesis of NADCs is not well defined, and future researches should investigate the etiology of NADCs. In the last years there is a growing evidence that intensive chemotherapy regimens and radiotherapy could be safely administrated to HIV-positive patients while continuing HAART. This requires a multidisciplinary approach and a close co-operation of oncologists and HIV-physicians in order to best manage compliance of patients to treatment and to face drug-related side effects. Here we review the main epidemiological features, risk factors and clinical behavior of the more common NADCs, such as lung cancer, hepatocellular carcinoma, colorectal cancer and anal cancer, Hodgkin’s lymphoma and some cutaneous malignancies, focusing also on the current therapeutic approaches and preventive screening strategies.     

Discontinuation of maintenance therapy against toxoplasma encephalitis in AIDS patients with sustained response to anti-retroviral therapy

Discontinuation of maintenance therapy against toxoplasma encephalitis (TE) for individuals infected with human immunodeficiency virus (HIV) who are receiving successful anti-retroviral therapy is considered safe. Nevertheless, there are few published studies concerning this issue. Within the setting of the Swiss HIV Cohort Study, this report describes a prospective study of discontinuation of maintenance therapy against TE in patients with a sustained increase of CD4 counts to > 200 cells/microL and 14% of total lymphocytes, and no active lesions on cerebral magnetic resonance imaging (MRI). In addition to clinical evaluation, cerebral MRI was performed at baseline, and 1 and 6 months following discontinuation. Twenty-six AIDS patients with a history of TE agreed to participate, but three patients (11%) could not be enrolled because they still showed enhancing cerebral lesions without a clinical correlate. One patient refused MRI after 6 months while clinically asymptomatic. Among the remaining 22 patients who discontinued maintenance therapy, one relapsed after 3 months. During a total follow-up of 58 patient-years, there was no TE relapse among the patients who had remained clinically and radiologically free of relapse during the study. Thus, discontinuation of maintenance therapy against TE was generally safe, but may fail in a minority of patients. Patients who remain clinically and radiologically free of relapse at 6 months after discontinuation are unlikely to experience a relapse of TE.     

Comparison of Two Once-Daily Regimens with a Regimen Consisting of Nelfinavir,Didanosine, and Stavudine in Antiretroviral Therapy-Naïve Adults: 48-Week Results from the Antiretroviral Regimen Evaluation Study (ARES)

Abstract

Background: To improve the dosing frequency and pill burden of antiretroviral therapy, we compared two once-daily dosed regimens to a twice-daily dosed regimen. Method: HIV-1-infected, antiretroviral drug-naïve adults were randomized to either twice-daily nelfinavir and stavudine and once-daily didanosine (regimen A) or simplified once-daily dosed antiretroviral regimens consisting of nevirapine, didanosine, and lamivudine (regimen B) or saquinavir, ritonavir, didanosine, and lamivudine (regimen C). Results: At 48 weeks of therapy, the proportion of patients with a blood plasma HIV-1 RNA concentration (pVL) <50 copies/mL by intention-totreat analysis was 42.3%, 50.0%, and 56.5% for regimens A (n = 26), B (n = 22), and C (n = 23), respectively. The time to a pVL <50 copies/mL for the first time was significantly shorter in regimen C, and there was significantly more progression to CDC events in regimen B. These differences are possibly due to differences in baseline characteristics. Adverse events were lowest for regimen C; more signs associated with mitochondrial toxicity occurred in regimen A. Increase in CD4 count was comparable between arms. Conclusion: No statistically significant difference in efficacy was found between the two investigated once-daily dosed treatment regimens (B and C) and the reference (A). Regimen C possibly had a better virological response and less toxicity than regimens A and B.