U.S. Public Health Service Task Force recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV-1 transmission in the United States.

These recommendations update the February 4,2002, guidelines developed by the Public Health Service for the use of zidovudine (ZDV) to reduce the risk for perinatal human immunodeficiency virus type 1 (HIV-1) transmission. This report provides healthcare providers with information for discussion with HIV-1-infected pregnant women to enable such women to make an informed decision regarding the use of antiretroviral drugs during pregnancy and use of elective cesarean delivery to reduce perinatal HIV-1 transmission. Various circumstances that commonly occur in clinical practice are presented, and the factors influencing treatment considerations are highlighted in this report. The Perinatal HIV Guidelines Working Group recognizes that strategies to prevent perinatal transmission and concepts related to management of HIV disease in pregnant women are rapidly evolving and will continually review new data and provide regular updates to the guidelines. The most recent information is available from the HIV/AIDS Treatment Information Service (available at http.//www.hivatis.org). In February 1994, the results of Pediatric AIDS Clinical Trials Group (PACTG) Protocol 076 documented that ZDV chemoprophylaxis could reduce perinatal HIV-1 transmission by nearly 70%. Epidemiologic data have since confirmed the efficacy of ZDV for reduction of perinatal transmission and have extended this efficacy to children of women with advanced disease, low CD4+ T-lymphocyte counts, and prior ZDV therapy. Additionally, substantial advances have been made in the understanding of the pathogenesis of HIV-1 infection and in the treatment and monitoring of persons with HIV-1 disease. These advances have resulted in changes in standard antiretroviral therapy for HIV-1-infected adults. More aggressive combination drug regimens that maximally suppress viral replication are now recommended. Although considerations associated with pregnancy may affect decisions regarding timing and choice of therapy pregnancy is not a reason to defer standard therapy. Use of antiretroviral drugs in pregnancy requires unique considerations, including the possible need to alter dosage as a result of physiologic changes associated with pregnancy the potential for adverse short- or long-term effects on the fetus and newborn, and the effectiveness of the drugs in reducing the risk for perinatal transmission. Data to address many of these considerations are not yet available. Therefore, offering antiretroviral therapy to HIV-1-infected women during pregnancy, whether primarily for HIV-1 infection, for reduction of perinatal transmission, or for both purposes, should be accompanied by a discussion of the known and unknown short- and long-term benefits and risks of such therapy to infected women and their infants. Standard antiretroviral therapy should be discussed with and offered to HIV-1-infected pregnant women. Additionally, to prevent perinatal transmission, ZDV chemoprophylaxis should be incorporated into the antiretroviral regimen.     

Directly observed therapy (DOT): from tuberculosis to HIV

BACKGROUND: Combination antiretroviral therapy, which is the standard of care since 1996, has been demonstrated to be very effective in suppressing plasma viral load in patients infected with HIV. Optimal benefit from antiretroviral drugs, however, is obtained when the patient adheres strictly to the rigorous treatment regimen. For some patients it is difficult to obtain good adherence to antiretroviral regimens. In response to these concerns, different strategies, such as directly observed therapy, have been proposed to attempt to improve adherence to antiretroviral treatment. Directly observed therapy is a strategy that has its roots in the treatment of tuberculosis and it consists essentially of taking the medication in the presence of a health care provider or another designated person. This strategy has been recently tried in the treatment of HIV but its efficacy remains unknown. METHOD: A Medline and Medscape search was performed to review all pertinent publications on the use of directly observed therapy in HIV infection. RESULTS: Twenty-five papers published between 1996 and 2004 were selected. Almost all the studies were performed in industrialized countries in North America and Europe. The majority of the studies are retrospective, six of them comparing at least two strategies (directly observed therapy vs standard of care). Only one randomized trial has been found. The patients involved in the studies are intravenous drug users or particularly non-adherent patients. Almost all studies show a better rate of adherence or a better control of the viremia in patients on directly observed therapy. CONCLUSIONS: The directly observed therapy seems to be a valuable and feasible way to raise the adherence rate in HIV patients with a problem of non-adherence to antiretroviral treatments. Clinical trials are needed to evaluate the efficacy of this strategy to raise the adherence rate among patients who need additional support to take their antiretrovirals.     

艾滋病母婴传播阻断抗病毒治疗规范用药影响因素现况研究

目的 了解艾滋病母婴传播阻断抗病毒治疗的规范用药水平,探索其影响因素,为制定规范用药的措施提供依据.方法 采用现况调查方法在云南省5个艾滋病高、中流行县(市、区)对2005年1月至2007年6月接受母婴传播阻断服务的167例孕产妇及57名提供服务的医务人员进行调查,对艾滋病母婴传播阻断抗病毒治疗方案的选择与应用是否合理及艾滋病病毒(HIV)感染孕产妇依从性的主要影响因素进行定性和定量调查.结果 接受母婴传播阻断服务的167例HIV感染产妇中,抗病毒治疗规范用药率为65.87%(110/167);其中方案选择合理率为88.02%(147/167),产时用药合理率81.37%(131/161),依从率为87.42%(146/167).艾滋病母婴传播阻断抗病毒治疗规范用药的主要影响因素为确诊时间(OR=2.617;95%CI: 1.184～5.783),是否在阻断定点机构分娩(OR=0.064;95%CI:0.007～0.607),民族(OR=0.344;95%CI:0.162～0.730),是否知道服药阻断的目的 (OR=6.843;95%CI:1.449～32.312),以及医生对抗病毒治疗的认识不够,5个关键知识点(母婴阻断目的 、不按要求服药后果、各方案疗效、CD4高低与选择方案的关系、有关药物可能出现的副作用)的正确认识率为47.72%(136/285).结论 艾滋病母婴传播阻断抗病毒治疗规范用药的总体水平不高,受医患双方及社会等多种因素影响,有必要针对主要影响因素制定规范用药的措施.     

艾滋病7年高效抗逆转录病毒治疗的多中心前瞻性观察

目的前瞻性长期观察人免疫缺陷病毒感染者和获得性免疫缺陷综合征(HIV/AIDS)患者的高效抗逆转录病毒治疗(highly active antiretroviral therapy,HAART)一线药物抗HIV及免疫重建效果和主要毒副反应,探索我国艾滋病长期抗病毒治疗的规律。方法 437例HIV/AIDS患者先后启动HAART,一线方案为2个核苷类逆转录酶抑制剂(NRTI)加1个非核苷类逆转录酶抑制剂(NNRTI)。随访监测CD4+T细胞数量、HIV病毒载量,追踪血常规和主要生化指标的变化;观察发生的机会感染和药物毒副反应并及时处理,对出现病毒学失败或严重毒副反应者及时调整用药。结果对437例接受HAART的HIV/AIDS患者平均追踪了4.69年(3.15～7.34年),总病死率6.86%,大部分死亡发生在HAART启动的6个月内。启动HAART 12个月时,90.80%的患者HIV载量小于可检测下限;至治疗4、5、6、7年(±1个月)时,仍分别有63.46%、69.41%、70.00%和72.22%的患者病毒载量小于可检测下限。CD4+细胞数量在治疗的O、1、2、3、4、5、6、7年(±1个月)时分别为115、246、301、334、363、356、386和373个/μL。67.73%出现过各种可能与药物毒副作用相关的表现,主要有消化道症状、神经系统症状、肝功能损害、骨髓毒性、皮疹和血脂升高等,多发生于治疗启动12个月内;血脂分布异常和乳酸酸中毒较少见,多发生于启动2年以后;41例患者先后发生过Ⅲ/Ⅳ级毒副反应。因毒副反应而更换为其他一线药物者占19.22%,因病毒耐药或毒副反应而更换为二线药物者占11.67%。结论通过对HIV/AIDS患者HAART3～7年的多中心前瞻性观察,明确我国2个NRTI加1个NNRTI的HAART一线方案对大多数HIV/AIDS患者长期有效,病毒持续抑制,CD4+细胞增加;主要的毒副反应和死亡多发生在启动治疗12个月内。大多数HIV/AIDS患者可长期坚持一线药物治疗,少数因药物毒副反应或病毒耐药须换为二线药物治疗。     

艾滋病病毒杰出控制感染者中的免疫效应机制

HIV感染者在没有抗病毒治疗的情况下其病毒复制控制在＜50拷贝/mL水平的,被称为杰出控制者(EC),这些患者也被称为杰出抑制者,或是HIV控制者,同时他们又区别于传统的长期不进展者,在没有抗病毒治疗的情况下能维持稳定的CD4细胞数以及无症状状态.此文对这类患者中被认为在控制病毒复制中发挥作用的效应机制进行了综述.     

142例农村艾滋病病毒感染者/艾滋病患者免费抗病毒治疗效果及生存分析

目的 了解艾滋病病毒感染者/艾滋病患者(HIV/AIDS)接受国家免费抗病毒治疗后的依从性、免疫学变化和生存情况.方法 选择闻喜县2004年7月1日至2006年底所有纳入免费抗病毒治疗项目,且年满18周岁的HIV/AIDS纳入研究分析,所有患者在治疗前和治疗后的第0.5、1、2、3、6、9……个月均接受相关流行病学调查和实验室检查,监测服药依从性、CD4+T淋巴细胞计数变化和生存情况等.结果 病例平均随访时间为16.5个月[四分位距(IQR):15.5～20.8个月].经抗病毒治疗前,病例CD4+T淋巴细胞计数中位数值为154个/μl[四分位距(IQR):81～212个/μl];治疗后,CD4+T淋巴细胞计数均不同程度升高,治疗初3个月增长幅度最大,从基线水平的154个/μl上升到220个/μl(P<0.001),随后增长减缓,保持在相对稳定水平.相比基线CO4+T淋巴细胞计数≥100个/μl的病例,<100个/μl的病例治疗初3个月该细胞计数增长幅度更大.病例治疗后第3、12、24个月累计生存率分别为0.94、0.88和0.87,应用Cox比例风险回归模型做多因素分析发现,控制初始治疗方案(NVP组和EFV/IDV组)变量后,与基线CD4+T淋巴细胞计数<50个/μl比较,≥50个/μl的病例存活时间更长,死亡危险比(HR)为0.21(95%CI:0.06～0.68).结论 抗病毒治疗对HIV/AIDS具有较好的免疫学治疗效果;患者治疗后生存时间与基线CD4+T淋巴细胞计数水平密切相关.     

Adherence to HIV combination therapy

The emergence of drug-resistant strains of HIV virus and treatment failure can result from non-adherence to antiretroviral therapy. While non-adherence to therapy is not a new issue or specific to HIV/AIDS, it has received renewed attention because of the complicated combination treatment regimens being prescribed. This paper reviews the relevant background literature on the contributions of social and behavioural science to non-adherence to HIV medications. Data indicating problems with adherence prior to combination therapy are reported. Despite limitations, even self-report assessments have already succeeded in showing that adherence to combination therapy is significantly related to HIV viral load. Recent research data are discussed. Implications of findings for counselling patients to increase their adherence are presented.     

艾滋病感染者抗病毒治疗的服药依从性及其相关因素的研究

目的 了解河南省艾滋病病毒感染者／艾滋病患者(HIV／AIDS）高效联合抗病毒疗法(HAART)的服药依从性及其相关因素。方法 抽取了2个AIDS综合防治示范区、1个AIDS高发县。未服药和服药在2—12个月的HIV感染者作为被调查对象，分别对服药依从性、不良反应及临床表现，治疗前后临床症状改善状况及治疗保障措施等项目，通过访谈问卷调查；同时抽取静脉血，测定评价服药者CD4^ T淋巴细胞，病毒载量，用逆转录聚合酶链反应(RT-PCR)方法扩增HIV-1 POL区基因，进行基因型耐药性分析。结果 治疗组治疗时间在4—8个月的人数最多占78．24％，服药依从性达到90％～100％的占67．51％，停服和漏服药物的主要原因是不良反应占66．95％，最显著的不良反应是服药后引起的恶心、呕吐、皮疹等不适。治疗组坚持服药症状明显改善的占87．57％，停服和漏服药症状未明显改善的占11．01％。服药依从性对病情趋势变化具有显著影响(P＜0．05)。治疗组服药后CD4^ T细胞总数保持稳定或有所增加，但实际速度较缓慢。抗病毒治疗3个月和6个月时，患者的病情好转率分别是55．1％和50．8％，CD4^ T细胞数较未服药治疗的患者显著提高。耐药性毒株的流行率显著增加，由未服药人群的13．9％快速上升到服药3个月的45．4％和服药6个月的62．7％，其中对非核苷类逆转录酶抑制剂(NNRTI)类药物耐药性的增加最为明显，导致中高度以上耐药率的显著增加。结论 采取有效的抗病毒治疗以后，HIV／AIDS患者在接受抗病毒治疗过程中，服药依从性直接关系治疗效果以及对治疗计划的实施。避免耐药毒株的出现，必须提高服药依从性，这对今后评价治疗效果具有重要意义。     

A decision tree to help determine the best timing and antiretroviral strategy in HIV-infected patients

Optimal antiretroviral strategies for HIV-infected patients still need to be established. To this end a decision tree including different antiretroviral strategies that could be adopted for HIV-infected patients was built. A 10-year follow-up was simulated by using transitional probabilities estimated from a large cohort using a time-homogeneous Markov model. The desired outcome was for patients to maintain a CD4 cell count of >500 cells/mm3 without experiencing AIDS or death. For patients with a baseline HIV viral load ≥5 log10 copies/ml, boosted protease inhibitor-based immediate highly active antiretroviral therapy (HAART) allowed them to spend 12% more time with CD4 ≥500/mm3 than did delayed HAART (6·40 vs. 5·69 and 5·57 vs. 4·90 years for baseline CD4 ≥500 and 350-499/mm3, respectively). In patients with a baseline HIV viral load ≤3·5 log10 copies/ml, delayed HAART performed better than immediate HAART (6·43 vs. 6·26 and 5·95 vs. 5·18 for baseline CD4 ≥500 and 350-499/mm3, respectively). Immediate HAART is beneficial in patients with a baseline HIV viral load 5 log10 copies/ml, whereas deferred HAART appears to be the best option for patients with CD4 ≥350/mm3 and baseline HIV viral load <3·5 log10 copies/ml.     

Adherence to antiretroviral therapy: a qualitative study with physicians from Rio de Janeiro, Brazil

Brazil provides free antiretroviral (ARV) therapy to some 150,000 individuals living with HIV/ AIDS). ARV regimens require optimal adherence to achieve undetectable viral loads and to avoid viral resistance. Physicians play a key role to foster ARV adherence, but until now little is known about the communication between physicians/ people living with HIV/AIDS in this setting. In-depth interviews were conducted with 40 physicians treating people living with HIV/AIDS at six public reference centers in Rio de Janeiro, Brazil. Interview topics included: experiences in the treatment of people living with HIV/AIDS, relationship and dialogue with patients, barriers/facilitators to adherence, and effectiveness of available services. Barriers to ARV adherence were mainly related to the low quality of patient-provider relationship. Other barriers were related to "chaotic" patients' lifestyles, and inadequate knowledge and/or negative beliefs about HIV/AIDS and ARV effectiveness. It is necessary to improve networking between services, establish agile referral systems, and improve health professionals' integration. These structural changes could contribute to improved adherence, resulting in improved quality of life for people living with HIV/AIDS.     

Safety,immunogenicity and efficacy assessment of HIV immunotherapy in a multi-centre,double-blind,randomised, Placebo-controlled Phase Ib human trial

Background

Combination antiretroviral therapy (cART) is the main therapeutic management tool for HIV/AIDS. Despite its success in controlling viral load and disease progression, cART is expensive, associated with a range of significant side effects and depends for its efficacy on the patient's life-long commitment to high levels of treatment adherence. Immunotherapeutic agents can provide potential solutions to these shortcomings. Here we describe a Phase Ib trial of HIV-v, a synthetic immunotherapy that elicits T- and B-cell effector responses against HIV infected cells.

Methods

Fifty-nine cART-naive HIV-infected males aged 18–50 years with viral load of 5000–500,000 copies/ml and CD4 counts >350/μl were recruited for this multi-centre, randomised, double blind study. Volunteers received one low (250 μg) or high (500 μg) dose of HIV-v, either alone or adjuvanted (ISA-51). Safety, immunogenicity, CD4 count and viral load were monitored over 168 Days.

Results

HIV-v was well tolerated and the adjuvanted formulations elicited IgG responses in up to 75% of volunteers. The high adjuvanted dose also elicited cellular responses in 45% of tested volunteers. In these responding subjects viral loads were reduced by over 1 log (p = 0.04) compared to Placebo and non-responders. No changes in CD4 count were observed.

Conclusions

HIV-v is safe and can elicit T- and B-cell responses in ART-naive HIV patients that significantly reduce viral load. Improved dosing regimens and further research on long term efficacy are required, but HIV-v appears to have potential as an immunotherapeutic anti-viral agent.Trial registered as EudraCT-2009-010593-37 (ClinicalTrials.gov Identifier: NCT01071031).     

山东省50岁及以上HIV感染者和艾滋病患者抗病毒治疗效果分析

目的 分析山东省50岁及以上首次接受艾滋病免费抗病毒治疗的HIV感染者和艾滋病患者抗病毒治疗情况。方法 收集2003-2014年底在山东省内接受艾滋病抗病毒治疗的50岁及以上HIV感染者和艾滋病患者基线和治疗后的相关资料,分析抗病毒治疗效果。结果 共纳入研究对象322例,其中男性占76.7%,女性占23.3%;平均年龄为（56.9±6.4）岁;以已婚或同居者为主,占63.4%;感染途径以异性性传播为主,占54.3%;基线时CD4+T淋巴细胞计数中位数是194.0（83.5～301.0）个/mm3,基线时仅不同感染途径者CD4+T淋巴细胞计数差异有统计学意义（H=14.200,P=0.003）。治疗后不同时间段与基线时CD4+T淋巴细胞计数进行比较,显示差异均有统计学意义（均有P<0.001）,多因素分析结果显示性别和治疗前机会性感染情况是影响治疗效果的因素（均有P<0.05）。治疗后不同时间段病毒完全抑制的比例差异无统计学意义（χ2=2.093,P=0.719）。结论 山东省50岁以上的HIV感染者和艾滋病患者接受艾滋病抗病毒治疗能有效提高机体免疫力,降低病毒载量。     

Monitoring adherence to antiretroviral treatment in Brazil: an urgent challenge

The aim of this study was to describe the effect of non-adherence on the main laboratory outcomes, TCD4+ lymphocyte count and viral load, routinely used to monitor patients initiating treatment according to three different approaches to measure adherence to antiretroviral therapy. Among 288 participants, 22.9%, 31.9% and 74.3% were considered non-adherent, according to medical charts, self-report and pharmacy records, respectively. Depending on the adherence measures used, the average gain in TCD4+ lymphocyte count ranged from 142.4 to 195.4 cells/mm3 among adherent patients, and from 58.5 to 99.8 lymphocytes TCD4+/mm3 among those non-adherent. The average reduction on viral load ranged from 4.25 to 4.62 log copies/mL among the adherent patients, and from 1.99 to 4.07 log among those non-adherent. Monitoring antiretroviral adherence should be considered a priority in these public AIDS referral centers in order to identify patients at high risk of developing virologic failure. Early interventions are necessary in order to maintain the initial therapeutic regimens for longer periods.     

山东省艾滋病抗病毒治疗病毒学评价

[目的]评价山东省艾滋病抗病毒治疗病毒学效果。[方法]对山东省2012年6月30日前治疗满6个月的艾滋病病人,使用荧光实时定量PCR（NucliSensEasyQ）进行病毒载量检测,使用流式细胞学技术进行CD4＋T淋巴细胞计数。[结果]925例艾滋病病人中,826例病毒载量结果〈400cp／ml,病毒抑制率为89．30％;99例载量结果〉400cp／ml病人中,28例出现了病毒反弹,1例为持续性低水平病毒血症,CD4＋T淋巴细胞计数均值为312个／mm3,14例出现了机会性感染。54例采用二线抗病毒治疗方案的病人,病毒抑制率为81．48％。[结论]山东省艾滋病抗病毒治疗病毒抑制效果良好。     

高效抗反转录病毒治疗双药简化方案的研究进展

高效抗反转录病毒治疗三联方案是治疗HIV感染的主流,然而,随着治疗人群扩大到所有HIV感染者,以及治疗时间延长,人们对高效、高依从性、低不良反应、低耐药及低治疗成本方案的需求日益增加,双药简化治疗成为个性化治疗的备选方案,一些方案已经被纳入国内外抗病毒治疗指南。本文对近年来双药简化方案的发展进行综述,为临床正确应用该方案提供依据。     

Adherence, stereotyping and unequal HIV treatment for active users of illegal drugs

Adherence to antiretroviral therapy promotes viral suppression and extends the lives of individuals with HIV, yet illegal drug users are underrepresented among eligible persons receiving HIV treatment. One explanation for this is the assumption that drug users are less capable than others of adhering to complicated medication regimens. This paper investigates this assumption by making explicit a number of its underlying propositions and examining them in light of data collected from 52 active drug users living in and around Boston, USA, who were taking highly active antiretroviral therapy for HIV (HAART). The propositions are: (1) drug users lead "chaotic" lives; (2) active drug users are always using drugs; (3) being under the influence of drugs precludes taking medications as prescribed; and (4) drug users are intrinsically different from non-users in the lives they lead and the problems they face. Data collection consisted of a series of qualitative interviews with each participant. An analytic approach informed by grounded theory was used to construct thematic content categories from the data. Results revealed stability and control as well as "chaos" in the lives of study participants. Frequency of drug use varied considerably. Using did interfere with adherence, but not in every circumstance or all cases. Not "carrying" medications, competing priorities, and re-defining regimens were the most salient of a number of non-drug-use-related obstacles observed. Documentation of patterns of variation in corresponding data highlights the stereotypical quality of the propositions. Stereotyping risks overemphasis on drug use as a barrier to adherence for active users, and underemphasis on non-drug-use-related obstacles. Adherence capabilities of users, in contrast to inadequacies, are also obscured through stereotyping. As a medium for stigmatization, stereotyping may contribute to unequal treatment for drug users and other populations living with HIV.