中国高效抗逆转录病毒治疗中HIV检测技术的支撑作用与发展

高效抗逆转录病毒治疗(HAART)是目前治疗AIDs行之有效的方法.但是,作为遏制MIDS的一项公共卫生策略,涉及到政府行为.自2003年以来我国政府积极响应联合国的号召,做出了政府的承诺,制定了"四免一关怀"的政策,全面开展全国性的HAART治疗工作.HIV及相关的检测技术是HAART治疗推广和应用的重要技术保障,包括HIV感染者和AIDS病例的确诊、治疗的准入、药物疗效和毒副反应的观察、药物的置换、HIV耐药的发现和变化,均以HIV检测技术为基础,当然也包括了有关研究.本期刊载的6篇有关HAART治疗及其相应检测技术的研究,有力地证明我国HIV检测技术在为国家免费MDS治疗中发挥的作用,也在服务中对发现的问题加强研究,又促使HIV检测技术本身的不断开拓与创新,为进一步完善HAART治疗的发展,提供了科学依据.     

Opt-out HIV testing: an ethical analysis of women's reproductive rights

As the HIV epidemic continues to grow worldwide, women are increasingly and disproportionally affected. With the introduction of anti-retroviral medications that have been found to effectively prevent perinatal transmission of HIV, the approach to HIV testing in pregnant women has grown increasingly more controversial. In recent years, the model of voluntary counseling and testing (VCT) has come into question with opt-out testing now advocated for by the Centers for Disease Control and occurring widely in pregnancy. The benefits of opt-out testing are numerous and may justify its use in replacing the VCT that many have come to see as insufficient. An ethical analysis of opt-out testing suggests it may be at odds with true informed consent and involve a degree of coercion that would not be allowed outside the prenatal setting. If opt-out testing is going to remain the standard of care then the ethical issues it raises must be made transparent. Strategies need to be designed for ensuring that HIV counseling and testing in pregnancy is done in accordance with ethical and reproductive rights principles.     

The role of resistance testing in clinical trial design and product labelling: a regulatory perspective

Assays that attempt to characterize HIV susceptibility or resistance are among the latest technologies that are likely to impact HIV clinical trial design, antiretroviral drug development and patient management. However, at present the Food and Drug Administration (FDA) have yet to approve any phenotypic or genotypic HIV resistance assay and the role of resistance testing in clinical management of patients and in drug development is ill defined. In November 1999, the Division of Antiviral Drug Products at the FDA convened a meeting of its advisory committee to consider the available information about HIV resistance testing, and to generate some recommendations about how these assays could be utilized in antiretroviral drug development. In addition, the committee was presented with several hypothetical regulatory scenarios in order to illustrate how HIV resistance testing might be incorporated in antiretroviral drug development and drug labelling. In this article, we discuss the regulatory history of resistance testing in antimicrobial drug development, the current use of resistance testing for antiretrovirals, as well as a summary of the hypothetical scenarios that were presented to the committee and the discussion of the committee members regarding those scenarios.     

Anti-retroviral treatment in Nigeria: a review

Research studies in Nigeria have been done primarily in the areas of epidemiology, clinical practice, virology, and laboratory diagnosis. Therapy for infection with human immunodeficiency virus (HIV) types 1 and 2 has largely focussed on the treatment of the HIV disease (AIDS) rather than the infection. Therefore, opportunistic infections such as tuberculosis, diarrhea, Herpes zoster, and other skin conditions, and tumors (Kaposi's sarcoma) are essentially the targets for therapy. Two reasons are responsible for the dearth of data on anti-retroviral therapy in Nigeria: there was scepticism about zidovudine, the first anti-retroviral drug to be developed, because of its toxicity, and the subsequent reluctance of the Federal Government to allow it into the country. The other reason was the prohibitive cost, making it impossible for patients to afford. That notwithstanding, there have been several uncoordinated and unpublished clinical trials by hospitals in the private sector, as expected, without firm laboratory monitoring or back-up. This review discusses such attempts and the claims of traditional medicine practitioners, as well as pilot studies on private patients with the combination therapy of zidovudine and lamivudine, which agents were allowed into the country in the late 1990s. The patients showed appreciable rises in their CD4 counts, an indirect way of monitoring viral load. This finding was corroborated with results of clinical wellbeing, indicating that they benefitted from the administration of zidovudine and lamivudine. Received: April 6, 2000 / Accepted: August 13, 2000     

Experience in international clinical research: the HIV Prevention Trials Network

The HIV Prevention Trials Network (HPTN) is supported by the NIH to conduct randomized clinical trials to assess the efficacy of HIV prevention strategies and technologies to reduce HIV transmission between adults. A special focus of attention is on the use of antiretroviral drugs to prevent HIV transmission, both by reducing infectiousness among HIV-infected persons taking combination antiretroviral therapy (cART) and also by reducing susceptibility among HIV-uninfected persons taking antiretrovirals for pre-exposure prophylaxis. Studies may be developmental in nature to assess novel ideas for interventions or for assessing trial feasibility. However, pivotal efficacy trials to test HIV-specific prevention strategies and technologies are the main HPTN priority. Examples include a major protocol investigating the impact of expanded testing and linkage to care on HIV surveillance indicators in the USA (HPTN 065). Another protocol is addressing similar issues while also investigating how combinations of prevention approaches are best deployed to make a community-level impact in southern Africa (HPTN 071). HPTN 068 is evaluating a novel conditional cash transfer structural intervention to increase school completion rates in young girls and thereby reduce their HIV risk. Studies outside the US address the epidemic in most at-risk populations and include an assessment of opiate agonist therapy to reduce risk of HIV seroconversion among injection drug users (HTPN 058), methods to increase HIV testing rates (HTPN 043), as well as methods for reducing high-risk behaviors, and increasing adherence to cART in HIV-infected individuals (HPTN 062 and HPTN 063, respectively). The recent HPTN 052 study demonstrated that a 96% reduction in HIV transmission could be achieved between serodiscordant sexual partners by providing the infected partners with cART at a CD4(+) cell count (350-550/μl) above the level that would usually qualify them for therapy in low- and middle-income countries. The immediate relevance to public health policy showcased in these trials is a paradigm for the HPTN: design and conduct of clinical trials using available licensed tools that can be rapidly translated for implementation ('Prevention NOW!').     

Exacerbation of microcytic anemia associated with cessation of anti-retroviral therapy in an HIV-1-infected patient with beta thalassemia

We report a patient with Japanese minor β thalassemia and HIV-1 infection.The patient showed prolonged anemia, which was originally attributed to chronic parvovirus B19 infection. Twelve years later, the patient presented with exacerbation of microcytic anemia following cessation of anti-retroviral therapy; the exacerbation resolved when anti-retroviral therapy was resumed. Sequencing of the β globin gene revealed heterozygosity for a four-nucleotides deletion at codon 41/42 and minor β thalassemia was confirmed.Because HIV-1-infected patients frequently show anemia due to nutritional deficiencies, opportunistic infections, AIDS-related malignancies, drug treatment and a direct effect of HIV-1 on the bone marrow, it is likely to overlook other causes of anemia.Thalassemia should be considered in the differential diagnosis of anemia even in HIV-1 infected patients, when microcytic anemia without iron deficiency is observed.Our case suggested that active HIV infection may have worsened β thalassemia, and early introduction of anti-retroviral therapy is beneficial for the recovery of anemia.     

Development and Implementation of a Model to Improve Identification of Patients Infected with HIV Using Diagnostic Rapid Testing in the Emergency Department

Objectives Infection with the human immunodeficiency virus (HIV) continues to expand in nontraditional risk groups, and the prevalence of undiagnosed infection remains relatively high in the patient populations of urban emergency departments (EDs). Unfortunately, HIV testing in this setting remains uncommon. The objectives of this study were 1) to develop a physician‐based diagnostic rapid HIV testing model, 2) to implement this model in a high‐volume urban ED, and 3) to prospectively characterize the patients who were targeted by physicians for testing and determine the proportions who completed rapid HIV counseling, testing, and referral; tested positive for HIV infection; and were successfully linked into medical and preventative care. Methods An interdisciplinary group of investigators developed a model for performing physician‐based diagnostic rapid HIV testing in the ED. This model was then evaluated using a prospective cohort study design. Emergency physicians identified patients at risk for undiagnosed HIV infection using clinical judgment and consensus guidelines. Testing was performed by the hospital's central laboratory, and clinical social workers performed pretest and posttest counseling and provided appropriate medical and preventative care referrals, as defined by the model. Results Over the 30‐month study period, 105,856 patients were evaluated in the ED. Of these, 681 (0.64%; 95% confidence interval [CI] = 0.60% to 0.69%) were identified by physicians and completed rapid HIV counseling, testing, and referral. Of the 681 patients, 15 (2.2%; 95% CI = 1.2% to 3.6%) patients tested positive for HIV infection and 12 (80%; 95% CI = 52% to 96%) were successfully linked into care. Conclusions A physician‐based diagnostic HIV testing model was developed, successfully implemented, and sustained in a high‐volume, urban ED setting. While the use of this model successfully identified patients with undiagnosed HIV infection in the ED, the overall level of testing remained low. Innovative testing programs, such as nontargeted screening, more specific targeted screening, or alternative hybrid methods, are needed to more effectively identify undiagnosed HIV infection in the ED patient population.     

Blood screening by nucleic acid amplification technology: current issues, future challenges.

BACKGROUND: Nucleic acid amplification technology (NAT) is presently being evaluated in US clinical trials to determine the safety and efficacy of mini-pool testing for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) RNA in the blood-donor population. Although the risk for transfusion-transmitted HIV and HCV infection is extremely low, there is still a small chance that blood donated by infected individuals before seroconversion can escape detection by current antibody-based assays. METHODS: This report describes the amplification technologies being used and reviews several issues surrounding NAT-based blood screening. The performance features of NAT and current enzyme immunoassay technologies are compared, and the benefits of NAT in reducing transfusion-transmitted infections are discussed. CONCLUSIONS: The current US clinical trials of mini-pool NAT testing for HIV and HCV RNA have successfully identified preseroconversion infectious blood units. Although the current NAT-based screening systems are semiautomated, mini-pool testing represents an unprecedented innovation among government and nongovernment agencies in the highly regulated blood transfusion industry. Despite cost-effectiveness issues, based on the public perception of infectious diseases acquired through blood transfusion, NAT-based screening of the blood supply is expected to become a standard in transfusion medicine.     

An improved method for monitoring efficacy of anti-retroviral therapy in HIV-infected individuals: a highly sensitive HIV p24 antigen assay.

Circulating human immunodeficiency virus (HIV) p24 antigen levels were measured by a highly sensitive HIV p24 antigen-capture enzyme-linked immunosorbent assay (ELISA) in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex (ARC) otherwise negative for HIV p24 antigen measured by a commercial antigen-capture ELISA. The assays were performed at baseline and at several intervals during treatment with either zidovudine (ZDV) or dideoxyinosine (ddl). To further enhance the rate of antigen detection, serum was pretreated with hydrochloric acid to denature antibody in immune complexes. Utilizing this assay system, we monitored these patients for drug efficacy. HIV p24 antigen levels obtained by using this sensitive assay decreased in 3 of 8 patients receiving ZDV during 8 weeks of ZDV treatment. Similarly, ddl administration was associated with a decrease of HIV p24 antigen levels in 3 of 5 patients. Thus, the use of the highly sensitive HIV p24 antigen assay permitted the monitoring of surrogate HIV p24 antigen as a measure of efficacy of anti-retroviral therapy in all of these patients who were otherwise HIV p24 antigen-negative at the onset of anti-retroviral therapy.     

浙江省宁波市HIV/AIDS流动病例的流行病学特征分析

目的分析浙江省宁波市2013 — 2017年近5年艾滋病病毒感染者/艾滋病患者（HIV/AIDS）人口流动情况,掌握疫情特征,为制定防控措施提供参考依据。方法对2013 — 2017年宁波市报告的HIV/AIDS疫情数据,采用描述性流行病学方法分析宁波市流动病例的流行病学特征。结果宁波市近5年共报告HIV/AIDS病例3 034例,其中22.45%病例已流出至外市/外省;近5年宁波市现住址管理的病例共2 642例,其中11.05%的病例为外地流入。 流入流出的病例主要以未婚青壮年为主。流出本市的病例中大部分患者是外地户籍;流入本市的病例中大部分患者非本地户籍。 流出病例文化程度集中在初中及以下,主要经异性性接触感染。 流入病例文化程度集中在初中及以上,主要经同性性接触感染。流出至外地的病例接受抗病毒治疗比例相对较低（P＜0.05）,流入至本地的病例接受抗病毒治疗比例较高（P＞0.05）。 死亡病例抗病毒治疗比例较低,不同流动方式的未治疗死亡病例从发现到死亡时间上,差异有统计学意义（P＜0.05）,死因分类上差异无统计学意义（P＞0.05）。结论宁波市HIV/AIDS病例流动性较大,流出本市的病例治疗比例普遍偏低,作为传染源存在较大的传播风险。 因此,在病例转入转出的过程中,建议随访医生进一步加强流动病例的随访管理及抗病毒治疗工作,对于减少二代传播意义重大。     

我国HIV检测技术水平正在稳步提高

近年来我国HIV检测工作在政府"四免一关怀"政策的推动下得到了飞速发展.全国HW检测数量迅速增加,检测的领域也在不断扩大,从单一以血清学检测的诊断和血液筛查为主,扩展到为临床治疗、科学研究和为国家防治策略服务.HIV检测工作已逐渐由CDC系统为主转变为多系统共同参与,而且许多HIV检测新领域是由临床医疗部门的实验室开拓的.这既适应了我国AIDS检测工作的实际需求,也推动了我国HIV检测技术水平的稳步提高.     

Long-term non-progression of HIV-1 in a patient coinfected with HTLV-II

A 37-year-old man coinfected with HIV-1 and human T-lymphotropic virus type II presumably through injection drug use had a high CD4+ count and low HIV viral load without anti-retroviral therapy for over six years. As an HIV long-term non-progressor, his case supports the hypothesis that coinfection with HTLV-II does not adversely affect the course of HIV disease.     

Challenges of the anti-retroviral therapy

Anti-retroviral therapy has still many difficulties for the continuous viral suppression, although it has markedly improved the prognosis of the patients with HIV/AIDS. It is essential that anti-retroviral therapy requires strict adherence of the patients. More than 95% of adherence to have medicine is required for the success of the therapy. Severe and frequent adverse reactions, many pill burden, food restriction and patients' poor recognition to the therapy influence adherence. Of those, adverse reaction of the drugs is the strongest factor for disturbing adherence. Digestive tract symptoms such as nausea, vomiting, abdominal pain and/or diarrhea are common and affect to reduce adherence. Recently, lactic acidosis/hepatic steatosis and lipodystrophy syndrome have been recognized as novel and important adverse reactions with anti-retroviral medicines. Physicians should be aware of the importance of adherence, and assist the patients to improve it with multiple approaches.     

Pain in patients with HIV infection: issues for the new millennium

Pain is a common problem in people infected with the human immunodeficiency virus (HIV), particularly when they develop the acquired immune deficiency syndrome (AIDS). Until recently AIDS was a progressive fatal illness with a short prognosis, so the assessment and treatment of AIDS-related pain was logically based on the approach taken for the management of cancer pain. The cancer pain paradigm may no longer be appropriate for pain in patients with HIV infection, however, because the natural history of HIV disease has been transformed into a chronic illness by highly active anti-retroviral therapy (HAART), available since the late 1990s. In resource-poor countries of the Asia Pacific region where access to HAART is limited, the cancer pain paradigm may still be relevant. In this paper, the clinical characteristics of pain in HIV disease are described, along with current approaches to assessment and treatment. These are compared and contrasted with the characteristics, assessment and treatment of cancer pain. Data are presented which emphasize these similarities and differences, and highlight the need for a multidisciplinary, comprehensive approach to managing pain in HIV disease, now a chronic illness. There is a great need for more research on HIV-related pain in the HAART era.     

Recent advances in molecular pathogenesis of HIV infection

Highly active anti-retroviral therapy (HAART) dramatically improves the prognosis of individuals infected with HIV, and changes the pathophysiology of HIV infection. However, the eradication of HIV has not been achieved by HAART due to presence of reservoir cells. More potent strategy of therapy against HIV is needed for further suppression of the replication and eradication of reservoirs. The recent advances about molecular pathogenesis of HIV infection are reviewed in this paper, that leads to discovery of the new molecular targets of anti-HIV drugs.     

2010 HIV Diagnostics Conference

During the 2010 HIV Diagnostics Conference, which took place in Orlando (FL, USA) between 24 and 26 March 2010, salient new data related to three aspects of HIV testing (rapid point-of-care testing, laboratory assays and new technologies) were presented and discussed. A conundrum central to HIV diagnostics in the USA for the last few years has resulted from technological developments in HIV testing that have outpaced recommendations for screening and confirmatory testing. Perhaps in response, one of the major outcomes of this 2010 meeting was the proposal of a novel laboratory testing algorithm. The proposed algorithm aims to take advantage of all of the capabilities of currently available tests (sensitivities for HIV-1 and HIV-2 IgG and IgM antibodies, and p24 antigen), while at the same time enhancing the turnaround time of results. This report will summarize the presentations at the meeting.     

A comprehensive theoretical framework for the implementation and evaluation of opt‐out HIV testing

Opt‐out HIV testing (in which patients are offered HIV testing as a default) is a potentially powerful strategy for increasing the number of people who know their HIV status and thus limiting viral transmission. Like any change in clinical practice, implementation of opt‐out HIV testing in a health service requires a change management strategy, which should have theoretical support. This paper considers the application of three theories to the implementation and evaluation of an opt‐out HIV testing programme: Behavioural Economics, the Health Belief Model and Normalisation Process Theory. An awareness, understanding and integration of these theories may motivate health care providers to order HIV tests that they may not routinely order, influence their beliefs about who should be tested for HIV and inform the operational aspects of opt‐out HIV testing. Ongoing process evaluation of opt‐out HIV testing programmes (based on these theories) will help to achieve individual health care provider self‐efficacy and group collective action, thereby improving testing rates and health outcomes.     

HIV drug resistance testing: is the evidence really there?

OBJECTIVES: To assess the strength of evidence supporting the routine use of HIV drug resistance testing. DESIGN: A critical review of all studies relating to the clinical utility of HIV resistance testing, with a focus on randomized trials. RESULTS: Two cohort studies found no evidence of a difference in virological response in patients who had resistance testing compared with matched controls. We identified nine published randomized trials that were specifically designed to assess the clinical utility of drug resistance testing. In a meta-analysis of these trials, resistance testing increased the proportion of patients who achieved undetectable viral load by an average of 7% (95% confidence interval: 3-11%). However, this may be an over-estimate of the impact of resistance testing in clinical practice because of the idealized design and analytical approaches used in most of the studies. CONCLUSIONS: The available evidence does not clearly demonstrate that HIV drug resistance testing is clinically effective. To optimize their value for health decision-making, future trials of HIV resistance testing should be carefully designed to mimic the circumstances of routine clinical practice.     

Design and Implementation of a Controlled Clinical Trial to Evaluate the Effectiveness and Efficiency of Routine Opt-out Rapid Human Immunodeficiency Virus Screening in the Emergency Department

In 2006, the Centers for Disease Control and Prevention (CDC) released revised recommendations for performing human immunodeficiency virus (HIV) testing in health care settings, including implementing routine rapid HIV screening, the use of an integrated opt-out consent, and limited prevention counseling. Emergency departments (EDs) have been a primary focus of these efforts. These revised CDC recommendations were primarily based on feasibility studies and have not been evaluated through the application of rigorous research methods. This article describes the design and implementation of a large prospective controlled clinical trial to evaluate the CDC's recommendations in an ED setting. From April 15, 2007, through April 15, 2009, a prospective quasi-experimental equivalent time-samples clinical trial was performed to compare the clinical effectiveness and efficiency of routine (nontargeted) opt-out rapid HIV screening (intervention) to physician-directed diagnostic rapid HIV testing (control) in a high-volume urban ED. In addition, three nested observational studies were performed to evaluate the cost-effectiveness and patient and staff acceptance of the two rapid HIV testing methods. This article describes the rationale, methodologies, and study design features of this program evaluation clinical trial. It also provides details regarding the integration of the principal clinical trial and its nested observational studies. Such ED-based trials are rare, but serve to provide valid comparisons between testing approaches. Investigators should consider similar methodology when performing future ED-based health services research.