Guidelines for antiretroviral therapy for HIV infection

OBJECTIVE: To develop guidelines for health care providers and their HIV-positive patients on the clinical use of antiretroviral agents for HIV infection. OPTIONS: Recommendations published in 1996 by an international panel. OUTCOMES: Improvement in clinical outcomes or in surrogate markers of disease activity. EVIDENCE AND VALUES: The Canadian HIV Trials Network held a workshop on Oct. 19-20, 1996, to develop Canadian guidelines that incorporate information from recent basic and clinical research. RECOMMENDATIONS: Recommendations for the use of antiretroviral drugs in HIV infection are provided for initial therapy, continuing therapy, primary infection, vertical transmission, pediatric therapy and postexposure prophylaxis. VALIDATION: The guidelines are based on consensus of the participants attending the workshop: Canadian investigators, clinicians and invited representatives from the community, government and the pharmaceutical industry. They are subject to review and updating as new information on clinical benefits is published. SPONSORS: The workshop was organized by the National Centre of the Canadian HIV Trials Network. Unrestricted educational grants were provided by 8 pharmaceutical companies. Additional support was provided from the National AIDS Strategy of Health Canada.     

Antiretroviral Therapy for HIV Infection in 1998: Updated Recommendations of the International AIDS Society-USA Panel

Charles C. J. Carpenter, MD; Margaret A. Fischl, MD; Scott M. Hammer, MD; Martin S. Hirsch, MD; Donna M. Jacobsen; David A. Katzenstein, MD; Julio S. G. Montaner, MD; Douglas D. Richman, MD; Michael S. Saag, MD; Robert T. Schooley, MD; Melanie A. Thompson, MD; Stefano Vella, MD; Patrick G. Yeni, MD; Paul A. Volberding, MD

JAMA. 1998;280:78-86.

Objective.— To provide recommendations for antiretroviral therapy based on information available in mid-1998.

Participants.— An international panel of physicians with expertise in antiretroviral research and care of patients with human immunodeficiency virus (HIV) infection, first convened by the International AIDS Society–USA in December 1995.

Evidence.  —The panel reviewed available clinical and basic science study results (including phase 3 controlled trials; clinical, virologic, and immunologic end point data; data presented at research conferences; and studies of HIV pathophysiology); opinions of panel members were also considered. Recommendations were limited to drugs available in mid-1998.

Consensus Process.  —Panel members monitor new clinical research reports and interim results. The full panel meets regularly to discuss how the new information may change treatment recommendations. Updated recommendations are developed through consensus of the entire panel at each stage of development.

Conclusions.  —Accumulating data from clinical and pathogenesis studies continue to support early institution of potent antiretroviral therapy in patients with HIV infection. A variety of combination regimens show potency, expanding choices for initial regimens for individual patients. Plasma HIV RNA assays with increased sensitivity are important in monitoring therapeutic response; however, more data are needed to determine precisely the HIV RNA levels that define treatment failure. Long-term adverse drug effects are beginning to emerge, requiring ongoing attention. Some issues regarding optimal long-term approaches to antiretroviral management are unresolved. The increased complexity in HIV management requires ongoing monitoring of new data for optimal treatment of HIV infection.

     

Antimicrobial Treatmdent of "Complicated" Intra-Abdominal Infections and The New IDSA Guidelines - A Commentary and an Alternative European Approach According to Clinical Definitions

Recently, an update of the IDSA guidelines for the treatment of complicated intraabdominal infections has been published. No guideline can cater for all variations in ecology, antimicrobial resistance patterns, patient characteristics and presentation, health care and reimbursement systems in many different countries. In the short time the IDSA guidelines have been available, a number of practical clinical issues have been raised by physicians regarding interpretation of the guidelines. The main debatable issues of the new IDSA guidelines are described as follows: The authors of the IDSA guidelines present recommendations for the following subgroups of "complicated" IAI: community-acquired intra-abdominal infections of mild-to-moderate and high severity and health care-associated intra-abdominal infections (no general treatment recommendations, only information about antimicrobial therapy of specific resistant bacterial isolates). From a clinical point of view, "complicated" IAI are better differentiated into primary, secondary (community-acquired and postoperative) and tertiary peritonitis. Those are the clinical presentations of IAI as seen in the emergency room, the general ward and on ICU. Future antibiotic treatment studies of IAI would be more clinically relevant if they included patients in studies for the efficacy and safety of antibiotics for the treatment of the above mentioned forms of IAI, rather than conducting studies based on the vague term "complicated" intra-abdominal infections. - The new IDSA guidelines for the treatment of resistant bacteria fail to mention many of new available drugs, although clinical data for the treatment of "complicated IAI" with new substances exist. Furthermore, treatment recommendations for cIAI caused by VRE are not included. This group of diseases comprises enough patients (i.e. the entire group of postoperative and tertiary peritonitis, recurrent interventions in bile duct surgery or necrotizing pancreatitis) to provide specific recommendations for such antimicrobial treatment. - A panel of European colleagues from surgery, intensive care, clinical microbiology and infectious diseases has developed recommendations based on the above mentioned clinical entities with the aim of providing clear therapeutic recommendations for specific clinical diagnoses. An individual patient-centered approach for this very important group of diseases with a substantial morbidity and mortality is essential for optimal antimicrobial treatment.     

预防艾滋病母婴传播抗病毒治疗药物耐药性研究进展

艾滋病病毒可以通过母体直接传播给婴儿,目前最常使用的预防艾滋病母婴传播抗病毒治疗药物包括齐多夫定（AZT）、奈韦拉平（NVP）.近年来有报道显示,在新感染HIV的孕妇和经艾滋病抗病毒治疗后的HIV抗体阳性孕产妇及其所生的感染儿童体内发现耐药HIV病毒株.     

Challenges of Childhood TB/HIV Management in Malawi

The diagnosis and management of childhood tuberculosis (TB) are major challenges in countries such as Malawi with high incidence of TB and human immunodeficiency virus (HIV) infection. Diagnosis of TB in children often relies only on clinical features but clinical overlap with the presentation of HIV and other HIV-related lung disease is common. The tuberculin skin test (TST), the standard marker of M. tuberculosis infection in immune competent children, has poor sensitivity in HIV-infected children and is not usually available in Malawi. HIV test should be routine in children with suspected TB as it improves clinical management. HIV-infected children are at increased risk of developing active disease following TB exposure which justifies the use of isoniazid preventive therapy (IPT) once active disease has been excluded but this is difficult to implement and appropriate duration of IPT is unknown. HIV-infected children with active TB experience higher mortality and relapse rates on standard TB treatment compared to HIV-uninfected children, highlighting the need for further research to define optimal treatment regimens. HIV-infected children should also receive appropriate supportive care including cotrimoxazole prophylaxis and anti-retroviral treatment (ART) if indicated. There are concerns about concurrent use of some anti-TB drugs such as rifampicin with some ARTs.     

Short-course therapy for tuberculosis in infants and children. Infectious Diseases and Immunization Committee, Canadian Paediatric Society.

OBJECTIVE: To improve efficacy of and compliance with therapy for tuberculosis in children. OPTIONS: Short-course (6-month) multi-drug therapy, either non-supervised or directly supervised, versus long-course (more than 6-month) multi-drug therapy. OUTCOMES: Success (more than 90% of cases cured without relapse or serious side effects), development of drug resistance and compliance with treatment. EVIDENCE: Review of published reports of efficacy trials of tuberculosis therapy in children, side effects and compliance studies; consensus of expert opinion. VALUES: Values were assigned to the evidence by the Infectious Disease and Immunization Committee of the Canadian Paediatric Society through review of the data and consensus. BENEFITS, HARMS AND COSTS: Improved efficacy and compliance with short-course protocols should lower the rate of treatment failure among children in Canada and the cost of tuberculosis care. RECOMMENDATIONS: A short-course (6-month) protocol of four drugs for the first 2 months and two drugs for the subsequent 4 months is recommended to treat pulmonary tuberculosis or extrapulmonary disease causing lymphadenopathy. Tuberculous meningitis, disease involving bones and joints and tuberculosis with HIV infection require longer courses of treatment. Asymptomatic tuberculosis should be treated with daily doses of isoniazid for 9 months. Intermittent directly observed therapy is recommended if compliance cannot be ensured. Routine liver function testing is not recommended for prepubescent children taking isoniazid, but monthly assessment for clinical symptoms and periodic liver function evaluation is advised in adolescent women, especially post partum. VALIDATION: This report was reviewed by the directors of the Canadian Paediatric Society, the Hepatitis and Special Pathogens Division of the Laboratory Centre for Disease Control and the Canadian Thoracic Society. The recommendations are similar to those of the American Academy of Pediatrics. SPONSOR: The recommendations were developed and endorsed by the Infectious Disease and Immunization Committee of the Canadian Paediatric Society.     

An evidence-based approach to the management of uninvestigated dyspepsia in the era of Helicobacter pylori

OBJECTIVES: To provide Canadian primary care physicians with an evidence-based clinical management tool, including diagnostic and treatment recommendations, for patients who present with uninvestigated dyspepsia. RECOMMENDATIONS: The management tool has 5 key decision steps addressing the following: (1) evidence that symptoms originate in the upper gastrointestinal tract, (2) presence of alarm features, (3) use of nonsteroidal anti-inflammatory drugs (NSAIDs), (4) dominant reflux symptoms and (5) evidence of Helicobacter pylori infection. All patients over 50 years of age who present with new-onset dyspepsia and patients who present with alarm features should receive prompt investigation, preferably by endoscopy. The management options for patients with uninvestigated dyspepsia who use NSAIDs regularly are: (1) to stop NSAID therapy and assess symptomatic response, (2) to treat with NSAID prophylaxis if NSAID therapy cannot be stopped or (3) to refer for investigation. Gastroesophageal reflux disease can be diagnosed clinically if the patient's dominant symptoms are heartburn or acid regurgitation, or both; these patients should be treated with acid suppressive therapy. The remaining patients should be tested for H. pylori infection, and those with a positive result should be treated with H. pylori-eradication therapy. Those with a negative result should have their symptoms treated with optimal antisecretory therapy or a prokinetic agent. VALIDATION AND EVIDENCE: Evidence for resolution of the dyspepsia symptoms was the main outcome measure. Supporting evidence for the 5 steps in the management tool and the recommendations for treatment were graded according to the strength of the evidence and were endorsed by consensus of committee members. If no randomized controlled clinical trials were available, the recommendations were based on the best available evidence. LITERATURE REVIEW: Evidence was obtained from MEDLINE searches for pertinent articles published from 1966 to October 1999. The searches focused on dyspepsia, diagnosis and treatment. Additional articles were retrieved through a manual search of bibliographies and abstracts from international gastroenterology conferences.     

The feasibility of automating audit and feedback for ART guideline adherence in Malawi

Objective

To determine the feasibility of using electronic medical record (EMR) data to provide audit and feedback of antiretroviral therapy (ART) clinical guideline adherence to healthcare workers (HCWs) in Malawi.

Materials and methods

We evaluated recommendations from Malawi''s ART guidelines using GuideLine Implementability Appraisal criteria. Recommendations that passed selected criteria were converted into ratio-based performance measures. We queried representative EMR data to determine the feasibility of generating feedback for each performance measure, summed clinical encounters representing each performance measure''s denominator, and then measured the distribution of encounter frequency for individual HCWs across nurse and clinical officer groups.

Results

We analyzed 423 831 encounters in the EMR data and generated automated feedback for 21 recommendations (12%) from Malawi''s ART guidelines. We identified 11 nurse recommendations and eight clinical officer recommendations. Individual nurses and clinical officers had an average of 45 and 59 encounters per month, per recommendation, respectively. Another 37 recommendations (21%) would support audit and feedback if additional routine EMR data are captured and temporal constraints are modeled.

Discussion

It appears feasible to implement automated guideline adherence feedback that could potentially improve HCW performance and supervision. Feedback reports may support workplace learning by increasing HCWs'' opportunities to reflect on their performance.

Conclusion

A moderate number of recommendations from Malawi''s ART guidelines can be used to generate automated guideline adherence feedback using existing EMR data. Further study is needed to determine the receptivity of HCWs to peer comparison feedback and barriers to implementation of automated audit and feedback in low-resource settings.     

Are recommendations about routine antenatal care in Australia consistent and evidence-based?

OBJECTIVE: To describe the variability and evidence base of recommendations in Australian protocols and national policies about six aspects of routine antenatal care. DESIGN: Comparison of recommendations from local protocols, national guidelines and research about number of visits, screening for gestational diabetes (GDM), syphilis, hepatitis C (HCV), and HIV, and advice on smoking cessation. SETTING: Australian public hospitals with more than 200 births/year, some smaller hospitals in each State and Territory, and all Divisions of General Practice were contacted in 1999 and 2000. We reviewed 107 protocols, which included 80% of those requested from hospitals and 92% of those requested from Divisions. MAIN OUTCOME MEASURES: Frequency and consistency of recommendations. RESULTS: Recommendations about syphilis testing were notable in demonstrating consistency between local protocols, national policies and research evidence. Most protocols recommended screening for GDM, despite lack of good evidence of its effectiveness in improving outcomes. Specific approaches to screening for GDM varied widely. Coverage and specific recommendations about testing for HIV and HCV were also highly variable. Smoking-cessation information and advice was rarely included, despite good evidence of the effectiveness of interventions in improving outcomes. No national policies about the number of routine visits and smoking cessation could be identified. There were inconsistent national policies for both HIV and GDM screening. CONCLUSIONS: Antenatal care recommended in protocols used in Australia varies, and is not always consistent with national policies or research evidence. Producing and disseminating systematic reviews of research evidence and national guidelines might reduce this variability and improve the quality of Australian antenatal care.     

国产仿制抗逆转录病毒药物疗效分析

目的为目前大规模免费国产抗病毒药物治疗提供技术依据。方法分析116例使用国产抗逆转录病毒治疗患者的临床变化、依从性、副反应和部分免疫学及病毒学资料。结果国产抗病毒治疗药物对患者治疗有效。结论依从性是决定抗病毒治疗好坏的关键因素，基层因缺乏实验室检测会影响对疗效的判断。     

Appendix to the German-Austrian HIV Therapeutic Guidelines: strategies for treating morphological and metabolic alterations under antiretroviral treatment (current as of December 2004)

The recommendations made in this review are based on the current clinical knowledge with regard to the origin and therapy of lipodystrophy. They should be regarded as provisional and will change with expanding knowledge. The recommendations for treating dyslipidaemia in particular are oriented closely on the American recommendations of the National Cholesterol Education Program (NCEP III), and may be regarded both by HIV practitioners and patients as excessive and too rigid. The therapeutic goals of the NCEP in the first intervention studies in HIV-positive individuals were only achieved for a small proportion of the HIV patients. In addition, preliminary results suggest a potentially higher risk of adverse events in HIV-patients under statins or fibrates. The clinical efficacy of interventions with lipid lowering drugs has not been validated in HIV-seropositive patients. However, therapeutic decisions so far have been based on data obtained in non-HIV cardiovascular intervention studies. With more and more results becoming available from the HIV patient population a revision of these recommendations will be required.     

German-Austrian recommendations for HIV-therapy in pregnancy and in HIV-exposed newborn - update 2005

In Germany during the last years about 200-250 HIV infected pregnant women delivered a baby each year, a number that is currently increasing. To determine the HIV-status early in pregnancy voluntary HIV-testing of all pregnant women is recommended in Germany and Austria as part of prenatal care. In those cases, where HIV infection was known during pregnancy, since 1995 the rate of vertical transmission of HIV was reduced to 1-2%. - This low transmission rate has been achieved by the combination of anti-retroviral therapy of pregnant women, caesarean section scheduled before onset of labour, anti-retroviral post exposition prophylaxis in the newborn and refraining from breast-feeding by the HIV infected mother. To keep pace with new results in research, approval of new anti-retroviral drugs and changes in the general treatment recommendations for HIV infected adults, in 1998, 2001 and 2003 an interdisciplinary consensus meeting was held. Gynaecologists, infectious disease specialists, paediatricians, pharmacologists, virologists and members of the German AIDS Hilfe (NGO) were participating in this conference to update the prevention strategies. A third update became necessary in 2005. The updating process was started in January 2005 and was terminated in September 2005. The guidelines provide new recommendations on the indication and the starting point for therapy in pregnancies without complications, drugs and drug combinations to be used preferably in these pregnancies and updated information on adverse effects of anti-retroviral drugs. Also the procedures for different scenarios and risk constellations in pregnancy have been specified again. With these current guidelines in Germany and Austria the low rate of vertical HIV-transmission should be further maintained.     

广东省艾滋病免费抗病毒治疗维持状况调查

目的：调查广东省艾滋病免费抗病毒治疗的维持状况,探讨影响病人治疗维持时间的因素。方法：利用国家统一的成人DataFax抗病毒治疗信息数据库,收集全省1307名接受抗病毒治疗病人的资料,采用COX比例风险模型,对影响抗病毒治疗的维持时间之因素进行分析。结果：2004年10月至2008年5月全省共免费治疗1307名病人,其中66．7％病人在出现艾滋病相关症状后才被检测出HIV阳性;52．3％开始治疗时已经进入临床Ⅲ期;29．9％进入了临床Ⅳ期。88．2％的人开始治疗时CD4^＋T细胞低于200个／μL;结束治疗病人中,88．9％维持治疗时间小于1年,维持治疗时间最长的达到3年,影响病人维持治疗时间的主要因素是漏服次数、更换方案次数、治疗开始时CD4^＋T细胞水平、静脉吸毒感染。结论：应采取措施尽量延长病人治疗时间,加强对患者特别是静脉吸毒者的服药依从性教育,及时监测病人的服药情况,必要时及时调整方案。     

Therapy of hepatitis C in HIV-coinfection

One third of all European and American HIV-patients are coinfected with hepatitis C. HIV accelerates hepatitis C virus liver disease especially when HIV-associated immune deficiency progresses. Indeed, liver cirrhosis rate is five times higher in HIV/HCV-coinfected patients than in HCV-monoinfected patients. With the introduction of pegylated interferon and ribavirin combination therapy sustained virological response rates of up to 40 % could be obtained in HIV/HCV-coinfected individuals. Moreover, cohort analyses could demonstrate that with the use of highly active antiretroviral therapy (HAART) an improved course of hepatitis C and a reduction in liver disease-associated mortality can be achieved. Under consideration of the increased rate of hepatotoxicity due to the presently available antiretroviral treatment regimens in HIV/HCV coinfected patients, however, the development of treatment strategies and guidelines for management of hepatitis coinfection in HIV remains of great clinical significance.     

Viewpoint: A Pragmatic Approach to Constructing a Minimum Data Set for Care of Patients with HIV in Developing Countries

Providing quality health care requires access to continuous patient data that developing countries often lack. A panel of medical informatics specialists, clinical human immunodeficiency virus (HIV) specialists, and program managers suggests a minimum data set for supporting the management and monitoring of patients with HIV and their care programs in developing countries. The proposed minimum data set consists of data for registration and scheduling, monitoring and improving practice management, and describing clinical encounters and clinical care. Data should be numeric or coded using standard definitions and minimal free text. To enhance accuracy, efficiency, and availability, data should be recorded electronically by those generating them. Data elements must be sufficiently detailed to support clinical algorithms/guidelines and aggregation into broader categories for consumption by higher level users (e.g., national and international health care agencies). The proposed minimum data set will evolve over time as funding increases, care protocols change, and additional tests and treatments become available for HIV-infected patients in developing countries.     

Epidemiological composition,clinical and treatment characteristics of the patient cohort of the german competence network for HIV/AIDS

Objective

As its central basis for research, the Competence Network for HIV/AIDS (KompNet) established a nationwide cohort study on HIV-positive patients being in medical care in Germany. In this paper, we describe the epidemiological composition, and clinical as well as treatment characteristics of the KompNet cohort over time.

Methods

The KompNet cohort is an open, retrospective and prospective, multi-center, disease-specific and nationwide cohort study that started gathering data in June 2004. Semiannually, follow up visits of the patients are documented, covering a wide range of clinical and sociodemographic data. At enrolment and three years afterwards, an EDTA-sample is taken; a serum-sample is taken at every follow up.

Results

As of 20.10.2008, a total of 15,541 patients were enrolled by 44 documenting sites. In September 2007, the cohort size was reduced to ten outpatient clinics and fifteen private practitioners, covering a total of 9,410 patients. The documentation of these patients comprised 24,117 years of follow up-time since enrolment (mean: 2.6 years), 62,862 person years inclusive data documented retrospectively on course of HIV-infection and antiretroviral therapy (ART, mean: 6.7 years). Due to the short period of recruitment till now, rates of death (0.3%-0.8%) and losses to follow up (1.1%-5.5%) were low.84.9% of patients were men. Main risk of transmission was sex between men (MSM: 62.9%). Mean age was 45 years. About two third of patients were classified as CDC-stage B or C. Therapy regimens of currently treated patients complied with recent guidelines. Trends of mean CD4 cell count/μl regarding the initial therapy and concerning the population under treatment reflected the developments and the changing standards of antiretroviral therapy over time.

Conclusion

The KompNet cohort covers about a quarter of all patients estimated as being under treatment in Germany. Its composition can be accounted approximately representative for the situation of clinical care and treatment in the scope of HIV/AIDS in Germany. Therefore, it is an important instrument for measuring the course of HIV/AIDS, the reality of use of antiretroviral therapy and its clinical and psychosocial outcomes in Germany.     

艾滋病的临床与基础研究进展

全球约有85%的人类免疫缺陷病毒(HIV-1)感染是通过性传播途径获得,避孕套的推广已在几个国家成功地控制了HIV-1的传播。高效抗逆转录病毒治疗(HAART)的出现从根本上改变了人类HIV-1的感染进程。HAART的运用可以抑制HIV-1的复制,可将血浆病毒载量控制在检测限以下,并增加CD4 T淋巴细胞的数量,但也存在耐药性和毒副作用等问题。未来几年面临的挑战是:确定预期将出现的新的药物类型的作用和治疗方法的发展,解决HIV/肝病/结核病双重感染的问题,更好地进行补救治疗,解决资源有限国家在防治艾滋病方面的问题以及努力获得预防艾滋病的成功。