Therapeutic Drug Monitoring of Indinavir in HIV-Infected Patients Undergoing HAART

Background: Therapeutic drug monitoring (TDM) of protease inhibitors (PI) is gaining increasing importance for the management of HIV-infected patients undergoing highly active antiretroviral therapy (HAART). The PI indinavir (IDV) is widely used in HAART regimens. Combinations of IDV with ritonavir (RTV) have been used to increase the plasma concentration of IDV. However, the desirable IDV concentration range in clinical practice remains to be elucidated. Patients and Methods: To study the value of TDM for IDV in clinical practice, a retrospective analysis of 501 plasma samples of patients treated with IDV in various dosages was performed. IDV levels were determined during routine outpatient visits. Analysis was performed by high pressure liquid chromatography (HPLC) with UV detection. Results: A widespread range of IDV plasma concentrations was seen both within and between patients. The mean IDV level during therapy with IDV 2.4 g/d was 3,260 ng/ml (95% CI: 2,903 ng/ml; 3,618 ng/ml). IDV levels at a dose of IDV 1.6 g/d in combination with RTV resulted in a mean IDV plasma concentration of 4,191 ng/ml (95% CI: 3,356 ng/ml; 5,016 ng/ml). There was no significant difference between plasma levels at the doses of 2.4 g/d and 1.6 g/d. 35 of all 130 patients treated with IDV reached only suboptimal IDV plasma concentrations below the limit of 150 ng/ml. There was no statistically significant difference between the number of patients below an IDV plasma concentration of 150 ng/ml in the various dosage regimens. Conclusion: During therapy with IDV in a b.i.d. scheme, similar IDV plasma concentrations and a comparable number of patients with subinhibitory plasma concentrations were observed when compared to a therapeutic regimen with t.i.d. dosing. In this study, even at various times of plasma sampling after oral ingestion, TCM facilitated the surveillance of patients compliance. Received: August 07, 2000 · Revision accepted: August 27, 2001     

广东省AIDS病人的医疗保健费用预测

目的 预测艾滋病(AIDS)流行对广东省社会经济造成的直接危害——医疗保健费用激增的程度。方法 通过定性调查和病历研究，揭示广东省艾滋病病毒(HIV)／AIDS发生发展的一般规律，结合社会经济发展相关指标进行假设推断，计算个体医疗保健花费和2000～2010年广东省HIV／AIDS累计医疗费用。结果 1999年1例AIDS患者的门诊医疗费用约1．6万元／年，住院医疗费用约10．17万元／年；到2010年，1例AIDS患者含抗病毒治疗在内的门诊医疗费用约8．08万元／年，住院医疗费用约12．65万元／年。随着AIDS的流行，广东省2000～2010年AIDS医疗花费累计将达38．9亿～58．8亿元。结论 AIDS在危害居民身心健康的同时，将造成极大的医疗经济负担，目前应抓住机遇，利用一切可以利用的资源遏制AIDS的流行。     

HIV-disease progression in Swedish haemophiliacs and the influence of replacement therapy

HIV-disease progression in terms of the decline in CD4⁺ cell count, the development of AIDS-related symptoms and death was studied in 100 Swedish HIV-positive haemophiliacs and correlated to age and haemophilia treatment.
On average 15 years after seroconversion, 66% of the patients had CD4⁺ cell counts of < 200×10⁶ L⁻¹, 48% had developed AIDS and 56% had died. Age was found to correlate to all three endpoints, also after adjustment for age, annual clotting factor concentrate (CFC) consumption and HIV-related therapy, i.e. pneumocystis prophylaxis and antiretroviral drugs ( P  < 0.05). Total annual CFC consumption showed no significant relationship to the decline in CD4⁺ cell counts but was inversely correlated to both the development of AIDS-related symptoms ( P  = 0.033) and mortality ( P  = 0.014). Prophylactic treatment was not associated with significantly better survival than on-demand treatment after adjustment for age, CFC consumption and HIV-therapy. The use of monoclonal-antibody-purified CFCs was not found to stabilize the decline in CD4⁺ cell counts. However, the use of these CFCs was inversely correlated both to the development of AIDS-related symptoms and to mortality ( P  = 0.042 and 0.027, respectively). A similar trend was associated with the use of low- and intermediate-purity CFCs. As compared with the severe haemophilia A subgroup, the moderate haemophilia A patients showed a trend toward slower disease progression, possibly attributable to a lower incidence of haemarthrosis and arthropathy among the latter.
We conclude that replacement therapy in HIV-infected haemophiliacs is important also for HIV-disease progression, whereas the purity of the CFCs and the regimen used are of minor importance.     

An algorithm-based genotypic resistance score is associated with clinical outcome in HIV-1-infected adults on antiretroviral therapy

OBJECTIVES: The aim of this study was to evaluate the association between genotypic drug resistance and the occurrence of HIV-related diseases and death in HIV-1-infected adults on antiretroviral therapy. METHODS: We performed an observational study on patients from an out-patient clinic in a university hospital. Genotypic drug resistance analysis after virological treatment failure was performed in 141 patients receiving two or more antiretroviral drugs. All patients had follow up of at least 6 months after the resistance test. An algorithm was developed to estimate the level of genotypic drug resistance and to assign an actual resistance score (ARS) for the drugs prescribed to each patient. The patient population was divided into quartiles according to patients' ARS values. Our endpoint was the risk of developing an HIV-related disease [Centers for Disease Control and Prevention (CDC) category B or C] during the period starting 6 months prior to and ending 6 months after the genotypic resistance test, or death during the 6 months following the resistance test. RESULTS: There was a significant association between the level of resistance to the drugs prescribed (ARS) and our clinical endpoint: the odds ratio for an endpoint (with 95% confidence interval) was 3.20 (1.28-7.99), adjusted for CD4 cell count and HIV RNA, in patients in the highest ARS quartile compared with patients in the other three quartiles. CONCLUSIONS: Our study indicates that patients with high-level genotypic drug resistance are at increased risk of developing an HIV-related disease. This association could not be explained by differences in CD4 cell count or HIV RNA levels.     

Antibodies to factor VIII in plasma of patients with hemophilia A and normal subjects

 Non-neutralizing factor VIII (FVIII) antibodies (FVIII-Ab) in hemophilia A may be associated with an abnormal clinical response to FVIII concentrates. Patients with FVIII inhibitors may develop noncoagulation FVIII-Ab after the induction of immunotolerance. Natural FVIII-Ab may be detected in the plasma of some healthy subjects. The aim of this study was to analyze the presence of FVIII-Ab in the plasma of 53 normal blood donors and 124 patients with hemophilia A (18 patients had a previous history of FVIII inhibitor, but only 12 had inhibitor at the moment this study was performed). FVIIII inhibitor was measured using the Bethesda method. FVIII-Ab were analyzed by a specific ELISA assay using purified FVIII from a monoclonal concentrate and a standard plasma containing 26 Bethesda units (BU) of FVIII inhibitor. Purified FVIII was used to coat wells of a microtiter plate and was incubated with dilutions of plasma to be tested. Bound human IgG FVIII-Ab were detected by incubation with polyclonal sheep anti.human IgG alkaline phosphatase conjugate, and the OD₄₀₅ was quantitated. A linear fit was obtained (by plotting FVIII-Ab positivity [OD 405nm] versus BU titer) when serial dilutions of this standard inhibitor plasma, containing titers of 0.5 BU or higher, were used. Four different levels of FVIII-Ab positivity [OD 405nm] were distinguished in this assay: Negative levels (–) were obtained with dilutions of the standard inhibitor containing <0.5 BU. Mild levels (+) were obtained with dilutions of 0.5–5 BU. Moderate levels (++) were obtained for dilutions ranging from 5–25 BU. Maximum positivity (+++) was obtained for dilutions of titers > 25 BU. FVIII-Ab positivity was detected in eight of the normal subjects (15%): three were found to be moderately positive (++) and five mildly positive (+). No inhibitory activity was detectable when whole plasma was used. All the hemophilic patients with a presence of FVIII inhibitor at the time of the study were found to be positive for FVIII-Ab. In addition, the level of positivity correlated with the corresponding BU. Four of the six patients who had a history of inhibitor were negative and two positive. Twenty additional patients (16.12%) in whom no inhibitory activity was detected were found to be positive for FVIII-Ab: 16 + and four ++. The mean age of patients with FVIII-Ab positivity was significantly higher than that of patients of the FVIII-Ab negative group (p<0.005). In conclusion, FVIII-Ab positivity in patients with hemophilia A was 17.7% higher than the level of positivity detected by an inhibitory assay. We propose that this method for FVIII-Ab analysis could be used for patients with hemophilia A, at least to complement the functional inhibitor assay. FVIII recovery or half-life should be assessed in patients who test positive for FVIII-Ab and who show no evidence of inhibitor. Received: 31 July 1995 / Accepted: 25 January 1996     

海南省吸毒人群HIV感染状况调查

目的摸清海南省吸毒人群艾滋病病毒（HIV）感染的相关行为的信息，为针对这组人群开展艾滋病干预措施提供依据。方法采用筛查的方法，在规定的时间内，对全省强制戒毒所的4243名戒毒人员进行HIV检测和问卷调查。结果在4243名戒毒者中，检出35名HIV抗体阳性者，平均检出率为0．82％。35名阳性者分布在东方（6．45％）、乐东（4．29％）、儋州（3．03％）、三亚（2．30％）等6个市县；有注射毒品行为者占50．3％～82．9％。感染的主要原因是通过共用针具静脉注射毒品引起，共用针具率14．2％～24．9％。结论海南省吸毒人员HIV总体上虽处于低流行水平，但是在东方、乐东、儋州、三亚等市县存在着局部流行现象，与艾滋病相关的危险行为依然存在，必须引起相关部门的关注。     

中国农村地区AIDS临床发病特点及应对策略

目的　提高对农村地区艾滋病 (AIDS)临床发病特点的认识。方法　对农村地区 10多个村庄的有偿供血员中近 10 0 0名艾滋病病毒 (HIV)感染者 /AIDS患者的临床特点进行实地调查分析。结果　 (1)临床特点呈现高发病率、高丙型肝炎 (丙肝 )病毒 (HCV)感染率和高母婴传播率 ,低乙型肝炎 (乙肝 )病毒 (HBV)感染率 (三高一低 ) ;临床表现为发热、腹泻、口腔霉菌感染 (口腔溃疡 )、皮疹四大主症。 (2 )同一时间对 5 0 0例患者进行免疫功能调查显示 :CD+ 4 >5 0 0 / μl 90例 (18% ) ,CD+ 4 2 0 0～ 5 0 0 / μl 2 89例 (5 7 8% ) ,CD+ 4 <2 0 0 / μl 12 1例 (2 4 2 % )。 结论　中国农村地区HIV/AIDS目前正处于发病高峰时期 ,发病速度为 2 4 2 % ;三高一低 ,四大主症是农村地区AIDS患者的主要临床特点 ;尽快为农村地区的AIDS患者提供医疗支持是当前最为紧迫的任务 ;积极、稳妥、持续、科学的医疗支持策略将是农村地区AIDS临床工作顺利开展的可靠保障。     

非职业针刺伤及意外伤害HIV暴露后预防现状及干预研究

目的为了解艾滋病病毒（HIV）非职业针刺及意外伤害暴露及暴露后预防的现状,以及暴露后预防的影响因素,探讨HIV非职业针刺伤及意外伤害暴露后预防的必要性和可行性.方法对北京地坛医院2001年1月至2002年12月收治的2 637例HIV非职业暴露者,实施或未实施暴露后预防（PEP）的结果进行了统计分析.结果全部非职业暴露者均提出了实施PEP的要求,但根据危险性评估,两年里共对52人实施了PEP.其中仅19人（36.54%）完成了28天的疗程,33例（63.46%）因副作用等而中止治疗.心理干预可以降低PEP的实施率.对实施或未实施PEP的1 486非职业暴露者于暴露后1个月,948例于暴露后3个月,689例于暴露后6个月,检测HIV抗体,均未发现阳性者.影响非职业暴露PEP完成的因素是：暴露源情况不明,HIV感染的危险性低及抗逆转录病毒治疗的副作用.结论HIV非职业意外伤害暴露感染的危险性极低.提示PEP对于那些暴露源HIV情况不明,HIV感染的危险性小,而又有明显的副作用时应该受到限制.     

Outcome of HIV-infected patients with invasive squamous-cell carcinoma of the anal canal in the era of highly active antiretroviral therapy

PURPOSE: Before the development of highly active antiretroviral therapy for the treatment of HIV infection, HIV patients diagnosed with invasive squamous-cell carcinoma of the anal canal carried a very poor prognosis. This study was designed to determine the outcome in a similar group of patients in the era of highly active antiretroviral therapy.METHODS: HIV-positive patients treated for invasive squamous-cell carcinoma of the anal canal at the University of Texas Medical Center affiliated hospitals from 1980 to 2001 were identified from operative data and cancer registries. We reviewed these records and collected data regarding age, CD4 count, highly active antiretroviral therapy, cancer treatment, complications, and survival. The patients were divided into two groups based on the presence or absence of highly active antiretroviral therapy and compared using a Kaplan-Meier approach.RESULTS: Fourteen patients with HIV and invasive squamous-cell carcinoma of the anal canal were identified. Six were in the prehighly active antiretroviral therapy group and eight in the highly active antiretroviral therapy group. All were considered for treatment with chemotherapy and radiation. In the prehighly active antiretroviral therapy group, one patient refused therapy and three were unable to complete the squamous-cell carcinoma therapy as planned because of complications. Four of eight highly active antiretroviral therapy patients were unable to complete the squamous-cell carcinoma therapy as planned. The prehighly active antiretroviral therapy patients had a mean age of 40 years and a mean CD4 count of 190 at the time of diagnosis. The highly active antiretroviral therapy patients had a mean age of 44 years and a mean CD4 count of 255 at the time of diagnosis. The 24-month survival was 17 percent in the prehighly active antiretroviral therapy group and 67 percent in the highly active antiretroviral therapy group (P = 0.0524). All six patients in the prehighly active antiretroviral therapy group died with active squamous-cell carcinoma vs. two in the highly active antiretroviral therapy group. Four of the remaining six patients had no evidence of active squamous-cell carcinoma at the last follow-up visit.CONCLUSIONS: A review of patients with HIV and invasive squamous-cell carcinoma of the anal canal suggests a trend toward a higher CD4 count at the time of diagnosis and improved survival in patients receiving highly active antiretroviral therapy. In this new era, HIV-positive patients should be on highly active antiretroviral therapy. If not, highly active antiretroviral therapy should be initiated, and standard multimodality therapies for invasive squamous-cell carcinoma of the anal canal are recommended.Read at the meeting of The American Society of Colon and Rectal Surgeons, New Orleans, Louisiana, June 21 to 26, 2003.     

在娱乐场所服务小姐中开展艾滋病预防干预试点研究

目的 了解娱乐场所服务小姐中艾滋病的有关知识、态度和行为,探索在该人群中开展预防艾滋病宣传教育的措施和评价方法。方法 采用快速评估,现场访谈和咨询、免费发放艾滋病预防宣传折页、安全套和同伴教育等方法进行干预,运用问卷调查和定性访谈方法评价干预效果。结果 基线调查124名服务小姐,干预后调查135名,干预后性病和艾滋病预防知识知晓率等均有显著性提高,但态度及行为干预前后无显著性差异。85.0％的人愿意使用安全套,但实际只有42.1％的人每次都使用安全套。结论 干预活动中不仅要提供性病艾滋病的防治知识,还要提供改变高危行为的技能。定性访谈资料可信性较高,可做为定量资料的补充和评价,但如何把定量与定性资料有机的结合起来还有待进一步探讨。