An audit of antiretroviral treatment use in HIV-infected patients in a London clinic: the limitations of observational databases when auditing antiretroviral treatment use

Objective

To audit the use of antiretroviral (ARV) treatment in a large treatment clinic in the UK against the British HIV Association (BHIVA) ARV treatment guidelines.

Methods

All patients under follow‐up between 1st January 2000 and 1st January 2001 were included. The most recent CD4 count and HIV RNA level prior to 1st January 2001, and the nadir CD4 count and peak HIV RNA level over follow‐up, were used to identify which patients should be receiving HAART according to the guidelines.

Results

One thousand two hundred and sixty‐four patients were included in the analysis (63.8% homosexual, 29.0% heterosexual risk; 72.9% white; 79.2% male). Almost half of patients had ever had a CD4 count below 200 cells/µL and over 80% had previously had a viral load above 4 log₁₀ HIV‐1 RNA copies/mL. Under 2000 BHIVA guidelines, treatment would be recommended in 77.4% patients. Overall, 819 patients were receiving ARV therapy. Two hundred and eighty‐five patients were not receiving treatment when guidelines suggest they should (including 33 patients who were receiving regimens not recommended in the guidelines). These patients were younger, less likely to be homosexual and had higher CD4 nadirs than those who were receiving ARV treatment. Almost half of these patients had previously received ARV therapy but were not currently receiving it.

Conclusion

Only a small proportion of patients at our centre were not receiving ARV treatment in line with national guidelines. While genuine reasons may exist for these departures from optimal care, this may simply reflect the limitations of using observational databases when auditing treatment use in a clinic setting.

     

Treatment of human immunodeficiency virus-related lymphoma with haematopoietic stem cell transplantation

The advent of highly active antiretroviral therapy (HAART) and its co-administration with chemotherapy in patients with human immunodeficiency virus (HIV)-related lymphoma has lead to the exploration of potentially curative combination chemotherapy and myeloablative therapy followed by autologous haematopoietic stem cell transplantation (ASCT). Applying the same principles used for patients with HIV-negative aggressive lymphoma, in 1998 we developed a program of high-dose therapy and ASCT at City of Hope for patients with HIV-related lymphoma and Hodgkin's disease. Our studies have primarily included patients with chemosensitive lymphoma in relapse or first remission with poor-risk features at diagnosis. Filgrastim (G-CSF)-primed peripheral blood stem cell mobilization and apheresis have been successful while patients were receiving HAART and chemotherapy. To date, ASCT has been performed in 19 patients with HIV-related lymphoid malignancies, representing the largest single-institution experience reported to date. Most patients received a chemotherapy-based conditioning regimen consisting of high-dose carmustine, etoposide and cyclophosphamide. Early infections, namely bacteremias and neutropenic fever were similar to those observed in the HIV-negative transplant setting. Opportunistic infections were rare and easily treatable. There were three early deaths, two from relapsed lymphoma and one from multi-organ failure in an older patient. The remaining 16 patients are alive and in remission. In summary, ASCT is well tolerated, can result in long-term remissions, and is potentially curative in selected HIV-related lymphoma patients with chemosensitive relapse and high-risk disease in first remission defined by the age-adjusted International Prognostic Index criteria (i.e., two or three of the following: elevated LDH, advanced stage, and poor performance status). Acquisition of resistance to HAART remains as a potential problem for HIV-positive patients who are cured of their lymphoma.     

IL-7 induces sCD127 release and mCD127 downregulation in human CD8+ T cells by distinct yet overlapping mechanisms,both of which are impaired in HIV infection

The IL-7 receptor specific α chain, CD127, can be expressed both as a membrane-associated (mCD127) and a soluble form (sCD127), however, the mechanisms involved in their regulation remain to be defined. We first demonstrated in primary human CD8⁺ T cells that IL-7-induced downregulation of mCD127 expression is dependent on JAK and PI3K signaling, whereas IL-7-induced sCD127 release is also mediated by STAT5. Following stimulation with IL-7, expression of alternatively spliced variants of the CD127 gene, sCD127 mRNA, is reduced, but to a lesser degree than the full-length gene. Evaluation of the role of proteases revealed that MMP-9 was involved in sCD127 release, without affecting the expression of mCD127, suggesting it does not induce direct shedding from the cell surface. Since defects in the IL-7/CD127 pathway occur in various diseases, including HIV, we evaluated CD8⁺ T cells derived from HAART-treated HIV-infected individuals and found that IL-7-induced (1) downregulation of mCD127, (2) release of sCD127, and (3) expression of the sCD127 mRNA were all impaired. Expression of mCD127 and sCD127 is, therefore, regulated by distinct, but overlapping, mechanisms and their impairment in HIV infection contributes to our understanding of the CD8⁺ T cell dysfunction that persists despite effective antiretroviral therapy.     

Resolution of dilated cardiomyopathy in an adolescent with change of a failing highly active antiretroviral drug therapy

BackgroundCardiovascular dysfunction is a recognized complication of HIV infection in children. Cardiac complications of HIV usually occur late in the course of the disease; they may be associated with drug therapy, and hence become more common as therapy and survival improve. Left ventricular (LV) dysfunction at baseline is a risk factor for death independent of the CD4 cell count, HIV viral load, and neurological disease.ConclusionImmunological recovery following a switch of a failing or potentially cardiotoxic HAART in addition to improved HAART adherence may result in resolution of left ventricular dysfunction. Early and regular cardiology evaluation may improve outcomes in these patients.     

接受HAART治疗的1718例HIV／AIDS患者中医证候研究

目的：通过调查接受HAART治疗的HIV／AIDS患者的症状分布规律,探讨该类患者的中医证候特点。方法：选取接受HAART治疗3个月以上的HIV／AIDS患者1718例进行横断面调查,采集中医四诊信息和现代生物学信息,对这些患者进行症状、体征、证候出现频率（次）的描述性统计。结果：常见症状依次为：乏力、纳呆、咳嗽、头痛、月经失常（女性）、关节痛、皮肤瘙痒、腰痛、肌肉痛、发热;舌色以红、绛红、淡白及紫色为主,舌形以薄舌、胖大舌、齿痕舌为主,舌苔则以薄白苔和黄腻、厚腻苔多见;脉象以复合脉象为主,分解后脉象以细脉、滑脉、弦脉最为多见。共出现中医证型24种,气血两亏、气阴两虚是最常见的证型,其次为痰热内扰证、肝郁气滞火旺证、脾肾亏虚及湿邪阻滞证。多为复合证型,分解后出现的单证达32种。单证以虚证为主,其次为实证,虚实夹杂最少。脏腑的发病率由高至低依次为脾、肺、肾、肝、心,其中脾系发病率最高,且常与肺、肝、肾合而为病。发病脏腑数目由高至低依次为：三脏同病、二脏同病、四脏同病、一脏发病、五脏同病。结论：接受HAART治疗的HIV／AIDS患者临床症状体征表现多样,病情复杂,证候多见虚实夹杂,以虚为主,涉及脏腑主要为脾、肺、肾,常见多脏腑同病。     

AIDS患者红细胞沉降率的检测及意义

红细胞沉降率（ESR,血沉）测定是一种非特异性试验,能指示人体内某些疾病的发展和预后判断,AIDS患者在高效抗逆转录病毒联合治疗（HAART）过程中出现严重的代谢紊乱。本文通过对AIDS患者在HAART治疗前后ESR的检测,探讨其的变化及临床意义。     

湖南省艾滋病病人抗病毒治疗死亡病例分析

目的探讨影响艾滋病抗病毒治疗病人死亡的主要因素,为降低病人死亡率,提高治疗效果提供参考。方法1 346例艾滋病抗病毒治疗病例信息均来自国家艾滋病综合防治信息系统,用SPSS13.0统计软件进行数据处理,对病例进行生存分析,计算病死率[/（100人.年）],分析可能影响病人死亡率的临床和基线CD4计数等因素。结果从2003年到2008年,共有1 346名艾滋病人接受抗病毒治疗,其中死亡221例,死亡病例中艾滋病相关疾病死亡198例,其他原因死亡23例;总病死率为13.6/[（100人.年）],12个月生存率为14.0%,按病死率[/（100人.年）]计算为19.8;接受治疗前94.9%（188/198）的患者出现过1种临床症状,77.3%（153/198）的病例同时具有2种或2种以上临床症状;基线CD4计数（个/mm3）在〈50,50~200,〉200各组间病死患者生存时间差异有统计学意义,P〈0.05;1年以内病死的与生存1年以上的病例基线CD4计数水平差异也有统计学意义,P〈0.01。结论接受抗病毒治疗患者1年以内的生存率变化最大,病死率与开始治疗时的基线CD4细胞计数水平及病人的一般情况密切相关,加强病人的早期发现和及时治疗,构建社会综合支持网络,才能有效地降低病人死亡率,提高治疗效果。     

Evaluation of affordable screening markers to detect CD4+ T‐cell counts below 200 cells/μl among HIV‐1‐infected Ugandan adults

Objective To evaluate validity of WHO staging, low body mass index (BMI) and anaemia in detecting HIV‐infected adults with CD4+ T‐cell counts < 200 cells/μl. Methods Between October 1995 and April 2006, we screened Ugandans aged 16 or older at enrolment into an open cohort. We analysed highly active anti‐retroviral therapy (HAART)‐naïve HIV‐infected patients with WHO stages 1–3 and complete data in a secondary cross‐sectional study. Low BMI was a BMI < 18.5 kg/m². Anaemia was a haemoglobin level < 11 or 12 g/dl among women and men respectively. Results Among 2892 HAART‐naïve patients, the median age was 32 years. 71% were women, 54% had WHO stage 3 AIDS, 34% had anaemia, 16% had a low BMI and 43% had CD4+ T‐cell counts < 200 cells/μl. WHO stage 3 compared to combined WHO stages 1 and 2 had a sensitivity (95% CI) of 70% (67, 72) and a specificity of 57% (55, 60) respectively to detect CD4+ T‐cell counts < 200 cells/μl. Anaemia compared to normal haemoglobin had sensitivity (95% CI) of 47% (44, 50) and a specificity of 76% (74, 78). Low BMI compared to normal BMI had sensitivity (95% CI) of 23% (20, 25) and a specificity of 89% (87, 90) against CD4+ T‐cell counts < 200 cells/μl. Conclusion Only WHO stage 3 had reasonably high sensitivity in detecting CD4+ T‐cell counts below 200 cells/μl in this setting. Targeted low‐cost CD4 testing strategies are urgently needed to detect patients eligible for HAART in rural Africa and other resource‐limited settings.