New trends in antiretroviral therapy for HIV infection

The treatment of HIV infection is a dynamic topic. More than 15 compounds, derived from three classes of antiretroviral drugs, are now available. A large number of clinical trials have determined the combinations that are optimal to use as first-line therapy; further investigations are needed to establish the value of simplified regimens (reduced number of doses and/or pills per day) in any attempt to increase the adherence of patients to therapy. In patients experiencing virological failure, assessment of adherence to treatment is helpful to determine the mechanisms of failure and to choose an alternative therapeutic option. The value of in vitro viral resistance evaluation by genotypic and/or phenotypic methods is currently being investigated. The value of therapeutic regimens available at the present time to treat HIV infection is hampered by their side effects. Metabolic toxicity has recently been identified as a major point of concern, and a better understanding of its mechanisms is urgently needed. Finally, in patients with long-term response to treatment, the value of passive immunotherapy to reduce the size of the viral reservoir and the effect of transient treatment interruption on specific immunological response have recently been investigated, but the first results are disappointing.     

Risk of premature atherosclerosis and ischemic heart disease associated with HIV infection and antiretroviral therapy

The use of new potent protease inhibitor-based antiretroviral therapies in patients with human immunodeficiency virus (HIV) infection has been increasingly associated with cardiovascular risk factors, including hyperlipidaemia, fat redistribution syndrome, insulin resistance, and diabetes mellitus. The introduction of highly active antiretroviral therapy (HAART) in clinical practice has remarkably changed the natural history of HIV disease, leading to a notable extension of life expectancy, and prolonged lipid and glucose metabolism abnormalities are expected to lead to significant effects on the long-term prognosis and outcome of HIV-infected patients. Prediction modeling, surrogate markers and hard cardiovascular endpoints suggest an increased incidence of cardiovascular diseases in HIV-infected subjects receiving HAART, even though the absolute risk of cardiovascular complications remains still low, and must be balanced against the evident virological, immunological, and clinical benefits descending from combination antiretroviral therapy. Nevertheless, the assessment of cardiovascular risk should be performed on regular basis in HIV-positive individuals, especially after initiation or change of antiretroviral treatment. Appropriate lifestyle measures (including smoking cessation, dietary changes, and aerobic physical activity) are critical points, and switching HAART may be considered, although maintaining viremic control should be the main goal of therapy. Pharmacological treatment of dyslipidaemia (usually with statins and fibrates), and hyperglycaemia (with insulin-sensitizing agents and thiazolidinediones), becomes suitable when lifestyle modifications and switching therapy are ineffective or not applicable.     

合理选择艾滋病母婴传播阻断抗病毒治疗方案的影响因素

目的 探索艾滋病母婴传播阻断中,合理选择抗病毒治疗方案的主要影响因素,为制定艾滋病病毒(HIV)感染孕妇及其所生婴儿的抗病毒治疗合理用药提供依据.方法 在云南省5个全面开展了母婴传播阻断、且妇幼保健网络相对健全的艾滋病高、中度流行县(市、区),对抗病毒治疗合理选择方案的影响因素进行病例对照研究和定性调查.结果 对158例HIV感染孕产妇进行问卷调查,并对15名管理医生、24名HIV感染孕产妇及其家属进行个人深入访谈.定量与定性研究发现,抗病毒治疗方案合理选择的主要相关因素为:产次顺序(OR=3.135)、少数民族(OR=3.393)、未知情选择(OR=5.745)、方案是医生要求的(OR=0.329)、为了孩子不被感染的愿望、医生对方案的认识等.结论 多个因素对HIV感染孕产妇合理选择抗病毒治疗方案有影响,在方案选择时要针对主要影响因素开展工作.     

Influence of antiretroviral therapy and cardiovascular disease on the immature platelet fraction in patients living with HIV

Abstract

Cardiovascular disease is an important contributor to morbidity and mortality in people living with HIV . The immature platelet fraction (IPF) is increased in HIV-negative patients with cardiovascular disease and evidence suggests that an enlarged IPF is associated with adverse cardiovascular events. In this multi-center observational study, we aimed to investigate how the IPF in people living with HIV is influenced by antiretroviral therapy and cardiovascular disease. Subjects without cardiovascular disease that received antiretroviral therapy showed a smaller IPF accompanied by lower D-dimer and C-reactive protein (CRP) levels compared to therapy-naïve subjects (mean IPF: 2.9% vs. 3.9%, p = .016; median D-dimer: 252 µg/L vs. 623 µg/L, p < .001; median CRP: 0.2 mg/dL vs. 0.5 mg/dL, p = .004). No significant differences for the IPF, D-dimer or CRP were found between subjects on antiretroviral therapy with documented cardiovascular disease and therapy-naïve subjects. In conclusion, we observed a reduction in the IPF among subjects on therapy only in the absence of cardiovascular disease. In contrast, subjects receiving therapy that had documented cardiovascular disease showed an IPF comparable to therapy-naïve subjects. Future studies are needed to investigate if an enlarged IPF may serve as a biomarker in predicting adverse cardiovascular events in people living with HIV.     

我国的艾滋病抗病毒治疗模式与现状

随着高效抗反转录病毒疗法的开展,世界上越来越多的艾滋病病毒感染者和病人得到了治疗。近年来,世界各国都投入了大量的人力、物力,努力探寻符合自己国情的抗病毒治疗模式,以便最大程度地遏制艾滋病疫情的蔓延。文章就中国当前对艾滋病抗病毒治疗模式的有关研究进展进行综述,以期为找到更加合理、更加适合中国国情的治疗模式提供理论依据。     

成人艾滋病抗病毒治疗效果及影响因素研究

目的通过对国内外文献及指南的全面回顾,描述并分析国内外成人抗病毒治疗病毒学效果及影响因素。方法收集并分析国内外抗病毒治疗相关文献和指南。结果病毒学效果受到治疗时间的影响,随着时间的延长,失败的病人比例会逐渐升高。同时病毒亚型、基线耐药、治疗方案、依从性、不良反应以及一些人口学因素,都会影响到病毒学效果。结论在资源有限地区开展大规模的抗病毒治疗,应尽可能延长一线治疗方案对病毒的抑制时间,提高治疗成功率。通过为病人提供病毒载量和耐药检测,改良治疗方案、提高依从性以及开展耐药监测等措施,能够进一步提高病毒学效果。     

HIV-related symptoms and management in HIV and antiretroviral therapy patients in KwaZulu-Natal,South Africa: A longitudinal study

Abstract

Aim: The study aimed to determine the prevalence, predictors, and self-reported management of HIV- or ARV-related symptoms among HIV patients prior to antiretroviral therapy (ART) and over three time points while receiving ART in KwaZulu-Natal, South Africa. Method: A total of 735 consecutive patients (29.8% male and 70.2% female) who attended three HIV clinics completed assessments prior to ARV initiation, 519 after 6 months, 557 after 12 months, and 499 after 20 months on ART. Results: The HIV patients reported an average of 7.5 symptoms (prior to ART), 1.2 symptoms after 6 months on ART, 0.3 symptoms after 12 months on ART, and 0.2 symptoms after 20 months on ART on the day of the interview, with a higher symptom frequency amongst patients who were not employed, had lower CD4 cell counts, experienced internalised stigma, and used alcohol. The most common symptoms or conditions identified by the self-report included tuberculosis, diarrhoea, headaches, rash, nausea and vomiting, pain, neuropathy, lack of appetite, cough, and chills. Overall, the participants reported medications as the most frequently occurring management strategy, with the second being spiritual, and the third being complementary or traditional treatments. The use of all other management strategies decreased over the four different assessment periods from prior to ART to 20 months on ART. Conclusion: This study found a high symptom burden among HIV patients, which significantly decreased with progression on antiretroviral treatment. Several symptoms that persisted over time and several sociodemographic factors were identified that can guide symptom management. The utilisation of different symptom management strategies (medical, spiritual, complementary, and traditional) should be taken into consideration in HIV treatment.     

Evaluation of adherence to a triple antiretroviral therapy in HIV-positive patients

The purpose of the study is to know the adherence to a triple antiretroviral therapy, to analyse the treatment attachment associated factors and to evaluate the impact on therapeutic response related to adherence. Adherence degree was estimated by direct questionnaire. The CD4+ cells counts and viral load were made before initiating treatment and also 4 months after it. The impact of introducing a protocolized informing system for each patient about the treatment is analysed also. We studied 164 patients. Differences within adherence degree depending on age or sex were not found. Adherence rates were worse in IDU patients. We did not find differences on adherence related to nucleoside analogues, but patients on a bid regimen were found to have better adherence than those in the group receiving a tid regimen. Patients who received protocolized information presented a non significant trend to have better adherence. Adherence to therapy is related to higher CD4+ cells increases at the fourth month and a greater viral load decrease. At least 24.4% of patients with triple therapy do not reach a proper adherence degree; the IDU patients are the ones with lower adherence rates. Treatments administered bid have better adherence than those administrated tid. Introducing a standardized information protocol might improve adherence rates. The response to antiretroviral therapy is conditioned by adherence degree.     

Drug interactions between antineoplastic and antiretroviral therapies: Implications and management for clinical practice

Despite the impact of combined antiretroviral therapy (cART) on human immunodeficiency virus (HIV)-related mortality, malignancies remain the second most common cause of death in HIV infection in developed countries. In addition to the AIDS-defining malignancies, other cancers such as Hodgkin's lymphoma and anal cancer, are more frequent in HIV-infected patients who survive longer even though they do not have complete immune restoration The use of concomitant antineoplastic chemotherapy and cART have been demonstrated to be feasible and effective in patients with HIV-related malignancies; however, many drugs used in cART regimens have the potential for causing drug interactions as a result of their ability to either inhibit or induce the cytochrome P450 (CYP) enzyme system. Since many antineoplastic drugs are also metabolised by the CYP system, co-administration with cART could result in either drug accumulation and possible toxicity, or rapid drug metabolism and decreased efficacy. Unfortunately, very limited prospective interaction data are available to safely guide the combined use of cART and chemotherapy. This paper reviews the potential drug interactions and therapeutic considerations of the antiretroviral agents used to treat HIV and the most common anticancer agents used in the treatment of malignancies found in patients with HIV infection.     

HIV/AIDS病人HAART致肝功能损害66例分析

目的探讨高效抗反转录病毒治疗（HAART）对艾滋病病毒（HIV）感染者/艾滋病（AIDS）病人（简称HIV/AIDS病人）肝功能的影响。方法回顾性分析HIV/AIDS病人抗病毒治疗24个月内肝功能的变化情况。结果共计调查755例HIV/AIDS病人,肝功能损害发生率为8.7%（66/755）,以单项转氨酶或胆红素升高为主,轻、中度肝损害占84.8%（56/66）,发生异常的时间为30-485天,中位数75天。其中含奈韦拉平（NVP）方案治疗者肝功能损害的发生率为7.1%（33/467）、含依非韦伦（EFV）方案发生率为11.5%（33/288）。肝损害级别：1级34例,2级22例,3级10例。结论 HIV/AIDS病人在抗病毒治疗过程中轻中度肝损害常见,应严密观察,及时处理,以保证HAART的顺利进行。     

Statin therapy/lipid lowering therapy among Indian adults with first acute coronary event: The dyslipidemia Residual and Mixed Abnormalities IN spite of Statin therapy (REMAINS) study

ObjectiveThe primary objective was to evaluate the effect of statin therapy/lipid lowering therapy (LLT) on lipid profile, in adults presenting with first acute coronary event.Methods and materialA multicentre, observational, prospective cohort study of lipid profiles pre- and post-statin therapy/LLT, among adult patients with confirmed diagnosis of first acute coronary event. The primary outcome measures were low-density lipoprotein cholesterol (LDL-C) in mg/dl, high-density lipoprotein cholesterol (HDL-C) in mg/dl and triglycerides (TG) in mg/dl at baseline and end of study (EOS, 12 weeks [mean: 13.5 weeks]).ResultsTotally 474 patients completed the study. Number of patients with any LDL-C abnormality (LDL-C [all; LDL was abnormal, either alone or along with other lipid parameter(s)]) decreased from 118 (24.9%) to 27 (5.7%), and for LDL-C (only; only the LDL was abnormal), from 46 (9.7%) to 13 (2.7%), both from baseline to EOS. Of 118 patients with high LDL-C (all) at baseline, 91 (77.1%) had reduction in LDL-C to <100 mg/dl, of which 54 (45.8%) had LDL-C <70 mg/dl at EOS. The patients with LDL-C fraction abnormalities decreased, while HDL-C abnormalities increased at EOS from baseline. No major difference was observed at baseline and EOS in levels of TG (all [TG was abnormal, either alone or along with other lipid parameter(s)]) and TG (only [only the TG was abnormal]). Six (1.3%) had seven serious adverse events.ConclusionsThough statin therapy is effective in lowering LDL-C, there still remains residual dyslipidemia, which probably should be tackled with therapeutic and non-therapeutic options.     

Factors associated to modification of first-line antiretroviral therapy due to adverse events in people living with HIV/AIDS

Antiretroviral therapy (ART) has modified the outcome of patients with HIV infection, providing virological control and reducing mortality. However, there are several reasons as to why patients may discontinue their antiretroviral therapy, with adverse events being one of the main reasons reported in the literature. This is a case-control nested in a cohort of people living with HIV/AIDS, conducted to identify the incidence of ART modification due to adverse events and the associated factors, in two referral services in Recife, Brazil, between 2011 and 2014. Of the modifications occurred in the first year of ART, 25.7% were driven by adverse events. The median time elapsed between initiating ART and the first modification due to adverse events was 70.5 days (95% CI: 26-161 days). The main adverse events were dermatological, neuropsychiatric and gastrointestinal. Dermatological events were the earliest to appear after initiating ART. Efavirenz was the most prescribed and most modified drug during the study period. The group of participants who used zidovudine, lamivudine, and efavirenz had a 2-fold greater chance (adjusted OR: 2.16 95% CI: 1.28-3.65) of switching ART due to adverse events when compared to the group that used tenofovir with lamivudine and efavirenz.     

吸毒艾滋病病人参加抗病毒治疗的影响因素及促进策略

尽管艾滋病抗病毒治疗能对吸毒艾滋病病人的健康状况产生积极作用,但目前治疗覆盖率仍较低。文章针对影响吸毒艾滋病病人参加抗病毒治疗的因素进行了综述,并总结了一些国家针对该人群实施的以成瘾治疗和社区卫生服务为基础的艾滋病治疗策略,以期为进一步促进中国吸毒艾滋病病人参加抗病毒治疗提供参考。     

Better physician-patient relationships are associated with higher reported adherence to antiretroviral therapy in patients with HIV infection

BACKGROUND: There is little evidence to support the widely accepted assertion that better physician-patient relationships result in higher rates of adherence with recommended therapies. OBJECTIVE: To determine whether and which aspects of a better physician-patient relationship are associated with higher rates of adherence with antiretroviral therapies for persons with HIV infection. DESIGN: Cross-sectional analysis. SETTING: Twenty-two outpatient HIV practices in a metropolitan area. PARTICIPANTS: Five hundred fifty-four patients with HIV infection taking antiretroviral medications. MEASUREMENTS: We measured adherence using a 4-item self-report scale (alpha= 0.75). We measured core aspects of physician-patient relationships using 6 previously tested scales (general communication, HIV-specific information, participatory decision making, overall satisfaction, willingness to recommend physician, and physician trust; alpha > 0.70 for all) and 1 new scale, adherence dialogue (alpha= 0.92). For adherence dialogue, patients rated their physician at understanding and solving problems with antiretroviral therapy regimens. RESULTS: Mean patient age was 42 years, 15% were female, 73% were white, and 57% reported gay or bisexual sexual contact as their primary HIV risk factor. In multivariable models that accounted for the clustering of patients within physicians' practices, 6 of the 7 physician-patient relationship quality variables were significantly (P < .05) associated with adherence. In all 7 models worse adherence was independently associated (P < .05) with lower age, not believing in the importance of antiretroviral therapy, and worse mental health. CONCLUSIONS: This study showed that multiple, mutable dimensions of the physician-patient relationship were associated with medication adherence in persons with HIV infection, suggesting that physician-patient relationship quality is a potentially important point of intervention to improve patients' medication adherence. In addition, our data suggest that it is critical to investigate and incorporate patients' belief systems about antiretroviral therapy into adherence discussions, and to identify and treat mental disorders.     

我国艾滋病病毒感染孕产妇及所生儿童应用抗反转录病毒药物的状况及变化趋势

目的了解我国部分艾滋病(AIDS)高流行地区,艾滋病感染孕产妇及所生儿童应用抗反转录病毒(ARV)药物状况及变化趋势。方法 2005年1月至2008年12月,在艾滋病病毒(HIV)感染相对高发的5省23个市(县、区),对1 414名HIV-1感染孕产妇及所生儿童进行问卷调查及随访管理,收集研究对象所应用ARV药物种类、方案等一系列信息。结果1 414名研究对象中,2005-2008年各年分别有77.13%、77.73%、78.26%和84.20%的HIV感染孕产妇应用了ARV药物,并呈现逐年递增的趋势(χ2=5.90,P=0.01)。艾滋病感染产妇三联ARV药物应用比例呈现逐年上升趋势,而单一NVP应用比例逐年下降(χ2=237.17,P<0.000 1;χ2=276.49,P<0.000 1)。预防性及治疗性三联药物方案应用比例仍不足40%和15%,上升幅度有限(χ2=45.79,P<0.0001;χ2=151.96,P<0.0001)。结论继续扩大艾滋病感染孕产妇及所生儿童应用高效抗反转录病毒治疗(HAART)覆盖面,提高ARV药物的可及性,尤其是三联ARV药物方案的应用。