HIV感染抗逆转录病毒治疗时机的研究进展

何时启动抗逆转录病毒治疗在获得性免疫缺陷综合征(AIDS)抗病毒治疗领域一直存在争议。随着研究证据的不断充实,近期国际上各权威指南对成人和青少年患者抗逆转录病毒治疗的起始治疗时机进行了修订,均主张尽早治疗,有"越早越好"的趋势。本文就国内外对抗逆转录病毒治疗时机的研究进展进行综述。     

平均红细胞体积在HIV感染者高效抗反转录病毒治疗疗效评价中的应用

高效抗反转录病毒治疗（HAART）能最大限度地抑制HIV的复制,保存和恢复机体免疫功能,有效升高CD。^＋T淋巴细胞的数量和比例,降低病死率和HIV相关疾病的发病率,是治疗和预防艾滋病的有效手段。由于HIV耐药、治疗时机、治疗方案、经济条件及严重的药物不良反应等原因,HAART在部分患者中疗效不佳。     

Virologic,clinical and immunologic responses following failure of first-line antiretroviral therapy in Haiti

Background

Since HIV-1 RNA (viral load) testing is not routinely available in Haiti, HIV-infected patients receiving antiretroviral therapy (ART) are monitored using the World Health Organization (WHO) clinical and/or immunologic criteria. Data on survival and treatment outcomes for HIV-1 infected patients who meet criteria for ART failure are limited. We conducted a retrospective study to compare survival rates for patients who experienced failure on first-line ART by clinical and/or immunologic criteria and switched to second-line ART vs. those who failed but did not switch.

Methods

Patients receiving first-line ART at the GHESKIO Center in Port-au-Prince, Haiti, who met WHO clinical and immunologic criteria for failure were identified. Survival and treatment outcomes were compared in patients who switched their ART regimen and those who did not. Cox regression analysis was used to determine predictors of mortality after failure of first-line ART.

Results

Of 3126 patients who initiated ART at the GHESKIO Center between 1 March 2003 and 31 July 2008, 482 (15%) met WHO immunologic and/or clinical criteria for failure. Among those, 195 (41%) switched to second-line ART and 287 (59%) did not. According to Kaplan–Meier survival analysis, the probability of survival to 12 months after failure of first-line ART was 93% for patients who switched to second-line ART after failure and 88% for patients who did not switch. Predictors of mortality after failure of first-line ART were weight in the lowest quartile for sex, CD4 T cell count ≤ 100, adherence < 90% at the time of failure and not switching to second-line ART.

Conclusions

Patients who failed first-line ART based on clinical and/or immunologic criteria and did not switch to second-line therapy faced a higher mortality than those who switched after failure. To decrease mortality, interventions to identify patients in whom ART may be failing earlier are needed urgently. In addition, there is a major need to optimize second-line antiretroviral regimens for improved potency, lower toxicity and greater convenience for patients.     

HIV treatment and care in resource‐constrained environments: challenges for the next decade

Many successes have been achieved in HIV care in low‐ and middle‐income countries (LMIC): increased number of HIV‐infected individuals receiving antiretroviral treatment (ART), wide decentralization, reduction in morbidity and mortality and accessibility to cheapest drugs. However, these successes should not hide existing failures and difficulties. In this paper, we underline several key challenges. First, ensure long‐term financing, increase available resources, in order to meet the increasing needs, and redistribute the overall budget in a concerted way amongst donors. Second, increase ART coverage and treat the many eligible patients who have not yet started ART. Competition amongst countries is expected to become a strong driving force in encouraging the least efficient to join better performing countries. Third, decrease early mortality on ART, by improving access to prevention, case‐finding and treatment of tuberculosis and invasive bacterial diseases and by getting people to start ART much earlier. Fourth, move on from WHO 2006 to WHO 2010 guidelines. Raising the cut‐off point for starting ART to 350 CD4/mm³ needs changing paradigm, adopting opt‐out approach, facilitating pro‐active testing, facilitating task shifting and increasing staff recruitments. Phasing out stavudine needs acting for a drastic reduction in the costs of other drugs. Scaling up routine viral load needs a mobilization for lower prices of reagents and equipments, as well as efforts in relation to point‐of‐care automation and to maintenance. The latter is a key step to boost the utilization of second‐line regimens, which are currently dramatically under prescribed. Finally, other challenges are to reduce lost‐to‐follow‐up rates; manage lifelong treatment and care for long‐term morbidity, including drug toxicity, residual AIDS and HIV‐non‐AIDS morbidity and aging‐related morbidity; and be able to face unforeseen events such as socio‐political and military crisis. An old African proverb states that the growth of a deep‐rooted tree cannot be stopped. Our tree is well rooted in existing field experience and is, therefore, expected to grow. In order for us to let it grow, long‐term cost‐effectiveness approach and life‐saving evidence‐based programming should replace short‐term budgeting approach.     

Glucose metabolism continuous deteriorating in male patients with human immunodeficiency virus accepted antiretroviral therapy for 156 weeks

BACKGROUND The dynamic characteristics of glucose metabolism and its risk factors in patients living with human immunodeficiency virus(PLWH) who accepted primary treatment with the efavirenz(EFV) plus lamivudine(3TC) plus tenofovir(TDF)(EFV + 3TC + TDF) regimen are unclear and warrant investigation.AIM To study the long-term dynamic characteristics of glucose metabolism and its contributing factors in male PLWH who accepted primary treatment with the EFV + 3TC + TDF regimen for 156 wk.METHODS Th...     

广西壮族自治区一线抗病毒方案治疗儿童艾滋病患者的临床特点及疗效分析

目的描述和评价广西壮族自治区接受一线高效抗反转录病毒治疗方案的儿童艾滋病患者的临床特点及疗效。方法以68例以往未接受过抗反转录病毒治疗的儿童艾滋病患者作为研究对象进行队列分析,对治疗基线以及治疗后每3～6个月患儿的CD4+T淋巴细胞百分比以及病毒载量进行统计分析,以评估该组儿童艾滋病患者抗病毒治疗效果。结果患儿平均年龄为3岁(0.2～8岁),其中男39例,女29例,感染途径皆为母婴传播。高效抗反转录病毒治疗方案:行AZT+3TC+NVP者52例,D4T+3TC+NVP者16例。患儿接受抗反转录病毒治疗后,CD4+T淋巴细胞百分比显著升高,治疗满12个月、24个月、36个月的患儿CD4+T淋巴细胞百分比分别为23.8%、28.0%、30.0%。治疗1年以上,病毒载量控制在400拷贝/ml以下的患儿比例为62%～83%。结论在资源有限地区,规范使用一线AZT/D4T+3TC+NVP方案,可以明显改善儿童艾滋病患者免疫学和病毒学状况。     

抗病毒治疗致药疹的HIV/AIDS患者97例临床分析

目的分析抗逆转录病毒药物所致HIV/AIDS患者药疹的临床资料,为药疹防治提供参考。 方法采用回顾性分析方法,收集2008年11月至2016年12月首都医科大学附属北京地坛医院收治的行抗逆转录病毒药物治疗（ART）而引起药疹的HIV/AIDS患者临床资料,将患者分为依非韦伦（EFV）组（63例）和奈韦拉平（NVP）组（34例）,对发生药疹患者的年龄、性别、合并用药、过敏史、药疹分级、潜伏期、CD4⁺ T淋巴细胞计数、嗜酸性粒细胞百分比（EO%）以及治疗措施等进行分析。 结果97例药疹患者中男性87例,女性10例,年龄18～68岁,合并用药6～20种。有过敏史者23例,69例（74.19%）患者伴EO%升高。NVP组患者重症药疹发生率（47.06%）显著高于EFV组患者（14.29%）,差异有统计学意义（χ²= 12.398、P < 0.001）。70.10%（68/97）患者药疹发生在ART治疗2周内,其中EFV组患者中51例（81.95%）,NVP组患者中17例（50.00%）,差异无统计学意义。治疗2～4周内,NVP组患者药疹发生率显著高于EFV组（χ²= 4.750、P = 0.029）。CD4⁺T细胞≤200个/μl患者易发生药疹（54/97,55.67%）,EFV组患者药疹发生率高于NVP组,差异有统计学意义（χ²= 4.705,P= 0.030）;CD4⁺ T细胞为201～499个/μl患者中NVP组药疹发生率显著高于EFV组（χ²= 7.109、P= 0.008）;CD4⁺ T细胞≥500个/μl患者中两组药疹发生率差异无统计学意义。97例药疹患者经治疗均好转出院。NVP组停药者显著多于EFV组（79.41% vs. 22.22%,χ²= 7.109,P= 0.008）;NVP组接受甘草酸制剂和糖皮质激素治疗的药疹患者比例显著高于EFV组,差异具有统计学意义（44.44%vs. 70.59%,χ²= 6.069、P= 0.014）。 结论尽管EFV和NVP引起皮疹特点各异,但通常均发生在抗病毒治疗4周内,NVP更易引起重症皮疹;CD4⁺T≤200个/μl患者更易发生药疹,合并用药种类多为危险因素,药疹发生时患者EO%可升高,EO%可作为监测皮疹发生的指标。     

Prioritization of antiretroviral therapy in patients with high CD4 counts,and retention in care: lessons from the START and Temprano trials

Initiation of antiretroviral therapy is not a once in a lifetime opportunity. In some resource constrained settings financial limitations make it necessary to prioritize treatment initiation for some groups of patients. In developed countries, there are patients who are reluctant to initiate treatment. Subgroup analysis of the START trial can inform recommendations for which patients with CD4 counts >500 cells mm³ temporary postponement of treatment initiation is safer. These include individuals aged <30 years and/or with CD4/CD8 ratio of >0.8 and/or viral load of <5000. This is because these individuals are at very low risk of disease progression in the subsequent 2 to 3 years, the risk is minimally diminished by antiretroviral therapy and is virtually identical in the first 18 months of therapy regardless of treatment initiation. In addition, asymptomatic young individuals are at higher risk of loss‐to‐follow and of low adherence to treatment, and those with low viral loads are less likely to transmit the virus. In addition, lessons from START and Temprano can help design trials to investigate strategies to decrease losses‐to‐follow‐up, while minimizing risks to patients.     

广西壮族自治区横县HIV/AIDS患者早期抗逆转录病毒疗效评估

目的分析人类免疫缺陷病毒感染者/获得性免疫综合征患者（HIV/AIDS）早期抗逆转录病毒治疗（ART）的疗效,为早期ART提供依据。 方法对2013年1月至12月广西横县的HIV/AIDS患者疗效进行观察并随访1年,观察早期治疗组及延迟治疗组发生死亡或患AIDS、失访、停药、维持治疗情况、病毒抑制、免疫学恢复情况及药物不良反应。 结果共入组288例患者,其中早期治疗组52例,延迟治疗组236例。早期治疗组死亡或患AIDS者2例（3.8%）,失访2例（3.8%）,停药9例（17.3%）,维持治疗40例（76.9%）。延迟治疗组死亡或患AIDS者68例（28.8%）,失访13例（5.5%）,停药24例（10.2%）,维持治疗173例（74.0%）。早期治疗组死亡或患AIDS率显著低于延迟组（χ²= 14.438、P = 0.000）。两组失访率（χ²= 0.238、P = 0.625）、停药率（χ²= 2.140、P = 0.143）和维持治疗率（χ²= 0.290、P = 0.590）差异均无统计学意义。延迟治疗组CD4⁺T细胞计数增幅为144.00（13.00～228.00）/μl,早期治疗组增幅为131.00（72.00～195.00）/μl,两组增幅差异无统计学意义（Z =-0.026、P = 0.980）。早期组病毒完全抑制患者38例（95.0%）,延迟组161例（93.1%）,两组差异无统计学意义（χ² = 0.198、P = 0.656）。两组患者发生各级药物不良反应差异无统计学意义（1级：χ² = 1.297、P = 0.255,2级：χ² = 2.122、P = 0.145,3级：χ² = 0.394、P = 0.530,4级：χ² = 1.426、P = 0.232,5级：χ² = 0.000、P = 1.000）。 结论早期ART可显著降低死亡和AIDS相关疾病的发生率,且安全性良好。     

The next generation of the World Health Organization's global antiretroviral guidance

The 2013 World Health Organization’s (WHO) Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection provide more than 50 new recommendations across the continuum of HIV care, including recommendations on HIV testing, using antiretroviral drugs for prevention, linking individuals to HIV care and treatment services, initiating and maintaining antiretroviral therapy (ART) and monitoring treatment. Guidance is provided across all age groups and populations of adults, pregnant and breastfeeding women, adolescents and key populations. The guidelines are based on a public health approach to expanding the use of ARV drugs for HIV treatment and prevention, with a particular focus on resource‐limited settings. The most important new clinical recommendations include: treating adults, adolescents and older children earlier – starting ART in all individuals with a CD4 cell count of 500 cells/mm³ or less (but giving priority to those with advanced clinical disease or a CD4 cell count less than 350 cells/mm³); starting ART at any CD4 cell count in certain populations, including those with active TB (existing recommendation), Hepatitis B infection and severe chronic liver disease, HIV‐positive partners in serodiscordant couples (existing recommendation), pregnant and breastfeeding women, and children younger than 5 years of age; a preferred first‐line ART regimen of Tenofovir+3TC or FTC+ Efavirenz as a once‐daily fixed‐dose combination for adults, pregnant women, and children aged 3 years and older; and the use of viral load testing as the preferred approach to monitoring the response to ART and to diagnose treatment failure. Guidance is also provided on enhancing the efficiency and effectiveness of HIV services, including strategies to improve retention in care, and adherence to ART; task‐shifting to address human resource gaps; decentralizing delivery of ART to primary health care, and integrating ART services within maternal and child health, TB or drug dependency clinics. There is additional guidance for programme managers on how to plan HIV programmes and use resources most efficiently.     

Maximizing the benefits of antiretroviral therapy for key affected populations

Introduction

Scientific research has demonstrated the clinical benefits of earlier initiation of antiretroviral treatment (ART), and that ART can markedly reduce HIV transmission to sexual partners. Ensuring universal access to ART for those who need it has long been a core principle of the HIV response, and extending the benefits of ART to key populations is critical to increasing the impact of ART and the overall effectiveness of the HIV response. However, this can only be achieved through coordinated efforts to address political, social, legal and economic barriers that key populations face in accessing HIV services.

Discussion

Recent analyses show that HIV prevalence levels among key populations are far higher than among the general population, and they experience a range of biological and behavioural factors, and social, legal and economic barriers that increase their vulnerability to HIV and have resulted in alarmingly low ART coverage. World Health Organization 2014 consolidated guidance on HIV among key populations offers the potential for increased access to ART by key populations, following the same principles as for the general adult population. However, it should not be assumed that key populations will achieve greater access to ART unless stigma, discrimination and punitive laws, policies and practices that limit access to ART and other HIV interventions in many countries are addressed.

Conclusions

Rights-based approaches and investments in critical enablers, such as supportive legal and policy environments, are essential to enable wider access to ART and other HIV interventions for key populations. The primary objective of ART should always be to treat the person living with HIV; prevention is an important, additional benefit. ART should be provided only with informed consent. The preventive benefits of treatment must not be used as a pretext for failure to provide other necessary HIV programming for key populations, including comprehensive harm reduction and other prevention interventions tailored to meet the needs of key populations. An end to AIDS is only possible if we overcome the barriers of criminalization, stigma and discrimination that remain key drivers of the HIV epidemics among key populations.     

Treatment of lumbar disc herniation in the second decade of life

Lumbar disc herniation is rare in patients under the age of 20 years. In the department of orthopaedic surgery of the University Hospital of Frankfurt, 33 patients below the age of 20 with lumbar disc herniation were treated over a period of 10 years. Eighteen were managed conservatively and 15 surgically. The purpose of this study is to report on the long-term outcome of these patients and to compare the results of conservative and surgical treatment. We analysed information obtained from the medical records, and for the long-term follow-up we prepared a questionnaire. The questionnaire was composed of general questions about the patients' lifestyle and their ability to return to a normal life and activity after treatment, together with a request for them to score their pain level and remaining symptoms. We found that the longest duration of symptoms before diagnosis was 72 months, with a mean duration of 11.1 months. Low back pain and monoradicular sciatica were the main complaints, but findings of neurological deficits were rare. Lasegue's sign and tight hamstrings seemed to be strong diagnostic signs in this age group. On the day of discharge, 94% of patients reported excellent or good results. The outcomes after a mean follow-up period of 5.4 years were similar in both treatment groups. Almost all patients were able to attain a normal activity level and few reported restrictions on their daily life. Only 14% complained of permanent pain and 7% reported poor results regarding their activity capabilities. In conclusion, we believe that in all cases of lumbar disc herniation in the second decade of life, conservative treatment should be pursued as a mainstay of treatment. Only after a certain time, if conservative treatment is ineffective, should surgical treatment be considered.