HIV感染抗病毒治疗的副作用

HIV感染通过联合应用抗逆转录药物 ,可以将病毒载量抑制至检测不到的水平并升高CD4T细胞计数。然而 ,因为药物的毒副作用 ,长期联合治疗难于坚持。所有抗逆转录药物都有短期和长期副作用。每个药物、药物种类和患者 ,其副作用小同。因此 ,了解抗逆转录药物的副作用有益于优化HIV的治疗。     

HIV/AIDS患者贫血的研究进展

HIV/AIDS患者的贫血可以有多种原因 :机会性感染、肿瘤、营养不良、失血和药物等。贫血和CD4以及病毒载量一样是疾病进展和死亡的独立预测因素。贫血还能导致疲劳感 ,影响生活质量。贫血的纠正能降低疾病进展的危险 ,改善生活质量。治疗贫血的方法主要包括去除病因、输血以及应用人重组红细胞生成素等。本文就这几方面问题进行综述。     

Securing and Sustaining Employment: Concerns of HIV Patients in Singapore

Employment sustainability is one of the most pressing issues inflicting people living with HIV (PLHIV). A qualitative approach was used to elucidate the perceived challenges in sustaining their employment and the perceived barriers in re-entering the workforce for HIV patients. In-depth interviews were conducted with 16 patients from an acute hospital in Singapore. The main challenges raised in sustaining employment were: (1) ability to ensure secrecy of diagnosis from employers, (2) ability to secure financial resources for treatment and sustenance, (3) ability to ensure stable health to meet job requirements, (4) ability to cognitively sit with the concerns of uncertainty and limitations in career, and (5) ability to work through discriminatory workplace practices. The perceived barriers in gaining workforce re-entry were: (1) fear of pre-employment medical screening and potential discriminatory practices at workplace, (2) concerns over health (frequent hospital admissions, physical weakness, and existing medical co-morbidities), and (3) psychosocial challenges (unstable accommodation, older age, financial issues, and trade skills limitation). The overarching factor that influences the success of sustaining and securing an employment among HIV patients is secrecy of the diagnosis. The individuals' health status, financial status and access to healthcare, and other psychosocial challenges further compound the issue.     

HIV相关神经认知功能障碍的研究进展

HIV感染不仅损害免疫系统,而且还可引起一系列神经系统的病变,其中包括HIV相关神经认知功能障碍(HAND),影响了HIV感染者和AIDS患者的生存质量及生存率.同时,尽管HAART的应用能明显改善HAND症状,但是真正能有效渗透进中枢神经系统的抗逆转录病毒药物相当有限,HAND的研究进展缓慢.本文就HAND概念、发病机制、流行病学状况及特点、影响因素、诊断、治疗等方面进行综述,从而为临床研究提供参考.     

Does problem drinking affect employment? Evidence from England

In this paper, we use data from the Health Survey of England to show that problem drinking is negatively and significantly associated with the probability of being in work, once the endogenous relationship between these outcomes is accounted for. Being a problem drinker leads to a substantial reduction in the probability of working by between 7 and 31%, the former figure being roughly equivalent to the positive effect of having a degree relative to no qualifications in our data. This finding is robust to a variety of identifying restrictions and definitions of problem drinking. Moreover, we find that problem drinking defined by the observed psychological and physical symptoms of alcohol is an important predictor of employment, and allows for the fact that individuals differ in their tolerance or susceptibility to alcohol. Our results suggest that there may be important labour market benefits from public health policies aimed at the prevention and treatment of problem drinking.     

Aging and HIV Infection

With the advent of highly active antiretroviral therapy (HAART) in mid-1995, the prognosis for HIV-infected individuals has brightened dramatically. However, the conjunction of potent antiviral therapy and longer life expectancy may engender a variety of health risks that, heretofore, HIV specialists have not had to confront. The long-term effects of HIV infection itself and exposure to antiretroviral agents is unknown. Several aspects of aging, including psychiatric disease, neurocognitive impairment, and metabolic and hormonal disorders, may be influenced by chronic exposure to HIV and/or HIV therapeutics. In this paper, we discuss the health issues confronting HIV-infected older adults and areas for future research. Dr. Klein and Dr. Schoenbaun are with the Division of Infectious Diseases, Department of Medicine and The AIDS Research Program, Department of Epidemiology and Population Health, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY; Dr. Anastos is with the Division of Infectious Diseases, Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY; Dr. Minkoff is with the Department of Obstetrics and Gynecology, Maimonides Medical Center, Brooklyn, NY; Dr. Sacks is with the Department of Community and Preventive Medicine, Mount Sinai School of Medicine, New York, NY.     

Employment loss following HIV infection in the era of highly active antiretroviral therapies

BACKGROUND: Employment is a major factor in maintaining living conditions of patients with chronic diseases. This study aimed to quantify the frequency and to identify the determinants of employment loss during the first years of HIV disease in the era of highly active antiretroviral therapies (HAART). METHODS: The French PRIMO multicentre prospective cohort of 319 patients enrolled during primary HIV-1 infection between 1996 and 2002. Employment loss was defined as moving from employment to inactivity between two visits. Characteristics associated with employment loss were assessed using generalized estimating equations. RESULTS: During a median follow-up time of 2.5 years, 56 employment losses occurred among 51 patients (18.0%). In multivariate analysis, female gender (adjusted odds ratio 3.1; 95% confidence interval 1.1-8.5), non-permanent job (3.8; 1.5-9.3) and poor accommodation (4.2; 1.6-11.2) constituted independent risk factors for employment loss; subjects with a high occupational position had a decreased risk of job loss. Moreover, an updated HIV viral load above 10 000 copies/ml either persistent (2.4; 1.1-5.0) or incident (3.7; 1.0-13.9) and hospitalization in the preceding 6 months (3.9; 1.6-9.7) constituted independent risk factors for employment loss, as tended to be a baseline CD4 cell count <350/mm(3) (1.9; 0.9-4.3) and chronic comorbidity (1.8; 0.9-3.6). CONCLUSIONS: In the HAART era, employment loss is frequent from the first months of HIV infection. Employment loss occurs especially in women and in patients with adverse socioeconomic conditions, severe HIV infection and/or comorbidity. Social interventions should seek to prevent HIV-infected patients from leaving their job from the earliest times of the disease.     

HIV感染者抗病毒治疗及性行为情况凋查

目的研究河南省高效抗逆转录病毒治疗效果和耐药情况,为防止耐药株流行提供理论依据。方法采用问卷调查方法,了解人类免疫缺陷病毒（HIV）感染者人口学、治疗和漏服情况及安全套使用情况,RT-PCR和套式PCR扩增HIV pol区基因,双脱氧法测定逆转录酶和蛋白酶基因序列,与国际耐药数据库比对辨别耐药变异。结果本次调查人群文化程度较低,家庭经济条件差;治疗组病毒载量显著低于未治疗组（P〈0.01）;安全套使用率低（23.1%）;服药依从性较差（72.2%）：治疗人群中发现6例存在耐药突变,未治疗感染者发现1例存在耐药变异。结论抗病毒治疗初期疗效显著,耐药变异率低,但漏服和较低的安全套使用率将导致耐药变异快速产生和流行,应加强用药督导和安全套普及。     

Joint modelling of bivariate longitudinal data with informative dropout and left-censoring, with application to the evolution of CD4+ cell count and HIV RNA viral load in response to treatment of HIV infection

Several methodological issues occur in the context of the longitudinal study of HIV markers evolution. Three of them are of particular importance: (i) correlation between CD4+ T lymphocytes (CD4+) and plasma HIV RNA; (ii) left-censoring of HIV RNA due to a lower quantification limit; (iii) and potential informative dropout. We propose a likelihood inference for a parametric joint model including a bivariate linear mixed model for the two markers and a lognormal survival model for the time to drop out. We apply the model to data from patients starting antiretroviral treatment in the CASCADE collaboration where all of the three issues needed to be addressed.     

HAART过程中285例HIV/AIDS患者口腔病损的临床观察

[目的]观察"高效抗逆转录病毒治疗(HAART)"过程中,人免疫缺陷病毒感染(HIV)/艾滋病(AIDS)患者口腔病损发生情况.[方法]2007年3月对上蔡县正在实施HAART的285例HIV/AIDS患者进行口腔病损调查,CD<,4>细胞计数分析,观察实施HAART 1至2年后HIV/AIDS患者口腔病损发生情况.[结果]在本组HIV/AIDS患者中,27例出现口腔病损,其中口腔白色念珠菌病14例、单纯疱疹性口炎3例、非特异性口腔溃疡2例、卡波济肉瘤2例、可单发或同时伴发.[结论]实施HAART能显著降低HIV/AIDS患者口腔病损的发生.     

Impacts of HIV infection and HAART use on quality of life

Background: Studies have shown the detrimental effect of HIV disease on quality of life (QOL). Changes in QOL related to the use of highly active antiretroviral therapy (HAART) have been inconsistent and it is unknown how QOL after HAART compares to pre-infection levels. Objective: The objective of this study was to determine the impacts of becoming HIV infected and using HAART on QOL within individuals followed in the Multicenter AIDS Cohort Study (MACS). Methods: Using the standard Medical Outcome Study SF-36 form, QOL data were collected pre-seroconversion, post-seroconversion but before HAART initiation, and after HAART initiation for 68 seroconverters. The QOL physical health summary score (PHS) and mental health summary score (MHS) were used as outcomes. The effects of HIV infection and HAART use on QOL summary scores were determined using random effects mixed linear models after controlling for possible confounders. The clinical significance of QOL change was assessed using the Cohen’s effect size method. Results: Compared to pre-seroconversion values, the PHS decreased after seroconversion (mean difference (diff) = −1.62; 95% confidence interval (CI): [−3.20, −0.03]) and after HAART initiation (diff = −4.20; 95% CI: [−5.86, −2.54]) with small to medium effect sizes. The score remained significantly lower than prior to HIV infection (diff = −6.16; 95% CI: [−8.09, −4.23]) after being on HAART for more than 4 years. The MHS did not significantly differ upon seroconversion (diff = −1.16; 95% CI: [−3.32, 1.00]). After using HAART for more than 4 years, the MHS was significantly greater than prior to HIV infection (diff = 2.93; 95% CI: [0.31, 5.55]) with a small effect size. Conclusion: The QOL of participants has been dynamic over the HIV disease course. HIV infection deteriorated physical but not mental QOL. In this group, although the PHS following HAART has remained lower than that prior to infection, HAART has enhanced mental health functioning.     

HIV/AIDS患者免疫重建综合征

随着HAART的广泛应用,HIV/AIDS患者在重获健康的同时却自相矛盾地在治疗的前几个月内病情反复,这时候各系统器官功能已稳定的患者中会出现原有机会性感染的重燃或者另一种机会性感染的发生,特别在病毒载量低至不可检测范围以及CD4 T细胞迅速上升的情况中,甚至会引起生命危象。对于这种发生于HAART后出现免疫重建过程中的疾病,经过多年的大量研究和证实后,现称之为免疫重建炎性综合征或者免疫重建疾病。文中就免疫重建综合征的概况、诊断及几种主要的免疫重建综合征进行了综述。     

HAART治疗AIDS患者基线CD4^+细胞水平对免疫重建效果的预测价值

目的探讨高效抗逆转录病毒治疗(HAART)AIDS患者基线CD4+细胞计数和CD4/CD8水平对免疫重建效果的预测价值。方法选取2008年6月至2017年12月于南京市第二人民医院完成24个月HAART治疗且病毒载量<50拷贝/毫升的患者共90例纳入研究,根据其治疗完成后CD4+细胞数分为3组:免疫无反应者(INRs)(<200个/μL),免疫应答不足(IIRs)(200~500个/μL)和免疫应答(IRs)(>500个/μL);比较3组之间的特征及动态CD4+细胞计数,进行免疫重建的因素分析。结果3组基本特征比较发现,CD4+细胞基线值与确认HIV至HAART治疗开始时间的方面差异具有统计学意义(P<0.05)。经抗病毒治疗后,IRs组CD4+细胞计数明显高于INRs和IIRs组,差异具有统计学意义(P<0.001)。ROC曲线下面积表明HAART治疗1年时CD4+细胞数达到最高预测价值。结论早期开启HAART可以减少免疫重建失败率。结合CD4+细胞基线数和CD4/CD8比值可以作为一个有效预测HAART治疗后免疫重建诊断的指标。     

ISSQoL: A New Questionnaire for Evaluating the Quality of Life of People Living with HIV in the HAART Era*

Objective: To design a Health-related Quality of Life (HRQoL) instrument for HIV-infected people in the era of highly active antiretroviral therapy (HAART). Methods: The self-administered questionnaire was developed by an Italian network including researchers, physicians, people living with HIV, national institutions and community-based organizations (CBO) through several steps: (1) review of existing HRQoL literature and questionnaires for HIV-infected people; (2) selection of relevant domains measuring HRQoL in HIV-infected people, and identification of new domains related to new aspects of HRQoL concerning HAART-treated individuals; (3) conduction of two pre-test analyses in independent groups of Italian HIV-positive people (n≌100) distributed throughout the country. The objectives of the first pre-test were to verify the usefulness of the questionnaire, to construct a form easily understandable by everyone, to define the domains and their significance; the second pre-test aimed at evaluating and reshaping the questionnaire based on a statistical analysis of the outcomes of first pre-test; (4) validation analysis. A large cohort of people with HIV infection was recruited for the last step.Results: The internal consistence reliability (Cronbach’s α) was ≥0.70 for all domains. Most domains had Cronbach’s coefficient >0.80. All domains demonstrated convergent and discriminant validity. The final version of ISSQoL includes two sections: HRQoL Core Evaluation Form (9 domains) and Additional Important Areas for HRQoL (6 domains). The ISSQoL was administered together with two additional forms: a Daily Impact of Symptoms Form and a Demographic Information Form. The Additional Important Areas for HRQoL include social support, interaction with medical staff, treatment impact, body changes, life planning, and motherhood/fatherhood.Conclusion: The data reported in the present paper provide preliminary evidence of the reliability and validity of the ISSQoL questionnaire for the measurement of HRQoL in HIV-infected people. The direct involvement of HIV-positive people in all the phases of the project was a key aspect of our work. All the authors of this paper belong to ISSQoL Group.     

Bimodal virological response to antiretroviral therapy for HIV infection: an application using a mixture model with left censoring

STUDY OBJECTIVE: To assess whether HIV RNA levels (log(10) scale) in highly active antiretroviral therapy (HAART) treated population have a bimodal distribution, suggesting optimal or suboptimal response to HAART. METHODS: The study population from two ongoing cohort studies comprised 564 men (4785 person visits) and 1173 women (8675 person visits) with known dates of HAART initiation and with HIV RNA measurements before and after initiation. Values below detection limit of assays were treated in the analysis as left censored. Maximum likelihood methods were used to estimate parameters and to determine possible bimodality of HIV RNA distributions. RESULTS: A two component mixture model fitted HIV RNA levels significantly better than did a single component distribution at different years from HAART initiation in both therapy experienced and therapy naive patients. In the fifth year after HAART initiation, 32% of men and 44% of women had HIV RNA in the higher component with medians of 5247 and 9253 copies/ml, respectively, suggesting suboptimal virological response to HAART, which was associated with poor adherence and lower frequency of CCR5 heterozygous genotype. CONCLUSION: The bimodal distribution of HIV RNA persisted during the years after HAART initiation. The high occurrence of suboptimal virological response at the fifth year after HAART initiation underscore the needs for careful monitoring and patient education about the importance of treatment adherence. This data analysis overcomes limitations of measurement techniques of observations having values below detection limits and serves to characterise the dynamics of the virological response to therapies.     

吉林市HIV/AIDS患者病程及抗病毒效果评价

目的研究吉林市93例HIV感染者/AIDS病人疾病进展情况;采用高效抗逆转录病毒治疗(HAART)的疗效,为HIV/AIDS综合防治措施提供科学依据。方法通过现场流行病学调查分析HIV感染者/AIDS病人一般情况,检测抗丙型肝炎病毒(HCV)抗体,定期进行CD4+、CD8+T淋巴细胞绝对计数检测以监测疾病进展,用HAART治疗HIV感染者/AIDS病人,监测病毒学及免疫学变化,观察抗病毒药物的毒副作用及服药依从性。结果吉林市93例HIV感染者/AIDS病人中86例(92.5%)经血液感染且合并HCV感染。估计感染时间在8年以上者88例,其中20.5%CD4+T淋巴细胞数<200/mm3,50%为200~500/mm3,29.5%>500/mm3。接受HAART治疗的23例HIV感染者/AIDS病人治疗前平均病毒载量为5.06 log拷贝/ml(4.39×105拷贝/ml),治疗12个月后平均下降3.47log拷贝/ml(P<0.001),其中16例达到检测不出的水平(<400拷贝/ml),CD4+T淋巴细胞数平均上升48个/mm3(P<0.05)。结论吉林市存在部分疾病进展缓慢的HIV感染者;HAART治疗取得了较好的疗效,但司他夫定和去羟肌苷联合应用使周围神经病变发生率较高;加强对感染者疾病进展和抗病毒疗效及不良反应监测,有助于确定开始抗病毒治疗的时机和及时调整治疗方案。     

Comorbidity-Related Treatment Outcomes among HIV-Infected Adults in the Bronx,NY

Aging, HIV infection, and antiretroviral therapy have been associated with increasing rates of chronic comorbidities in patients with HIV. Urban minority populations in particular are affected by both the HIV/AIDS and chronic disease epidemics. Our objectives were to estimate the prevalence of and risk factors for hypertension, dyslipidemia, and diabetes among HIV-infected adults in the Bronx and describe comorbidity-related treatment outcomes. This was a cross-sectional study of 854 HIV-positive adults receiving care at 11 clinics which provide HIV primary care services; clinics were affiliated with a large urban academic medical center. Data on blood pressure (BP), cholesterol, and glycemic control were collected through standardized chart review of outpatient medical records. We found prevalence rates of 26%, 48%, and 13% for hypertension, dyslipidemia, and diabetes, respectively. Older age, obesity, family history, and current protease inhibitor use were consistently associated with comorbidity. Diabetes treatment goals were achieved less often than BP and lipid goals, and concurrent diabetes was a significant predictor for BP and lipid control. In conclusion, major cardiovascular-related comorbidities are prevalent among HIV-positive adults in the Bronx, especially older and obese individuals. Differences exist in comorbidity-related treatment outcomes, especially for patients with concurrent diabetes. Because cardiovascular risk is modifiable, effective treatment of related comorbidities may improve morbidity and mortality in HIV-infected patients.