Neurocognitive impairment and survival in a cohort of HIV-infected patients treated with HAART

Before the introduction of HAART, HIV-associated neurocognitive impairment (NCI) was recognized as an independent risk factor for death. Since 1996, we conducted a prospective study to assess whether NCI still represents a negative prognostic factor for mortality. Patients were administered measures of neurocognitive function (a battery of 17 neuropsychological tests), clinical and neurological evaluation, laboratory testing, and brain imaging studies. Among the 412 enrolled patients, 224 (54.4%) were neurocognitively impaired and 188 (45.6%) were neurocognitively unimpaired. A durable virological suppression under highly active antiretroviral therapy (HAART) was achieved by 63.3% of unimpaired patients and by 49.6% of impaired patients (p = 0.007). Overall, 47 deaths were recorded, 38 among impaired and 9 among unimpaired patients. At 84 months, the estimated survival proportions in impaired and unimpaired patients were 68.5% and 84.9%, respectively (p < 0.001). At univariate analysis the virological response to HAART was the variable most strongly associated with survival, since patients with virological failure had a nearly 10-fold increased risk of death than those with durable virological suppression (HR = 9.9, 95% CI: 3.9-25.0). After stratification for virological response to HAART, an increased risk of death for neurocognitively impaired patients was seen only among the 182 patients with virological failure (HR: 2.9, 95% CI: 1.2-7.1), while the survival probability of the 230 patients with durable virological suppression was not affected by neurocognitive impairment (p = 0.89). Our results highlight the clinical relevance of HIV-related central nervous system (CNS) involvement in the HAART era, and raise concerns regarding the clinical relevance of CNS involvement as potent antiretroviral therapies become less effective.     

甘肃省接受HAART的AIDS病人的生活质量测评

目的通过调查接受抗病毒治疗前后艾滋病病人的生活质量,评估抗病毒治疗对艾滋病病人生活质量的影响,为进一步提高病人的生活质量提供参考。方法应用简体中文版MOS-艾滋病病毒（HIV）量表,在定点收治医院抽取艾滋病病人,在其接受抗病毒治疗前后进行调查,内容包括病人的生活质量、人口学特征和与HIV感染相关特征,采用t检验、方差检验等对调查资料进行统计分析。结果共调查病人99例,治疗前其生理领域得分为（49.44±9.85）分,心理领域得分为（24.85±11.17）分;健康转变0.31分、健康压力0.37分、心理功能0.46分、总体健康感0.46分,4个维度得分率较低;治疗后,其生理领域得分为（57.84±3.59）分,心理领域得分为（56.00±5.01）分,11个维度的得分均较治疗前提高,差异有统计学意义（P〈0.001）。结论在艾滋病抗病毒治疗过程中,医务人员在给予病人必要的临床治疗的基础上,提供心理咨询和关怀服务,可以改善他们的生活质量,同时亦提示要进一步拓展艾滋病病人医疗服务的内容,将有助于提高病人的生活质量。     

MOS—HIV量表评价艾滋病抗病毒治疗病人生活质量现状

目的调查中国部分地区艾滋病抗病毒治疗病人的生活质量现状。方法应用简体中文版MOS—HIV量表评价中国部分地区艾滋病抗病毒治疗病人的生活质量现状,同时调查可能影响生活质量的人口学特征和与HIV感染相关的特征。采用t检验、方差分析进行均数显著性检验。结果用简体中文版MOSHIV量表测量中国部分地区艾滋病抗病毒治疗病人的生活质量得分,生理健康总分为（46．47±9．96）分,心理健康总分为（47．14±11．20）分。统计结果显示,不同年龄组中,23～29岁年龄组生理和心理健康总分最高;静脉吸毒途径感染的患者生理、心理健康总分均高于其他感染途径的患者;血CD4＋T淋巴细胞计数水平〉300／μl组,其生理、心理健康总分均高于CD4〈200／μl组;抗病毒治疗24个月以上的患者,其生理、心理健康总分低于治疗24个月以下的患者。结论中国艾滋病抗病毒治疗病人的生活质量水平较低,年龄、感染途径、血CD4^＋T淋巴细胞计数和抗病毒治疗时间等因素,对生活质量均有一定程度的影响。     

Time perspective and quality of life among HIV-infected patients in the context of HAART

We explored associations between time perspective (TP) and quality of life (QOL) among HIV-infected patients. With the French validated version of the Zimbardo Time Perspective Inventory, we evaluated the TP of patients. A self-administered questionnaire gathered information about QOL (WHOQOL-HIV), TP, relationship with medical staff and self-reported side effects of HAART. Six scores of QOL - physical, psychological, social relationship, environment, patient independence and spirituality were used as dependent variables in the linear regressions to identify factors associated with QOL. The sample (n=72) for this study was recruited from a hospital department specialising in HIV care and consisted of 48 (67%) HIV-infected women and 24 (33%) HIV-infected men with a mean age of 42 years. Using hierarchical regression analysis adjusted on socio-demographic characteristics, clinical characteristics and co-factors, significant relationships were observed between the several TP orientations and an impaired physical, environmental QOL as well as level-of-independence QOL. Specific dimensions of QOL are influenced by specific orientations of TP, which provides information on self-perception and subjective evaluation of QOL. The TP construct provides keys to managing HIV infection in order to improve QOL.     

Statins and fibrates for the treatment of hyperlipidaemia in HIV-infected patients receiving HAART

OBJECTIVES: The aim of our work is to evaluate the role of statins and fibrates in the management of hyperlipidaemia in HIV-infected patients receiving highly active antiretroviral therapy. DESIGN: Open-label, randomized, prospective study of the efficacy and safety of bezafibrate, gemfibrozil, fenofibrate, pravastatin and fluvastatin as pharmacologic treatment for protease inhibitor-related dyslipidaemia. METHODS: Plasma lipid levels of 656 HIV-infected patients who referred to our tertiary care centre and were on protease inhibitor-based antiretroviral therapy for at least 12 months have been evaluated. All patients had HIV viral load < 50 copies/ml and presented with hypertriglyceridaemia of at least 6 months duration that was unresponsive to a hypolipidaemic diet; all have been treated with bezafibrate, gemfibrozil, fenofibrate, pravastatin, or fluvastatin for 12 months. RESULTS: Of the 656 patients observed 113 (17.2%) received pharmacological therapy, while seven patients were excluded from evaluation due to early drop-out. Of the 106 evaluable subjects, bezafibrate was used in 25 cases, gemfibrozil in 22, fenofibrate in 22, pravastatin in 19, and fluvastatin in 18. At the close of 1-year follow-up, fibrates led to a reduction of 40.7% and 21.9% versus baseline triglyceridaemia and cholesterolaemia, respectively (P < 0.001), and statins led to a reduction of 34.8% and 25.2% versus baseline triglyceride and total cholesterol levels, respectively (P < 0.001), without significant differences according to each different administered hypolipidaemic drug. CONCLUSIONS: All administered statins and fibrates revealed a similar, significant efficacy in the treatment of diet-resistant hyperlipidaemia, and showed a favourable tolerability profile.     

Reconstitution of antimycobacterial immune responses in HIV-infected children receiving HAART

OBJECTIVE: Recent epidemiological studies in adults suggest that HAART can prevent the development of tuberculosis in HIV-infected individuals, but the mechanisms are incompletely understood and no data exist in children. We investigated whether changes in mycobacterial-specific immune responses can be demonstrated in children after commencing antiretroviral therapy. DESIGN: We measured mycobacterial growth in vitro using a novel whole-blood assay employing reporter-gene tagged bacillus Calmette-Guérin (BCG) in a prospective cohort study in the tuberculosis-endemic environment of South Africa. Key cytokines were measured in supernatants collected from the whole-blood assay using cytometric bead array. PATIENTS: A cohort of 15 BCG-vaccinated HIV-infected children was evaluated prospectively for in-vitro antimycobacterial immune responses before and during the first year of HAART. All children had advanced HIV disease. Nine children completed all study timepoints. RESULTS: Before HAART, blood from children showed limited ability to restrict the growth of mycobacteria in the functional whole-blood assay. The introduction of HAART was followed by rapid and sustained reconstitution of specific antimycobacterial immune responses, measured as the decreased growth of mycobacteria. IFN-gamma levels in culture supernatants did not reflect this response; however, a decline in TNF-alpha was observed. CONCLUSION: This is the first study using a functional in-vitro assay to assess the effect of HAART on immune responses to mycobacteria in HIV-infected children. Our in-vitro data mirror the in-vivo observation of decreased susceptibility to tuberculosis in HIV-infected adults receiving antiretroviral agents. This model may be useful for further characterizing immune reconstitution after HAART.     

Effects of lipodystrophy on quality of life and depression in HIV-infected men on HAART

The aim of the study was a prospective assessment of the possible consequences of a diagnosis of lipodystrophy on health-related quality of life (HRQL) and depressive symptomatology in HIV-seropositive men who have sex with men. A standardized physical assessment for lipodystrophy was introduced within a prospective study in April 1999. Over a 2-year follow- up, 37 HIV-seropositive men who met the criteria for lipodystrophy were longitudinally compared to 92 HIV-seropositive men without lipodystrophy and 88 HIV-seronegative men on measures of HRQL and depression. A series of questionnaires, which included the Medical Outcomes Study Short-Form 36 (SF-36) and the Center for Epidemiological Studies-Depression (CES-D), were administered to assess HRQL and depression, respectively. SF-36 scores were summarized using the mental and physical components; CES-D results were reported as both dichotomous (with or with clinical depression) and continuous scores. Neither the mental nor physical components of the SF-36 showed any significant differences between patients with lipodystrophy versus HIV-seropositive patients without lipodystrophy. Similarly, lipodystrophy status was not significantly associated with either continuous depression scores or presence of clinical depression. However, consistent with previous results, HIV-seropositive men without lipodystrophy (compared to HIV-seronegative men) reported higher scores on both components of the SF-36 scales and both categorizations of the CES-D. The results of this study suggest that lipodystrophy does not negatively affect HRQL or depression, above and beyond, the diagnosis of HIV infection, although the impact of the severity of lipodystrophy on these conditions will require further study.     

HAART对HIV感染者/AIDS病人短期生活质量影响研究

目的 探讨艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人接受抗病毒治疗6个月时,生活质量有无变化.方法 给予安徽省两地40名HIV感染者/AIDS病人高效抗逆转录病毒治疗(HAART),应用病历报告表的形式收集参加治疗病人的人口学信息、流行病学、临床及实验室检查信息,同时采用MOS-HIV量表,对病人治疗前和治疗6个月时生活质量进行调查,对相关数据进行统计分析.结果 40名HIV感染者/AIDS病人平均年龄(42.2±8.8)岁(26～62岁),治疗前CD4平均为(197±41)个/μl(94～271),治疗6个月时体重平均增加(5.1±4.5)kg(t＝7.24,P＜0.01),CD4平均增加(122±109)个/μl(t＝7.07,P＜0.01).采用MOS-HIV量表评定,病人躯体状况及精神状况在治疗后均有显著改善;维度分析显示,在健康感知、认知功能、疼痛、精神健康、精力与劳累、健康压力、生活状况、健康的变化方面,治疗前后的差异有显著的统计学意义(P＜0.01).结论 抗病毒治疗6个月时病人CD4细胞计数明显升高、体重增加、生活质量改善,躯体及精神状况均有所提高.     

The risk of myocardial infarction in HIV-infected patients receiving HAART: a case report

With the advent of highly active antiretroviral therapy (HAART), HIV-related morbidity and mortality has declined. Patients are surviving longer but with serious side effects, especially those receiving protease inhibitors (PIs). We report a case of a healthy young man receiving triple therapy with typical angina symptoms that were not recognized by physicians.     

Metabolic profile and cardiovascular risk factors among Latin American HIV-infected patients receiving HAART

ObjectiveDetermine the prevalence of metabolic abnormalities (MA) and estimate the 10-year risk for cardiovascular disease (CVD) among Latin American HIV-infected patients receiving highly active anti-retroviral therapy (HAART).MethodsA cohort study to evaluate MA and treatment practices to reduce CVD has been conducted in seven Latin American countries. Adult HIV-infected patients with at least one month of HAART were enrolled. Baseline data are presented in this analysis.ResultsA total of 4,010 patients were enrolled. Mean age (SD) was 41.9 (10) years; median duration of HAART was 35 (IQR: 10-51) months, 44% received protease inhibitors. The prevalence of dyslipidemia and metabolic syndrome was 80.2% and 20.2%, respectively. The overall 10-year risk of CVD, as measured by the Framingham risk score (FRF), was 10.4 (24.7). Longer exposure to HAART was documented in patients with dyslipidemia, metabolic syndrome and type 2 diabetes mellitus. The FRF score increased with duration of HAART. Male patients had more dyslipidemia, high blood pressure, smoking habit and higher 10-year CVD than females.ConclusionsTraditional risk factors for CVD are prevalent in this setting leading to intermediate 10-year risk of CVD. Modification of these risk factors through education and intervention programs are needed to reduce CVD.     

139例中国儿童AIDS病人抗病毒药物浓度监测分析

目的研究中国儿童的抗病毒药物药代动力学特点,为儿童抗病毒治疗积累更多的药代动力学数据。方法收集了139名儿童艾滋病(AIDS)病人的342份血液标本,采用高效液相色谱-质谱联用的方法监测其血浆抗病毒药物的浓度。结果 139名患儿中,47名使用包含依非韦伦(EFV)的方案,94名使用包含洛匹那韦/利托那韦(LPV/r)的方案(其中2名儿童是由使用包含EFV方案更换为使用LPV/r方案)。监测药物中,EFV的个体内差异最小(15.8%),个体间差异最大(104.9%),3TC,LPV,RTV的个体内差异均在40%左右,个体间差异约为70%。以文献报道中EFV和LPV的治疗浓度范围(TR)为评判标准,在47名使用EFV的患儿中,有8名(8/47,17.0%)患儿的9份(9/115,7.8%)血标本EFV浓度低于TR,11名(11/47,23.4%)患儿的21份(21/115,18.3%)血标本EFV浓度高于TR;在94名使用LPV的患儿中,有19名(19/94,20.2%)患儿的30份(30/222,13.5%)血标本的LPV浓度低于TR,有46名(46/94,48.9%)患儿的67份(67/222,30.2%)血标本的LPV浓度高于TR。结论有相当比例的儿童艾滋病病人服用EFV和LPV/r以后出现血浆药物浓度过高,提示有必要进一步设计临床研究评估我国儿童艾滋病病人的用药剂量。血浆药物浓度监测对儿童的抗病毒治疗能够起到很好的补充作用。     

Decreased pregnancy rate after in-vitro fertilization in HIV-infected women receiving HAART

A study on in-vitro fertilization (IVF) was conducted among HIV-infected women. In these patients, a reduced pregnancy rate after IVF was observed if the patient's own oocytes were used. However, no significant reduction in the pregnancy rate was found if donated oocytes were used. The CD4 lymphocyte count was independently associated with ovarian resistance to hyperstimulation. Subclinical hypogonadism mediated by immunosuppression may explain these observations, suggesting the need to optimize the immunological status of the patient before considering assisted reproduction treatments.     

Determinants of health-related quality of life in HIV-infected patients

In the era of new antiretroviral treatments that have dramatically reduced both morbidity and mortality, a primary goal is to maximize function and wellbeing in the everyday life of HIV-infected patients. To be able to do so, it would be important for clinicians and policy makers to identify factors that influence health-related quality of life (HRQoL). The objective of this multicentre prospective cohort study was to identify determinants of HRQoL in a cohort of Italian HIV-infected patients, the majority of whom were taking highly active antiretroviral therapy (HAART). A total of 809 patients were enrolled. The MOS-HIV Health Survey (summarized using two scores, physical health (PHS) and mental health (MHS)), and an HIV-related symptom scale were administered at enrolment and six months later. At baseline, low CD4+ cell count, hospitalization during the three months before the enrollment and symptoms were independently related to poor PHS; hospitalization during the three months before the enrollment, symptoms and poor satisfaction with information from providers were independently related to MHS. Predictors of PHS at six months included the stage of HIV infection, baseline CD4+ cells count, PHS and symptom score; while age, baseline MHS, symptom score and education predicted six-month MHS. Among these factors, symptoms, recent hospitalization and satisfaction with information are most amenable to clinical intervention.     

Diarrhea and quality of life in ambulatory HIV-infected patients

Our objectives were to determine HIV-infected patients' awareness and recognition of diarrheal symptoms; and to assess the impact of diarrhea on quality of life. The design was a cross-sectional study utilizing a structured telephone interview. The setting was the HIV/AIDS outpatient clinic of a tertiary referral hospital. HIV-infected patients who attended the clinic in 1994 were interviewed. The main outcome measure was the quality-of-life score (QLS). Fifty percent of patients acknowledged having diarrhea in the previous month. All four categories of diarrhea (self-reported or elicited, within the preceding week or month) were significantly associated with decreased QLS. Patients with diarrhea who did not recognize their symptoms as diarrhea also had significantly lower QLS than patients without diarrhea. Diarrhea in all categories was independently predictive of decreased QLS by multivariable analysis. Chronic diarrhea (symptoms for more than one month) was significantly associated with decreased QLS in patients with high as well as low CD4 cell counts. Lack of recognition of diarrhea may result in significant underreporting of diarrhea by patients to physicians. Diarrhea is highly prevalent in the HIV-infected population and is strongly associated with diminished quality of life.     

Neurocognitive performance and quality of life in patients with HIV infection

We examined the relationship of HIV-related cognitive impairment and health-related quality of life (QoL). Subjects were administered measures of cognitive function (a battery of 17 neuropsychological tests) and of QoL (the MOS-HIV questionnaire). Study measures also included comprehensive clinical and neurological evaluation, laboratory testing, and brain imaging studies in patients with impaired neuropsychological evaluation. One-hundred and eleven subjects were examined. Cognitively impaired patients (33.3%) reported poorer QoL scores in all domains (p < 0.05): physical health summary score (PHS) (44.6 vs. 49.9), mental health summary score (MHS) (37.7 vs. 44.4), pain (67.6 vs. 79.4), physical functioning (75.9 vs. 87.7), role functioning (32.4 vs. 41.5), social functioning (70.3 vs. 83.5), mental health (48.2 vs. 61.0), energy (53.1 vs. 63.0), health distress (60.8 vs. 75.5), cognitive functioning (CF) (60.5 vs. 71.8), general health perceptions (29.2 vs. 43.4), and QoL (36.5 vs. 47.0). The number of altered neuropsychological tests correlated significantly with MHS (p < 0.001), PHS (p < 0.03), CF (p < 0.02), and QoL (p < 0.02) scores. A correlation between seven of seven neuropsychological measures exploring speed of mental processing, three of four exploring mental flexibility, four of six exploring memory, and two of two exploring fine motor functioning and MHS, PHS, CF, or QoL scores was also found. Poor performance on the Digit Symbol test was most strongly associated with poor MHS (OR 1.04, 95% CI 1.01-1.08, p < 0.009) and PHS (OR 1.04, 95% CI 1.01-1.08, p < 0.01) scores, controlling for CD4 count, previous AIDS diagnosis, receiving HAART, and drug abuse. Cognitive impairment is associated with poor QoL. People with more severe cognitive impairment have the highest probability of having a poor QoL. Cognitive impairment in any cognitive domain explored in our battery is also associated with poor QoL. Poor performance on the Digit Symbol Test is the strongest predictor of poor QoL.     

Health-related quality of life of HIV-infected adults receiving combination antiretroviral therapy in Addis Ababa

Health-related quality of life (HRQoL) is an important outcome measure among HIV-infected patients receiving combination antiretroviral therapy (cART), but has not been studied extensively in resource-limited settings. Insight in the predictors or correlates of poor HRQoL may be helpful to identify patients most in need of additional support and to design appropriate interventions. A cross-sectional study was conducted between September 2012 and April 2013 in 10 healthcare facilities in Addis Ababa, Ethiopia. Patients who were at least 6 months on cART were randomly selected and individual patient data were retrieved from medical records. HRQoL was measured by the WHOQoL-HIVBREF, depressive-symptoms by the Kessler-6 scale, and stigma by the Kalichman internalized AIDS-related stigma scale. Multivariate linear regression analysis was carried-out to examine associations between HRQoL and the other variables. A total of 664 patients (response-rate 95%) participated in the study. A higher level of depressive-symptoms was most strongly and consistently associated with a lower HRQoL, both in terms of the magnitude of the relationship and in the number of HRQoL domains associated with it. Also, a higher level of HIV-stigma was associated with a lower HRQoL except for the physical domain, while obtaining sufficient nutritious food and job opportunity were associated with a better HRQoL except for the spiritual and social domains, respectively. Demographics, clinical, and treatment characteristics yielded few significant associations with HRQoL. Our study findings suggest that interventions to improve HRQoL should focus on reducing depressive-symptoms and HIV-stigma, and on enhancing food security and job opportunity.     

Neurocognitive and quality of life study in perinatally HIV-infected young people and their peers. NeuroCoRISpeS study

BackgroundAssessing the role of HIV and non-HIV related factors is essential for a better understanding of the neurocognitive outcomes in perinatally HIV-infected (PHIV+) young people. The aim of our study was to assess cognition and quality of life (QoL) of a PHIV+ cohort of young people and to compare it with a control group.MethodsThirty PHIV+ and 30 HIV(−) healthy young adults matched by age, sex and socioeconomic status completed a protocol that included neurocognitive tests, a psychosocial semi-structured interview and a QoL questionnaire (PedsQL). Neurocognitive domain-specific and domain-general (NPZ-5) Z-scores were calculated. CDC AIDS-defining category C or not C (PHIV+/C, PHIV+/noC) was considered to evaluate differences within the PHIV+ group. Univariate and multivariate analysis were performed.ResultsSixty patients were included; 67% were female; median age (IQR) 19 years (18–21). Regarding PHIV+ young people, 27% showed CDC C category (none encephalopathy), 93% were on ART and 77% had undetectable viral load. No differences regarding occupation were found, although the HIV(−) group repeated less grades (p = 0.028) and had a higher education level (p = 0.021).No differences were found between PHIV+/noC and HIV(−) participants. However, the PHIV+/C group showed poorer performance than PHIV+/noC (NPZ-5, p = 0.037) and HIV(−) subjects (crystallised intelligence, p = 0.025; intelligence quotient, p = 0.016). Higher nadir CD4+ T-cell count was related to better Z-score in memory (p = 0.007) and NPZ-5 (p = 0.025). Earlier and longer exposure to ART resulted in better performance in memory (p = 0.004) and executive functions (p = 0.015), respectively.ConclusionsNo significant differences were found in the neurocognitive profile nor QoL between PHIV+/noC and HIV(−) adolescents; however, PHIV+/C participants obtained lower scores. The use of longer and earlier ART seems to have a beneficial effect.     

High prevalence of food insecurity among HIV-infected individuals receiving HAART in a resource-rich setting

This study aimed to assess the prevalence and correlates of food insecurity in a cohort of HIV-infected individuals on highly active antiretroviral therapy (HAART) in British Columbia (BC), Canada. Adults receiving HAART voluntarily enrolled into the Longitudinal Investigations into Supportive and Ancillary Health Services (LISA) cohort. Individual food insecurity was measured using a modified version of the Radimer/Cornell Questionnaire. We performed bivariate analyses to determine differences between explanatory variables for individuals who were food secure and food insecure. We performed logistic regression to determine independent predictors of food insecurity. Of the 457 individuals enrolled in the LISA cohort, 324 (71.0%) were found to be food insecure. Multivariate analysis indicated that individuals who had an annual incomes less than $15,000 (odds ratio [OR] 3.15, 95% confidence interval [CI] 1.83, 5.44), used illicit drugs (OR 1.85, 95% CI 1.03, 3.33), smoked tobacco (OR 2.30, 95% CI 1.30, 4.07), had depressive symptoms (OR 2.34, 95% CI 1.38, 3.96), and were younger (OR 0.95, 95% CI, 0.92, 0.98) were more likely to be food insecure. Our results demonstrated a high (71%) prevalence of food insecurity among HIV-infected individuals receiving HAART in this resource-rich setting, and that food insecurity is associated with a compendium of environmental and behavioral factors. More research is needed to understand the biological and social pathways linking food insecurity to these variables in order to identify program strategies that can effectively improve food security among HIV-infected populations.