Effectiveness of highly active antiretroviral therapy among HIV-1 infected women

STUDY OBJECTIVE: To describe the impact of highly active antiretroviral therapy (HAART) on mortality, morbidity, and markers of HIV disease progression in HIV infected women. DESIGN: Data collected from the Women's Interagency HIV Study, a prospective cohort study that enrolled women between October 1994 and November 1995. SETTING: Six clinical consortia based in five cities in the United States (New York, NY; Washington, DC; Los Angeles, CA; San Francisco, CA; and Chicago, IL). PARTICIPANTS: A total of 1691 HIV seropositive women with a study visit after April 1996. MAIN RESULTS: Beginning in April 1996, the self reported use of HAART increased over time, with more than 50% of the cohort reporting HAART use in 1999. There was a 23% decline per semester in the incidence of AIDS from April 1996 (95% confidence intervals (CI) -29% to -16%). Furthermore, there was a 21% decline of the semiannual mortality rates among those with AIDS at baseline (95% CI -27% to -14%) and an 11% decline among those AIDS free at baseline (95% CI -3% to -18%). CD4+ lymphocyte counts either increased (women with baseline AIDS) or stabilised (women without baseline AIDS) after April 1996, and HIV RNA levels dramatically declined in both groups, although the percentage of women with HIV RNA above 4000 cps/ml remained stable at approximately 40% since mid-1997. CONCLUSIONS: Despite concerns regarding the use of antiretroviral therapies in this population, the use of therapies led to improved immunological function, suppressed HIV disease activity, and dramatic declines in morbidity and mortality.     

Role of metabolic syndrome and antiretroviral therapy in adiponectin levels and oxidative stress in HIV-1 infected patients

ObjectiveHIV-1 infection is accompanied by severe metabolic and immune dysfunction. The aim of this study was to evaluate the role of metabolic syndrome (MetS) and antiretroviral therapy (ART) utilization on the adiponectin levels and oxidative stress in patients infected with HIV-1.MethodsWe allocated 285 patients into four groups: group 1: patients without MetS who were not using ART; group 2: patients without MetS using ART; group 3: patients with MetS who were not using ART; and group 4: patients with MetS using ART. Biochemical, immunologic, and oxidative stress parameters were measured.ResultsGroup 4 exhibited higher lipoperoxides when compared with group 1 (P < 0.0001) and higher advanced oxidation protein products (AOPP) compared with group 2 or group 1 (P < 0.0001). Group 3 also presented higher AOPP than group 2 (P < 0.05). Group 4 showed lower adiponectin levels compared with groups 1 or 2 (P < 0.0001). Similarly, group 3 presented lower adiponectin levels compared with group 2 (P < 0.05) or group 1 (P < 0.0001). Multivariate analysis showed that both an increase in AOPP and a decrease in total radical-trapping antioxidant parameter/uric acid were independently associated with MetS in HIV-1 patients. Regarding immunologic markers of HIV-1 disease progression and viral replication, group 4 exhibited significantly higher CD45⁺, CD3⁺, and CD4⁺ T cells count compared with group 2 (P < 0.01).ConclusionHIV-1–infected patients with MetS exhibited hypoadiponectinemia and increased oxidative stress, and these findings were not influenced by ART use. The findings of the present study allow the suggestion that MetS and inflammation might be mainly responsible for the aforementioned features. More studies are needed to verify whether drugs or food, which yield increased adiponectinemia and decreased oxidative stress, could reduce cardiovascular risk in HIV-infected patients.     

HIV-1感染者抗病毒治疗后HIV-1 DNA载量动力学变化及影响因素分析

目的:分析云南省德宏傣族景颇族自治州（德宏州）HIV感染者抗病毒治疗后HIV-1 DNA载量的动力学变化及影响因素,为HIV-1 DNA定量检测的临床应用提供参考依据。方法:研究对象来源于德宏州CDC建立的2009-2018年HIV新发感染队列,构建HIV-1 DNA载量随抗病毒治疗时间动力学变化曲线图。采用logis...     

Epidemiological and clinical features of HIV-2 infection in Dakar

OBJECTIVE: The aim of this article was to describe the epidemiological and clinical aspects of HIV-2 infection in Dakar. DESIGN AND METHODS: This retrospective study was made on 217 HIV-2 infected patients hospitalized between 1986 and 2003; the epidemiological, clinical, and paraclinical data was collected and analyzed using the Epi-Info software version 6.04. RESULTS: The mean age was 40 years+/-9.6 and the male to female sex ratio was 1.33. The mode of transmission was primarily heterosexual. Some risk factors (travel abroad, heterosexual multi-partners, and unprotected sexual intercourse) were more frequently observed in men while others (blood transfusion, HIV positive partners) were noted among HIV-2 infected women. The most frequent symptoms were weight loss (88%), diarrhea (77%), fever (72.4%), asthenia (70.5%), chronic cough, and dermatosis (50.7%). The main opportunistic infections were oral candidiasis (61.8%), tuberculosis (26.3%), intestinal parasitosis (20.3%). The lethality rate was 33.2% and it was correlated with a low CD4 rate. Meningoencephalitis and bacterial infections were associated with a high lethality rate. CONCLUSIONS: The epidemiological and clinical aspects of HIV-2 infection were the same as in HIV-1 infected patients. However the lethality rate remained high among patients hospitalized with a low CD4 cell count. Early HIV testing and improving the diagnostic approach for opportunistic infections remains a high priority.     

抗病毒治疗后不同免疫重建水平HIV感染者基线生化指标及艾滋病直接相关合并症差异

目的 了解抗病毒治疗(ART)后不同免疫重建水平HIV感染者的基线生化指标及艾滋病直接相关合并症差异。方法 以2010年1月至2017年12月广州医科大学附属市八医院感染门诊随访超过24个月成年初治HIV感染者为研究对象。根据基线CD4⁺ T淋巴细胞计数<200、200~350和>350个/µl的不同水平分为免疫重建不良组、部分免疫重建组和免疫重建良好组。采用Kruskal-Wallis H和χ²检验分析不同组的基线社会人口学特征、生化指标及艾滋病直接相关合并症的差异。采用SPSS 20.0软件进行统计学分析。结果 共纳入研究对象3 900例,免疫重建不良组、部分免疫重建组和免疫重建良好组分别为385例(9.9%)、1 206例(30.9%)和2 309例(59.2%)。免疫重建不良组的基线白细胞、血小板、血红蛋白、TG、TC、FPG、AST、ALT及总胆红素等生化指标与免疫重建良好组差异有统计学意义(均P<0.05)。免疫重建不良组的基线合并肺结核、耶氏肺孢子菌肺炎、播散性真菌病、食管念珠菌病、肺外结核、皮炎、口腔念珠菌感染、口腔黏膜毛状白斑、持续腹泻 ≥ 1个月及持续或间断发热 ≥ 1个月等艾滋病直接相关合并症的占比明显高于免疫重建良好组,差异有统计学意义(均P<0.05)。结论 ART后获得不同免疫重建水平的HIV感染者基线生化指标和艾滋病直接相关合并症存在明显差异,需加强基线异常生化指标的监测和合并症的诊治。     

广西99例AIDS患者经高效抗逆转录病毒治疗后脂代谢的初步研究

目的了解艾滋病（acquired immunodeficiency syndrome,AIDS）患者经高效抗逆转录病毒治疗（highly active antiretroviral therapy,HAART）后体脂肪的代谢情况。方法采用生物电阻抗法对99例经HAART治疗的AIDS患者进行体成分定量测定,用偏相关分析了解总体脂肪量与各部位脂肪量的关系,通过建立多重线性回归方程对脂肪量进行预测。结果男女患者的总脂肪量、皮下、躯干和四肢脂肪含量差异均有统计学意义（均有P〈0．05）。偏相关分析显示,AIDS患者的总脂肪量与内脏脂肪量、皮下脂肪量及右上肢脂肪量均呈正相关（均有P〈0．05）。多重线性回归分析结果显示,总脂肪量与皮下脂肪量、内脏脂肪量及体重关系密切。结论本研究获得了广西AIDS患者体脂肪的基线资料,可为开展AIDS病人脂代谢的防控等提供科学依据。     

艾滋病7年高效抗逆转录病毒治疗的多中心前瞻性观察

目的前瞻性长期观察人免疫缺陷病毒感染者和获得性免疫缺陷综合征(HIV/AIDS)患者的高效抗逆转录病毒治疗(highly active antiretroviral therapy,HAART)一线药物抗HIV及免疫重建效果和主要毒副反应,探索我国艾滋病长期抗病毒治疗的规律。方法 437例HIV/AIDS患者先后启动HAART,一线方案为2个核苷类逆转录酶抑制剂(NRTI)加1个非核苷类逆转录酶抑制剂(NNRTI)。随访监测CD4+T细胞数量、HIV病毒载量,追踪血常规和主要生化指标的变化;观察发生的机会感染和药物毒副反应并及时处理,对出现病毒学失败或严重毒副反应者及时调整用药。结果对437例接受HAART的HIV/AIDS患者平均追踪了4.69年(3.15～7.34年),总病死率6.86%,大部分死亡发生在HAART启动的6个月内。启动HAART 12个月时,90.80%的患者HIV载量小于可检测下限;至治疗4、5、6、7年(±1个月)时,仍分别有63.46%、69.41%、70.00%和72.22%的患者病毒载量小于可检测下限。CD4+细胞数量在治疗的O、1、2、3、4、5、6、7年(±1个月)时分别为115、246、301、334、363、356、386和373个/μL。67.73%出现过各种可能与药物毒副作用相关的表现,主要有消化道症状、神经系统症状、肝功能损害、骨髓毒性、皮疹和血脂升高等,多发生于治疗启动12个月内;血脂分布异常和乳酸酸中毒较少见,多发生于启动2年以后;41例患者先后发生过Ⅲ/Ⅳ级毒副反应。因毒副反应而更换为其他一线药物者占19.22%,因病毒耐药或毒副反应而更换为二线药物者占11.67%。结论通过对HIV/AIDS患者HAART3～7年的多中心前瞻性观察,明确我国2个NRTI加1个NNRTI的HAART一线方案对大多数HIV/AIDS患者长期有效,病毒持续抑制,CD4+细胞增加;主要的毒副反应和死亡多发生在启动治疗12个月内。大多数HIV/AIDS患者可长期坚持一线药物治疗,少数因药物毒副反应或病毒耐药须换为二线药物治疗。     

Adherence to antiretroviral therapy,virological response,and time to resistance in the Dakar cohort

In 1998, with the launch of the Senegalese Initiative for Antiretroviral Access (ISAARV), Senegal became one of the first African countries to propose an antiretroviral access program. Our objective in this paper is to study the time to any first drug resistance, as well as predictors of the time to resistance. We propose a joint model to study the effect of adherence to the HAART therapy, and virological response on the time to resistance mutations. A logistic mixed model is used to model the time‐dependent adherence process; and a Markov model is used to study the virological response. Given the presence of missing data in the adherence process and in the virological response, the latent adherence and virological states are then included in the linear predictor of the time to resistance model. The proposed time to resistance model takes into account interval‐censored data as well as null hazard periods, during which the viral replication is very low. A Bayesian approach is used for accommodating with missing data and for prediction. We also propose model checking tools to study model adequacy. Copyright © 2009 John Wiley & Sons, Ltd.     

A coronary heart disease risk model for predicting the effect of potent antiretroviral therapy in HIV-1 infected men

BACKGROUND: Many HIV-infected patients on highly active antiretroviral therapy (HAART) experience metabolic complications including dyslipidaemia and insulin resistance, which may increase their coronary heart disease (CHD) risk. We developed a prognostic model for CHD tailored to the changes in risk factors observed in patients starting HAART. METHODS: Data from five cohort studies (British Regional Heart Study, Caerphilly and Speedwell Studies, Framingham Offspring Study, Whitehall II) on 13,100 men aged 40-70 and 114,443 years of follow up were used. CHD was defined as myocardial infarction or death from CHD. Model fit was assessed using the Akaike Information Criterion; generalizability across cohorts was examined using internal-external cross-validation. RESULTS: A parametric model based on the Gompertz distribution generalized best. Variables included in the model were systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, triglyceride, glucose, diabetes mellitus, body mass index and smoking status. Compared with patients not on HAART, the estimated CHD hazard ratio (HR) for patients on HAART was 1.46 (95% CI 1.15-1.86) for moderate and 2.48 (95% CI 1.76-3.51) for severe metabolic complications. CONCLUSIONS: The change in the risk of CHD in HIV-infected men starting HAART can be estimated based on typical changes in risk factors, assuming that HRs estimated using data from non-infected men are applicable to HIV-infected men. Based on this model the risk of CHD is likely to increase, but increases may often be modest, and could be offset by lifestyle changes.     

联合雷特格韦用于HIV-1初次治疗有效性和安全性的Meta分析

目的 评价联合雷特格韦治疗方案用于人类免疫缺陷病毒-1（human immunodeficiency virus 1,HIV-1）初次抗病毒治疗的安全性和有效性。方法 检索联合雷特格韦用于HIV-1感染者初次抗病毒治疗的临床随机对照试验（randomized controlled trial,RCT）,采用Rev Man 5.2软件和Stata 12.0进行Meta分析。结果 纳入17个RCT,Meta分析结果：以血浆病毒载量<50拷贝/ml为治疗有效。在治疗48周及96周,试验组有效率分别为84.21%、87.30%,与对照组相比差异均无统计学意义（均有P>0.05）;治疗240周,试验组有效率高于对照组（70.2%和61.5%）,合并效应量（RR=1.15,95% CI：1.03~1.28,P=0.010）。试验组与对照组在腹泻、恶心、头晕、头痛、失眠等常见不良反应差异均无统计学意义（均有P>0.05）;其中96周及144/156周时脂质代谢异常增高合并效应量RR（95% CI）分别为：低密度脂蛋白0.16（0.05~0.49）、0.20（0.08~0.48）,甘油三酯0.12（0.02~0.59）、0.12（0.03~0.59）,总胆固醇0.04（0.00~0.40）、0.04（0.00~0.34）。脂质代谢指标异常增高发生率,试验组均少于对照组,差异均有统计学意义（均有P<0.05）。结论 雷特格韦联合核苷类逆转录酶抑制剂、非核苷类逆转录酶抑制剂或蛋白酶抑制剂可以作为HIV-1/艾滋病初次抗病毒治疗的可选方案,与目前推荐的抗病毒治疗方案疗效相当,且安全性较好,其中脂质代谢异增高常明显减少,但受纳入研究对象的限制,需要更多研究进一步证验证。     

四川省部分地区HIV-1感染者二线方案抗病毒治疗效果及耐药突变分析

目的分析四川省部分地区接受一线方案并发生耐药的HIV-1感染者更换二线方案后抗病毒治疗(ART)效果及耐药突变。方法采用队列研究方法, 2019年1月1日至2021年12月31日对接受一线方案发生耐药的HIV-1感染者随访2年, 采用χ2检验分析观察终点CD4+T淋巴细胞(CD4)计数、病毒载量(VL)变化及耐药突变情况的差异, 使用多因素logistic回归模型分析更换二线方案且依从性较好的HIV-1感染者ART效果的影响因素。结果共招募HIV-1感染者737例, 在持续保持较好依从性的情况下, 及时更换二线方案HIV-1感染者持续CD4计数>200个/μl和持续病毒抑制的比例较高(P<0.05), 其中基线不同耐药程度HIV-1感染者持续CD4计数>200个/μl和持续VL<200拷贝数/ml(持续病毒抑制)的比例差异无统计学意义(P>0.05)。更换二线方案后, 部分蛋白酶抑制剂和非核苷类反转录酶抑制剂的耐药突变位点分别呈上升和下降趋势(P<0.05)。多因素logistic回归分析结果显示, 在更换二线方案且依从性较好的HIV-1感染者中, ...     

Illicit drug use and HIV-1 disease progression: a longitudinal study in the era of highly active antiretroviral therapy

This study assessed the association between longitudinal patterns of illicit drug use and clinical progression of human immunodeficiency virus (HIV) disease. Confidential computer-based interviews, which addressed illicit drug use and other factors, were completed by HIV-infected participants in Baltimore, Maryland, at 6-month intervals from 1998 onward. To assess this association, the authors used a random-effects model in which clinically defined opportunistic conditions were linked to self-reported periods of drug use, enabling four categories of drug use to be distinguished: nonusers, intermittent users during abstinent periods, intermittent users during active periods, and persistent users. Included in the analysis were 1,851 participants who completed > or = 1 survey. For participants who used drugs intermittently over time, the risk of developing new opportunistic conditions during periods of abstinence was similar to that for those who never used drugs (odds ratio = 1.2, 95% confidence interval: 0.9, 1.7). In contrast, compared with that for nonusers, the risk of opportunistic infection was significantly higher for intermittent drug users during periods of active use (odds ratio = 2.2, 95% confidence interval: 1.4, 2.9) and for persistent drug users (odds ratio = 1.9, 95% confidence interval: 1.2, 2.8). Active drug use is temporally linked to HIV disease progression and mortality. Effectively targeting and treating active substance abuse in HIV treatment settings may provide a mechanism to improve clinical outcomes.     

The EuroSIDA study: Regional differences in the HIV-1 epidemic and treatment response to antiretroviral therapy among HIV-infected patients across Europe--a review of published results

EuroSIDA is a pan-European observational study that follows 14,265 HIV-infected patients from 31 European countries, Israel and Argentina, of which 2,560 are patients from eastern Europe (EE). The study group has performed several analyses addressing regional differences in the HIV-epidemic across Europe, where all countries were divided into five regions: south, west central, north, east central Europe and EE. Significant regional differences in patients' characteristics and pattern of AIDS diagnoses were documented. More patients from EE were diagnosed with tuberculosis compared to other regions. Significantly fewer HIV-infected patients in EE, who fulfilled the criteria for starting combination antiretroviral therapy (cART), actually received cART as compared with other regions of Europe. Those, receiving cART in EE had a lower initial virologic response rate irrespectively of the regimen used, although it has improved within years. Besides, treatment failure was more common in this region. Thus, improvements in the clinical management of HIV patients in EE are urgently needed. Strategies include creating scientific collaborations for HIV clinicians as well as teaching clinicians about the most advanced HIV management at clinically oriented courses held in eastern Europe.