德州市2005-2015年艾滋病免费抗病毒治疗效果及影响因素评价北大核心

目的评价德州市艾滋病抗病毒治疗的效果,为制定有针对性的艾滋病防治策略提供科学依据。方法以德州市2005-2015年所有接受艾滋病抗病毒治疗的艾滋病病毒（HIV）感染者/艾滋病（AIDS）病人（简称HIV/AIDS病人）为研究对象,以CD4^＋T淋巴细胞（简称CD4细胞）及病毒载量为客观指标,结合患者转归,综合分析抗病毒治疗的疗效。结果243例接受高效抗反转录病毒疗法（HAART）的HIV/AIDS病人,平均年龄（38.40±10.16）岁,基线CD4细胞计数均值为（239.96±161.10）个/μL,治疗后CD4细胞平均增长211.01个/μL（t=-11.604,P=0.000）。在开始治疗的36个月内,不同基线CD4细胞组计数增长存在统计学差异（F=5.701,P=0.001）。接受HAART平均时长（30.71±23.82）个月,治疗12个月病毒抑制率为88.69%（149/168）,累计死亡率为7.82%（19/243）。多因素Cox比例风险回归模型分析显示,随着确证时年龄的增长,HIV/AIDS病人的死亡率增加;基线CD4细胞计数≤200个/μL的HIV/AIDS病人的死亡风险,是基线CD4细胞计数〉200个/μL病人的12.683倍[95%可信区间（CI）：2.769-58.079]。结论抗病毒治疗可以有效促进免疫重建。提高早期发现能力,及早采取规范的治疗措施,加强依从性教育,对于提高艾滋病抗病毒治疗效果具有重要意义。     

甘肃省某机构2015年抗病毒治疗病人HIV耐药结果分析北大核心

目的了解甘肃省当前艾滋病抗病毒治疗人群中艾滋病病毒(HIV)耐药株的流行状况,为甘肃省有效开展艾滋病抗病毒治疗提供依据。方法采用横断面调查方法,对甘肃省某机构初始抗病毒治疗9-15个月的43例成人病人进行访谈和采集血样,检测免疫学指标(CD4+T淋巴细胞)、病毒载量(VL)和耐药性指标(基因型突变)。对病毒载量≥1000拷贝/mL的血样进行耐药基因型检测。结果调查的43例病人,男性93.0%(40例)、汉族93.0%(40例)、大专及以上文化程度39.5%(17例)、城镇户口65.1%(28例)、同性性传播46.5%(20例)。3例病毒抑制失败,其中2例出现耐药,治疗人群中的耐药率为4.7%(2例),所有耐药病人均同时对核苷类及非核苷类反转录酶抑制剂耐药,没有病人对蛋白酶抑制剂耐药。耐药病人服药依从性良好。结论甘肃省抗病毒治疗人群中已经出现耐药现象,治疗失败病人主要是因为发生耐药,应加强开展规范合理的抗病毒治疗,及时进行耐药监测以预防耐药株的传播和流行。     

郑州市HIV/AIDS病人一线抗病毒治疗失败发生规律及影响因素分析

目的研究艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人(简称HIV/AIDS病人)一线抗病毒治疗失败的发生规律,分析其影响因素。方法运用回顾性队列研究方法,分析郑州市城区接受艾滋病抗病毒治疗病人的基本信息、基线特征以及随访信息。使用寿命表法分析一线抗病毒治疗失败的发生率,Log-Rank法检验各组差异,并通过单因素和多因素COX比例风险模型分析一线失败的影响因素。结果本研究共纳入1 173例HIV/AIDS病人,47例发生一线抗病毒治疗失败,失败率为4%(47/1 173),其中24例一线失败发生在抗病毒治疗1年内,第1、3、5、7年抗病毒治疗一线成功率分别为98%、96%、93%、91%。多因素COX比例风险模型分析结果显示,基线CD4~+T淋巴细胞(简称CD4细胞)计数中"201～350个/μL"组、"351个/μL"组相对于"0～200个/μL"组的风险比(HR)[95%可信区间(CI)]分别为0.248(0.109～0.565)、0.203(0.071～0.584),合并乙型肝炎(HR=2.893,95%CI:1.131～7.403)一线失败风险高,确证到治疗的时间间隔(月)"12～23"组、"≥24"组相对于"12"组的HR(95%CI)分别为2.588(1.060～6.317)、2.579(1.289～5.159)。结论艾滋病抗病毒治疗一线失败多发生在治疗早期,且与病人的基线CD4细胞计数、合并乙型肝炎、确证到抗病毒治疗的时间间隔有关。     

成人HIV/AIDS病人HAART前血小板减少的发生率及相关因素分析

目的描述成人艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人(简称HIV/AIDS病人)在高效抗病毒治疗(HAART)前,发生血小板减少的基本特征,探讨HIV合并血小板减少的发生率及相关因素。方法以2003年6月至2015年12月,在北京地坛医院门诊就诊的3452例HIV/AIDS病人为研究对象,比较HAART前不同基本情况[人口学资料、身体质量指数(BMI)、CD4+T淋巴细胞(简称CD4细胞)计数、病毒载量、是否合并机会性感染及症状体征、其他混合性感染的合并情况及是否服用复方新诺明(SMZ-TMP)情况]的血小板减少的发生率,通过Logistic回归分析HIV/AIDS病人合并血小板减少症的相关因素。结果 HAART前合并血小板减少的有137例(3.97%),其中轻度104例(3.01%),中度19例(0.55%),重度14例(0.41%)。血小板减少的发生率随CD4细胞计数的增加而降低(P0.001)。HAART前HIV RNA≥105拷贝/mL[调整OR值(AOR)=1.903,95%CI:1.125~3.218,P=0.016],CD4细胞计数≤50个/μL(AOR=8.828,95%CI:2.939~26.519,P0.001)及CD4细胞计数51~199个/μL(AOR=3.714,95%CI:1.317~10.479,P=0.013),HBsAg+(AOR=4.949,95%CI:2.372~10.323,P0.001)是发生血小板减少的危险因素。结论成人HIV/AIDS病人HAART前血小板减少发生率较低。低基线CD4细胞计数、高基线病毒载量及合并乙型肝炎是HAART前发生血小板减少的相关因素,因此对存在这些危险因素的病人及早的诊断和治疗是必须的。     

抗病毒治疗HIV/AIDS病人停药后耐药突变位点变化研究

目的了解接受抗病毒治疗(ART)的艾滋病病毒(HIV)感染者/艾滋病病人停药后,病毒载量及耐药突变位点变化的情况。方法在河南和安徽两县市,回顾性队列调查接受ART的停药病人,分析停药前后病毒载量、CD4+T淋巴细胞(简称CD4细胞)数及HIV耐药变化情况。结果共纳入64名停药病人,停药12个月和24个月后分别随访到52人和40人;在停药前,有34人血浆病毒载量≥1 000拷贝/mL,CD4细胞中位数为285个/μL,停药后12个月和24个月,病毒载量≥1 000拷贝/mL的病人分别有48人和40人,CD4细胞中位数分别为223个/μL和282个/μL;停药前共有19人存在耐药突变位点,停药12个月和24个月后,分别有20人和10人有耐药位点;8个核苷类耐药突变位点,如M41L、K65R、D67G、K70N、L74V、F116Y、L210W、T215Y在停药后12个月即消失,3个非核苷类耐药突变位点,如K101E、H221Y、K238RT停药12个月消失,Y188HL在停药后24个月检测不到,而有些非核苷类耐药突变位点K103NRS、Y181C、G190ARS,在停药后24个月仍然存在。结论接受抗病毒治疗的艾滋病病人停药后,病毒载量明显上升,耐药突变位点以不同速度发生变化,核苷类耐药突变位点比非核苷类耐药突变位点更易消失。     

成人HIV/AIDS病人HAART前血小板减少的发生率及相关因素分析北大核心

目的描述成人艾滋病病毒（HIV）感染者/艾滋病（AIDS）病人（简称HIV/AIDS病人）在高效抗病毒治疗（HAART）前,发生血小板减少的基本特征,探讨HIV合并血小板减少的发生率及相关因素。方法以2003年6月至2015年12月,在北京地坛医院门诊就诊的3452例HIV/AIDS病人为研究对象,比较HAART前不同基本情况[人口学资料、身体质量指数（BMI）、CD4^＋T淋巴细胞（简称CD4细胞）计数、病毒载量、是否合并机会性感染及症状体征、其他混合性感染的合并情况及是否服用复方新诺明（SMZ-TMP）情况]的血小板减少的发生率,通过Logistic回归分析HIV/AIDS病人合并血小板减少症的相关因素。结果 HAART前合并血小板减少的有137例（3.97%）,其中轻度104例（3.01%）,中度19例（0.55%）,重度14例（0.41%）。血小板减少的发生率随CD4细胞计数的增加而降低（P〈0.001）。HAART前HIV RNA≥105拷贝/mL[调整OR值（AOR）=1.903,95%CI：1.125-3.218,P=0.016],CD4细胞计数≤50个/μL（AOR=8.828,95%CI：2.939-26.519,P〈0.001）及CD4细胞计数51-199个/μL（AOR=3.714,95%CI：1.317-10.479,P=0.013）,HBsAg＋（AOR=4.949,95%CI：2.372-10.323,P〈0.001）是发生血小板减少的危险因素。结论成人HIV/AIDS病人HAART前血小板减少发生率较低。低基线CD4细胞计数、高基线病毒载量及合并乙型肝炎是HAART前发生血小板减少的相关因素,因此对存在这些危险因素的病人及早的诊断和治疗是必须的。     

安岳县42例HIV/AIDS病人免费抗病毒治疗情况分析

目的探讨四川省安岳县艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人(HIV/AIDS病人)抗病毒治疗的效果及相关状况,为艾滋病的综合防治提供基础资料和科学依据。方法采用前瞻性随访研究方法,对HIV/AIDS病人的实验室检查相关结果、治疗方案及随访情况做描述性分析、重复测量方差分析、Logistic回归分析。结果 42例病人治疗前、治疗半年后及治疗1年后,CD+4T淋巴细胞(简称CD4细胞)计数的变化差异有统计学意义(F=307.93,P0.001);当基线CD4细胞计数200个/μL时,其出现治疗效果较差的危险性是基线CD4细胞计数≥200个/μL的5.675倍;基线CD4细胞计数200个/μL,发生艾滋病相关死亡的风险较大。按医嘱定期检查肝功、血常规等的次数,随着治疗时间的延长而逐渐减少。结论抗病毒治疗后,病人身体素质有所提高;基线CD4细胞计数越低,治疗效果就越差;抗病毒治疗病人随着治疗时间的增加,依从性逐渐降低。     

广西桂南地区男男性行为人群HIV/AIDS病人抗病毒治疗效果分析

目的了解男男性行为(MSM)人群艾滋病病毒(HIV)/艾滋病(AIDS)病人(简称HIV/AIDS病人)抗反转录病毒治疗(ART)情况并进行疗效评估。方法选取进行ART 1年的HIV/AIDS病人89例作为研究对象,检测患者治疗后不同时间CD4+T淋巴细胞(简称CD4细胞)及病毒载量抑制率的变化情况。结果 89例HIV/AIDS病人基线CD4细胞计数为(233.9±151.5)个/μL;治疗3、6、9、12个月后的CD4细胞计数分别为(339.6±167.5)个/μL、(373.4±177.3)个/μL、(380.7±186.8)个/μL、(397.6±208.2)个/μL。患者治疗后不同时间CD4细胞计数均高于基线CD4细胞计数(P均0.01);患者CD4细胞计数随治疗时间的延长不断增加(F=13.517,P0.01)。ART 6个月后,基线CD4细胞计数水平50个/μL患者病毒载量抑制(20拷贝/m L)比例为50.00%,50~199个/μL、200~350个/μL、350个/μL患者病毒载量抑制比例分别为61.90%、60.71%、66.76%。基线CD4细胞计数不同水平病人病毒抑制率比较差异无统计学意义(P0.05)。ART 12个月后,基线CD4细胞计数水平50个/μL患者病毒载量抑制比例为75.00%,50~199个/μL、200~350个/μL、350个/μL者病毒载量抑制比例分别为84.21%、80.76%、81.00%。基线CD4细胞计数不同水平病人的病毒抑制率比较差异无统计学意义(P0.05)。结论 MSM人群中HIV/AIDS病人ART的临床效果确切,可显著改善患者的免疫功能,降低病毒载量水平;对MSM人群HIV/AIDS病人开展ART有利于控制疫情蔓延。     

武汉市≥50岁HIV/AIDS病人抗病毒治疗效果分析

目的了解武汉市≥50岁艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人(简称HIV/AIDS病人)抗病毒治疗(ART)效果及其相关因素。方法对武汉市≥50岁HIV/AIDS病人基线时一般人口学资料、HIV感染途径、目前抗病毒治疗方案、基线和最近一次CD4+T淋巴细胞(简称CD4细胞)与病毒载量(VL)的检测结果以及当次随访时的服药依从性数据进行整理分析,多元Logistic回归分析相关因素。结果共纳入HIV/AIDS病人778人,男635人(81.6%),女143人(18.4%)。年龄范围50～84岁,中位数57岁(53～64岁)。基线和最近一次VL检测中,VL20拷贝/mL的分别有2人(0.3%)、606人(77.9%)。基线和最近一次随访中,CD4细胞≥200个/μL的分别有425人(54.6%)、646人(83.0%)。无漏服药以及较少的漏服药次数者病毒学完全抑制率较高,基线时HIV/AIDS病人CD4细胞≥200个/μL者免疫学效果较好,抗病毒治疗时间较长者病毒抑制效果和免疫学效果均较好(P0.05)。结论武汉市≥50岁HIV/AIDS病人抗病毒治疗效果较好,抗病毒治疗时间、服药依从性和基线CD4细胞水平与抗病毒治疗效果有关。     

温州市974例AIDS病人免费HAART的疗效分析

目的分析温州市艾滋病病人高效抗反转录病毒治疗(HAART)的效果,为今后开展HAART提供科学依据。方法利用国家"艾滋病综合防治信息系统-抗病毒治疗管理"数据库收集相关信息,对2005-2013年接受艾滋病免费HAART的974例病人的免疫改善状况、病毒抑制情况以及不良反应发生情况进行分析。结果随着治疗时间的增加,艾滋病病人CD+4T淋巴细胞(简称CD4细胞)计数持续上升,以治疗3个月时增幅最大,治疗不同时间CD4细胞计数变化差异有统计学意义(P0.0001),基线CD4细胞计数越高,治疗后增长的水平也越高。治疗后病毒载量低于检测限的比例达84.7%~87.3%。56.6%的病人发生不同程度的药物不良反应,有6.0%病人因不能耐受严重不良反应更换治疗方案。结论温州市艾滋病免费HAART的疗效显著,可显著地抑制体内艾滋病病毒的复制,重建机体的免疫功能,较早启动HAART有望取得更好的治疗效果。     

High levels of adherence do not prevent accumulation of HIV drug resistance mutations

OBJECTIVES: To assess the relationship between development of antiretroviral drug resistance and adherence by measured treatment duration, virologic suppression, and the rate of accumulating new drug resistance mutations at different levels of adherence. METHODS: Adherence was measured with unannounced pill counts performed at the participant's usual place of residence in a prospective cohort of HIV-positive urban poor individuals. Two genotypic resistance tests separated by 6 months (G1 and G2) were obtained in individuals on a stable regimen and with detectable viremia (> 50 copies/ml). The primary resistance outcome was the number of new HIV antiretroviral drug resistance mutations occurring over the 6 months between G1 and G2. RESULTS: High levels of adherence were closely associated with greater time on treatment (P < 0.0001) and viral suppression (P < 0.0001) in 148 individuals. In a subset of 57 patients with a plasma viral load > 50 copies/ml on stable therapy, the accumulation of new drug resistance mutations was positively associated with the duration of prior treatment (P = 0.03) and pill count adherence (P = 0.002). Assuming fully suppressed individuals (< 50 copies/ml) do not develop resistance, it was estimated that 23% of all drug resistance occurs in the top quintile of adherence (92-100%), and over 50% of all drug resistance mutations occur in the top two quintiles of adherence (79-100%). CONCLUSION: Increasing rates of viral suppression at high levels of adherence is balanced by increasing rates of drug resistance among viremic patients. Exceptionally high levels of adherence will not prevent population levels of drug resistance.     

The virological response to highly active antiretroviral therapy over the first 24 weeks of therapy according to the pre-therapy viral load and the weeks 4-8 viral load

OBJECTIVES: To describe the viral response to HAART by weeks 4 and 8 in previously antiretroviral-naive patients. To assess whether the weeks 4 or 8 viral loads are useful predictors of viral suppression by week 24. DESIGN: A large clinical database including 453 antiretroviral-naive patients whose plasma viral load was monitored every 4 weeks. METHODS: Observed probabilities of achieving a viral load < or = 500 copies/ml by week 24 (days 84-168) from starting highly active antiretroviral therapy (HAART) were calculated according to viral loads at weeks 4 and 8. RESULTS: A total of 42.4% of patients (153/361) reached < or = 500 copies/ml viral load by week 4 and 70.4% (245/348) by week 8. Viral suppression below 500 copies/ml by 4-8 weeks was similar irrespective of the pre-HAART viral load. In patients with viral loads above 10000 copies/ml at week 4, 60.6% (20/33) achieved < or = 500 copies/ml by week 24. In patients with viral loads still above 10000 copies/ml at week 8, only 42.3% (11/26) achieved < or = 500 copies/ml by week 24, and only 33.3% (3/9) maintained viral suppression below 500 copies/ml to week 48. CONCLUSION: Viral loads at weeks 4 and 8 should be monitored to detect early signs of low subsequent viral suppression. For previously antiretroviral-naive patients whose viral loads after 8 weeks of HAART are still above 10000, there is an urgent need to assess adherence to therapy, drug levels and resistance, so management can be modified accordingly to reduce the rate of week 24 virological failure.     

Treatment interruptions predict resistance in HIV-positive individuals purchasing fixed-dose combination antiretroviral therapy in Kampala, Uganda

OBJECTIVE: To evaluate adherence, treatment interruptions, and outcomes in patients purchasing antiretroviral fixed-dose combination (FDC) therapy. DESIGN: Ninety-seven participants were recruited into a prospective 24-week observational cohort study of HIV-positive, antiretroviral-naive individuals initiating self-pay Triomune or Maxivir therapy in Kampala, Uganda. Adherence was measured by monthly structured interview, unannounced home pill count, and electronic medication monitors (EMM). Treatment interruptions were measured as continuous intervals greater than 48 h without opening the EMM. The primary outcomes were survival with viral suppression below 400 copies/ml, CD4 cell increases, and genotypic drug resistance at 24 weeks. RESULTS: The median baseline CD4 cell count was 56 cells/microl and median log10 copies RNA/ml was 5.54; mean adherence ranged from 82 to 95% for all measures but declined significantly over time. In an intent-to-treat analysis, 70 (72%) patients had an undetectable plasma HIV-RNA level at week 24. Sixty-two of 95 (65%) individuals with continuous EMM data had a treatment interruption of greater than 48 h. Treatment interruptions accounted for 90% of missed doses. None of 33 participants who did not interrupt treatment for over 48 h had drug resistance, whereas eight of 62 (13%) participants who did interrupt therapy experienced drug resistance. Antiretroviral resistance was seen in 8% of individuals and overall mortality was 10% at 24 weeks. CONCLUSION: HIV-positive individuals purchasing generic FDC antiretroviral therapy have high rates of adherence and viral suppression, low rates of antiretroviral resistance, and robust CD4 cell responses. Adherence is an important predictor of survival with full viral suppression. Treatment interruptions are an important predictor of drug resistance.     

Reassessing the role for lamivudine in chronic hepatitis B infection: a four-year cohort analysis

BACKGROUND/OBJECTIVES:

Lamivudine is readily available and inexpensive. Guidelines recommend other antiviral medications because they achieve superior virological suppression with less resistance. These data are based on clinical trial populations and may not be representative of typical hepatitis B virus (HBV) populations. The authors assessed lamivudine in maintaining long-term viral suppression in an adherent, frequently monitored, noninvestigational HBV-infected population.

METHODS:

All HBV patients (n=369) between 2000 and 2010 were evaluated in a retrospective, single-centre study. Virological response was defined by complete suppression of HBV DNA (<400 copies/mL) and was assessed at six to 12 month intervals over four years. Enzymatic and serological outcomes, as well as treatment failures were assessed.

RESULTS:

Forty-seven patients (36 men; mean age 44 years, mean alanine aminotransferase level 123 U/L; METAVIR stage 3/4 [n=21], treatment naive [n=41]) received lamivudine 100 mg to 300 mg daily. The mean pretreatment viremia was 5.19 log₁₀ copies/mL, and was above the limit of detection (>6.91 log₁₀ copies/mL) in 11 patients (23%). The mean (± SD) dosing duration was 32±22 months. Virological suppression was achieved in 45 (96%) patients. Mean viremia declined to 3.06 log₁₀ copies/mL (n=27) and 2.68 log₁₀ copies/mL (n=18) at 12 and 48 months, respectively, with 78% and 88% with undetectable viremia at these time points, respectively. The mean alanine aminotransferase level declined to 31 U/L and 36 U/L at 12 and 48 months, respectively. Seven of 13 (54%) hepatitis B e antigen-positive patients seroconverted. The treatment failure rate was 11%.

CONCLUSIONS:

In a selected group of HBV patients, successful long-term viremia suppression was achieved with low treatment failure rates. With strict dosing adherence and monitoring for virological breakthrough, sustained virological suppression can be reliably achieved with lamivudine in carefully selected patients.     

Clinical progression of HIV-1 infection according to the viral response during the first year of antiretroviral treatment. Groupe d'Epidémiologie du SIDA en Aquitaine (GECSA)

OBJECTIVE: To compare HIV-disease progression according to changes of plasma HIV RNA observed in the year following initiation of a new antiretroviral treatment. DESIGN: Prospective cohort treated with two nucleoside analogues or a triple combination including a protease inhibitor. METHODS: A Cox model was used to estimate the effect of viral response during the first year after initiation of treatment on the subsequent occurrence of new AIDS-defining events or death. Viral response was fitted either as HIV RNA reduction during the initial 4-12 months of treatment or reduction during the first month. RESULTS: Among 773 patients (47% with triple drug combination) followed for a median period of 27 months, 62 patients experienced a clinical event. Poor viral responders (at least two measurements > 3.7 log10 copies/ml during 4-12 months of treatment) had a higher risk of disease progression than good responders (RNA < 2.7 log10 copies/ml) after adjustment [hazard ratio (HR), 2.24; 95% confidence interval (CI), 1.1 7-4.29]. Intermediate responders (2.7 < or = RNA < or = 3.7 log10 copies/ml) had a risk of progression comparable with that of good responders (HR, 1.43; 95% CI, 0.64-3.22). A large initial viral reduction was also a protective factor for clinical progression (HR, 0.51 for 1 log10 copies/ml increase of the reduction; 95% CI, 0.31-0.85) and was associated with the viral response during the subsequent 4-12 month period. No patient with a reduction < 0.5 log10 copies/ml in the first month was classified as a good responder in the subsequent 4-12 month period (P < 0.01). CONCLUSIONS: A sustained HIV RNA > 3.7 log10 copies/ml should suggest a prompt change of treatment. When the reduction in HIV RNA is < 0.5 log10 after 1 month of treatment, this action should be anticipated. A sustained HIV RNA level between 2.7 and 3.7 log10 copies/ml may permit the deferral of a change of drug regimen according to the patient's history and therapeutic options.