Correlation of selenium and zinc levels to antiretroviral treatment outcomes in Thai HIV-infected children without severe HIV symptoms

Background/Objectives:Deficiencies in antioxidants contribute to immune dysregulation and viral replication. To evaluate the correlation of selenium (Se) and zinc (Zn) levels on the treatment outcomes in HIV-infected children.Subjects/Methods:HIV-infected Thai children 1-12 years old, CD4 15-24%, without severe HIV symptoms were included. Se and Zn levels were measured by graphite furnace atomic absorption spectrometry at baseline and 48 weeks. Deficiency cutoffs were Se <0.1?μmol/l and Zn <9.9?μmol/l. Serum ferritin and C-reactive protein (CRP) were measured every 24 weeks. No micronutrient supplement was prescribed.Results:In all, 141 children (38.3% male) with a median (interquartile range (IQR)) age of 7.3 (4.2-9.0) years were enrolled. Median baseline CD4% was 20%, HIV-RNA was 4.6?log(10)copies/ml. At baseline, median (IQR) Se and Zn levels were 0.9 (0.7-1.0) μmol/l and 5.9 (4.8-6.9) μmol/l, respectively. None had Se deficiency while all had Zn deficiency. Over 48 weeks, 97 initiated antiretroviral therapy (ART) and 81% achieved HIV-RNA <50 copies/ml with 11% median CD4 gain. The mean change of Se was 0.06?μmol/l (P=0.003) and Zn was 0.42?μmol/l (P=0.003), respectively. By multivariate analysis in children who received ART, predictors for greater increase of CD4% from baseline were lower baseline CD4% (P<0.01) and higher baseline Zn level (P=0.02). The predictors for greater decrease of HIV-RNA from baseline were higher baseline HIV-RNA and higher ferritin (both P<0.01). No association of CRP with the changes from baseline of CD4% or HIV-RNA was found.Conclusion:In HIV-infected Thai children without severe immune deficiency who commenced ART, no correlation between Se and ART treatment outcomes was found. Higher pre-ART Zn levels were associated with significant increases in CD4% at 48 weeks.     

四川省凉山州布拖县HIV-1耐药基因检测情况分析

摘要:目的　了解凉山州布拖县艾滋病毒-I型（HIV-1）耐药基因突变情况,优化抗病毒治疗（ART）方案,提高治疗效果。方法　采用反转录式聚合酶链反应（RT -PCR）方法,检测2008、2010、2012年三年ART后病毒学失败患者的HIV-1耐药基因型。结果　截至2012年12月凉山州布拖县累计治疗艾滋病（AIDS）患者1755人,检测HIV-1病毒载量（VL）1 324次人,HIV-1 VL＜50拷贝/ml者为25.4%（336/1324）,VL 51～1 000拷贝/ml者为16.3%（216/1324）,VL＞1000拷贝/ml为58.3%（772/1324）,三年有 218例进行了耐药基因突变检测,获得可用序列148例,其中未检出耐药突变者为 42.6%（63/148）,发生耐药突变者为 57.4%（85/148）。非苷类反转录酶抑制剂（NNRTI）,蛋白酶抑制剂（PI）和核苷和核苷酸类反转录酶抑制剂（NRTI）相关的耐药基因突变率分别为33.8%（50/148）、33.1%（49/148）、10.8%（16/148）。NNRTI相关的耐药基因突变位点前3位依次是K103N/KN（47.1%）、Y181C/CY（10.3%）、Y188FY/C/L/CY（10.3%）、G190AG/A（8.8%）;PI相关的耐药基因突变位点前3位的是T71V/AT/AV（67.2%）、L10IL（20.0%）、L33IL（3.6%）;NRTI相关的耐药基因突变位点前3位依次是M184V（33.3%）、T69N/S/AT（19.0%）、D67N（9.5%）、G333E（9.5%）。结论　凉山州布拖县抗病毒治疗后病毒学失败患者中,以NNRTI耐药最多,其次为NRTI,PI较少,但PI是以次要位点（T71V/AT/AV）耐药突变较NRTI多。     

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。     

Effect of release from prison and re-incarceration on the viral loads of HIV-infected individuals

OBJECTIVES: The purpose of this study was to determine the effect of release from prison and subsequent re-incarceration on the viral loads of HIV-infected individuals receiving highly active antiretroviral therapy (HAART). METHODS: Fifteen re-incarcerated HIV-infected prisoners on HAART were identified from a retrospective cohort of HIV-infected prison inmates released from January 1, 1997, to August 31, 1999. The re-incarcerated prisoners were matched (1:2) to 30 HIV-infected incarcerated prisoners on HAART who remained incarcerated during the re-incarcerated participants' release time period. The outcomes measured were plasma HIV RNA levels, CD4+ lymphocyte counts, percentage of re-incarcerated and incarcerated participants with plasma HIV RNA levels <400 copies/mL, and the median change in plasma HIV RNA levels of the re-incarcerated and incarcerated participants at the end of the study. RESULTS: At the beginning of the study, 8/15 re-incarcerated participants had plasma HIV RNA levels <400 copies/mL, compared with 15/30 incarcerated participants. At the end of the study, only three of those eight re-incarcerated participants had plasma HIV RNA levels <400 copies/mL, compared with 14/15 incarcerated participants (p=0.0086). The median change in plasma HIV RNA levels of the re-incarcerated participants was 1.29 log10 copies/mL (interquartile range 0.04 to 1.70), compared with -0.03 log10 copies/mL (interquartile range -0.65 to 0.09) in the incarcerated participants (p=0.0183). CONCLUSIONS: Release from prison was associated with a deleterious effect on virological and immunological outcomes. These data suggest that comprehensive discharge planning efforts are required to make certain that HIV-infected inmates receive access to quality care following incarceration.     

黑龙江省未治疗艾滋病患者耐药及病毒载量结果分析

目的了解黑龙江省未治疗艾滋病病毒感染者(HIV)/艾滋病患者(AIDS)耐药情况,进行病毒载量结果相关性分析,为黑龙江省艾滋病精准防控提供依据。方法对黑龙江省132例未治疗HIV/AIDS进行基因型耐药及病毒载量检测,分析耐药突变位点及耐药发生情况以及病毒载量结果相关性。结果 132例未治疗的HIV/AIDS中,11例存在原发性耐药情况,占总检测数的8. 3%(11/132)。其中,非核苷类逆转录酶抑制剂(NNRTI)耐药率为36. 4%(4/11),核苷类逆转录酶抑制剂(NRTI)耐药率为18. 2%(2/11),蛋白酶类(PI)耐药率为45. 4%(5/11)。原发性耐药患者的病毒载量平均值为3. 04×10~5拷贝/m L(最高值为8. 65×10~5拷贝/m L,最低值为1. 41×10~2拷贝/m L),未发生原发性耐药患者的病毒载量平均值为4. 59×10~5拷贝/m L(最高值为1. 00×10~7拷贝/m L,最低值为1. 31×10~2拷贝/m L)。结论证据显示耐药毒株已经开始在黑龙江省进行传播。在开展抗病毒治疗前有必要进行治疗前耐药检测,同时应将艾滋病也有耐药毒株传播情况增加到艾滋病防治宣传内容中,进一步加强黑龙江省艾滋病防控工作力度。     

Treatment interruption in HIV infected patients: clinical and biological evolution

OBJECTIVE: The authors had for aim to evaluate the clinical and biological evolution in HIV-infected patients with viraemia lower than 30,000 copies/mL having decided to interrupt their treatment. PATIENTS AND METHODS: Patients with highly active antiretroviral therapy (HAART) for more than 3 months followed by treatment interruption longer than 1 month were included in a retrospective analysis. RESULTS: Forty-six patients having stopped treatment between November 1999 and July 2003 were included. The median duration of treatment interruption was 9.5 months. During the study, no clinical event occurred for 21 patients, and at least 1 clinical event occurred for the 25 others. The median CD4(+) cell counts (CD4) before and at the end of treatment interruption were 597/mm(3) and 437/mm(3), respectively (P<0.001). The median values of viral load before and at the end of treatment interruption were <50 and 23749 copies/mL, respectively (P<0.001). Among the 26 patients having started a new HAART, pre-treatment interruption and post-new HAART median CD4 (with a median delay after HAART of 9.7 months) were 548 and 432.5/mm(3) (P=0.02). Pre-treatment interruption and post-new HAART median viral load were 131.5 and 94.5 copies/mL (NS). CONCLUSIONS: Treatment interruption must be used with caution in spite of the absence of virological impact, because CD4 cell count after new HAART is lower than CD4 preceding treatment interruption. Treatment interruption is contraindicated for patients with AIDS. Physicians must carefully follow other patients who decide on a treatment interruption.     

粤西某市406例病毒抑制失败艾滋病患者基因型耐药分析

目的了解病毒抑制失败的艾滋病患者基因型耐药流行特点。方法收集2014-2018年粤西某市病毒抑制失败患者血浆共406例,扩增HIV-1蛋白酶全长及逆转录酶部分基因,测序拼接后基因亚型,提交斯坦福大学HIV-1耐药数据库获得耐药突变位点,分析比较耐药突变位点及耐药情况。结果 406例病毒抑制失败患者中,共检出696个耐药相关突变位点。PI区耐药位点L10V为3.7%和L10I为3.4%;NRTI主要突变位点为M184V(22.7%);NNRTI主要突变位点为K103N(20.2%)、Y181C(16.2%)和G190A(10.6%);耐药率为48.0%,在发生不同程度耐药的195例患者中,3.1%(6例)对PI、NRTI和NNRTI 3类药物都耐药,1.5%(3例)对PI和NNRTI两类药物都耐药,54.4%(106例)对NRTI和NNRTI两类药物都耐药,41.0%(80例)对单一药物耐药。结论粤西某市病毒抑制失败者M184V和K103N突变位点检出率高,耐药发生率偏高,其中以NNRTIs的耐药为主。应加强监测防止耐药株传播。     

A decision tree to help determine the best timing and antiretroviral strategy in HIV-infected patients

Optimal antiretroviral strategies for HIV-infected patients still need to be established. To this end a decision tree including different antiretroviral strategies that could be adopted for HIV-infected patients was built. A 10-year follow-up was simulated by using transitional probabilities estimated from a large cohort using a time-homogeneous Markov model. The desired outcome was for patients to maintain a CD4 cell count of >500 cells/mm3 without experiencing AIDS or death. For patients with a baseline HIV viral load ≥5 log10 copies/ml, boosted protease inhibitor-based immediate highly active antiretroviral therapy (HAART) allowed them to spend 12% more time with CD4 ≥500/mm3 than did delayed HAART (6·40 vs. 5·69 and 5·57 vs. 4·90 years for baseline CD4 ≥500 and 350-499/mm3, respectively). In patients with a baseline HIV viral load ≤3·5 log10 copies/ml, delayed HAART performed better than immediate HAART (6·43 vs. 6·26 and 5·95 vs. 5·18 for baseline CD4 ≥500 and 350-499/mm3, respectively). Immediate HAART is beneficial in patients with a baseline HIV viral load 5 log10 copies/ml, whereas deferred HAART appears to be the best option for patients with CD4 ≥350/mm3 and baseline HIV viral load <3·5 log10 copies/ml.     

Hormonal levels among HIV-1-seropositive women compared with high-risk HIV-seronegative women during the menstrual cycle. Women's Health Study (WHS) 001 and WHS 001a Study Team

There is a paucity of normative data on hormonal levels among HIV-infected women. Hormonal levels may influence fertility and HIV-related immunological and virological factors. The objective of this study was to determine progesterone and estradiol levels during the menstrual cycle in HIV-seropositive women compared with high-risk seronegative women. The study enrolled 55 HIV-infected and 10 high-risk uninfected women with self-reported regular menstrual cycles (25-30-day cycles). Progesterone and estradiol levels were determined on a weekly basis for 8 weeks. The analysis included evaluations from the first complete menstrual cycle for the 54 HIV-infected and 9 uninfected women who had at least one complete cycle. The median age was 35 years for HIV-infected women and 36 years for uninfected women. The median CD4+ count for HIV-seropositive women was 210 cells/mm3. The median menstrual cycle length was 28 days (range 22-49 days) for HIV-infected women and 25 days (range 24-44 days) for uninfected women. The maximum progesterone level during the luteal phase was normal (>3.0 ng/ml) for 52 (96%) of 54 HIV-seropositive women and 7 (78%) of 9 HIV-seronegative women (p = 0.09, Fisher's exact test). The median maximum progesterone level was 12.2 ng/ml in HIV-seropositive women and 7.2 ng/ml in HIV-seronegative women (p = 0.07, Wilcoxon test). The median maximum estradiol value during the follicular phase was 148 pg/ml for HIV-seropositive women and 111 pg/ml for HIV-seronegative women (p = 0.04, Wilcoxon test). Among HIV-infected women, there were no significant differences in progesterone and estradiol levels by antiretroviral therapy, baseline plasma viral load, or median CD4+ cell count. We conclude that HIV-infected women with self-reported normal menstrual cycles have normal levels of progesterone and estradiol during the menstrual cycle.     

乙肝后肝硬化失代偿期HBeAg阴性与阳性患者 病毒学特点及肝功能指标的比较

摘要:目的　分析乙型肝炎后肝硬化失代偿期患者中HBeAg阴性者与HBeAg阳性者的血清病毒学指标、肝功能检测结果的差异。方法　将90例乙肝后肝硬化失代偿患者分为HBeAg阴性组和HBeAg阳性组,观察年龄、性别、乙肝病毒基因型、血清病毒DNA载量、肝功能指标等的差异。结果　HBeAg阴性组和HBeAg阳性组比较,年龄、性别、肝功能指标、Child-Pugh分级均无差异;HBeAg阴性组血清乙肝病毒DNA载量（5.14±0.63）log 10copies/ml 低于HBeAg阳性组（6.66±0.75）log10copies/ml,（t＝10.386,P＜0.001）;两组乙肝病毒基因型的比较差异有统计学意义,HBeAg阴性组基因型B占26.2%（11/42）,基因型C占54.8%（23/42）,B/C混合型占19.0%（8/42）,HBeAg阳性组基因型B占12.5%（6/48）,基因型C占87.5%（42/48）,（χ2＝14.580,P＜0.001）。结论　HBeAg阴性与阳性乙型肝炎后肝硬化失代偿期患者在乙肝病毒基因型构成特点、病毒DNA载量上有差异,两组肝功能受损程度没有显著差异。     

云南省140例HIV／AIDS患者抗病毒治疗效果和耐药检测分析

[目的]观察接受中国现行一线艾滋病抗病毒药物治疗的HIV／AIDS患者,在治疗1年内免疫学应答、病毒载量抑制效果,以及耐药性产生的情况。[方法]入组既往未接受过抗病毒治疗的HIV／AIDS患者140例,观察治疗0月、6月、12月CD41淋巴细胞计数（CD4）、病毒载量（vL）,对治疗后VL〉1000拷贝／ml的患者进行耐药检测。[结果]入纽患者治疗前的CD4平均值为164个／μl,在治疗6个月和12个月分别上升至327个／μl和377个／μl。基线VL〈1000拷贝／ml的患者比例为2．1％,治疗6个月和12个月后,分别上升至94．7％和94．4％。基线样本的耐药性检测未发现主要耐药突变位点。治疗6个月时有7例患者VL〉1000拷贝／ml,耐药检测未发现耐药突变位点。治疗12个月时有7例VL〉1000拷贝／ml,其中3例同时出现了对核苷类药物和非核苷类药物不同程度的耐药。[结论]云南省使用现行一线抗病毒治疗方案取得了良好的治疗效果。抗病毒治疗1年时,2．4％的患者出现了抗HIV药物耐药。出现耐药时需要及时更换抗病毒治疗方案,避免耐药位点的累积导致交叉耐药,保障抗病毒治疗疗效。     

2004 - 2016年贵州省艾滋病抗病毒治疗病毒抑制失败及耐药影响因素分析

目的 了解贵州省2004 - 2016年艾滋病抗病毒治疗病毒抑制失败及耐药病例情况。方法 选择艾滋病综合防治信息系统中2004 - 2016年6月在贵州省接受抗病毒治疗且做过病毒载量检测的4 349例艾滋病病毒感染者及病人进行横断面分析。结果 4 349例研究对象中,男性占68.5%(2 977/4 349),平均年龄为（45.0±13.7）岁,未婚者居多,占76.2%（3 316/4 349）,传播途径以异性传播为主,占67.2%（2 924/4 349）。4 349例病毒抑制失败占20.7%（899/4 349）,多因素logistic回归分析结果显示,年龄小于45岁(OR = 0.809,95%CI:0.694～0.9420),婚姻状况为未婚(OR = 0.500,95%CI:0.382～0.653)、已婚或同居(OR = 0.722,95%CI:0.539～0.967),感染途径为同性性行为(OR = 0.282,95%CI:0.205～0.388)和异性性行为(OR = 0.735,95%CI:0.608～0.889),治疗时长为6～47个月组(OR = 0.782,95%CI:0.634～0.964)与其他组比较,病毒抑制失败率差异有统计学意义（P＜0.05）;247例送检病例中耐药占59.5%（147/247）,多因素logistic回归分析结果显示,治疗时长为6～34个月的病人对耐药产生的差异有统计学意义（OR = 0.459,95%CI:0.211～0.998,P＜0.05）。结论 抗病毒治疗人群中病毒抑制失败率较高,耐药突变加重。