河南省长期接受抗病毒治疗的艾滋病患者耐药横断面分析

目的 阐明河南省长期接受艾滋病抗病毒治疗患者的耐药情况,为这类患者继续有效的治疗提供参考依据.方法 抽取河南省两个艾滋病重点县中2004年左右开始接受一线抗病毒治疗的艾滋病患者,进行CD4+T淋巴细胞、病毒载量和基因型耐药检测.结果 两个县共抽取164例艾滋病患者,这些患者的CD4+T淋巴细胞计数的中位数(四分位数)为398.00(242.00 ～489.50)个/μl,有32.32％的患者体内检测不到病毒.有95例患者的病毒载量大于1000拷贝/ml,其中的77例患者完成了耐药检测.在这77例患者中,有耐药突变(任意一种)发生的患者占到68.83％,其中NNRTIs类突变较高为64.94％,NRTIs类突变为55.84％,无PIs类突变发生.NNRTIs类耐药突变中发生最多的是K103N/S(44.16％),其次为G190A/S(19.48％)和Y181C/V(14.29％).NRTIs类耐药突变中发生最多的是胸苷类似物突变(thymidine analogue mutations,TAMs),≥1TAM占46.75％,TAM-1/TAM-2占24.68％,M184V/I为24.68％.77例患者中,对NRTIs类药物ddI、3TC、AZT、D4T和TDF产生耐药的患者分别占50.65％、33.77％、48.05％、50.65％和46.75％.对NNRTIs类药物EFV、NVP和DLV产生耐药的患者分别占64.94％、64.94％和62.34％.结论 河南省长期接受抗病毒治疗的艾滋病患者的耐药情况严峻,需要对这部分患者重点关注并及时调整治疗方案.     

抗HIV-1活性化合物作用靶点的快速判断方法

目前,艾滋病的防治工作主要依靠抗HIV-1药物,临床使用的抗HIV药物主要是逆转录酶抑制剂、蛋白酶抑制剂、融合抑制剂和整合酶抑制剂。逆转录酶抑制剂包括核苷类逆转录酶抑制剂（NRTI）,如Zidovudine（AZT）、Lamivudine（3TC）、Emtricitabine（FrC）等,非核苷类逆转录酶抑制剂（NNRTI）,如Efavirenz（EFV）、Nevirapine（NVP）、Delavirdine（DLV）等。蛋白酶抑制剂主要有Ritanovir（RTV）、Saquinavir（SQV）、Indinavir（IDV）等。     

HAART 促进艾滋病患者CD4+T 淋巴细胞增长的因素分析

目的:了解HAART中影响CD4+T淋巴细胞增长因素,为进一步优化治疗,提高患者预后提供理论依据.方法:收集整理2015年6月1日至2020年05月31日我院316例HIV感染者和242例艾滋病患者的基本情况及治疗0.5 y随访的资料,根据治疗后CD4+T淋巴细胞是否增长建立Logistic回归模型,筛选影响CD4+T淋巴细胞增长因素.结果:无症状HIV感染者不同的漏服情况和艾滋病患者不同的BMI指数,治疗前后CD4+T淋巴细胞增长率差异有统计学意义(P<0.05).多因素logistic回归分析结果显示,漏服药物(P=0.017,OR=0.438)、年龄(P=0.036,OR=0.69)和BMI指数(P=0.002,OR=0.309)为影响CD4+T淋巴细胞增长因素的危险因素(P<0.05).结论:增加患者的自身健康管理和提高患者的服药依从性,有利于提高HAART中CD4+T淋巴细胞数.     

多拉韦林/拉米夫定/替诺福韦初始治疗成年HIV-1感染者：DRIVE-AHEAD试验48周治疗结果分析

目的比较多拉韦林/拉米夫定/替诺福韦(doravirine/lamivudine/tenofovir, DOR/ 3TC/TDF)和依非韦伦/恩曲他滨/替诺福韦(efavirenz/emtricitabine/tenofovir disoproxil fumarate, EFV/FTC/TDF)在初治成年HIV-1感染者中的疗效及安全性。方法 DRIVE-AHEAD是一项双盲, 非劣效性3期临床试验。纳入HIV-1 RNA≥1 000拷贝/mL且未接受过抗逆转录病毒治疗的成年感染者, 按照1:1比例随机接受DOR/3TC/TDF或EFV/FTC/TDF治疗, 疗程96周。主要疗效终点是第48周HIV-1 RNA<50拷贝/mL的患者比例(非劣效界值10%)。结果 728例接受治疗并纳入研究(每组364例)。第48周时, DOR/3TC/TDF组和EFV/FTC/TDF组分别有84.3%(307/364)和80.8%(294/364)的患者达到HIV-1 RNA<50拷贝/mL(差异:3.5%;95%CI:-2.0～9.0)。DOR/3TC/TDF组出现头晕(8.8% vs ...     

CD4 +/CD8 +比值在HIV感染者/AIDS患者抗逆转录病毒治疗效果评估中的应用研究

目的:研究艾滋病病毒（HIV）感染者CD4 +T淋巴细胞数/CD8 +T淋巴细胞数（CD4 +/CD8 +比值）恢复的影响因素,揭示CD4 +/CD8 +比值在抗逆转录病毒治疗（ART）中的免疫恢复评估作用。 方法:以辽宁省治疗库数据为材...     

HIV/AIDS患者免疫激活相关分子的表达及其对疾病进程的影响

目的探讨HIV/AIDS患者外周血免疫激活相关分子的表达特征,分析其与艾滋病疾病进程的相关性。方法采用流式细胞仪检测80例HIV/AIDS患者和20例健康人外周血T淋巴细胞亚群及CD8+T淋巴细胞表面CD38、HLA-DR、Ki67分子的表达水平,比较健康人群与HIV/AIDS患者以及HIV/AIDS患者不同CD4+T分组间CD38+/CD8+、HLA-DR+/CD8+、Ki67+/CD8+的差异,分析CD8+T淋巴细胞CD38、HLA-DR、Ki67分子表达与CD4+T淋巴细胞及病毒载量之间的相关性。结果与健康人群相比,HIV/AIDS患者CD38+/CD8+、HLA-DR+/CD8+、Ki67+/CD8+明显升高(P0.05);HIV/AIDS患者不同CD4+T分组间比较显示,随着CD4+T水平的降低,CD38+/CD8+、HLA-DR+/CD8+、Ki67+/CD8+逐渐升高,且艾滋病患者(CD4200 cells/ml)明显低于慢性进展者(CD4≥200 cells/ml);CD38+/CD8+、HLA-DR+/CD8+、Ki67+/CD8+与血浆病毒载量均呈明显正相关。结论HIV感染能明显提高外周血CD38、HLA-DR和Ki67等分子的表达水平,且随着艾滋病疾病的进展,CD38、HLA-DR和Ki67的表达逐步升高,免疫系统异常激活的不断加剧与艾滋病疾病进程密切相关。     

HIV/AIDS患者外周血CD4~+T细胞亚群及中性粒细胞CD64的变化及临床意义

目的探讨HIV/AIDS患者外周血中CD4+T细胞亚群及中性粒细胞CD64的变化及临床意义。方法筛选2014年5月至9月河南中医学院第一附属医院艾滋病临床研究中心收治的47例HIV/AIDS患者,根据CD4+T淋巴细胞数将其分为A组(CD4≤350 cell/μl)23人,B组(CD4350 cell/μl)24人,同期选取健康对照组20人。用流式细胞仪(FCM)检测3组人员外周血中CD4+T细胞亚群(Th1、Th2、Th17、Treg)及中性粒细胞表面CD64表达水平,用SPSS17.0软件分析数据。所有数据用中位数表示,2组间比较采用Mann-Whitney检验,相关性分析采用Spearman秩相关。结果 A组和健康对照组Th1细胞(CD4+IFN-γ+)百分比均高于B组(P=0.040,P=0.028);A组Th2细胞(CD4+IL4+)百分比高于B组(P=0.015);A和B组Treg细胞(CD4+CD25+FOXP3+)百分比均高于健康对照组(P均0.05),A组Treg细胞高于B组(P=0.001);Th17细胞以及中性粒细胞表面CD64的表达量3组比较差异无统计学意义;Treg细胞与CD4+T细胞呈负相关(r=-0.734,P=0.000),Treg细胞与Th1/Th2比值呈负相关(r=-0.300,P=0.015)。结论 HIV/AIDS患者CD4+T细胞亚群之间的平衡失调,调节性T细胞处于优势状态,CD4+T细胞亚群变化可作为HIV/AIDS患者疾病进展的动态监测指标。CD64是机体急性炎症感染的一个重要参考指标,但在HIV/AIDS患者中变化不明显。     

HIV感染后CD8~+T细胞表面NK相关受体表达的变化

目的深入了解人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染后CD8+T细胞表面NK相关受体表达的变化。方法选取25例未经高效抗逆转录病毒治疗的HIV感染者、11例AIDS患者、15例进行高效抗逆转录病毒治疗(highly active antiretroviral therapy,HAART)者和13例HIV抗体阴性健康对照,用流式细胞仪检测研究对象外周血CD8+T细胞表面NKG2D、NKG2A和KIR3DL1的表达。结果 HIV感染后CD8+T细胞表面NKG2D表达的百分比显著低于健康对照,NKG2D+NKG2A-表达的百分比随疾病进展逐渐下降,且NKG2D+NKG2A-表达的百分比与CD4+T细胞的绝对数量呈正相关。AIDS患者CD8+T细胞表达NKG2A显著高于其它各组,随着疾病的进展CD8+T细胞表达NKG2A+NKG2D-百分比逐渐上升,AIDS患者显著高于其它各组,经抗逆转录病毒治疗后下降至健康对照的水平,且NKG2A+NKG2D-表达的百分比与CD4+T细胞的绝对数量呈负相关。HIV感染后CD8+T细胞KIR3DL1+表达的百分比较健康对照并无显著差异。结论 HIV感染机体后,CD8+T细胞NK相关受体表达变化与疾病进展相关,抗病毒治疗后可恢复其变化。     

艾滋病患者HAART治疗前后CD4+T细胞表面某些归巢分子和辅助受体表达变化分析

目的 探讨艾滋病(AIDS)患者高效抗逆转录病毒治疗(HAART)治疗前后CD4+T细胞表面CD49d、CCR9、CD62L和CCR5表达的变化情况.方法 采用流式细胞术检测42例艾滋病患者和18例HIV阴性健康对照的外周血CD4+T细胞表面CIM9d、CD62L、CCR9和CCR5的表达,并对CD4+CCR9+和CD4+CCR5+T细胞进一步进行CD45RO表型分析,采用BD FACSDiva软件分析计算各组细胞表达的百分率.结果 艾滋病患者尚未开始HAART治疗组(pre-HAART组)外周血CD4+细胞计数明显低于HAART治疗组(HAART组)(P<0.01);pre-HAART组外周血单个核细胞(PBMC)中CD3+CD4+,CD4+CCR9+,CD4+ CCR5+T细胞的百分率均明显低于HAART组(P<0.01),pre-HAART组CD4+CD49d+,CD4+CD62L+,CIM+CCR9+CD45RO+,CD4+CCR9+CD45RO-,CD4+CCR5+CD45RO+,CD4+CCR5+CD45RO-T细胞的百分率显著低于HAART组(P<0.001);HAART组PBMC中CD3+CD4+,CD4+CD62L+,CD4+CCB5+T细胞的百分率均显著低于HIV阴性对照(HIV-neg组)(P<0.001);pre-HAART组以上各组细胞群的百分率均显著低于HIV-neg组(P<0.05).结论 AIDS患者外周血CD4+T细胞表面肠道归巢分子CD49d、CCR9,淋巴结归巢分子CD62L,辅助受体CCR5异常改变,但HAART可以逆转以上部分病理变化.肠道归巢分子CD49d、CCR9和淋巴结归巢分子CD62L可作为艾滋病疾病进展和评价机体HAART后免疫重建情况的指标.     

HIV感染后CD4~+ T细胞表面NK相关受体表达的变化

目的研究人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染后CD4+T细胞表面NK相关受体表达的变化。方法选取25例未经高效抗逆转录病毒治疗的HIV感染者、11例AIDS患者、15例进行高效抗逆转录病毒治疗(highly activeantiretroviral therapy,HAART)者和13例HIV抗体阴性健康对照,用流式细胞仪检测研究对象外周血CD4+T细胞表面NKG2D、NKG2A和KIR3DL1的表达。结果 AIDS患者CD4+T细胞表面NKG2D表达的百分比显著高于其他各组,且NKG2D表达的百分比与CD4+T细胞的绝对数量呈负相关(R=-0.352,P<0.05),与HIV病毒载量呈正相关(R=0.426,P<0.05)。AIDS患者CD4+T表面NKG2A表达的百分比显著高于其他各组,NKG2A+NKG2D-表达的百分比显著高于其他各组,且NKG2A表达的百分比与CD4+T细胞的绝对数量呈负相关(R=-0.432,P<0.01)。结论 HIV感染机体后,CD4+T细胞NK相关受体表达变化与疾病进展相关。     

Prevalence and associated factors of treatment failure among HIV/AIDS patients on HAART attending University of Gondar Referral Hospital Northwest Ethiopia

Background

The initiation of highly active antiretroviral therapy (HAART) plays a significant role in the clinical management of HIV infected people by preventing morbidity and mortality. This benefit becomes, the most terrible when treatment failure develops. Thus, this research aims to assess the prevalence and associated factors of treatment failure among HIV/AIDS patients on HAART attending University of Gondar Referral Hospital Northwest Ethiopia.

Results

Patients on ART with a minimum of 6?months and up to 12?years of treatment were being enrolled. The prevalence of treatment failure, immunological failure and virological failure among people living with HIV/AIDS attending University of Gondar referral hospital were 20.3, 13.2, and 14.7%, respectively. Patients who had no formal education (Adjusted odds ratio (AOR): 3.8; 95% CI, 1.05–13.77), primary level education (AOR: 4.2; 95% CI, 1.16–15.01) and duration on ART <?6?years (AOR: 2.1; 95%CI, 1.12–3.81) were a significant risk factor. However, initial adult regimen D4T?+? 3TC+ EFV (AOR: 0.025; 95% CI, 0.002–0.36), AZT +3TC?+?NVP (AOR: 0.07; 95% CI, 0.01–0.71), AZT?+? 3TC?+?EFV (AOR: 0.046; 95% CI, 0.004–0.57) andTDF+3TC?+?EFV (AOR: 0.04; 95% CI, 0.004–0.46) were significantly protective for treatment failure.

Conclusions

Timely and early identification of associated factors and monitoring antiretroviral therapy treatment failure should be done to enhance the benefit and to prevent further complication of the patients. It is preferable to initiate ART using any one of the following ART regimens: AZT +3TC?+?NVP, AZT?+?3TC?+?EFV and TDF?+?3TC?+?EFV to prevent treatment failure. Since the prevalence of this treatment failure and its associated factor may be different from other ART centers and community in Ethiopia, further national representative institutional based cross-sectional researches are needed across all ART centers of Ethiopia in order to determine the prevalence of treatment failure and its associated factors.

     

Tenofovir disoproxil fumarate, emtricitabine, and efavirenz versus fixed-dose zidovudine/lamivudine and efavirenz in antiretroviral-naive patients: virologic, immunologic, and morphologic changes--a 96-week analysis

BACKGROUND: In antiretroviral-naive patients, tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV) demonstrated superior outcomes compared with fixed-dose zidovudine (ZDV)/lamivudine (3TC) and EFV through 48 weeks. Results through a 96-week extension phase are presented. METHODS: In this randomized, open-label, noninferiority trial, 517 antiretroviral-naive HIV-infected patients received TDF, FTC, and EFV (TDF + FTC + EFV) or ZDV/3TC and EFV (ZDV/3TC + EFV). The primary endpoint was the proportion of patients with an HIV RNA level <400 copies/mL in patients without baseline nonnucleoside resistance. RESULTS: Through week 96, significantly more patients receiving TDF + FTC + EFV achieved and maintained an HIV RNA level <400 copies/mL (75% receiving TDF + FTC + EFV vs. 62% receiving ZDV/3TC + EFV; P = 0.004). There was a trend toward greater virologic suppression to <50 copies/mL in the TDF + FTC + EFV group (67% vs. 61%; P = 0.16). The TDF + FTC + EFV group demonstrated a significantly greater increase in CD4 count (270 vs. 237 cells/mm; P = 0.036). No patient developed the K65R mutation. Limb fat at week 96 was significantly greater in the TDF + FTC + EFV group versus the ZDV/3TC + EFV group (7.7 vs. 5.5 kg; P < 0.001). CONCLUSION: Over 96 weeks, the combination of TDF, FTC, and EFV was superior to fixed-dose ZDV/3TC + EFV for achieving and maintaining an HIV RNA level <400 copies/mL and an increase in CD4 cells.     

Tenofovir disoproxil fumarate, emtricitabine, and efavirenz compared with zidovudine/lamivudine and efavirenz in treatment-naive patients: 144-week analysis

BACKGROUND: As antiretroviral regimens for the treatment of HIV infection improve, trials providing data on long-term follow-up are increasingly important. METHODS: A regimen of tenofovir disoproxil fumarate (TDF), emtricitabine (FTC), and efavirenz (EFV) demonstrated superior virologic, immunologic and morphologic effects compared with a regimen of fixed-dose zidovudine/lamivudine (ZDV/3TC) and EFV through 96 weeks in a randomized open-label trial. After 96 weeks, patients on TDF + FTC transitioned to fixed-dose combination TDF/FTC. RESULTS: Through 144 weeks, significantly more patients in the TDF/FTC arm reached and maintained an HIV RNA level <400 copies/mL (71% receiving TDF/FTC and EFV vs. 58% receiving ZDV/3TC and EFV; P = 0.004), with a trend toward greater CD4 cell increase in the TDF/FTC arm (312 vs. 271 cells/mm; P = 0.09). Over 144 weeks of follow-up, more patients in the ZDV/3TC arm discontinued therapy because of adverse events (11% vs. 5%; P = 0.01) and no patients discontinued because of renal events. Patients in the ZDV/3TC arm had significantly less limb fat than patients in the TDF/FTC arm (5.4 vs. 7.9 kg; P < 0.001) at 144 weeks. CONCLUSIONS: Cumulative results from 3 years of follow-up suggest that a regimen of TDF/FTC and EFV demonstrates superior durability of viral load suppression and an improved safety and morphologic profile compared with ZDV/3TC and EFV.     

Reasons for modification of generic highly active antiretroviral therapeutic regimens among patients in southern India

OBJECTIVE: To describe reasons for modification and discontinuation of antiretroviral regimens in association with adverse events (AEs), treatment failure, and cost among patients in southern India. METHODS: Secular trends of patients initiating highly active antiretroviral therapy (HAART) between January 1996 and October 2004 at a tertiary HIV referral center in India were analyzed using a previously validated natural history database. RESULTS: All previously antiretroviral therapy-naive patients who initiated HAART (N = 1443) and had at least 1 follow-up visit were evaluated. The median CD4 count at the time of initiating HAART was 108 cells/microL. The most common first-line regimens were stavudine (d4T) plus lamivudine (3TC) plus nevirapine (NVP) (63%), zidovudine (AZT) plus 3TC plus NVP (19%), d4T plus 3TC plus efavirenz (EFV) (9%), and AZT plus 3TC plus EFV (4%). Twenty percent of patients modified their first-line regimen. The most common reason for modifying therapy was the development of an AE (64%), followed by cost (19%) and treatment failure (14%), with median times to modify therapy being 40, 151, and 406 days, respectively. Common AEs were itching and/or skin rash (66%), hepatotoxicity (27%), and anemia (23%). Nine percent of patients discontinued therapy entirely after a median duration of 124 days, primarily because of cost (64%). CONCLUSION: The most common reason for modifying therapy was the occurrence of AEs, whereas cost was the most common reason for discontinuing therapy. Despite increasing access to lower cost generic HAART in India, even less expensive and more tolerable first-line regimens and cost-effective treatment monitoring tools need to be introduced to achieve better treatment outcomes and access in resource-constrained settings.     

Evaluation of antiretroviral therapy in HIV-infected adults in the Department of Haematology, University Hospital of Brazzavllle, Congo

A retrospective study was conducted during 32 months; from 1 May 2003 to 30 December 2005 in haematology department. The objective of the study was to assess the effectiveness of the anti retroviral therapy 157 patients receiving antiretroviral treatment for at least a twelve month-period and presenting AIDS symptoms based on revised CDC criteria were included. The average number of initial T4 lymphocytes is 133/mm3 (extremes 1 and 385) and the initial plasmatic average viral load, quantified in 96 patients is 214,000 copies (extreme 30,000 et 999,000) The initial antiretroviral combinations were as follows: ZDV or D4T + LMV + NVP (59.2%); ZDV or D4T + LMV + EFV (28.7%), ZDV or D4T + LMV + IDNV (8.9%); ZDV or D4T + DDI + NVP (3.2%). The results of the study are: observance rate during the first 12 months (84%), antiretroviral therapy taken irregularly (10.8%), early submission of therapy (5.2%), weight gain after 24 months: +18 kgs, clinical response globally positive. The immune response is characterised by an average increase of 353/mm3 of CD4 after 24 months. Among 96 patients tested, the plasmatic viral load was undetectable in 71% of cases after a 12 month-follow up. Mild adverse drug effects have been noticed, represented by cutaneous and nervous toxicity anaemia and digestive disorders due to indinavir These therapeutic results confirm the importance of the antiretroviral therapy in the improvement of the quality of life of HIV/AIDS patients but a concern remains on the possible drug resistance still not documented.     

The Safety and Efficacy of Switching Stavudine to Tenofovir DF in Combination with Lamivudine and Efavirenz in HIV-1—Infected Patients: Three-Year Follow–up After Switching Therapy

Abstract

Background: Study 903 is a phase 3 trial with a completed 144-week, double-blind phase comparing tenofovir DF (TDF) with stavudine (d4T), in combination with lamivudine (3TC) and efavirenz (EFV), and an ongoing 336-week open-label extension phase. Method: Patients in 3 countries completing the d4T treatment phase were allowed to switch d4T to TDF and receive once-daily TDF+3TC+EFV in the extension phase. Results: At the time of switch, 100% and 99% of patients (n = 85; 60% male, 64% White; mean age 37 years; mean CD4 = 650 cells/mm3) had HIV RNA <400 and <50 copies/mL. At 144 weeks after the switch, 89% (missing = failure) had HIV RNA <400 copies/mL and 87% had HIV RNA <50 copies/mL. Mean CD4 cell count increased 155 cells/mm3. No patient had virologic failure. Significant decreases from switch to week 144 in mean fasting total cholesterol (?22 mg/dL, p < .0001) and triglycerides (?78 mg/dL, p < .0001) were observed. Mean limb fat increased significantly from 4.5 kg to 5.8 kg, 144 weeks after switch (p < .0001). Conclusion: In virologically suppressed patients, switching d4T to TDF as part of a once-daily regimen with 3TC and EFV resulted in maintenance of virologic suppression and continued CD4 cell increases through 144 weeks, with significant improvements in metabolic parameters.     

Plasma HIV-1 RNA decline within the first two weeks of treatment is comparable for nevirapine, efavirenz, or both drugs combined and is not predictive of long-term virologic efficacy: A 2NN substudy

BACKGROUND: The initial rate of plasma HIV-1 RNA (pVL) decline has been proposed as a marker of early efficacy of antiretroviral therapy (ART) and a possible predictor of late efficacy. We compared the rate of pVL decline in patients starting ART with nevirapine (NVP), efavirenz (EFV), or both drugs combined in addition to lamivudine (3TC) and stavudine (d4T). METHODS: Analysis of the viral decay constant (VDc) during the first 2 weeks of treatment in patients enrolled in the 2NN study who remained on allocated treatment. RESULTS: The median VDc (log10 copies per day, [interquartile range]) was similar for NVP (0.30 [0.25-0.36], EFV (0.31 [0.27-0.37]), and NVP + EFV (0.30 [0.27-0.36]). Patients with a baseline pVL >100,000 copies/mL were 8.7 (95% confidence interval [CI]: 6.2-12.3) times more likely to have a VDc >75th percentile. A high VDc was not associated with plasma drug concentration or with a decreased risk of virologic failure at week 48 after the start of therapy (hazard ratio = 0.8, 95% CI: 0.6-1.2). CONCLUSION: NVP, EFV, or NVP + EFV in combination with 3TC and d4T show similar rates of pVL decline during the first 2 weeks of treatment. The VDc with these regimens is not predictive of late virologic efficacy.