目的:对河南省艾滋病患者抗病毒治疗（ART）失败后的基因型耐药检测，分析ART失败的耐药特征。方法:研究对象为2018年1月至2021年5月河南省18个城市接受ART时间≥6个月且病毒载量≥1 000拷贝数/ml艾滋病患者，收集艾滋病患者血液样本、社会人口学特征和ART信息。采用In-house方法进行HIV-1基因型耐药检测，将基因序列提交到美国斯坦福HIV-1耐药数据库分析耐药突变位点和药物耐药情况。结果:在887例ART失败的艾滋病患者中，样本成功扩增率为91.54%（812/887），总耐药率为83.25%（676/812），其中核苷类反转录酶抑制剂（NRTIs）、非核苷类反转录酶抑制剂（NNRTIs）、蛋白酶抑制剂（PIs）和整合酶抑制剂（INSTIs）的耐药率分别为73.40%（596/812）、80.54%（654/812）、5.54%（45/812）和2.56%（17/663），4类药物的耐药率差异有统计学意义（ χ2=1 686.34， P<0.001），对2类药物同时耐药率为66.38%（539/812），对3类药物同时耐药率为5.79%（47/812）。共检出9个HIV-1基因亚型，以B亚型为主（59.61%，484/812），其次是CRF01_AE亚型（22.17%，180/812）和CRF07_BC亚型（9.48%，77/812），不同基因亚型的耐药率差异有统计学意义（ χ2=21.33， P=0.001）。NRTIs相关突变位点中，M184V/I突变率最高（63.42%，515/812），其次是K65R（27.46%，223/812）；NNRTIs相关突变位点中，突变率位居前3位的是K103N/S（34.98%，284/812）、G190A/S（26.11%，212/812）和V106M/I（24.63%，200/812）；PIs相关突变位点中，突变率位居前3位的是M46I（4.31%，35/812）、V82A/F（3.82%，31/812）和I54V/MV（3.69%，30/812）；INSTIs相关突变位点中，E157Q/EQ突变率最高（3.47%，23/663），其次是R263K和G140A（均为0.75%，5/663）。在NRTIs中，拉米夫定和恩曲他滨以高度耐药为主（65.52%，532/812）；在NNRTIs中，奈韦拉平（77.46%，629/812）和依非韦伦（71.18%，578/812）以高度耐药为主；在PIs中，洛匹那韦/利托那韦中/高度耐药占比仅为4.19%（34/812）；在INSTIs中，艾维雷韦和拉替拉韦中、高度耐药分别占1.66%（11/663）和1.21%（8/663），未发现比克替拉韦和多替拉韦的高度耐药。 结论:河南省艾滋病患者ART失败的耐药率高，表现以NRTIs和NNRTIs耐药率高、耐药突变多样且复杂为特点。建议选择高耐药屏障药物，同时加强ART后病毒载量和耐药监测。

目的:分析整合酶(IN)区主要耐药突变对HIV-1 CRF01_AE毒株耐药的影响，并比较与B亚型毒株的差异。方法:根据美国斯坦福大学HIV耐药数据库选择7个IN区突变或联合突变(T66K、F121Y、Q148K、N155H、G118R、R263K、Q148K/N155H)，通过无缝克隆同源重组及点突变的方法引入到HIV-1 B亚型感染性克隆pNL4-3和CRF01_AE感染性克隆pGX002的IN区，转染293T细胞包装病毒，在MT2细胞上扩大培养并测定感染性滴度。检测4种整合酶链转移抑制剂(INSTIs)，拉替拉韦(RAL)、埃替拉韦(EVG)、多替拉韦(DTG)、比昔格韦(BIC)对14株突变病毒的半抑制浓度(IC 50)及其与野生型病毒相比提高的倍数。 结果:成功构建携带7个IN区突变或联合突变的B亚型和CRF01_AE质粒，包装获得14株重组病毒，感染性滴度为10 4~10 6半数组织细胞感染剂量(TCID 50)/ml，在MT2细胞高效复制，上清液中HIV-1 P24抗原浓度可达830~2 700 ng/ml。5个突变或突变组合(T66K、F121Y、Q148K、N155H、Q148K/N155H)均可导致CRF01_AE和B亚型毒株对RAL和EVG高度耐药，与野生病毒相比IC 50分别提高200倍和2 000倍以上，相同突变导致RAL和EVG对CRF01_AE的IC 50提高的倍数均显著低于B亚型( P<0.01)。Q148K/N155H突变导致B亚型和CRF01_AE对DTG和BIC高度耐药，IC 50提高50倍以上，其他突变对DTG和BIC的药物敏感性几乎无影响。 结论:构建了基于CRF01_AE和B亚型的14株携带不同INSTI耐药突变的HIV-1毒株，5个突变可导致对RAL和EVG的高水平交叉耐药，同一突变导致B亚型毒株耐药程度显著高于CRF01_AE毒株。Q148K和N155H突变组合可导致DTG和BIC的高度耐药，表明DTG和BIC耐药的遗传屏障高，可有效抑制携带INSTI耐药突变的毒株，且无明显的亚型耐药差异。

Background::This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings.Methods::We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022.Results::Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs. 3.40 ± 1.59 mmol/L in triglyceride ( P = 0.014), 4.82 ± 0.74 mmol/L vs. 4.88 ± 0.72 mmol/L in total cholesterol ( P = 0.038), 3.09 ± 0.70 mmol/L vs. 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P <0.001), and 0.99 ± 0.11 mmol/L vs. 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P <0.001). Conclusion::The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.

Background::Dual regimen dolutegravir (DTG) plus lamivudine (3TC) has demonstrated non-inferior efficacy compared to DTG-based three-drug regimens (3DRs), yet directly comparative data regarding the efficacy and safety of DTG + 3TC and bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for therapy-na?ve people with human immunodeficiency virus (HIV)-1 (PWH) are still limited. We aimed to assess the antiviral potency and safety profiles of DTG + 3TC vs. B/F/TAF based on antiretroviral therapy (ART)-na?ve PWH in China. Methods::This retrospective multicenter study enrolled PWH initiating ART with DTG + 3TC or B/F/TAF from 2020 to 2022 in Guangdong and Guangxi. We analyzed response rates based on target not detected (TND) status using intention-to-treat (ITT) analysis. Subgroups were formed based on baseline viral load (VL) (<100,000 vs. ≥100,000 copies/mL) and CD4 + cell count (<200 vs. ≥200 cell/μL). Median time to TND VL was assessed by Kaplan–Meier method. We also measured changes from baseline in CD4 + cell counts, CD4/CD8 ratio, lipid parameters, weight, creatinine (Cr), estimated glomerular filtration rate (eGFR), and drug-related adverse effects (DRAEs). Results::We enrolled 280 participants, including 137 (48.9%) on DTG + 3TC and 143 (51.1%) on B/F/TAF. At week 48, 96.4% (132/137) on DTG+3TC and 100% (143/143) on B/F/TAF achieved TND ( P = 0.064). At week 12, TND responses were higher with B/F/TAF (78.3% [112/143]) than DTG+3TC (30.7% [42/137]) ( P <0.001). This trend held across subgroups. B/F/TAF achieved TND faster (12 weeks) than DTG+3TC (24 weeks) ( P <0.001). No differences were seen in CD4 + cell count and CD4/CD8 ratio, except in the high-VL subgroup, where B/F/TAF showed better recovery. DRAEs were significantly lower with B/F/TAF (4.9% [7/143]) than with DTG + 3TC (13.1% [18/137]) ( P = 0.016). Lipid parameters, body weight, and Cr increased in both groups over 48 weeks, with DTG+3TC showing a more favorable effect on triglycerides, high-density lipoprotein (HDL) cholesterol, and weight gain. Conclusions::In this real-life study, B/F/TAF led to a faster viral decline and fewer DRAEs compared to DTG+3TC. No significant difference was observed in the TND rate at week 48, regardless of baseline VL and CD4 + cell count. CD4 + recovery was superior for B/F/TAF in participants with high VL. The DTG + 3TC regimen had less impact on metabolic changes than B/F/TAF.

Background::Single-tablet regimen (STR) provides a convenient once-daily regimen for the prevention of human immunodeficiency virus (HIV) infection. Here, we investigated the safety and tolerability of coformulated bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as a three-drug, STR for post-exposure prophylaxis (PEP) in Chinese individuals.Methods::This was a prospective, open-label, single-arm trial conducted in a sexually transmitted diseases and acquired immunodeficiency syndrome clinic of a tertiary hospital in Beijing, China. Adults requiring PEP were prescribed BIC/FTC/TAF one pill once a day for 28 days. Clinical and laboratory data were collected and analyzed at baseline, weeks 2, 4, 8, 12, and 24.Results::Of 112 participants enrolled in the study, 109 (97.3%) were male and the mean age was 30 ± 8 years. PEP completion was 96.4% (95% confidence interval: 91.1-99.0%). Two participants stopped PEP after 2 days because the source partner was identified as HIV uninfected. One participant was excluded due to hepatitis B virus infection according to the exclusion criteria. One discontinued due to the participant’s decision. No participant acquired HIV through week 24. Adherence was 98.9% (standard deviation [SD]: 3.3%) by self-reporting and 98.5% (SD: 3.5%) by pill count. Only five participants experienced mild clinical adverse events attributed to the study drug (including headache, diarrhea, and nausea) and four participants had elevated serum creatinine (grade 1).Conclusions::A once daily, STR of BIC/FTC/TAF used as PEP was safe and well-tolerated with a high rate of completion and adherence in Chinese. BIC/FTC/TAF may be a good option for PEP.Trial Registration::ChiCTR.org.cn, ChiCTR2100048080

Background::Antiretroviral therapy (ART) was often associated with dyslipidemia among human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients. This study aimed to assess treatment-na?ve adult male patients with HIV/AIDS who initiated ART with either co-formulated bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) or lamivudine, efavirenz, and tenofovir disoproxil fumarate (3TC+EFV+TDF), monitoring at weeks 4, 12, 24, and 48.Methods::A case-control retrospective study was conducted. The newly diagnosed HIV-infected individuals attending the sexual transmission disease (STD)/AIDS clinic of Beijing Youan Hospital, Capital Medical University, from January to December 2021. The patients were divided into BIC/FTC/TAF group or 3TC+EFV+TDF group. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) at different time points over 48 weeks between two groups were compared. A multivariate Cox regression model was used to identify relevant influencing factors for the population at high risk of increased LDL-C.Results::A total of 870 participants, with 510 in BIC/FTC/TAF group and 360 in 3TC+EFV+TDF group. There were no statistically significant differences in median age, baseline CD4/CD8 ratio, median body mass index (BMI) between the two groups. In both two groups, levels of TG, TC, and LDL-C were higher at 4 weeks, 12 weeks, and 24 weeks of treatment (all P <0.05), and there were no statistically significant differences at 48 weeks compared to those at baseline (all P >0.05). In addition, the differences in average changes of the level of TG, TC, HDL-C, and LDL-C from weeks 4, 12, 24, and 48 to baseline between two groups were not statistically significant (all P >0.05). Multivariate Cox proportional risk model analysis showed that initiating ART with HIV RNA ≥10 5 copies/mL (compared with <10 5 copies/mL) was associated with an increased risk of elevated LDL-C (hazard ratio = 1.26, 95% confidence interval: 1.07-1.48, P = 0.005). Conclusions::Transient elevations in blood lipid levels (TC, TG, HDL-C, and LDL-C) were observed in treatment-na?ve adult male HIV/AIDS patients with BIC/FTC/TAF at 4 weeks, 12 weeks, and 24 weeks of treatment. However, these levels did not differ significantly from baseline after 48 weeks of treatment, regardless of whether patients were in the BIC/FTC/TAF or 3TC+EFV+TDF group.

目的:评价并比较含整合酶抑制剂的单片制剂方案比克恩丙诺片(B/F/TAF)与拉米夫定多替拉韦片(3TC/DTG)用于初治艾滋病期患者的临床疗效及安全性。方法:本研究为一项回顾性队列研究，通过收集2020年10月至2023年7月在上海市(复旦大学附属)公共卫生临床中心使用B/F/TAF或3TC/DTG作为初始抗反转录病毒治疗方案且持续用药时间≥24周的艾滋病期患者的临床资料，比较B/F/TAF组与3TC/DTG组基线人类免疫缺陷病毒(HIV)-1 RNA，基线和治疗12周的CD4 ＋T淋巴细胞计数，治疗24周的病毒学抑制率和病毒学失败率，以及治疗前后总胆固醇、血肌酐、尿酸等指标变化。统计学分析采用独立样本 t检验、校正 t检验、曼-惠特尼 U检验、威尔科克森符号秩检验、 χ2检验。 结果:189例初治艾滋病期患者中，B/F/TAF组141例，3TC/DTG组48例。B/F/TAF组患者基线HIV-1 RNA为1.77(0.78，4.52)×10 5拷贝/mL，3TC/DTG组为0.97(0.24，2.20)×10 5拷贝/mL，差异有统计学意义( U＝2 221.00， P＝0.006)。B/F/TAF组治疗24周病毒学抑制率为77.3%(109/141)，无病毒学失败的患者；3TC/DTG组治疗24周病毒学抑制率为85.4%(41/48)，1例(2.1%)病毒学失败。治疗12周时，B/F/TAF组CD4 ＋T淋巴细胞计数较基线升高30%以上的患者占92.2%(130/141)，3TC/DTG组为85.4%(41/48)；B/F/TAF组CD4 ＋T淋巴细胞计数较基线升高>100.00/μL的比例为67.4%(95/141)，3TC/DTG组为52.1%(25/48)；两组间差异均无统计学意义( χ2＝1.91、3.61， P＝0.167、0.733)。B/F/TAF组和3TC/DTG组患者治疗24周时总胆固醇( W＝2 036.00, t＝－5.42)、血肌酐( W＝1 098.00、234.00)、尿酸( W＝2 188.00、299.00)水平均较治疗前升高，轻中度肾功能不全患者比例( χ2＝22.29、8.22)均较治疗前增加，差异均有统计学意义(均 P<0.01)。 结论:B/F/TAF与3TC/DTG用于初治艾滋病期患者具有良好的病毒学、免疫学疗效和安全性。

整合酶抑制剂(integrase inhibitors, INSTIs)是治疗人类免疫缺陷病毒(human immunodeficiency virus，HIV)感染者的最新一类药物。自2007年以来，已经有5种INSTIs上市：拉替拉韦(Raltegravir，RAL)、艾维雷韦(Elvitegravir，EVG)、多替拉韦(Dolutegravir，DTG)、比克替拉韦(Bictegravir，BIC)和卡博特韦(Cabotegravir，CAB)，这些药物均获得美国食品药品监督管理局(Food and Drug Administration，FDA)批准用于HIV感染者的起始抗逆转录病毒治疗(antiretroviral therapy，ART)。与其他类型抗病毒药物相比，INSTIs具有更好的疗效性及耐受性，因此全球众多国家把包含INSTIs的治疗方案列为HIV抗病毒治疗的优选方案。近年来，随着INSTIs的广泛使用，一些研究数据表明，INSTIs可能存在一些不良反应，比如出现中枢神经系统症状、血脂代谢异常、体重增加、肝肾功能异常等。本综述总结了目前用于成人HIV感染者的INSTIs，强调了5种INSTIs的临床疗效及其不良反应。

目的 为艾滋病合并肿瘤患者的药物治疗及药学监护提供参考.方法 针对1例艾滋病合并肺腺癌患者靶向治疗过程中多次出现间质性肺病,且无法排除细菌、真菌感染的复杂病情,临床药师对该患者开展了用药监护、药物重整、不良反应监测等药学服务.结果 该患者使用阿美替尼与间质性肺病等不良反应的相关性为"很可能相关",临床药师建议暂停肿瘤靶向治疗药物,制定激素用药监护计划;针对有艾滋病机会性感染可能的病原菌,建议停用厄他培南、膦甲酸钠,监测伏立康唑血药浓度,随访伏立康唑安全性及抗真菌疗程;结合药物相互作用及患者自身状况,调整抗艾滋病药物为比克恩丙诺片;针对患者有肺孢子菌肺炎、血栓、胃黏膜损伤可能,建议予以复方磺胺甲噁唑、那屈肝素钙、艾司奥美拉唑等.医师均采纳临床药师建议.患者经治疗后转归良好,未见明显不良反应及药物相互作用,顺利出院.结论 艾滋病合并肿瘤患者病情复杂、治疗药物多,临床药师可通过开展药物重整、治疗药物监测等手段对这类患者开展药物治疗管理,为患者提供个体化药学服务,保障用药安全.