Objective:To investigate the influence of ABCB1 polymorphisms on the plasma level of efavirenz in Thai adult cases infected with HIV-1.Methods:A single nucleotide polymorphism of ABCB13435 C>T(rs1045642)in the gene...Objective:To investigate the influence of ABCB1 polymorphisms on the plasma level of efavirenz in Thai adult cases infected with HIV-1.Methods:A single nucleotide polymorphism of ABCB13435 C>T(rs1045642)in the gene encoding ABCB1 was genotyped using real-time PCR-based alleles in 149 HIV-infected Thai adults receiving efavirenz treatment.Plasma concentrations of efavirenz were measured by high-performance liquid chromatography 12 hr after administration.The relationship between plasma efavirenz concentrations and ABCB13435 C>T polymorphisms was analyzed.Results:Logistic regression analysis showed no significant predictors of high plasma efavirenz concentration in relation to age,gender,body weight,CD4 count and plasma HIV-1 RNA,blood biochemical parameters,antiretroviral duration or ABCB13435 C>T polymorphisms,except for height(OR=0.902,95%CI:0.835-0.973)(P<0.05).The minor allele frequency of ABCB13435 C>T was0.446.The frequency of the heterozygous mutant ABCB13435 C/T was 53.02%(n=79),ABCB13435 T/T homozygous mutant was 18.12%(n=21)and the wild type ABCB13435 C/C genotype was 28.86%(n=43).The overall median plasma concentration of efavirenz in 149 HIV-infected Thai cases was 2.41 mg/L[IQR:(1.46-4.12)mg/L].The plasma concentration of efavirenz was higher in cases with ABCB13435 T/T homozygous mutant[2.73 mg/L,IQR:(2.02-4.19)mg/L]and ABCB13435 C/T heterozygous mutant[2.29 mg/L,IQR:(1.41-4.28)mg/L]genotypes compared to the wild type ABCB13435 C/C homozygous[2.1 mg/L,IQR:(1.37-3.53)mg/L].However,there was no statistically significant difference in the efavirenz concentration between the different genotypes(P>0.05).Objective:To investigate the influence of ABCB1 polymorphisms on the plasma level of efavirenz in Thai adult cases infected with HIV-1.Methods:A single nucleotide polymorphism of ABCB13435 C>T(rs1045642)in the gene encoding ABCB1 was genotyped using real-time PCR-based alleles in 149 HIV-infected Thai adults receiving efavirenz treatment.Plasma concentrations of efavirenz were measured by high-performance liquid chromatography 12 hr after administration.The relationship between plasma efavirenz concentrations and ABCB13435 C>T polymorphisms was analyzed.Results:Logistic regression analysis showed no significant predictors of high plasma efavirenz concentration in relation to age,gender,body weight,CD4 count and plasma HIV-1 RNA,blood biochemical parameters,antiretroviral duration or ABCB13435 C>T polymorphisms,except for height(OR=0.902,95%CI:0.835-0.973)(P<0.05).The minor allele frequency of ABCB13435 C>T was 0.446.The frequency of the heterozygous mutant ABCB13435 C/T was 53.02%(n=79),ABCB13435 T/T homozygous mutant was 18.12%(n=27)and the wild type ABCB13435 C/C genotype was 28.86%(n=43).The overall median plasma concentration of efavirenz in 149 HIV-infected Thai cases was 2.41 mg/L[IQR:(1.46-4.12)mg/L].The plasma concentration of efavirenz was higher in cases with ABCB13435 T/T homozygous mutant[2.73 mg/L,IQR:(2.02-4.19)mg/L]and ABCB13435 C/T heterozygous mutant[2.29 mg/L,IQR:(1.41-4.28)mg/L]genotypes compared to the wild type ABCB13435 C/C homozygous[2.1 mg/L,IQR:(1.37-3.53)mg/L].However,there was no statistically significant difference in the efavirenz concentration between the different genotypes(P>0.05).Conclusions:There is no statistical significance for a tendency toward higher plasma efavirenz concentration in the ABCB13435 T/T and ABCB13435 C/T genotypes.No parameters of physiological characteristics in this study except for height were found to be predictors of high plasma efavirenz concentration in Thai HIV-1 infected cases.展开更多
Background: There are two approved non-nucleoside reverse transcriptase inhibitor antiretroviral drugs;namely Nevirapine (NVP) and Efavirenz (EFV). Nevirapine and EFV have comparable clinical efficacy when administere...Background: There are two approved non-nucleoside reverse transcriptase inhibitor antiretroviral drugs;namely Nevirapine (NVP) and Efavirenz (EFV). Nevirapine and EFV have comparable clinical efficacy when administered in combination regimens. But there is a lack of recent evidence showing the effect of NVP and EFV-based ARTs on immunological responses in HIV infected individuals in Ethiopia in general and Addis Ababa in particular. Methods: Retrospective cohort study design was used to compare immunological response rate of NVP and EFV based HAART regimen in Addis Ababa. Four hundred ninety two HIV infected patients who started HAART in ten selected health facilities were included in the study. Rate of immunologic response was examined at the 6th, 12th, 18th, and 24th months of follow-up period. The time required to get immunological response was analyzed by Kaplan-Meier survival curve. Adjusted hazard ratio was calculated with a 95% confidence interval by Cox proportional hazards model to determine the rate of immunological response. To ascertain the association, bivariate and multi variable Cox proportional hazard model was used. Statistical significance was considered with two sides P-value of 0.05. Results: The mean CD4 count ranged between 132.2 cell/μl at baseline and 302.3 cell/μl at the end of the follow-up period. This change was significant at 95% of CI but did not show significant differences among the comparison group. The median time to get immunological response was 18 (75% percental 12) months. At the end of the follow-up period, 73.2% (76.6% for NVP and 69.8% for EVF P-value 0.13) of the study population had immunological response. Conclusion: As a conclusion, there was a robust and sustained CD4 response and the effect of NVP and EFV based ART on change of mean CD4 count and immunological response was comparable and effective. Initiation of ART with high baseline CD4 count, in combination of IPT and with either NVP or EFV based NNTI was recommended.展开更多
Therapeutic plasma concentrations of EFV （efavirenz） are between 1,000 ng/mL and 4,000 ng/mL. Concentrations below 1000 ng/mL are associated with higher risk of treatment failure, and concentrations above 4,000 ng/m...Therapeutic plasma concentrations of EFV （efavirenz） are between 1,000 ng/mL and 4,000 ng/mL. Concentrations below 1000 ng/mL are associated with higher risk of treatment failure, and concentrations above 4,000 ng/mL are associated with toxicity. The aim of the study was to appreciate EFV plasmas concentrations profile and the association between plasma levels and various characteristics in Beninese patients treated by a 600 mg standard daily-dose. Blood samples were collected and EFV plasma levels were measured by liquid chromatography coupled with mass spectrometry detection in HIV-infected patients receiving EFV in combination with other antiretroviral drugs for at least 14 days. Adverse effects occurring during treatment were collected through a questionnaire. An over-exposure to EFV among Beninese HIV patients were observed, with 46.4% of patients presenting EFV concentration above 4,000 ng/mL, although adverse effects were tolerated indicating that antiretroviral treatment is safe. The measurement of plasma concentration at the steady-state could contribute to early detection of treatment failure and adapt treatment in subjects presenting serious adverse effects within context of therapeutic drug monitoring.展开更多
Aim: To describe the pharmacokinetic parameters of efavirenz and estimate its clearance (CL/F) accounting simultaneously for drug-drug interactions and CYP2B6 genetic polymorphism. Methods: Genotyping of 516G > T s...Aim: To describe the pharmacokinetic parameters of efavirenz and estimate its clearance (CL/F) accounting simultaneously for drug-drug interactions and CYP2B6 genetic polymorphism. Methods: Genotyping of 516G > T single nucleotide polymorphism of CYP2B6 was performed using a PCR-based technology and plasma efavirenz concentrations were measured by high performance liquid chromatography on blood samples from 76 HIV adults co-infected with tuberculosis who had received an efavirenz-based regimen. Data were analyzed using population modeling with NONMEM. Results: The absorption rate constant and the apparent volume of distribution in the final model were 1.9 h-1 and 580 L/70kg, respectively. The CL/F at baseline was 11.8 L/h/70kg, 8.8 L/h/70kg and 3.9 L/h/70kg for patients carrying the G/G, G/T and T/T genotypes of CYP2B6 516G > T, respectively, in patients who were administered tuberculosis (TB) treatment prior to HIV treatment (Group A);and 16.7 L/h/70kg, 10.6 L/h/70kg and 1.8 L/h/70kg for G/G, G/T and T/T genotype patients respectively, in patients with previous exposure to HIV treatment (Group B). The CL/F at baseline and steady state was always higher in Group B compared to Group A patients. Expectedly, carriers of CYP2B6 516G/G and T/T genotypes exhibited higher and lower CL/F, respectively. Conclusion: Our results indicated that the CL/F of efavirenz in the population studied was predictably different due to whether the patients were mono-treated for TB with HAART deferred or for HIV before initiation of TB therapy, and to CYP2B6 516G > T variant, implying that both CYP2B6 genetic polymorphisms and previous efavirenz-based HAART should be taken into account when adjusting efavirenz dose.展开更多
Integrase strand transfer inhibitors(INSTIs)have emerged as the first‐line choice for treating human immunodeficiency virus(HIV)infection due to their superior efficacy and safety.However,the impact of INSTIs on the ...Integrase strand transfer inhibitors(INSTIs)have emerged as the first‐line choice for treating human immunodeficiency virus(HIV)infection due to their superior efficacy and safety.However,the impact of INSTIs on the development of neuropsychiatric conditions in people living with HIV(PLWH)is not fully understood due to limited data.In this study,we conducted a cross‐sectional examination of PLWH receiving antiretroviral therapy,with a specific focus on HIV‐positive men who have sex with men(MSM)on INSTI‐based regimens(n=61)and efavirenz(EFV)‐based regimens(n=28).Participants underwent comprehensive neuropsychiatric evaluations and multimodal magnetic resonance imaging(MRI)scans,including T1‐weighted images and resting‐state functional MRI.Compared to the EFV group,the INSTI group exhibited primarily reduced gray matter volume(GMV)in the right superior parietal gyrus,higher regional homogeneity(ReHo)in the left postcentral gyrus,lower ReHo in the right orbital part of the inferior frontal gyrus,and increased voxel‐wise functional connectivity for the seed region in the left inferior temporal gyrus with clusters in the right cuneus.Furthermore,the analysis revealed a main effect of antiretroviral drugs on GMV changes,but no main effect of neuropsychiatric disorders or their interaction.The repeated analysis of participants who did not switch regimens confirmed the GMV changes in the INSTI group,validating the initial findings.Our study demonstrated gray matter atrophy and functional brain changes in PLWH on INSTI‐based regimens compared to those on EFV‐based regimens.These neuroimaging results provide valuable insights into the characteristics of brain network modifications in PLWH receiving INSTI‐based regimens。展开更多
Background:Central nervous system(CNS)symptoms after efavirenz(EFV)treatment in people living with human immunodeficiency virus(HIV)could persist and impact their quality of life.We assessed the impact of EFV-based re...Background:Central nervous system(CNS)symptoms after efavirenz(EFV)treatment in people living with human immunodeficiency virus(HIV)could persist and impact their quality of life.We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide(E/C/F/TAF),which is considered an alternative option for subjects who do not tolerate EFV.Most specifically,we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants’neuropsychiatric toxicity symptoms in a real-life setting.Methods:A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity≥grade 2.The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks.The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire,as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index.The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12,24,and 48.Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch.Results:One hundred ninety-six participants(96.9%men,median age:37.5 years,median:3.7 years on prior EFV-containing regimens)were included in the study.Significant improvements in anxiety and sleep disturbance symptoms were observed at 12,24,and 48 weeks after switching to E/C/F/TAF(P<0.05).No significant change in depression symptom scores was observed.At 48 weeks after switch,HIV viral load<50 copies/mL was maintained in all of the participants,median fasting lipid levels were moderately increased(total cholesterol[TC]:8.2 mg/dL,low-density lipoprotein cholesterol[LDL-C]:8.5 mg/dL,high-density lipoprotein cholesterol[HDL-C]:2.9 mg/dL,and triglyceride(TG):1.6 mg/dL,and the TC:HDL-C ratio remained stable.Conclusions:The single-pill combination regimens E/C/F/TAF is safe and well tolerated.This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.展开更多
目的了解男男同性性行为人群(men who have sex with men,MSM)中人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者(MSM-HIV)接受含依非韦伦的抗反转录病毒治疗(antiretroviral therapy,ART)持续>6个月的治疗效果及影响因...目的了解男男同性性行为人群(men who have sex with men,MSM)中人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者(MSM-HIV)接受含依非韦伦的抗反转录病毒治疗(antiretroviral therapy,ART)持续>6个月的治疗效果及影响因素。方法2021年11月17—24日,在全国31个地区(包括22个省、4个直辖市和5个自治区)通过调查问卷的方式收集患者信息。采用滚雪球抽样方法,线上通过网站社区工作人员宣传,并在微信朋友圈中招募参与者,线下工作人员访问同性恋群体聚集场所招募参与者,采用自编问卷进行调查。采用多因素logistic回归模型分析MSM-HIV ART效果的影响因素。结果本研究共纳入1311例患者,年龄(29.51±8.38)岁,ART失败297例(22.65%)。多因素logistic回归分析显示,年龄40~<50岁(OR=1.62,95%CI:1.09~2.40)、基线病毒载量>200拷贝/ml(OR=1.52,95%CI:1.12~2.07)、ART持续时间>24个月(OR=0.49,95%CI:0.32~0.75)是MSM-HIV感染者采用含依非韦伦的ART效果的影响因素。结论应更多关注高龄、基线病毒载量水平较高的MSM-HIV群体,针对其接受含依非韦伦的治疗方案的病毒学治疗失败状况,加强健康教育,提供经济援助与医疗保障,优化治疗方案,使用抗病毒治疗效果更佳且不良反应更少的药物。展开更多
基金supported by Mahidol University,Thailand Research Fund,Thailand Office of the Higher Education Commission under New Researchers Grant(MRG 5480136)the project CICECOAveiro Institute of Materials,national funds through the FCT/MCTES(FCT Ref.UID/CTM/50011/2019)Rachadapisek Sompote Fund for Postdoctoral Fellowship,Chulalongkorn University
文摘Objective:To investigate the influence of ABCB1 polymorphisms on the plasma level of efavirenz in Thai adult cases infected with HIV-1.Methods:A single nucleotide polymorphism of ABCB13435 C>T(rs1045642)in the gene encoding ABCB1 was genotyped using real-time PCR-based alleles in 149 HIV-infected Thai adults receiving efavirenz treatment.Plasma concentrations of efavirenz were measured by high-performance liquid chromatography 12 hr after administration.The relationship between plasma efavirenz concentrations and ABCB13435 C>T polymorphisms was analyzed.Results:Logistic regression analysis showed no significant predictors of high plasma efavirenz concentration in relation to age,gender,body weight,CD4 count and plasma HIV-1 RNA,blood biochemical parameters,antiretroviral duration or ABCB13435 C>T polymorphisms,except for height(OR=0.902,95%CI:0.835-0.973)(P<0.05).The minor allele frequency of ABCB13435 C>T was0.446.The frequency of the heterozygous mutant ABCB13435 C/T was 53.02%(n=79),ABCB13435 T/T homozygous mutant was 18.12%(n=21)and the wild type ABCB13435 C/C genotype was 28.86%(n=43).The overall median plasma concentration of efavirenz in 149 HIV-infected Thai cases was 2.41 mg/L[IQR:(1.46-4.12)mg/L].The plasma concentration of efavirenz was higher in cases with ABCB13435 T/T homozygous mutant[2.73 mg/L,IQR:(2.02-4.19)mg/L]and ABCB13435 C/T heterozygous mutant[2.29 mg/L,IQR:(1.41-4.28)mg/L]genotypes compared to the wild type ABCB13435 C/C homozygous[2.1 mg/L,IQR:(1.37-3.53)mg/L].However,there was no statistically significant difference in the efavirenz concentration between the different genotypes(P>0.05).Objective:To investigate the influence of ABCB1 polymorphisms on the plasma level of efavirenz in Thai adult cases infected with HIV-1.Methods:A single nucleotide polymorphism of ABCB13435 C>T(rs1045642)in the gene encoding ABCB1 was genotyped using real-time PCR-based alleles in 149 HIV-infected Thai adults receiving efavirenz treatment.Plasma concentrations of efavirenz were measured by high-performance liquid chromatography 12 hr after administration.The relationship between plasma efavirenz concentrations and ABCB13435 C>T polymorphisms was analyzed.Results:Logistic regression analysis showed no significant predictors of high plasma efavirenz concentration in relation to age,gender,body weight,CD4 count and plasma HIV-1 RNA,blood biochemical parameters,antiretroviral duration or ABCB13435 C>T polymorphisms,except for height(OR=0.902,95%CI:0.835-0.973)(P<0.05).The minor allele frequency of ABCB13435 C>T was 0.446.The frequency of the heterozygous mutant ABCB13435 C/T was 53.02%(n=79),ABCB13435 T/T homozygous mutant was 18.12%(n=27)and the wild type ABCB13435 C/C genotype was 28.86%(n=43).The overall median plasma concentration of efavirenz in 149 HIV-infected Thai cases was 2.41 mg/L[IQR:(1.46-4.12)mg/L].The plasma concentration of efavirenz was higher in cases with ABCB13435 T/T homozygous mutant[2.73 mg/L,IQR:(2.02-4.19)mg/L]and ABCB13435 C/T heterozygous mutant[2.29 mg/L,IQR:(1.41-4.28)mg/L]genotypes compared to the wild type ABCB13435 C/C homozygous[2.1 mg/L,IQR:(1.37-3.53)mg/L].However,there was no statistically significant difference in the efavirenz concentration between the different genotypes(P>0.05).Conclusions:There is no statistical significance for a tendency toward higher plasma efavirenz concentration in the ABCB13435 T/T and ABCB13435 C/T genotypes.No parameters of physiological characteristics in this study except for height were found to be predictors of high plasma efavirenz concentration in Thai HIV-1 infected cases.
文摘Background: There are two approved non-nucleoside reverse transcriptase inhibitor antiretroviral drugs;namely Nevirapine (NVP) and Efavirenz (EFV). Nevirapine and EFV have comparable clinical efficacy when administered in combination regimens. But there is a lack of recent evidence showing the effect of NVP and EFV-based ARTs on immunological responses in HIV infected individuals in Ethiopia in general and Addis Ababa in particular. Methods: Retrospective cohort study design was used to compare immunological response rate of NVP and EFV based HAART regimen in Addis Ababa. Four hundred ninety two HIV infected patients who started HAART in ten selected health facilities were included in the study. Rate of immunologic response was examined at the 6th, 12th, 18th, and 24th months of follow-up period. The time required to get immunological response was analyzed by Kaplan-Meier survival curve. Adjusted hazard ratio was calculated with a 95% confidence interval by Cox proportional hazards model to determine the rate of immunological response. To ascertain the association, bivariate and multi variable Cox proportional hazard model was used. Statistical significance was considered with two sides P-value of 0.05. Results: The mean CD4 count ranged between 132.2 cell/μl at baseline and 302.3 cell/μl at the end of the follow-up period. This change was significant at 95% of CI but did not show significant differences among the comparison group. The median time to get immunological response was 18 (75% percental 12) months. At the end of the follow-up period, 73.2% (76.6% for NVP and 69.8% for EVF P-value 0.13) of the study population had immunological response. Conclusion: As a conclusion, there was a robust and sustained CD4 response and the effect of NVP and EFV based ART on change of mean CD4 count and immunological response was comparable and effective. Initiation of ART with high baseline CD4 count, in combination of IPT and with either NVP or EFV based NNTI was recommended.
文摘Therapeutic plasma concentrations of EFV （efavirenz） are between 1,000 ng/mL and 4,000 ng/mL. Concentrations below 1000 ng/mL are associated with higher risk of treatment failure, and concentrations above 4,000 ng/mL are associated with toxicity. The aim of the study was to appreciate EFV plasmas concentrations profile and the association between plasma levels and various characteristics in Beninese patients treated by a 600 mg standard daily-dose. Blood samples were collected and EFV plasma levels were measured by liquid chromatography coupled with mass spectrometry detection in HIV-infected patients receiving EFV in combination with other antiretroviral drugs for at least 14 days. Adverse effects occurring during treatment were collected through a questionnaire. An over-exposure to EFV among Beninese HIV patients were observed, with 46.4% of patients presenting EFV concentration above 4,000 ng/mL, although adverse effects were tolerated indicating that antiretroviral treatment is safe. The measurement of plasma concentration at the steady-state could contribute to early detection of treatment failure and adapt treatment in subjects presenting serious adverse effects within context of therapeutic drug monitoring.
基金The Swedish International Development Cooperation Agency (Sida) [Agreement 2008-03-04, Decision no 2006-006238, Contribution no 75007334].
文摘Aim: To describe the pharmacokinetic parameters of efavirenz and estimate its clearance (CL/F) accounting simultaneously for drug-drug interactions and CYP2B6 genetic polymorphism. Methods: Genotyping of 516G > T single nucleotide polymorphism of CYP2B6 was performed using a PCR-based technology and plasma efavirenz concentrations were measured by high performance liquid chromatography on blood samples from 76 HIV adults co-infected with tuberculosis who had received an efavirenz-based regimen. Data were analyzed using population modeling with NONMEM. Results: The absorption rate constant and the apparent volume of distribution in the final model were 1.9 h-1 and 580 L/70kg, respectively. The CL/F at baseline was 11.8 L/h/70kg, 8.8 L/h/70kg and 3.9 L/h/70kg for patients carrying the G/G, G/T and T/T genotypes of CYP2B6 516G > T, respectively, in patients who were administered tuberculosis (TB) treatment prior to HIV treatment (Group A);and 16.7 L/h/70kg, 10.6 L/h/70kg and 1.8 L/h/70kg for G/G, G/T and T/T genotype patients respectively, in patients with previous exposure to HIV treatment (Group B). The CL/F at baseline and steady state was always higher in Group B compared to Group A patients. Expectedly, carriers of CYP2B6 516G/G and T/T genotypes exhibited higher and lower CL/F, respectively. Conclusion: Our results indicated that the CL/F of efavirenz in the population studied was predictably different due to whether the patients were mono-treated for TB with HAART deferred or for HIV before initiation of TB therapy, and to CYP2B6 516G > T variant, implying that both CYP2B6 genetic polymorphisms and previous efavirenz-based HAART should be taken into account when adjusting efavirenz dose.
基金supported by the National Natural Science Foundation of China(82072271,82241072,82072294)the National Key Research and Development Program of China(2021YFC2501402,2021YFC0122601)+8 种基金the Beijing Natural Science Foundation(7222095,7222091)the Peak Talent Program of Beijing Hospital Authority(DFL20191701)the Capital’s Funds for Health Improvement and Research(2022-1-1151)the Research and Translational Application of Clinical Characteristic Diagnostic and Treatment Techniques in Capital City(Z221100007422055)the Beijing Research Center for Respiratory Infectious Diseases(BJRID2024-001)the Beijing Hospitals Authority Innovation Studio of Young Staff Funding Support(2021037)the High-level Public Health Technical Personnel Construction Project(2022-1-007)the High-level Public Health Specialized Talents Project of Beijing Municipal Health commission(2022-02-20)the Beijing Key Laboratory for HIV/AIDS Research(BZ0089).
文摘Integrase strand transfer inhibitors(INSTIs)have emerged as the first‐line choice for treating human immunodeficiency virus(HIV)infection due to their superior efficacy and safety.However,the impact of INSTIs on the development of neuropsychiatric conditions in people living with HIV(PLWH)is not fully understood due to limited data.In this study,we conducted a cross‐sectional examination of PLWH receiving antiretroviral therapy,with a specific focus on HIV‐positive men who have sex with men(MSM)on INSTI‐based regimens(n=61)and efavirenz(EFV)‐based regimens(n=28).Participants underwent comprehensive neuropsychiatric evaluations and multimodal magnetic resonance imaging(MRI)scans,including T1‐weighted images and resting‐state functional MRI.Compared to the EFV group,the INSTI group exhibited primarily reduced gray matter volume(GMV)in the right superior parietal gyrus,higher regional homogeneity(ReHo)in the left postcentral gyrus,lower ReHo in the right orbital part of the inferior frontal gyrus,and increased voxel‐wise functional connectivity for the seed region in the left inferior temporal gyrus with clusters in the right cuneus.Furthermore,the analysis revealed a main effect of antiretroviral drugs on GMV changes,but no main effect of neuropsychiatric disorders or their interaction.The repeated analysis of participants who did not switch regimens confirmed the GMV changes in the INSTI group,validating the initial findings.Our study demonstrated gray matter atrophy and functional brain changes in PLWH on INSTI‐based regimens compared to those on EFV‐based regimens.These neuroimaging results provide valuable insights into the characteristics of brain network modifications in PLWH receiving INSTI‐based regimens。
基金the 13th Five-year National Major Project for HIV/AIDS and Hepatitis B Control and Prevention and the Chinese Ministry of Science and Technology(No.2017ZX10202102005004).
文摘Background:Central nervous system(CNS)symptoms after efavirenz(EFV)treatment in people living with human immunodeficiency virus(HIV)could persist and impact their quality of life.We assessed the impact of EFV-based regimen replacement with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide(E/C/F/TAF),which is considered an alternative option for subjects who do not tolerate EFV.Most specifically,we assessed the safety and the efficacy of E/C/F/TAF and its effects on the participants’neuropsychiatric toxicity symptoms in a real-life setting.Methods:A prospective cohort study was conducted among virologic suppressed HIV-positive participants receiving EFV-based regimens with ongoing CNS toxicity≥grade 2.The participants were switched to single-pill combination regimens E/C/F/TAF and followed up for 48 weeks.The neuropsychiatric toxicity symptoms were measured using a CNS side effects questionnaire,as well as the Hospital Anxiety and Depression Scale and the Pittsburgh Sleep Quality Index.The primary outcome measure was the proportion of participants experiencing grade 2 or higher CNS toxicity after EFV switch off at weeks 12,24,and 48.Secondary endpoints included virologic and immunological responses and the effect on fasting lipids at week 48 after switch.Results:One hundred ninety-six participants(96.9%men,median age:37.5 years,median:3.7 years on prior EFV-containing regimens)were included in the study.Significant improvements in anxiety and sleep disturbance symptoms were observed at 12,24,and 48 weeks after switching to E/C/F/TAF(P<0.05).No significant change in depression symptom scores was observed.At 48 weeks after switch,HIV viral load<50 copies/mL was maintained in all of the participants,median fasting lipid levels were moderately increased(total cholesterol[TC]:8.2 mg/dL,low-density lipoprotein cholesterol[LDL-C]:8.5 mg/dL,high-density lipoprotein cholesterol[HDL-C]:2.9 mg/dL,and triglyceride(TG):1.6 mg/dL,and the TC:HDL-C ratio remained stable.Conclusions:The single-pill combination regimens E/C/F/TAF is safe and well tolerated.This study reveals that switching from EFV to E/C/F/TAF significantly reduces neuropsychiatric toxicity symptoms in people living with HIV with grade 2 or higher CNS complaints.
文摘目的了解男男同性性行为人群(men who have sex with men,MSM)中人类免疫缺陷病毒(human immunodeficiency virus,HIV)感染者(MSM-HIV)接受含依非韦伦的抗反转录病毒治疗(antiretroviral therapy,ART)持续>6个月的治疗效果及影响因素。方法2021年11月17—24日,在全国31个地区(包括22个省、4个直辖市和5个自治区)通过调查问卷的方式收集患者信息。采用滚雪球抽样方法,线上通过网站社区工作人员宣传,并在微信朋友圈中招募参与者,线下工作人员访问同性恋群体聚集场所招募参与者,采用自编问卷进行调查。采用多因素logistic回归模型分析MSM-HIV ART效果的影响因素。结果本研究共纳入1311例患者,年龄(29.51±8.38)岁,ART失败297例(22.65%)。多因素logistic回归分析显示,年龄40~<50岁(OR=1.62,95%CI:1.09~2.40)、基线病毒载量>200拷贝/ml(OR=1.52,95%CI:1.12~2.07)、ART持续时间>24个月(OR=0.49,95%CI:0.32~0.75)是MSM-HIV感染者采用含依非韦伦的ART效果的影响因素。结论应更多关注高龄、基线病毒载量水平较高的MSM-HIV群体,针对其接受含依非韦伦的治疗方案的病毒学治疗失败状况,加强健康教育,提供经济援助与医疗保障,优化治疗方案,使用抗病毒治疗效果更佳且不良反应更少的药物。
