Chinese HIV-infected Patients Research Articles

Do Chinese HIV-infected adult patients with altered renal function need to adjust tenofovir disoproxil fumarate dosage? A population pharmacokinetics analysis

Tenofovir disoproxil fumarate (TDF), a prodrug of tenofovir (TFV), is an effective drug in treating patients infected with human immunodeficiency virus (HIV). Previous population pharmacokinetics (PPK) studies have showed the large variabilities in PK of TFV. Furthermore, limited information was known in Chinese populations. Therefore, the aim of this study was to characterize PPK of TDF in Chinese and identify factors that may affect its PK. TFV concentrations (n = 552) from 30 healthy subjects and 162 HIV-infected Chinese adult patients were pooled for PPK analysis by a nonlinear mixed-effects method. The PK of TFV was adequately described as a two-compartment model with first order absorption and elimination. The typical apparent clearance (CL/F) of TFV in 70-kg adults was 137 L/h, higher than that reported in Caucasians and Blacks (45.8–93 L/h). Estimated glomerular filtration rate was identified to be a significant factor influencing CL/F. Monte Carlo simulation showed that the exposure of standard dosing regimen of TDF 300 mg every 24 h in Chinese people with mild renal impairment (60 to 90 ml/min/1.73 m2) was close to that in individuals with normal renal function (90 mL/min). Dose adjustment is not required for patients with mild renal impairment. Our study might offer new clues for optimal dosing strategies in Chinese patients with HIV-infected.

State of mental health, sleep status, and the interaction with health-related quality of life in HIV-infected Chinese patients during the COVID-19 pandemic

ObjectiveTo describe how mental health and sleep status influence the health-related quality of life (HRQOL) of people living with HIV/AIDS (PLWHA) during the novel coronavirus disease 2019 (COVID-19) pandemic, and to apply targeted interventions to improve the HRQOL.MethodsA web-based online questionnaire survey was administered. Descriptive analysis was used to depict the mental health and sleep status. Correlation analysis and the structural equation model (SEM) method were used to analyze the influence of mental health and sleep status on HRQOL in PLWHA.ResultsAfter excluding 24 unqualified questionnaires, a total of 490 participants in this survey were included in the statistical analysis. Of the participants, 66.1% and 55.1% reported mild or worse symptoms of depression and anxiety, respectively. Overall, 70.0% had varying degrees of sleep problems. Correlation analysis showed that anxiety had the strongest correlation with sleep disturbances and sleep quality (R = 0.588 and 0.551, respectively), while depression had the strongest correlation with the HRQOL psychological and physical domains (R = − 0.759 and − 0.682, respectively). SEM analysis showed that depression, sleep quality, and psychological domains had the greatest item load on mental health, sleep status, and HRQOL (093, 0.82, and 0.89, respectively). Mental health had a more significant influence than sleep status on HRQOL, as indicated by factor loading (− 0.75 and − 0.15, respectively).ConclusionsThere were more severe mental health and sleep problems among PLWHA during the COVID-19 pandemic, thus, mental health intervention, especially to relieve depression symptoms, may be the most important approach to improve the HRQOL among PLWHA.

Genotypic diversity and antifungal susceptibility of Cryptococcus neoformans species complex from China, including the diploid VNIII isolates from HIV-infected patients in Chongqing region.

Although previous studies on the genotypic diversity and antifungal susceptibility of the Cryptococcus neoformans species complex (CNSC) isolates from China revealed ST5 genotype isolates being dominant, the information of the CNSC isolates from Chinese HIV-infected patients is limited. In this study, 171 CNSC isolates from HIV-infected patients in the Chongqing region of Southwest China were genotyped using the International Society for Human and Animal Mycology-multilocus sequence typing (ISHAM-MLST) consensus scheme, and their antifungal drug susceptibilities were determined following CLSI M27-A3 guidelines. Among 171 isolates, six sequence types (STs) were identified, including the dominant ST5 isolates, the newly reported ST15, and four diploid VNIII isolates (ST632/ST636). Moreover, a total of 1019 CNSC isolates with STs and HIV-status information were collected and analyzed from mainland China in the present study. A minimum spanning analysis grouped these 1019 isolates into three main subgroups, which were dominated by the ST5 clonal complex (CC5), followed by the ST31 clonal complex (CC31) and ST93 clonal complex (CC93). The trend of resistance or decreasing susceptibility of clinical CNSC isolates to azole agents within HIV-infected patients from the Chongqing region is increasing, especially resistance to fluconazole (FLC).

The burden of anemia among Chinese HIV-infected patients following the initiation of antiretroviral therapy in the treat-all era: a nationwide cohort study

BackgroundTo assess the prevalence of anemia before and after antiretroviral therapy (ART) initiation and to identify impact of anemia on mortality among HIV-infected patients in China during the Treat-All era.MethodsAll HIV-infected patients who newly initiated ART between January 1, 2017 and December 31, 2020 were enrolled and followed up to December 31, 2021 in China. We analyzed the prevalence of anemia before and after ART initiation. Generalized estimating equations were fitted to determine factors associated with anemia after ART. Time-dependent cox proportional hazards models were performed to estimate the effect of anemia on death.ResultsOf 436,658 patients at the baseline of ART initiation, the overall prevalence of anemia was 28.6%. During a median 2.65 (IQR: 1.80–3.51) years of follow-up after ART initiation, 376,325 (86.2%) patients had at least one Hb measurement (a total of 955,300 hemoglobin measurements). The annual prevalence of anemia after ART was 17.0%, 14.1%, 13.4%, 12.6% and 12.7%, respectively. Being anemic at the baseline of ART initiation (adjusted odds ratio, aOR = 6.80, 95% confidence interval (CI): 6.67–6.92) was the strongest factor associated with anemia after ART. Anemia status after ART showed a strong association with death after multivariable adjustment (mild anemia: adjusted hazard ratio (aHR) = 2.65, 95% CI: 2.55–2.76; moderate anemia: aHR = 4.60; 95% CI:4.40–4.81; severe anemia: aHR = 6.41; 95% CI:5.94–6.91).ConclusionsIn the era of ART universal access, pre-ART anemia was common among HIV-infected patients. Notably, a certain proportion of anemia still persisted after ART, and was significantly associated with death. We recommend strengthening the monitoring of patients at risk of anemia, especially in patients with baseline anemia or during the first year of ART, and timely treatment for correcting anemia.

The effects of ART on the dynamics of lipid profiles in Chinese Han HIV-infected patients: comparison between NRTI/NNRTI and NRTI/INSTI.

This article aimed to compare the prevalence of dyslipidemia and determine risk factors associated with lipid levels in a cohort of HIV-infected patients receiving two different antiretroviral therapy (ART) regimens, nucleoside reverse transcriptase inhibitor/non-nucleoside reverse transcriptase inhibitor (NRTI/NNRTI) and nucleoside reverse transcriptase inhibitor/integrase strand transfer inhibitor (NRTI/INSTI). This longitudinal study analyzed 633 HIV-infected patients with complete blood lipid profile records for at least 1 year at the ART clinic of Zhongnan Hospital of Wuhan University, China, from June 2018 to March 2021. Demographic and clinical data, including age, gender, body weight, height, current/former/non-smoker, current drinker, diabetes mellitus, hypertension, were extracted from electronic medical records. Laboratory tests included hematology, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Lipoprotein(a) and CD4 cell count. The observation duration of this study was a maximum of 33 months. Data comparisons were performed using the Chi-square test, Student's t-test and Mann-Whitney U test. Generalized linear mixed-effects model (GLMM) and value of p < 0.05 were used to determine factors associated with serum lipid profiles. In this study, the effect of the NNRTIs group on the lipid profile over time was mainly an increase in TC and HDL-C, while a decrease in TC/HDL-C and LDL/HDL-C. However, the INSTIs group had higher mean TC and lower HDL-C compared to the NNRTIs group, with significantly increased levels of TC, TG, HDL-C, and LDL-C. In the analysis of dyslipidemia rates, there were significant differences in the prevalence of abnormal TG and TC/HDL-C in HIV-infected patients receiving two different ART regimen groups during different follow-up periods. Dyslipidemia, defined as hypercholesterolemia, hypertriglyceridemia, and low HDL-C, was more prevalent in the INSTIs group, with a higher risk of developing hypertriglyceridemia and a higher TC/HDL-C ratio compared to the NNRTIs group. GLMM analysis suggested significantly higher TG values in the INSTIs group (estimated 0.36[0.10, 0.63], SE 0.14, p = 0.008) compared to the NNRTIs group, even after adjusting for other covariates. In addition, GLMM analysis also showed that age, gender, BMI, CD4 count, and ART duration were associated with dyslipidemia. In conclusion, treatment with both commonly-used ART regimens can increase the mean values of lipid profiles and the risk of dyslipidemia. The findings indicated that TG values were significantly higher in the INSTIs group than in HIV-infected patients receiving the NNRTIs regimens. Longitudinal TG values are independently associated with the clinical types of ART regimens.Clinical Trial Number: ChiCTR2200059861.

Association of Human Leukocyte Antigen Alleles and Hypersensitivity of Efavirenz/Nevirapine in HIV-Infected Chinese Patients.

To examine the association between human leukocyte antigen (HLA) and nevirapine (NVP)- and efavirenz (EFV)-induced cutaneous adverse reactions in human immunodeficiency virus (HIV) patients, we conducted a case-control study at our center consisting of 96 patients. Patients were further assigned based on the occurrence of cutaneous adverse events and the drugs involved. All patients were subjected to next generation sequencing (NGS)-based screening with focus on HLA phenotype, including the presence of HLA-B, HLA-C, and HLA-DRB1. Our data indicated that the HLA-C*01:02:01 allele presence was observed in 47.4% (18/38) of patients in the EFV-hypersensitivity group compared with 18.9% (7/30) in the control group [odds ratio (OR) = 5.837; 95% confidence interval (CI) = 1.727-19.722, p = .005]. In contrast, the occurrence of HLA-DRB1*08:03 was found to be significantly lower in the EFV-hypersensitivity group (4/38, 10.5%) compared with the corresponding control group (12/37, 32.4%) (OR = 0.148; 95% CI = 0.035-0.625, p = .009). In addition, the HLA-DRB1*04:05:01 antigen was expressed more frequently in the NVP-hypersensitivity group (23.8%, 5/21) compared with the control group (10.8%, 4/37) (OR = 7; 95% CI = 1.265-38.793, p = .026). Our data not only revealed a significant association between HLA-C*01:02:01 and EFV-induced cutaneous adverse reactions but may also shed light on defining the treatment for Chinese HIV patients.

Clinical Features, Phenotypic Markers and Outcomes of Diffuse Large B-Cell Lymphoma between HIV-Infected and HIV-Uninfected Chinese Patients.

Background: The effect of HIV infection on the clinicopathological characteristics of diffuse large B-cell lymphoma (DLBCL) remains debatable. Methods: Fifty-three HIV-infected and ninety-three HIV-uninfected DLBCL patients were enrolled in the retrospective study by propensity score matching for sex, age, body mass index and international prognostic index (IPI) at a ratio of 1:2. The clinicopathological characteristics were compared between the two groups. Results: HIV-infected DLBCL patients had lower white blood cell counts [×109/L; 4.4 (3.4-5.6) vs. 6.1 (4.2-8.2), p &lt; 0.001], platelet counts (×109/L; 184.7 ± 89.3 vs. 230.0 ± 113.9, p = 0.014) and serum albumin (g/L; 37.3 ± 6.9 vs. 41.3 ± 6.2, p &lt; 0.001) but higher incidences of central nervous system (CNS) involvement (9.4% vs. 1.1%, p = 0.014), bone marrow involvement (24.5% vs. 11.5%, p = 0.044) and Epstein-Barr viremia (61.1% vs. 26.7%, p = 0.002) than HIV-uninfected patients. In terms of histopathology, HIV-infected patients had higher positivity of Epstein-Barr virus-encoded small RNA (EBER) (41.7% vs. 6.7%, p = 0.002), but lower CD20 (90.2% vs. 98.7%, p= 0.029) and CD79a (23.1% vs. 53.7%, p &lt; 0.001) expression. The overall response rate (ORR) at the end of chemotherapy (70.2% vs. 87.8%, p= 0.012) and 1-year overall survival (OS) (61.7% vs. 84.2%, log-rank p = 0.006) in HIV-infected patients were significantly lower than those in HIV-uninfected patients. Multivariate analysis suggested IPI ≤2.0 [adjusted odds ratio (AOR) (95% confidence interval): 5.0 (1.2-21.2), p = 0.030] was associated with ORR, hypoalbuminemia [AOR: 3.3 (1.3-9.1), p = 0.018] and CNS involvement [AOR: 3.3 (1.0-10.5), p = 0.044] were associated with reduced 1-year OS in HIV-infected patients. Conclusion: HIV-infected DLBCL patients have unique blood profiles and phenotypic markers. Low ORR and 1-year OS were observed in HIV-infected DLBCL patients in our study, even in the HAART era.

Population pharmacokinetics and model-informed precision dosing of lamivudine in Chinese HIV-infected patients with mild and moderate impaired renal function

ABSTRACT Background Lamivudine is a first-line medication used for human immunodeficiency virus (HIV) treatment. To date, the population pharmacokinetics of lamivudine in Chinese HIV-infected adults have not been assessed. This study aimed to develop a population pharmacokinetic model for oral lamivudine in Chinese HIV-infected adults and to determine the optimal lamivudine dosage regimens. Research design and methods A total of 1113 samples, from 828 Chinese HIV-infected patients treated with lamivudine 300 mg every 24 hours, were pooled from two open-label, prospective clinical trials. A population pharmacokinetics analysis was performed using a nonlinear mixed-effects modeling method. A Monte Carlo simulation was conducted to optimize lamivudine dosing. Results A two-compartment model adequately described the population pharmacokinetics of lamivudine. The typical population estimate for apparent clearance was 28.3 L/h. Creatinine clearance was identified as a significant factor influencing apparent clearance. According to the Monte Carlo simulation, patients with creatinine clearance between 50 and 70 mL/min should receive lamivudine 200 mg every 24 h or 300 mg every 36 h, to achieve optimal lamivudine exposure. Conclusions No obvious ethnic differences were observed in lamivudine pharmacokinetics between Chinese and Caucasian populations. Additionally, a model-informed dosage regimen is recommended for patients with impaired renal function.

MO177RENAL PROXIMAL TUBULAR DISORDER AND RENAL FUNCTION LOSS IN HIV-INFECTED PATIENTS TREATED WITH TENOFOVIR DISOPROXIL FUMARATE

Abstract Background and Aims Tenofovir disoproxil fumarate (TDF), as the most common antiviral drug, can cause both proximal tubular transportation dysfunctions and eGFR decline. The relationship between them is not clear due to lack of clinical data from large cohorts, especially in the Chinese population. In this study, we summarized the characteristics of proximal tubular injuries and eGFR decline in the cohort of HIV-infected patients treated with TDF, and explore the the impact of tenofovir on tubular transporters in vitro. Method We enrolled HIV-infected patients treated with TDF, who were regularly followed up in our hospital from Sep 1, 2001 to August 31, 2019. Their baseline and follow-up clinical data were collected. Proximal tubular dysfunction was defined as meeting two or more of the following criteria: hypophosphatemia, hypouricemia, low carbon dioxide binding capacity, positive urine glucose with normal plasma glucose level, and positive urine protein. Rapid deterioration of renal function was defined as the annual decline rate of eGFR exceeding 5ml/min/1.73m2. We also used human renal proximal tubular epithelial cell line (HK2) to further investigate the impact of tenofovir on transporters including SGLT2, NaPi-IIa, and URAT1 through immunofluorescence. Results A total of 375 HIV-infected patients receiving TDF were enrolled, mainly males (90.1%), with a median follow-up duration of 34(17, 58) months. The most common clinical manifestations were proteinuria (20.3%) and hypophosphatemia (12.3%). The prevalence of proximal tubular injury was 6.7%, which was significantly associated with low body weight, but was not associated with age, TDF course, baseline viral load, or baseline CD4+ T lymphocyte count. Their eGFR levels at the end of the follow-up were significantly lower than the baseline levels (104.6±15.2 vs. 110.6±14.2 ml/min/1.73m2, P&amp;lt;0.001). The average annual decline rate of eGFR was 5.0± 22.7 ml/min/1.73m2, and 23.6% of our patients had an annual decline rate of eGFR exceeding 5 ml/min/1.73m2. Rapid deterioration of renal function (≥ 5 ml/min/1.73m2 per year) was significantly associated with female but not related to proximal tubular dysfunction in multivariate logistic regression analysis. In vitro, the survival rate of HK2 cells was more than 95% when treated with tenofovir with a concentration of 1μmol/L for 48h. The expression levels of transporters (SGLT2, URAT1, and NaPi-IIa) were declined under the condition. Conclusion Among the HIV-infected Chinese patients treated with TDF, 6.7% had proximal tubular dysfunction and 23.6% showed accelerated annual decline rate of eGFR (≥ 5 ml/min/1.73m2 per year).

Pharmacodynamics of efavirenz 400 mg in treatment-na\xefve Chinese HIV-infected patients in a prospective cohort study

BackgroundThe plasma concentration of patients treated with efavirenz (EFV) 600 mg was found to exceed the upper limit of the proposed therapeutic window in most Chinese HIV-infected individuals; thus, dosage reduction of EFV to 400 mg daily warranted consideration. This study aimed to assess the pharmacodynamics of EFV 400 mg for HIV-1-infected patients in China.MethodTwenty cART-naïve individuals were enrolled in this study. EFV 400 mg combined with tenofovir (TDF) and lamivudine (3TC) as an initial antiretroviral regimen was administered for 48 weeks. EFV concentration and T cell subsets as well as HIV RNA load were evaluated at baseline and at 4, 12, 24, and 48 weeks. Moreover, neuropsychiatric adverse effects were also assessed by the Hamilton depression (HAMD) scale and Pittsburgh sleep quality index (PSQI).ResultsEighteen males and two females whose median age was 26 (interquartile range [IQR]: 23–32) years completed 48 weeks of follow-up. The median EFV concentrations were 1.88 (IQR: 1.54–2.42), 1.74 (IQR: 1.36–1.93), 1.93 (IQR: 1.66–2.22), and 1.85 (IQR: 1.54–2.14) mg/L at weeks 4, 12, 24, and 48, respectively. The viral load was 4.59 (IQR: 4.10–5.19) log10 copies/mL at baseline, and it decreased by 4.6 (IQR: 3.98–5.18) log10 copies/mL from baseline to week 48. Three of 20 (15%), 10 of 20 (50.0%), 17 of 20 (85%), and 18 of 19 (95%) participants had a plasma viral load less than 50 copies/mL at weeks 4, 12, 24, and 48, respectively. The median CD4 cell count was 330 (IQR: 237–410) cells/μL at baseline, and it increased to 473 (IQR: 344–574) cells/μL at 48 weeks. The HAMD score was 5 (IQR: 3–9.8) and 3 (IQR: 2.25–4) at baseline and 48 weeks, respectively. The PSQI score was 4 (IQR: 2–5.8) and 3 (IQR: 2–4) at baseline and 48 weeks, respectively. Dizziness was the most common event, occurring in 70% of patients within the first 2 weeks of treatment.ConclusionPatients prescribed with EFV 400 mg-containing agents demonstrated favourable virological and immunological responses. And the plasma EFV concentration was within the recommended therapeutic range, with fewer adverse reactions than with EFV 600 mg. EFV 400 mg was effective and safe in Chinese HIV-infected patients.Trial registrationNCT04596488; Registered 21 October, 2020; Retrospectively registered.

Asymptomatic cryptococcal antigenemia in HIV-infected patients: a review of recent studies.

The prevalence of asymptomatic cryptococcal antigenemia (ACA) in human immunodeficiency virus (HIV) infected individuals has been observed to be elevated. The prevalence of ACA ranges from 1.3% to 13%, with different rates of prevalence in various regions of the world. We reviewed studies conducted internationally, and also referred to two established expert consensus guideline documents published in China, and we have concluded that Chinese HIV-infected patients should undergo cryptococcal antigen screening when CD4 T-cell counts fall below 200 cells/μL and that the recommended treatment regimen for these patients follow current World Health Organization guidelines, although it is likely that this recommendation may change in the future. Early screening and optimized preemptive treatment for ACA is likely to help decrease the incidence of cryptococcosis, and is lifesaving. Further studies are warranted to explore issues related to the optimal management of ACA.

Cryptococcus Neoformans Meningitis Cases Among China's HIV-Infected Population may have been Severely Under-Reported.

Cryptococcal meningitis (CM) is the leading fungal infection of the central nervous system. Globally, most CM cases have been reported from patients with compromised immunities, especially those infected with HIV. However, reports from China have shown that most CM infections were from HIV-negative, immunocompetent hosts. Here, we reviewed the published reports and found those studies were almost exclusively based on patients from hospitals associated with Chinese universities but not from specialized infectious diseases hospitals where most Chinese HIV-infected patients have been treated. Thus, we believe CM cases among China’s HIV-infected population may have been severely under-reported. Analyses of CM cases in specialized infectious diseases hospitals are needed to identify the true epidemiological pattern of CM in China.

Widespread use of anti-retroviral therapy elevated the prevalence of dyslipidemia in HIV-infected Chinese patients

With the widespread use of high-efficiency antiretroviral therapy (HAART), the life expectancy of HIV-infected patients has been significantly extended. However, the metabolic complications among HIV-infected patients treated with HAART have become the most common problem in the world. It is very important to explore the incidence of dyslipidaemia and studies on the role of potential risk factors in HIV-infected Chinese patients treated with HAART are sparse. Therefore, we designed current study, to investigate the effects of therapeutic intervention and continuous information support on the lifestyle of HIV/AIDS patients with dyslipidaemia. Three hundred and six HIV/AIDS patients admitted to the AIDS clinic in Beijing from January 2016 to January 2017 were recruited and assigned into two groups: the treatment group (n=64) and the control group (n=64). The median age of the participants was 38.8±11.0 years (range 20-75 years). The prevalence of dyslipidemia in control and treatment group was (59/64) 92.2% and (53/64) 82.8%, respectively. In this study, low HDL-cholesterol (HDLC) led to abnormalities 47/64 (73.3%) in the control group and 35/64 (54.7%) in HAART-treatment group. Additionally, HAART group showed higher triglyceride, total cholesterol, and low-density lipoprotein (246.1±171.8, 1.73±1.61 mmol/L, 4.46±1.1 mmol/L, 2.54±0.74 mmol/L). In multivariate analysis, gender, marital status, high BMI, dietary habits and physical activity were potential risk factors for dyslipidemia in HIV-infected Chinese patients. In this study, we reported high prevalence dyslipidemiain two HIV infected groups. We suggest that the appropriate diagnosis should be performed for analyzing the metabolic complications in HIV-infected Chinese patients. Further studies are very important to understand the role of potential risk factors in metabolic complications.

A Review of Clinical Pharmacokinetic and Pharmacodynamic Profiles of Select Antiretrovirals: Focus on Differences among Chinese Patients.

To identify the pharmacokinetic differences of antiretroviral drugs between HIV-infected Chinese patients and patients of other race/ethnicities. Results from prospective, open-label pharmacokinetic studies among Chinese and historical data from other race/ethnicities. Pharmacokinetics of six commonly used antiretroviral drugs, including zidovudine, lamivudine, tenofovir disoproxil fumarate, nevirapine, efavirenz and lopinavir/ritonavir, was evaluated in HIV-infected Chinese patients and compared with historical data from other race/ethnicities. Pharmacokinetic analyses were performed at the steady state among HIV-infected Chinese patients. Safety data were collected during the follow-up. The pharmacokinetic parameters including maximal concentrations (Cmax), area-under-curve (AUC) and clearance (Cl/F) from the Chinese patients were compared to the historic data from other race/ethnicities. Current evidence, though limited, suggested that these antiretroviral agents were generally safe and effective among HIV-infected Chinese patients. However, compared with other racial groups, Chinese patients exhibited higher Cmax , AUC and lower Cl/F for most of the agents, and the incidences of adverse reactions, for example, liver toxicity, rash, and bone health, were more frequent. These pharmacokinetic differences suggest that lower dosages for commonly prescribed antiretroviral drugs in China might be appropriate to reduce drug-related adverse reactions, while maintain the antiviral efficacy.

Effect of rilpivirine on the pharmacokinetics of methadone in HIV-Infected Chinese patients

ABSTRACTBackground: The combination of rilpivirine with methadone may result in complex interactions secondary to the induction of oxidative metabolism by rilpivirine.Research design and methods: TMC278IFD4007 was a single-center, prospective, open-label, multiple-dose study with 12 HIV-infected Chinese participants. The objective was to evaluate the potential effect of rilpivirine on the pharmacokinetics of methadone. The participants received a daily dose of 25 mg rilpivirine for 11 days with individualized methadone ranging from 25 to 100 mg. Pharmacokinetic studies of methadone were conducted on day 1 and 11. Opiate withdrawal symptoms were evaluated.Results: A large inter-subject variability was noted in methadone pharmacokinetics. Rilpivirine increased methadone minimum and maximum plasma concentrations (Cmin; Cmax) and area under the plasma concentration-time curve versus methadone alone (least-square mean ratio; 90% confidence interval) by 5% (1.05; 0.46, 2.39), 5% (1.05; 0.73, 1.52), and 6% (0.75; 0.74, 1.50) as measured in S-methadone, and 5% (1.05; 0.50, 2.22), 5% (1.05; 0.74, 1.50), and 5% (1.05; 0.76, 1.46) as measured in R-methadone, respectively. No opioid withdrawal symptoms or methadone dose adjustments were reported. Co-administration was well tolerated without serious adverse effects or discontinuations.Conclusion: Concomitant administration of rilpivirine was unlikely to have significant effects on the pharmacokinetics of methadone.Trial registration: Chinese Clinical Trial Registry identifier: ChiCTR-TRC-14004908.

Predictive effects of body mass index on immune reconstitution among HIV-infected HAART users in China

BackgroundBody mass index (BMI) may contribute somewhat to drug metabolism, and thus affecting the efficacy of highly active antiretroviral therapy (HAART). This study aimed to determine the frequencies of underweight, normal and overweight/obesity at pre-HAART in a large cohort of HIV-infected Chinese patients, and investigate the prospective effects of BMI on immune reconstitution after HAART initiation.MethodsA longitudinal cohort study was performed to analyze the effects of BMI on immune reconstitution in HIV-infected patients treated with HAART. Multiple linear regression was used to evaluate the relationship between baseline BMI and increased CD4+ T lymphocyte levels at 12 and 30 months after initiating HAART. In addition, Cox proportional hazard model was used to assess the relationship between BMI and time to achieve immunologic reconstitution (CD4+ T lymphocytes>500cells/μL) during the follow-up period.ResultsAmong the 1612 enrolled patients, 283 (17.6%) were overweight/obese (BMI ≥ 25 kg/m2), 173 (10.7%) were underweight (BMI < 18.5 kg/m2) and the remaining were normal weight. Prior to HAART initiating, overweight HIV-infected patients were mostly males, older ages, exhibited higher CD4+ T lymphocytes and lower viral loads (p < 0.01 for all). Patients with higher baseline BMI had an independently positive effect on 30-month CD4+ T lymphocyte recovery (p = 0.028), but not 12-month CD4+ T lymphocyte gain (p = 0.104). In addition, a Cox proportional hazard model with baseline BMI as an independent variable indicated that BMI was correlated with an increased likelihood of achieving immunologic reconstitution over time (hazard ratios [HR] 1.03; 95% confidence intervals [CI] 1.01–1.06; p = 0.011), after adjusting for baseline age, gender, CD4+ T lymphocytes, CD4/CD8 ratio, viral load and WHO stage.ConclusionsHigher baseline BMI could predict better immune reconstitution in HIV-infected patients after HAART initiating.

Lipid profile and renal safety of tenofovir disoproxil fumarate-based anti-retroviral therapy in HIV-infected Chinese patients

BackgroundTenofovir disoproxil fumarate (TDF) is an important component of antiretroviral therapy (ART) that has been widely used. The aim of this study was to observe the long-term impact of TDF-based ART on lipid metabolism profiles and renal functions in Chinese patients. Methods414 and 124 HIV-infected, ART-naïve patients who initiated TDF-based regimens and non-TDF regimens respectively were retrospectively included. Demographic characteristics and clinical information of each patient was collected. Changes of lipid profiles and renal function, as well as the risk factors of hyperlipidemia and renal dysfunction were analyzed. ResultsAfter 96 weeks of ART, HIV viral loads were undetectable in 97.34% (403/414) of patients exposed to TDF. The plasma total cholesterol (TCH) increased from 3.97 ± 0.83 mmol/L to 4.53 ± 0.87 mmol/L (P < 0.001), which did not show a significant difference comparing with non-TDF exposed group. By contrast, the plasma triglyceride (TG) levels increased, but were still lower than that in the non-TDF exposed group (0.26 ± 1.24 vs. 0.89 ± 1.78, P < 0.001). The mean estimated glomerular filtration rate (eGFR) decreased from 127.29 ± 24.04ml∙min−1∙1.73 m−2 at baseline to 118.84 ± 22.74 ml∙min−1∙1.73 m−2(P < 0.001) in the TDF exposed group, while it increased in the non-TDF exposed group. In the TDF group, high body mass index (BMI) (OR = 1.13, P = 0.01), high baseline TG (OR = 2.33, P<0.001) and receiving protease inhibitors (PIs) (OR = 7.58, P < 0.001) were associated with hypertriglyceridemia after ART, while high baseline TCH predicted hypercholesterolemia (OR = 3.58, P < 0.001). MSM (OR = 0.22, P = 0.02) and baseline eGFR (OR = 0.90, P < 0.001) was associated with renal dysfunction after ART. ConclusionsTDF-based regimens are of good therapeutic effect among Chinese people. These regimens showed a better plasma lipid profile but mild renal dysfunction as compared to non-TDF based regimens. Patients with high BMI, high baseline TG, high baseline TCH and low baseline eGFR should be closely monitored when using TDF-based ART.

Acute Kidney Injury in Chinese HIV-Infected Patients: A Retrospective Analysis from the Intensive Care Unit.

To describe the epidemiology, outcomes, and risk factors of acute kidney injury (AKI) among human immunodeficiency virus (HIV)-infected patients admitted to the intensive care unit (ICU).We reviewed all the HIV-infected admissions to the ICU at Beijing Ditan hospital in the time span from June 2005 to May 2017 and collected demographic, clinical, and laboratory data for our sample. AKI was diagnosed and classified according to the Kidney Disease Improving Global Outcomes (KIDIGO) criteria. We analyzed the incidence of AKI and its associated mortality. The potential risk factors for severe AKI were also investigated in this study. A total of 225 HIV-infected patients were included in the final analysis. The incidences of no-AKI, AKI stage 1, AKI stage 2, and AKI stage 3, were 46.2% (104), 19.1% (43), 8.4% (19), and 26.2% (59), respectively. By logistic regression analysis, severe AKI (stages 2-3) was an important predicator for 60-day mortality with an odds ratio of 4.234. By multivariate analysis, a high acute physiology and chronic health evaluation, version II (APACHE-II) score (p = 0.024), low albumin (p < 0.031) at the first 24-h admission ICU, shock (p = 0.013), and bloodstream infection (p = 0.006) during hospitalization were all found to be significant risk factors for severe AKI. AKI is common in HIV-infected patients admitted to the ICU, and the mortality of patients with AKI stages 2-3 is significantly higher compared with those without such conditions. A high APACHE-II score and a lower albumin level at the first 24-h admission to ICU are significant predictors of severe AKI in this specific population. Shock and bloodstream infection during hospitalization can also lead to severe AKI.

Plasma metabolic changes in Chinese HIV-infected patients receiving lopinavir/ritonavir based treatment: Implications for HIV precision therapy

ObjectivesThe goal of this study is to profile the metabolic changes in the plasma of HIV patients receiving lopinavir/ritonavir (LPV/r)-based highly active antiretroviral therapy (HAART) relative to their treatment-naïve phase, aimed to identify precision therapy for HIV for improving prognosis and predicting dyslipidemia caused by LPV/r. Methods38 longitudinal plasma samples were collected from 19 HIV-infected patients both before and after antiretroviral therapy, and 18 samples from healthy individuals were used as controls. Untargeted metabolomics profiling of these plasma samples was performed using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC–MS). ResultsA total of 331 compounds of known identity were detected among these metabolites, a 67-metabolite signature mainly mapping to tryptophan, histidine, acyl carnitine, ketone bodies and fatty acid metabolism distinguished HIV patients from healthy controls. The levels of 19 out of the 67 altered metabolites including histidine, kynurenine, and 3-hydroxybutyrate (BHBA), recovered after LPV/r-based antiretroviral therapy, and histidine was positively correlated with the presence of CD4 + T lymphocytes. Furthermore, using receiver operating characteristic (ROC) analyses, we discovered that butyrylcarnitine in combination with myristic acid from plasma in treatment-naïve patients could predict dyslipidemia caused by LPV/r with 87% accuracy. ConclusionsMetabolites alterations in treatment-naïve HIV patients may indicate an inflammatory, oxidative state and mitochondrial dysfunction that is permissive for disease progression. Histidine may provide a specific protective function for HIV patients. Besides, elevated fatty acids levels including butyrylcarnitine and myristic acid after infection may indicate patients at risk of suffering from dyslipidemia after LPV/r-based HAART.

Identification of a Novel Serum Biomarker for Tuberculosis Infection in Chinese HIV Patients by iTRAQ-Based Quantitative Proteomics.

Tuberculosis (TB) is a major comorbidity in HIV patients as well as a serious co-epidemic. Traditional detection methods are not effective or sensitive for the detection of Mycobacterium tuberculosis at the early stage. TB has become a major cause of lethal on HIV patients. We employed isobaric tags for relative and absolute quantitation (iTRAQ) technology to identify the different host responses in HIV-noTB and HIV-TB patients’ sera. Given the diversity of HIV subtypes, which results in a variety of host responses in different human populations, we focused on the Chinese patients. Of the 25 proteins identified, 7 were increased and 18 were decreased in HIV-TB co-infected patients. These proteins were found to be involved in host immune response processes. We identified a candidate protein, endoglin (ENG), which showed an 4.9 times increase by iTRAQ and 11.5 times increase by ELISA. ENG demonstrated the diagnostic efficacy and presented a novel molecular biomarker for TB in HIV-infected Chinese patients. This study provides new insight into the challenges in the diagnosis and effective management of patients with HIV-TB.