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Background: Antiretroviral therapy (ART) improved the prognosis of people living with human immunodeficiency virus (HIV) (PLWH). Life-long treatment is required in PLWH and is accompanied by various metabolic abnormalities in the disease course. Data about the epidemiology and the dynamic changes of dyslipidemia in PLWH receiving antiretroviral therapy were scarce in Asian countries. This study aimed to explore the risk factors of dyslipidemia and analyze the longitudinal changes of dyslipidemia among Chinese PLWH receiving HAART. Methods: We conducted a longitudinal analysis of PLWH enrolled in two large multicenter clinical trials across China, and outpatients followed at the clinic of Peking Union Medical College Hospital. Demographic data and clinical parameters were collected. The risk factors and longitudinal changes in lipid profiles associated with HIV-1 infection were analyzed. The definition of dyslipidemia was made based on the National Cholesterol Education Program, Adult Treatment Panel (NCEP-ATP) III guidelines. Results: A total of 1542 PLWH were included. The median follow-up was 6 years. At baseline, the concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were 4.1 ± 0.91 mmol/L, 1.2 (interquartile ranges [IQR] 0.85–1.75) mmol/L, 1.1 ± 0.37 and 2.4 ± 0.76 mmol/L, respectively. The rate of hypercholesterolemia, hyperglyceridemia, high LDL-C, and low HDL-C were 10.18%, 26.39%, 9.08%, and 44.94%, respectively. The overall prevalence of dyslipidemia was 69.3%, which raised to 84.3% after antiretroviral therapy, substantially higher. CD4/CD8 ratio < 0.3 and viral load > 105 copies/mL were risk factors associated with any subtype of dyslipidemia. A negative correlation between CD8+CD38+ percentage and HDL-C concentration was found. The regimens including efavirenz (EFV) and tenofovir (TDF) showed better lipid profiles. Longitudinal analysis revealed that both the level and the percentage of abnormal TG and HDL-C occurred drastic change in the first 6 months after ART initiation (from 4.07 to 4.41, from 1.11 to 1.28mmol/L, from 26.39 to 31.1% and from 44.94 to 29.5%, respectively). Conclusions: The prevalence of dyslipidemia is high in PLWH and increases after ART, mainly represented as high TG and low HDL-C and associated with advanced stage of HIV-1 infection. The greatest changes in lipids occurred in the early stage after initiating ART therapy. The results suggest that dyslipidemia should be monitored and managed when starting ART. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the impact of a tenofovir disoproxil fumarate (TDF) plus ritonavir-boosted protease inhibitor (PI/r) regimen on renal function in Chinese HIV-infected patients.Methods: Seventy-five HIV-1 infected patients failing first-line antiretroviral therapy (ART) comprised the TDF+PI/r group. Seventy-five HIV-1 infected patients matched for gender, age, and renal function made up the control. All subjects completed follow-up visits over 48 weeks. CD4 cell count, plasma HIV-1 viral load, and urine protein level were assessed at the trial start (baseline, week 0) and at week 48. The serum creatinine and estimated glomerular filtration rate (eGFR) were monitored at each follow-up point. Change in eGFR from baseline to week 48 was also compared.Results: Compared to control, the TDF+PI/r group exhibited higher levels of serum creatinine (79 vs. 69.7 μmol/L, P<0.001) and a lower rate of eGFR (93.0 vs. 101.6 ml/min/1.73 m², P=0.009) at the end of week 48. Patients treated with TDF+PI/r showed greater decline in eGFR than control (-8.8 vs. 6.4 ml/min/1.73 m², P<0.001). Compared to baseline renal function of the control group, the TDF+PI/r group exhibited a greater median decline in eGFR at the end of week 48 (P<0.001).Conclusions: We found that a TDF+PI/r based ART regimen resulted in greater renal function decline over 48 weeks. Therefore, renal function should be monitored especially when TDF is used in combination with PI/r.Trial Registration: ClinicalTrials.gov identifier: NCT00872417. [ABSTRACT FROM AUTHOR]

Background: Factors predicting peripheral blood total HIV-1 DNA size in chronically infected patients with successfully suppressed viremia remain unclear. Prognostic power of such factors are of clinical significance for making clinical decisions.Methods: Two sets of study populations were included: 490 China AIDS Clinical Trial (CACT) participants (Training cohort, followed up for 144 to 288 weeks) and 117 outpatients from Peking Union Medical College Hospital (PUMCH) (Validation cohort, followed up for more than 96 weeks). All patients were chronically HIV-1-infected and achieved successful HIV-1 plasma RNA suppression within week 48. Total HIV-1 DNA in blood at baseline, 12, 24, 48, 96, 144 and 288 weeks after combined antiretroviral therapy (cART) initiation were quantified. Generalized estimating equations and logistic regression methods were used to derive and validate a predictive model of total HIV-1 DNA after 96 weeks of cART.Results: The total HIV-1 DNA rapidly decreased from baseline [median = 3.00 log10 copies/106 peripheral blood mononuclear cells (PBMCs)] to week 24 (median = 2.55 log10 copies/106 PBMCs), and leveled off afterwards. Of the 490 patients who had successful HIV-1 plasma RNA suppression by 96 w post-cART, 92 (18.8%) had a low total HIV-1 DNA count (< 100 copies/106 PBMCs) at week 96. In the predictive model, lower baseline total HIV-1 DNA [risk ratio (RR) = 0.08, per 1 log10 copies/106 PBMCs, P < 0.001] and higher baseline CD4+ T cell count (RR = 1.72, per 100 cells/μL, P < 0.001) were significantly associated with a low total HIV-1 DNA count at week 96. In an independent cohort of 117 patients, this model achieved a sensitivity of 75.00% and specificity of 69.52%.Conclusions: Baseline total HIV-1 DNA and CD4+ T cell count are two independent predictors of total HIV-1 DNA after treatment. The derived model based on these two baseline factors provides a useful prognostic tool in predicting HIV-1 DNA reservoir control during cART. [ABSTRACT FROM AUTHOR]

Background: The 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. Method: Twenty 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). Results: Eighteen 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. Conclusion: Patients 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 registration: NCT04596488; Registered 21 October, 2020; Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: The 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.Method: Twenty 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).Results: Eighteen 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.Conclusion: Patients 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 Registration: NCT04596488 ; Registered 21 October, 2020; Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: A more time saving, convenient, reproducible, and scalable method is needed to assess total HIV-1 DNA levels.Methods: Frozen whole blood and peripheral blood mononuclear cell (PBMC) samples both 200 μl at the same point were used to detect total HIV-1 DNA. Automatic extraction of total HIV-1 DNA was used to ensure the consistency of sample extraction efficiency. The detection reagent was HIV-1 DNA quantitative detection kit and real-time quantitative PCR was utilized.Results: Of the 44 included patients, 42 were male and 2 were female, with a median age of 33 years. Thirty-three cases were collected after receiving antiviral treatment, with a median duration of treatment of 3 months, and the other 11 cases were collected before antiviral treatment. The median viral load was 1.83 log10 copies/mL, the median CD4 and CD8 count were 94 and 680 cells/μL, and the median CD4/CD8 ratio was 0.18. The results of the two samples were 3.02 ± 0.39 log10 copies/106 PBMCs in PBMC samples and 3.05 ± 0.40 log10 copies/106 PBMCs in whole blood samples. The detection results of the two methods were highly correlated and consistent by using paired t test (P = 0.370), pearson correlation (r = 0.887, P < 0.0001) and intra-group correlation coefficient (ICC = 0.887, P < 0.0001) and bland-altman [4.55% points were outside the 95% limits of agreement (- 0.340 ~ 0.390)].Conclusions: The results of the whole blood sample test for total HIV-1 DNA are consistent with those of PBMC samples. In a clinical setting it is recommended to use whole blood samples directly for the evaluation of the HIV reservoir. [ABSTRACT FROM AUTHOR]

Background: The impact of HIV-1 subtype (CRF01_AE and non-CRF01_AE) on HIV-1 DNA levels in HIV-1 chronically infected patients with suppressive antiretroviral therapy (ART) remains poorly understood. To evaluate the correlation of HIV-1 subtype with DNA level, and identify baseline predictors of HIV-1 DNA decay.Methods: ART-naïve HIV-1-infected patients from two large multi-center studies in China were classified into CRF01_AE and non-CRF01_AE subtype groups. Peripheral blood samples were collected at baseline and week 12, 24, 48 and 96 after ART initiation and total HIV-1 DNA levels were quantified by real-time PCR. HIV-1 DNA levels at week 96 were categorized into high, moderate, and low levels, reflecting HIV-1 DNA ≥ 3, 2-3, ≤ 2 log10 copies/106 PBMCs, respectively, and the corresponding proportion of CRF01_AE and non-CRF01_AE subtype were compared. The baseline predictors of low HIV-1 total DNA levels (≤ 2 log10 copies/106 PBMCs) at week 96 were evaluated using a logistic regression model.Results: Compared to the non-CRF01_AE subtypes (n = 185), patients with CRF01_AE subtype (n = 188) harboured a higher level of HIV-1 DNA (median: 3.19 vs. 2.95 log10 copies/106 PBMCs, P < 0.001) prior to treatment. After 96 weeks of ART, HIV-1 DNA levels remained higher in the CRF01_AE subtype group (median: 2.63 vs. 2.39 log10 copies/106 PBMCs, P = 0.002). There was no significant difference in the proportion of patients achieving high (22.3% vs. 14.6%, P = 0.054), moderate (59.6% vs. 60.5%, P = 0.849) and low levels (18.1% vs 24.9%, P = 0.111) between CRF01_AE and non-CRF01_AE groups. In the multivariable analysis, baseline HIV-1 DNA level and CD4+ T cell count but not the subtype were independent risk factors for achieving HIV-1 DNA level ≤ 2 log10 copies/106 PBMCs.Conclusion: HIV-1 CRF01_AE subtype is neither correlated with HIV-1 DNA reservoir decline nor a prognostic factor for achieving lower HIV-1 DNA levels (≤ 2 log10 copies/106 PBMCs) after ART. However, higher HIV-1 DNA level in HIV-1 CRF01_AE patients should be aroused much attention and strengthen surveillance during ART. [ABSTRACT FROM AUTHOR]

Background: The HIV-1 DNA reservoir is an important marker that reflects viro-immunological status and can be affected by multiple viral or cellular factors. Determining the potential factors associated with the size of the HIV-1 DNA reservoir benefits the surveillance of disease progression and antiretroviral treatments.Methods: We conducted a case control study to explore the factors that may affect the level of HIV-1 DNA. The level of HIV-1 total DNA in peripheral blood at 5 time points was quantified by quantitative PCR. Chronically HIV-1-infected patients whose cell-associated HIV-1 DNA levels were below the detection limit after receiving antiretroviral therapy (ART) for 96 weeks were identified (group 1), and patients who still had detectable levels of cell-associated HIV-1 DNA after ATR treatment were used as the control (group 2).Results: Twenty-one patients with ultralow levels of cell-associated HIV-1 DNA [<20 copies/106 peripheral blood mononuclear cells (PBMCs)] presented with a lower CD8+ T-cell count (average: 511 ± 191 versus 715 ± 256 cells/μL, p = 0.013) and a higher CD4/CD8 ratio (average: 1.04 ± 0.37 versus 0.72 ± 0.32, respectively, p = 0.002) at week 96. In the multivariate analysis, patients with a higher CD4/CD8 ratio at week 96 were more likely to have levels of HIV-1 DNA below the detection limit (per 0.1 increase, OR = 1.29, 95% CI, 1.05-1.59, p = 0.017).Conclusion: After matching baseline HIV-1 DNA levels, a higher CD4/CD8 ratio at week 96 was the only factor associated with an ultralow level of HIV-1 DNA. The CD4/CD8 ratio can be used as an easy biomarker to help monitor patients on ART who will be selected to participate in eradication studies. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular disease (CVD) is an important cause of mortality among HIV-infected patients, however little is known about the burden of CVD among this population in Asia. We sought to quantify prevalence of CVD risk factors, 10-year CVD risk, and patterns of CVD risk factor treatment in a group of individuals with HIV in China.Methods: We retrospectively analyzed baseline data from treatment-naïve HIV-infected adults enrolled in two multicenter clinical trials in China. Data regarding CVD risk factors such as smoking, hypertension, diabetes, dyslipidemia and obesity were assessed. The Framingham Risk Score (FRS) and Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) risk scores were calculated to estimate 10-year CVD risk. The American College of Cardiology/American Heart Association Atherosclerotic Cardiovascular Disease (ASCVD) Risk Score was used to identify individuals meeting criteria for lipid-lowering therapy.Results: In total, 973 patients were included in the analysis. Mean age was 36.0 ± 10.2 years and 74.2% were men. The most common CVD risk factors were dyslipidemia (51.7%) and smoking (23.7%). Prevalence of hypertension, diabetes and obesity were 8.4%, 4.6% and 1.0%, respectively. Over 65% of patients had at least one CVD risk factor. The prevalence of 10-year risk of CVD ≥10% was 4.5% based upon FRS and was 3.3% based upon D:A:D risk score. Few patients with dyslipidemia, hypertension or diabetes were on treatment.Conclusions: CVD risk factors are common but under-treated among Chinese treatment-naïve individuals with HIV. Future interventions should focus on training HIV providers to appropriately recognize and manage CVD risk factors during routine clinical assessments. [ABSTRACT FROM AUTHOR]

Background: Dengue virus is transmitted by mosquito around the tropical and sub-tropical regions. There was a large-scale dengue epidemic in Guangdong province, China during 2014 and around fifty thousands dengue fever cases, including six deaths, have been reported. In this study, we aimed to understand the clinical characteristics of hospitalized patients with laboratory-confirmed dengue virus (DENV) infection and determined the origin of the virus from the outbreak.Methods: We have summarized the data from 138 hospitalized patients who were laboratory confirmed for dengue infection in Guangzhou city. Patients were classified as either non-severe dengue fever or severe dengue fever according to the guidelines from the WHO. Viral serotypes were determined by real time RT-PCR. Genetic sequences of the envelope and non-structural genes were amplified and analyzed from the serum samples of eleven patients.Results: Co-circulation of dengue serotype 1 and 2 were identified from the outbreak. Patients infected by serotype 1 or 2 showed similar clinical features. Patients with severe dengue fever showed prolonged hospitalization and significant impairment of organ functions. Four samples from serotype 1 and five samples from serotype 2 were closely related respectively and clustered with Guangzhou isolates from previous years. The remaining isolates of serotype 1 were related to viruses found in Malaysia, India, Bangladesh and Singapore.Conclusion: The phylogenetic grouping of Guangdong isolates suggests that dengue is no longer an imported disease in China. Analysis of the isolates obtained in this study together with the size of the outbreak are suggestive of endemic circulation in Guangdong province. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

Background: The effect of ART initiation time on HIV-1 DNA reservoir in chronically infected individuals is not well understood. Determining the potential influencing factors associated with a low HIV-1 DNA level in chronic infection is an important step toward drug-free control.Methods: A prospective study included 444 chronically HIV-infected adults was performed. Participants were divided into two groups: early initiation group (EIG) or delayed initiation group (DIG) based on their baseline CD4 count; 350 to 500 and < 350 cells/mm3, respectively. Total HIV-1 DNA was measured by quantitative PCR. Using the Mann-Whitney U test, the HIV-1 DNA level at week 48 was compared between the two groups. The influencing factors of the HIV-1 DNA and factors associated with achieving a low HIV-1 level at week 48 were analyzed.Results: The HIV-1 DNA at week 48 in EIG was significantly lower than in DIG [2.12 (1.80-2.51) vs 2.58 (2.21-2.87) log10 copies/106peripheral blood mononuclear cells (PBMCs); p = 0.001]. Early ART initiation was positively associated with lower HIV-1 DNA at week 48 (p = 0.025). Similarly, baseline HIV-1DNA (p = 0.001) was positively associated with HIV-1DNA at week 48 and baseline CD4/CD8 ratio (p = 0.001) was inversely associated with HIV-1DNA at week 48. Early ART initiation (p = 0.003) and baseline HIV-1 DNA level (p < 0.001) were positively associated with achieving HIV-1 DNA < 100 copies/106 PBMCs at week 48.Conclusion: Early ART initiation is positively associated with a smaller size of viral reservoir and a higher possibility of achieving a low HIV-1DNA level at week 48 in Chinese chronically HIV-1 infected adult.Trial Registration: NCT01844297 ; Registered 1 May, 2013. [ABSTRACT FROM AUTHOR]