Biomarkers are very useful in the diagnosis and identification of neurocognitive impairments (NCIs) or disorders (NCDs) in HIV-infected individuals, and in particular, blood biomarkers have become more promising because they are cheap and easy to obtain or accept. A systematically literature retrieval was conducted by using PubMed, CNKI, Wanfang and VIP databases for studies about blood biomarkers of neurocognitive impairment of HIV-infected individuals in 2008-2017, according to the inclusion and exclusion criteria. Finally, a total of 43 related articles were included for this systematic review for the purpose of providing scientific evidence for further research and clinical practices.
Adult ; Anti-Retroviral Agents/therapeutic use* ; Biomarkers/blood* ; Cognition Disorders/diagnosis* ; Female ; HIV Infections/drug therapy* ; Humans ; Neurocognitive Disorders/diagnosis*

BACKGROUND/AIMS: Advanced human immunodeficiency virus (HIV) infection, despite sustained viral suppression by highly active antiretroviral therapy (HAART), is a risk factor for poor immunologic recovery. However, some patients with advanced infection do show immunologic recovery. In this study, predictive factors of immunologic recovery were analyzed in advanced HIV patients showing sustained viral suppression. METHODS: A case-control study was conducted in HIV-infected adult patients with HIV-1 RNA < 50 copies/mL maintained for 4 years or longer and who were receiving HAART. Advanced HIV infection was defined as a baseline CD4 T cell count < 200/mm3. Immunologic responders were defined as patients showing immunologic recovery (CD4 T cell counts > or = 500/mm3 at 4 years with HAART). To analyze the CD4 T cell kinetics, the CD4 slope (monthly changes in the CD4 T cell count) was estimated for each patient using a linear regression between the CD4 T cell count and the time since HAART initiation. RESULTS: Of 102 eligible patients, 73 had advanced HIV, and 33 (45.2%) showed immunologic recovery. The median CD4 slopes (cells/mm3 per month) during 0 to 6 and 0 to 12 months of HAART in the 73 advanced patients were significantly higher in responders than in non-responders (0 to 6 months, 38.6 vs. 22.8; 0 to 12 months, 24.5 vs. 13.5). Multivariate analyses showed opportunistic infections at the start of HAART (adjusted odds ratio [OR], 0.28) and a CD4 slope > or = 20 during 0 to 12 months of HAART (adjusted OR, 10.10) were independently associated with immunologic recovery. CONCLUSIONS: The CD4 slope can be an early predictor of long-term immunologic recovery in advanced HIV patients.
Adult ; Anti-HIV Agents/therapeutic use ; Antiretroviral Therapy, Highly Active ; Biomarkers/blood ; *CD4 Lymphocyte Count ; Case-Control Studies ; Chi-Square Distribution ; Female ; HIV Infections/*diagnosis/drug therapy/*immunology/virology ; HIV-1/drug effects/genetics/*immunology ; Humans ; Linear Models ; Logistic Models ; Male ; Middle Aged ; Monitoring, Immunologic/*methods ; Multivariate Analysis ; Odds Ratio ; Predictive Value of Tests ; RNA, Viral/blood ; Time Factors ; Treatment Outcome ; Viral Load

Acute Kidney Injury ; blood ; etiology ; therapy ; Anti-Retroviral Agents ; administration & dosage ; CD4 Lymphocyte Count ; Disease Progression ; Embolization, Therapeutic ; methods ; Fatal Outcome ; Gastrointestinal Hemorrhage ; diagnostic imaging ; etiology ; physiopathology ; therapy ; Glucocorticoids ; administration & dosage ; HIV Infections ; complications ; diagnosis ; immunology ; HIV-1 ; drug effects ; isolation & purification ; Humans ; Male ; Middle Aged ; Purpura, Schoenlein-Henoch ; complications ; diagnosis ; physiopathology ; Radiography ; Renal Dialysis ; methods

PURPOSE: HIV-infected patients are at increased risk for cardiovascular disease, which may be mediated in part by inflammation. This study aimed to evaluate the risk factors of carotid plaque, and clinical factors associated with carotid atherosclerosis measured by carotid intima-medial thickness (cIMT) in HIV patients. MATERIALS AND METHODS: Clinical and cardiometabolic factors as well as cIMT were prospectively measured in 145 HIV-infected participants who had received combined antiretroviral therapy for > or =6 months. The mean value of the bilateral average cIMT level was used as Mean-IMT in the analysis, and the greatest value among the measured cIMT levels was used as Max-IMT. RESULTS: Among 145 patients, 34 (23.4%) had carotid plaque. Multivariate logistic regression analysis revealed three independent risk factors of carotid plaque: old age [odds ratio (OR) 6.16, 95% confidence interval (CI) 1.09-34.88; p=0.040], hypertension (OR 12.62, 95% CI 1.72-92.49; p=0.013) and higher low-density lipoprotein cholesterol (LDL-C) (OR 1.08, 95% CI 1.01-1.16; p=0.039). Levels of estimated glomerular filtration rate were inversely associated with Mean-IMT (r=-0.379, p<0.001) and Max-IMT (r=-0.389, p<0.001). Stepwise multivariate regression analyses revealed that age, total cholesterol and fasting glucose were positively correlated with cIMT, independent of other risk factors. CONCLUSION: The presence of hypertension, old age and a higher level of LDL-C were independent risk factors of carotid plaque among HIV-infected subjects.
Adult ; Age Factors ; Blood Glucose/analysis ; Carotid Artery Diseases/*etiology/*ultrasonography ; Carotid Intima-Media Thickness ; Cholesterol, LDL/blood ; Female ; Glomerular Filtration Rate ; HIV Infections/*complications/drug therapy/physiopathology ; Humans ; Hypertension/complications/physiopathology ; Logistic Models ; Male ; Middle Aged ; Odds Ratio ; Prospective Studies ; Risk Factors

OBJECTIVE: To observe the dynamic changes of 3 types of viral reservoir cells (NK cells, T lymphocytes and monocytes), and its relationship with treatment effect in Chinese HIV-1 infected patients receiving highly active antiretroviral treatment (HAART) for 2 years. METHODS: A total of 40 chronic HIV-1-infected adults who initiated HAART were enrolled in this study and followed up for 2 years. Peripheral whole blood was obtained from each patient at baseline (0 month), 6, 12, 18 and 24 months. Real-time fluorescent quantitative PCR was used to detect the HIV-1 RNA in the plasma and HIV-1 DNA in NK cells, T lymphocytes and monocytes. All the data were statistically analyzed. RESULTS: CD4 count increased with the decrease of the viral load during HAART. After HAART initiation, HIV-1 DNA showed a significant decrease in NK cells, T lymphocytes and monocytes. The HIV-1 DNA from T lymphocytes, NK cells and monocytes correlated positively with the HIV- 1 RNA (P<0.05) while NK cells and T lymphocytes correlated negatively with CD4+ T cell count. However we did not find significant correlation between CD4+ T cell count and HIV-1 DNA in monocytes at the baseline of HAART. CONCLUSION This study found that NK cell was an important HIV cellular reservoir besides T lymphocytes and monocytes. T lymphocytes may be the main long lasting HIV reservoir. HIV-1 proviral DNA may play an important role in the efficacy of treatment and monitoring the disease progression.
Adult ; Antiretroviral Therapy, Highly Active ; DNA, Viral ; analysis ; Female ; HIV Infections ; drug therapy ; virology ; HIV-1 ; genetics ; Humans ; Killer Cells, Natural ; virology ; Male ; Middle Aged ; Monocytes ; virology ; RNA, Viral ; blood ; T-Lymphocytes ; virology ; Viral Load

Metabolic syndrome is an important long term complication in chronic asymptomatic HIV-infected subjects under highly active antiretroviral therapy (HAART), because it can contribute to morbidity and mortality via cardiovascular disease (CVD). Therefore, a predictive marker for early detection of metabolic syndrome may be necessary to prevent CVD in HIV-infected subjects. Retinol-binding protein-4 (RBP-4) has been shown to be associated with metabolic syndrome in various non-HIV-infected populations. We performed a cross-sectional study to evaluate whether serum RBP-4 levels are correlated with metabolic syndrome in HIV-infected subjects receiving HAART. In total, 98 HIV-infected Koreans who had been receiving HAART for at least 6 months were prospectively enrolled. Metabolic syndrome was diagnosed according to the Adult Treatment Panel III criteria, and serum RBP-4 concentrations were measured using human RBP-4 sandwich enzyme-linked immunosorbent assay. Serum RBP-4 levels were significantly higher in HIV-infected subjects receiving HAART with metabolic syndrome (n=33, 33.9+/-7.7 microg/mL) than in those without it (n=65, 29.9+/-7.2 microg/mL) (p=0.012). In multivariate linear regression analysis, the number of components of metabolic syndrome presented and waist circumference were independently, significantly correlated with RBP-4 (p=0.018 and 0.030, respectively). In conclusion, we revealed a strong correlation between RBP-4 and the number of components of metabolic syndrome in HIV-infected subjects receiving HAART.
Adult ; *Antiretroviral Therapy, Highly Active ; Enzyme-Linked Immunosorbent Assay ; Female ; HIV Infections/*blood/*drug therapy ; Humans ; Male ; Metabolic Syndrome X/*blood/*drug therapy ; Middle Aged ; Retinol-Binding Proteins, Plasma/*metabolism

INTRODUCTIONEfavirenz is an inducer of drug metabolism enzymes. We studied the effect of efavirenz and ritonavir-boosted darunavir on serum unconjugated and conjugated bilirubin, as probes for UGT1A1 and bile transporters.

MATERIALS AND METHODSHealthy volunteers were enrolled in a clinical trial. There were 3 periods: Period 1, 10 days of darunavir 900 mg with ritonavir 100 mg once daily; Period 2, 14 days of efavirenz 600 mg with darunavir/ritonavir once daily; and Period 3, 14 days of efavirenz 600 mg once daily. Serum bilirubin (conjugated and unconjugated) concentrations were obtained at baseline, at the end of each phase and at exit.

RESULTSWe recruited 7 males and 5 females. One subject developed grade 3 hepatitis on efavirenz and was excluded. Mean serum unconjugated bilirubin concentrations were 6.09 μmol/L (95% confidence interval [CI], 4.99 to 7.19) at baseline, 5.82 (95% CI, 4.88 to 6.76) after darunavir/ritonavir, 4.00 (95% CI, 2.92 to 5.08) after darunavir/ritonavir with efavirenz, 3.55 (95% CI, 2.58 to 4.51) after efavirenz alone and 5.27 (95% CI, 3.10 to 7.44) at exit (P <0.01 for the efavirenz phases). Mean serum conjugated bilirubin concentrations were 3.55 μmol/L (95% CI, 2.73 to 4.36) at baseline, 3.73 (95% CI, 2.77 to 4.68) after darunavir/ritonavir, 2.91 (95% CI, 2.04 to 3.78) after darunavir/ritonavir with efavirenz, 2.64 (95% CI, 1.95 to 3.33) after efavirenz alone and 3.55 (95% CI, 2.19 to 4.90) at exit (P <0.05 for the efavirenz phases).

CONCLUSIONEfavirenz decreased unconjugated bilirubin by 42%, suggesting UGT1A1 induction. Efavirenz also decreased conjugated bilirubin by 26%, suggesting induction of bile efflux transporters. Ritonavir-boosted darunavir had no effect on bilirubin concentrations. These results indicate that efavirenz may reduce concentrations of drugs or endogenous substances metabolized by UGT1A1 or excreted by bile efflux transporters.

Adult ; Aged ; Anti-HIV Agents ; therapeutic use ; Benzoxazines ; pharmacology ; Biological Transport ; Confidence Intervals ; Darunavir ; Dose-Response Relationship, Drug ; Drug Interactions ; Enzyme Induction ; drug effects ; Female ; Glucuronosyltransferase ; biosynthesis ; blood ; HIV Infections ; drug therapy ; HIV Protease Inhibitors ; Humans ; Incidental Findings ; Male ; Membrane Transport Proteins ; drug effects ; metabolism ; Middle Aged ; Ritonavir ; pharmacology ; Sulfonamides ; pharmacology ; Young Adult

A retrospective review of 4,721 human immunodeficiency virus (HIV)-infected patients, followed at St. Luke's Roosevelt Hospital Center, New York City, was conducted from January 1, 2005 to December 31, 2009. HIV-Hepatitis B virus (HBV) co-infection rate was 218/4,721, 4.6%. Among co-infected patients, 19 patients (19/218, 8.7%) died; 13 patients (13/19, 68.4%) died from non-acquired immune deficiency syndrome (AIDS) defining including 2 patients with liver failure. More non-survivors (5 patients, 5/19, 26.3%) had liver cirrhosis than those who survived (8 patients, 8/199, 4.0%; P = 0.002). There were more patients with positive HBV e antigen (HBeAg) among non-survivors, (12 patients, 12/19, 63.2%) than among survivors (74 patients, 74/199, 37.2%; P = 0.047). HIV-HBV co-infection is associated with increased overall mortality. Therefore, use of dual active antiretrovirals, particularly, tenofovir (TDF) based regimen for optimal suppression of HIV-HBV and immune restoration with prevention of high risk behaviors may contribute to improved outcomes.
Adenine/analogs & derivatives/therapeutic use ; Adult ; Anti-HIV Agents/therapeutic use ; Coinfection/drug therapy/mortality ; Female ; HIV Infections/complications/*diagnosis/drug therapy ; Hepatitis B/complications/*diagnosis/drug therapy ; Hepatitis B e Antigens/blood ; Humans ; Liver Cirrhosis/etiology ; Male ; Middle Aged ; New York City ; Organophosphonates/therapeutic use ; Retrospective Studies

OBJECTIVETo explore the effects of Fuzheng Paidu Tablet (FPT) on serum levels of tumor necrosis factor-alpha (TNF-alpha) and neopterin (NPI) in patients with asymptomatic human immunodeficiency virus (HIV) carriers.

METHODSUsing flow cytometry detection technology, CD T lymphocyte in anticoagulant blood sample of 32 asymptomatic HIV infection patients who were taking FPT for 6 months was detected and compared with before treatment. The serum levels of TNF-alpha and NPI were determined using ELISA method and compared with 22 healthy volunteers.

RESULTSAfter 6 months of treatment by FPT, the CD4+ T lymphocyte of asymptomatic HIV carriers increased from (368.63 +/- 111.54)/mm3 to (412.72 +/- 159.63)/mm3. Before treatment the serum levels of TNF-alpha [(20.05 +/- 13.08) nmol/L] and NPI [(9.55 +/- 2.52) nmol/L] were obviously higher than those of the healthy volunteers [(12.20 +/- 4.07) nmol/L and (5.91 +/- 1.43) nmol/L] (P < 0.05). After 6 months of treatment by FPT, they were lower after treatment than before treatment (P < 0.05). But there was no statistical difference in the serum TNF-alpha level [(11.06 +/- 4.71) nmol/L] when compared with the healthy volunteers group (P > 0.05). But the serum NPI level [(8.08 +/- 2.13) nmol/L] was still higher than that of the healthy volunteers group (P < 0.05).

CONCLUSIONSOne of the pathological factors for asymptomatic HIV infection is abnormal immune activation represented by increased serum levels of TNF-alpha and NPI. FPT could lower the serum levels of TNF-alpha and NPI in asymptomatic HIV infection patients, which was one of its possible mechanisms for its efficacy.

Adult ; Aged ; CD4 Lymphocyte Count ; Case-Control Studies ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; HIV Infections ; blood ; drug therapy ; Humans ; Male ; Middle Aged ; Neopterin ; blood ; Tablets ; Tumor Necrosis Factor-alpha ; blood

BACKGROUNDThe pharmacokinetics of zidovudine (AZT) are possibly influenced by weight, age, sex, liver and renal functions, severity of disease, and ethnicity. Currently, little information is available on the steady-state pharmacokinetics of AZT in Chinese HIV-infected patients. The current study aimed to characterize the steady-state pharmacokinetics of AZT in a Chinese set-up.

METHODSEleven Chinese HIV-infected patients were involved in the steady-state pharmacokinetic study. In total, 300 mg of AZT, as a part of combination therapy, was given to patients, and serial blood samples were collected for 12 hours. The samples were measured by a high-performance liquid chromatography (HPLC) assay, and the results were analyzed by both the non-compartment model and the one-compartment model.

RESULTSThe C(max) of AZT in Chinese patients was higher than that in non-Asian patients. The half-life of AZT, analyzed by the non-compartment model (P = 0.02), in male patients ((1.02 ± 0.22) hours) was shorter than that of AZT in female patients ((1.55 ± 0.29) hours). The AZT clearance, analyzed by the one-compartment model (P = 0.045), in male patients ((262.60 ± 28.13) L/h) was higher than that in female patients ((195.85 ± 60.51) L/h).

CONCLUSIONThe present study provides valuable information for the clinical practice of AZT-based highly active antiretroviral therapy in a Chinese set-up.

Adult ; Anti-HIV Agents ; pharmacokinetics ; therapeutic use ; Asian Continental Ancestry Group ; Female ; HIV Infections ; blood ; drug therapy ; Humans ; Male ; Middle Aged ; Zidovudine ; pharmacokinetics ; therapeutic use