Pharmacokinetics of plasma efavirenz and CYP2B6 polymorphism in southern Chinese.

Cytochrome P450 2B6 (CYP2B6) is the main metabolizing pathway for efavirenz (EFV), the prescription of which is associated with neurologic side effects. The authors conducted a study on the prevalence of CYP2B6 polymorphism, profile of side effects, and pharmacokinetics of EFV in a group of human immunodeficiency virus (HIV)-infected southern Chinese. Patients with HIV were recruited at the Shenzhen City Third People's Hospital, China. The prevalence of CYP2B6 G516T and plasma EFV concentration were determined. Pharmacokinetics was assessed using blood samples of selected patients at time 0, 1, 2, 4, 8, 12, and 24 hours after the last dose of EFV. Between October 2007 and June 2008, 79 Chinese patients with HIV were recruited. Sequencing of CYP2B6 at position 516 gave 42 GG, 34 GT, and 3 TT genotypes, with corresponding mean spot plasma EFV level of 3.4, 4.1, and 8.1 mg/L, respectively. The allelic frequency of 516 G>T was 0.25. Univariate analysis showed that plasma EFV level correlated with genotype (P = 0.02). Eighteen patients completed the pharmacokinetic study: TT genotype gave the longest half-life (t 1/2), highest plasma EFV concentration, and largest area under the curve. The volume of distribution per surface area (Vd ss), total clearance (Cltot), and elimination rate constant (ke) were the lowest. There was no association between the occurrence of side effects and the EFV concentration (chi2 test, P > 0.05). The EFV pharmacokinetics of TT genotype differed significantly from GG and GT genotypes. Accumulation of EFV may potentially occur over time, causing toxicity in TT and GT genotypes.

Correlation between imaging features of Pneumocystis Jiroveci Pneumonitis (PCP), CD(4) (+) T lymphocyte count, and plasma HIV viral load: A study in 50 consecutive AIDS patients.

PURPOSE: To investigate the imaging manifestations of Pneumocystis Jiroveci Pneumonitis (PCP) in AIDS patients, and the correlation between imaging features, CD(4) (+) lymphocyte count, and plasma HIV viral load. MATERIALS AND METHODS: A total of consecutive 50 AIDS patients with PCP were reviewed retrospectively. Chest CT manifestations, CD(4) (+) lymphocyte count, and plasma HIV viral load were analyzed to investigate their correlation. RESULTS: PCP chest CT manifestations included ground-glass opacities dominated in 28 cases (28/50, 56%), lung cysts dominated in 10 cases (10/50, 20%), consolidation dominated in 6 cases (6/50, 12%), interstitial lesion dominated in 3 cases (3/50, 6%), and mixed lesions in 3 cases (3/50, 6%). In these 50 patients, CD(4) (+) lymphocyte count ranged from 2 to 373 cells/µL. Plasma HIV viral load ranged from 500 to 5.28×10(7) copies/mL. CD(4) (+) lymphocyte count in ground-glass opacities dominated patients was higher than that of lung cyst dominated patients (P<0.05). Plasma virus load of lung cysts dominated PCP patients was higher than that of consolidation dominated patients (P<0.05). CONCLUSIONS: The typical chest imaging features of PCP in AIDS patients included lung ground-glass opacities and lung cysts. The chest imaging features were correlated with CD(4) (+) T lymphocyte count and plasma HIV viral load.

Radiologic diagnosis for AIDS patients complicated with candidal esophagitis.

BACKGROUND: Candidal esophagitis is the primary infection among all digestive tract opportunistic ones in acquired immunodeficiency syndrome (AIDS) cases. X-ray manifestation reports of it are still rare. This study aimed to conduct a retrospective analysis on the X-ray data of 6 AIDS cases complicated with candidal esophagitis, and to study the X-ray characteristics of it combined with the findings from gastroscopy. METHODS: Among 6 cases in this series, all cases were confirmed by Shenzhen Center for Disease Control and Prevention (CDC) to be HIV positive and all of them had CD4 cell counts less than 150 × 10(6)/L. All cases underwent X-ray and gastroscopy, and mycelium were found in the mucous membrane of the esophagus. RESULTS: In this series, the findings of the X-ray were as follows: (1) Affected areas: Four cases in the whole esophagus, 2 cases in the middle and lower part of esophagus; (2) Abnormal motivity: Six cases had decreased tension, loose walls, weakened peristalsis, decreased number of peristalsis waves and delayed emptying of barium; (3) Abnormal contour: Six cases had the sign of "decorative border" or "brush", two cases had narrowed canal; (4) Abnormal membrane and "cobblestone sign": Six cases had thickened membrane and "cobblestone sign" on the surface of the abnormal membrane. The hyperemia of mucosa was covered tightly with yellow-white pseudomembrane spots. This was in accordance with the small cobblestone-like filling defect found by X-ray. CONCLUSIONS: If the AIDS cases have dysphagia, and X-ray shows that more than two sections of the esophagus are affected, with decreased motility, the walls in the sign of "brush" or "decorative edges", thickened membrane with "cobblestone sign", candidal esophagitis is highly possible.

[Preliminary study of the Th17/Treg immunoregulation in patients coinfected with TB and HIV before and after HAART].

OBJECTIVE: To study the Th17/Treg (regulatory T cells) immunoregulation in patients coinfected with TB and HIV before and after HAART(highly active anti-retroviral therapy). METHODS: 10 HIV cases coinfected with TB (HIV/TB group) and 10 cases infected with HIV only (HIV group) received HAART. PBMCs were stained and immunophenotyping of Th17 (IL-17 expressing T cells) and CD4+ CD25 T cells (Treg) were analysed by flow cytometry. RESULTS: The pre-treatment patients tended to have lower Th17 cells and higher Tregs cells compared to post-treatment (1.90% +/- 0.9% vs. 4.65% +/- 1.48%, 16.48% +/- 4.91% vs. 8.29% +/- 3.13% respectively). The percentage of IL-17 before and after HAART were 1.90 +/- 0.9% vs. 4.65 +/- 1.48% respectively in HIV/TB group patients (P < 0.01). The difference between the percentage of IL-17 before and after HAART in the HIV/TB group and the HIV group were 2. 65 +/- 1.62% vs. 0.67% +/- 0.46% respectively (P < 0.01). IL-17 expressing T cells were increased faster after HAART in the former group than the latter. The percentage of Treg before and after HAART were 16.48% +/- 4.91% vs. 8.29% +/- 3.13% respectively in HIV/TB group (P < 0.01). The difference between the percentage of Treg before and after HAART in the HIV/TB group and the HIV group were 8.91% +/- 4.82% vs. 2.63% +/- 2.34% respectively (P < 0.01). Treg were decreased more rapidly after HAART in the former than the latter. CONCLUSIONS: TB and HAART both had an effect on the Th17/Treg ratio of HIV/ TB co-infected patients, which can cause increased Th17 expression, the later plays a pro-inflammatory role. TB and HAART can decrease Treg expression and enhance anti-inflammation response. The fact that Th17/ Treg disorder are more likely to exist in patients with HIV/TB co-infection after HAART for one month suggests a potential role for Th17/Treg imbalance leading to tuberculosis-associated immune reconstitution inflammatory syndrome during patients receiving HAART period.

[Immunosuppression induced by measles virus in adult patients is not related to CD4+ CD25+ regulatory T cell induction].

OBJECTIVE: To investigate of the relationship of the immunosuppression induced by Measles virus in adult patients and CD4+ CD25+ regulatory T cell. METHODS: Thirty-four patients with measles and 27 healthy control subjects were included in this study. The whole blood was collected and CD4+ CD25+ cell and FoxP3+ cell were analyzed by flow cytometry, and CD4+ CD25- and CD4+ CD25+ T lymphocytes were isolated from PBMCs of patients with measles or healthy donors, CD4+ CD25- T cells were cultured in absence or presence of anti-CD3, or BCG, or live attenuated MV. The cell culture supernatant was collected after 72 hours and the concentration of IFN-gamma and IL-10 was determined. RESULTS: Compared to healthy donors, we observed a reduction of the number of white blood cells and lymphocytes in patients with measles, but there was not significantly different in the frequency of CD4+ CD25+ T cells and CD4+ CD25high T cells within the total CD4+ population in the blood. Treg from both measles patients and healthy controls significantly inhibited IFN-gamma production by CD4+ CD25- T cells in response to anti-CD3 stimulation. CONCLUSION: Induction and expansion of Treg may not represent a mechanism involved in the establishment of immune suppression by MV.