[Show abstract][Hide abstract] ABSTRACT: Human leukocyte antigen (HLA)-B*5701 is strongly associated with developing a hypersensitivity reaction to abacavir (ABC). Limited data exist on HLA-B*5701 prevalence in HIV-1-infected subjects in China. We investigated HLA-B*5701 prevalence in HIV-1-infected population including Han and non-Han ethnic groups.
A prospective multi-centre study was designed to determine status of HLA-B*5701 in HIV-1-infected adults at six sites across China. HLA-B*5701 was tested by the method of PCR-SSP.
From six centers, 3,000 HIV-infected patients [2,452 (81.7%) Han, 548 (18.3%) Non-Han] were recruited with a mean age of 36.7 years old. The overall HLA-B*5701 prevalence was 0.86% [95% confidence interval (CI) 0.55-1.26%]. The prevalence of HLA-B*5701 among Han subjects was similar to that among non-Han subjects, which was 0.88% (95% CI 0.54-1.34%) and 0.76% (95% CI 0.19-1.93%), respectively (p value = 0.787). There were no differences in prevalence of HLA-B*5701 between subjects born in Henan, Yunnan, Shanxi, Guangdong, Hebei, Beijing and other provinces (p = 0.999).
HLA-B*5701 prevalence is very low in HIV-infected Chinese subjects, both in the Han and Non-Han nationalities. And there are no differences among different birthplaces across China.
Preview · Article · Aug 2015 · AIDS Research and Therapy
[Show abstract][Hide abstract] ABSTRACT: As cellular reservoirs, CD16 monocyte subsets play important roles in the progression of HIV infection. Previous studies have shown that highly active antiretroviral therapy (HAART) reduced the percentages of CD14CD16 monocyte subsets, but did not recover the percentages of CD14CD16 subsets. Eighty-four chronic HIV-infected, HAART-naïve individuals and 55 HIV-negative subjects (31 without hyperlipidemia and 24 with hypertriglyceridemia) were enrolled. Plasma HIV-1 RNA levels, CD4 T-cell counts, triglycerides, total cholesterol, high-density lipoprotein, and low-density lipoprotein were followed up for 48 weeks during HAART treatment in the longitudinal study. We found that mild hypertriglyceridemia in HIV-negative subjects and HIV-infected patients, naïve to HAART, did not affect the percentage of monocyte subsets. However, a failure of CD14CD16 subset recovery was observed in patients with HAART-related hypertriglyceridemia at 48 weeks. Thus, HAART-related hypertriglyceridemia altered homeostasis of monocyte subsets to antiviral therapy, which might further affect immune reconstitution.
[Show abstract][Hide abstract] ABSTRACT: The important pathophysiological role of immune dysfunction, especially innate immune dysfunction in patients with acute-on-chronic liver failure (ACLF), has been investigated in recent years, but dysregulation of adaptive immunity remains poorly elucidated. The aim of this study was to (i) determine the CD3(+) T-lymphocyte count and the balance between CD4(+) regulatory T (Tregs) and conventional T cells (Tconv) in hepatitis B virus (HBV)-related ACLF patients; (ii) analyse the frequencies of Tregs subpopulations; and (iii) assess the suppressive potency of CD4(+) Tregs and each fraction.
We enrolled 20 HBV-ACLF patients, 10 septic shock subjects, 20 chronic hepatitis B (CHB) patients and 20 healthy volunteers (HC). Based on flow cytometry, we performed the absolute counting of circulating T lymphocytes and phenotyping of CD4(+) Tregs and quantified the effects of Tregs and each subpopulation on Tconv proliferation by CFSE staining.
Compared with CHB patients and HC, we observed an equal reduction in peripheral T subsets in HBV-ACLF and septic shock subjects; the number of CD4(+) Tregs remained unchanged and the Tconv count declined, promoting elevation of the Treg-to-Tconv ratio. The frequencies of Treg-II and -III were elevated in HBV-ACLF. Functional studies showed that the suppressive capacity of Tregs was preserved in the HBV-ACLF group and Treg-II came first.
Similar to septic shock subjects, in HBV-ACLF patients there exists a reduction in CD4(+) T lymphocytes, predominantly CD4(+) Tconv, and the development of suppressive CD4(+) Tregs greatly prevails over Tconv, constituting important characteristics of adaptive immune dysfunction of HBV-ACLF.
No preview · Article · Jun 2013 · Liver international: official journal of the International Association for the Study of the Liver
[Show abstract][Hide abstract] ABSTRACT: Objective:
T regulatory (Treg) cells are a heterogeneous population that consists of CD4(+)CD25(low)CD45RA(+) [naive Treg (nTreg) cells] and CD4(+)CD25(high)CD45RA(-) [activated Treg (aTreg) cells] subsets. We investigated the effects of HIV infection and HAART on distinct Treg subsets.
HIV-infected adult patients naive to HAART (n=57), patients with acute HIV infection (n=13), and healthy controls (n=92) were recruited for a cross-sectional study. Patients receiving HAART were followed up in a longitudinal study.
Compared with healthy controls, we observed a reduced proportion of nTreg cells and an elevated frequency of aTreg cells in peripheral blood from HAART-naïve patients. Moreover, nTreg cells showed a decreased CD31(+) frequency, whereas aTreg cells showed an increased CD31(+) frequency, indicating impaired thymic output and excessive conversion from nTreg to aTreg cells. nTreg and aTreg cells both displayed higher levels of Ki67(+), reflecting hyperproliferation. The longitudinal study showed that HAART successfully recovered nTreg but not aTreg cell frequency. Higher baseline naïve CD4 T-cell percentages were associated with faster reconstitution of nTreg cell frequency as well as CD4(+) T-cell count.
Our data suggest that the disturbed homeostasis of Treg cells in HIV-infected patients is probably caused by excessive conversion from nTreg to aTreg cells, and impaired thymic output of nTreg cells. nTreg cells can be recovered by HAART, which was associated with baseline naive CD4(+) T-cell percentages, indicating that reconstitution of nTreg cells may benefit from earlier antiretroviral treatment.
No preview · Article · Jan 2013 · AIDS (London, England)
[Show abstract][Hide abstract] ABSTRACT: To analyze the genotypic resistance profiles of HIV-infected children from rural China who were experiencing virologic failure to first-line antiretroviral therapy regimens and to evaluate 1-year regimen efficacy after switching to second-line therapy.
A prospective cohort study was performed. Seventy-six children from the first rural pilot program with HIV viral load >1000 copies per milliliter on 2 consecutive occasions were studied. We analyzed genotype results and observed second-line therapy efficacy to 12 months.
After 33.1 (23.3, 41.1) months on first-line treatment after enrollment into national program, 98.7% of genotyped patients developed high-level resistance to nevirapine and 81.6% of patients had high-level resistance to efavirenz. High-level resistance to lamivudine was observed in 82.9%, followed by 57.9% for stavudine and 52.6% for zidovudine. In the nonnucleoside reverse transcriptase inhibitor class, the most common mutations were K103N/S at 50% and Y181C/I at 48.7%. M184V/I was the most common nucleoside reverse transcriptase inhibitor resistance mutation at 77.6%, the mutation rate for ≥3 thymidine analogue mutations, Q151M, and K65R were 33%, 12%, and 9%, respectively. After 12 months of boosted protease inhibitor-based second-line therapy, CD4 counts had on average increased 256 cells per cubic millimeter compared with switch baseline and 83.1% of patients had undetectable viral loads (<50 copies/mL).
HIV-1-infected children who continued their first-line regimen regardless of virologic failure harbored multiple resistance mutations. Although the extent of resistance to nucleoside reverse transcriptase inhibitor class drugs would be expected to limit subsequent treatment options, the current second-line regimen remained effective during a 1-year observational period.
No preview · Article · Jun 2011 · JAIDS Journal of Acquired Immune Deficiency Syndromes