Renfang Zhang

Interferon-Gamma Release Assays for the Diagnosis of Active Tuberculosis in HIV-Infected Patients: A Systematic Review and Meta-Analysis

Background Interferon-gamma release assays (IGRAs) have provided a new method for the diagnosis of Mycobacterium tuberculosis infection. However, the role of IGRAs for the diagnosis of active tuberculosis (TB), especially in HIV-infected patients remains unclear. Methods We searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001–July 2011 that evaluated the evidence of using QuantiFERON-TB Gold in-tube (QFT-GIT) and T-SPOT.TB (T-SPOT) on blood for the diagnosis of active TB in HIV-infected patients. Results The search identified 16 eligible studies that included 2801 HIV-infected individuals (637 culture confirmed TB cases). The pooled sensitivity for the diagnosis of active TB was 76.7% (95%CI, 71.6–80.5%) and 77.4% (95%CI, 71.4–82.6%) for QFT-GIT and T-SPOT, respectively, while the specificity was 76.1% (95%CI, 74.0–78.0%) and 63.1% (95%CI, 57.6–68.3%) after excluding the indeterminate results. Studies conducted in low/middle income countries showed slightly lower sensitivity and specificity when compared to that in high-income countries. The proportion of indeterminate results was as high as 10% (95%CI, 8.8–11.3%) and 13.2% (95%CI, 10.6–16.0%) for QFT-GIT and T-SPOT, respectively. Conclusion IGRAs in their current formulations have limited accuracy in diagnosing active TB in HIV-infected patients, and should not be used alone to rule out or rule in active TB cases in HIV-infected patients. Further modification is needed to improve their accuracy.

Anti-Retroviral Therapy Decreases but Does Not Normalize Indoleamine 2,3-Dioxygenase Activity in HIV-Infected Patients

Background Indoleamine 2,3-dioxygenase (IDO), which is mainly expressed in activated dendritic cells, catabolizes tryptophan to kynurenine and other downstream catabolites. It is known to be an immune mediator in HIV pathogenesis. The impact of anti-retroviral therapy on its activity has not been well established. Methods We measured systemic IDO activity (the ratio of plasma kynurenine to tryptophan) in HIV-infected patients before and after highly active antiretroviral therapy (HAART) and its association with a microbial translocation marker, soluble CD14 (sCD14). Results Among 76 participants, higher baseline IDO activity was associated with lower CD4+ T cell counts (P<0.05) and higher plasma sCD14 levels (P<0.001). After 1 year of HAART, IDO activity decreased significantly (P<0.01), but was still higher than in healthy controls (P<0.05). The baseline IDO activity did not predict CD4+ T cell recovery after 1 year of therapy. The percentages of myeloid and plasmacytoid dendritic cells were not correlated with IDO activity. Conclusions IDO activity is elevated in HIV-infected patients, which is partially associated with microbial translocation. HAART reduced, but did not normalize the activity of IDO.

Prevalence and clinical management of cytomegalovirus retinitis in AIDS patients in shanghai, china

BackgroundCytomegalovirus retinitis is a common AIDS-associated illness, leading to blindness in up to 30% of patients. This study was to investigate the prevalence and clinical management of the cytomegalovirus retinitis associated with AIDS in a large municipality of China.MethodsClinical and laboratory data from 23 cytomegalovirus retinitis patients (35 eyes) out of 303 hospitalized AIDS individuals in a single medical center were analyzed retrospectively. Two of 23 patients were diagnosed cytomegalovirus retinitis just before hospitalization without anti-CMV therapy. Ganciclovir combined with the high active anti-retroviral therapy was installed for treatment of cytomegalovirus retinitis after diagnosis was confirmed. The data were analyzed by specialists and statistics was also applied.ResultsThe prevalence of cytomegalovirus retinitis in hospitalized AIDS patients was 7.6% in this study. The level of CD4+ T lymphocytes was correlated well with the occurrence of cytomegalovirus retinitis, showing 16.8% (19/113) (95% confidence interval: 10.4,25.0), 5.4% (3/56) (95% confidence interval: 1.1,14.9), and 1.4% (1/69) (95% confidence interval: 0.0,7.8) occurrence in the patients with CD4+ T lymphocyte counts < 50, 50~99, and 100~199 cells/μl, respectively. The mean CD4+ T lymphocyte counts was 31.7 ± 38.6 cells/μl in 23 AIDS patients with cytomegalovirus retinitis. Median CD4+ T lymphocyte count is 20 cells/μl with inter-quartile range as (5, 36). Seven patients died (11 eyes) and 16 patients (24 eyes) survived. The proportion of blindness and low vision in eyes infected with cytomegalovirus retinitis respectively was 20.8% (5/24) and 29.2% (7/24) when they were diagnosed in survivors. The ganciclovir therapy was effective in 16 patients (24 eyes). Clinical recovery of cytomegalovirus retinitis was 41.7% (10/24) and clinical improvement 58.3% (14/24). After anti-CMV treatment, the proportion of blindness or low vision was 16.7% (4/24).ConclusionsThe AIDS patients with CD4+ T lymphocyte < 50 cells/μl had increased susceptibility to cytomegalovirus associated retinitis. Cytomegalovirus retinitis is a serious disease causing blindness. The cytomegalovirus retinitis in the AIDS patients was response well to ganciclovir therapy. We should check their eyes routinely such as dilated fundus examination with an indirect ophthalmoscope in the AIDS patients with CD4+ T lymphocyte counts < 50 cells/μl.

Prevalence of hyperglycemia among adults with newly diagnosed HIV/AIDS in China

BackgroundThe prevalence of hyperglycemia among HIV-infected persons who are not receiving antiretroviral therapy is unknown. We conducted a cross-sectional survey to estimate the prevalence of hyperglycemia among Chinese adults with newly diagnosed HIV/AIDS.MethodsTwo thousand and six newly diagnosed HIV/AIDS patients from 10 provinces and municipalities in China were selected during 2009 to 2010. After an overnight fast, serum samples were collected to measure glucose concentrations. Demographics and medical histories were recorded. Factors associated with the presence of diabetes were analysed by logistic regression.ResultsAmong the 2006 patients, 75.67% were male. Median age was 40 years (range: 18–86 years). 19.99% had hyperglycemia, 9.47% had impaired fasting glucose (IFG) and 10.52% had diabetes. The prevalences of hyperglycemia, of IFG and of diabetes were 21.54%, 10.28% and 11.27% among men and 15.16%, 6.97% and 8.20% among women, respectively. The prevalence of diabetes increased with increasing age (7.00%, 13.36% and 21.21% among patients who were 18–40, 40–60, and ≥60 years of age respectively) and with decreasing CD4 count (6.74%, 8.45%, 9.69%, and 12.66% among patients with CD4 count of ≥350, 200–350, 50–200, and < 50/mm3 respectively). The prevalence of diabetes was higher among ethnic minority patients than among the Han patients (14.37% versus 9.24%). The logistic analysis showed that older age, lower CD4 count and minority ethnicity were significantly associated with an increased risk of diabetes.ConclusionsHyperglycemia is highly prevalent among Chinese adults with newly diagnosed HIV/AIDS. Older age, lower CD4 count and minority ethnicity are associated with increased risk of diabetes. All newly diagnosed HIV/AIDS individuals should be routinely evaluated for hyperglycemia.

Prevalence of Anemia among Adults with Newly Diagnosed HIV/AIDS in China

Background The prevalence of anemia among antiretroviral-naïve HIV-infected patients in China has not been well characterized. We conducted a cross-sectional study to estimate the prevalence of anemia among Chinese adults with newly diagnosed HIV/AIDS. Methods One thousand nine hundred and forty-eight newly diagnosed HIV-infected patients in China were selected during 2009 and 2010. Serum samples obtained from each individual were collected to measure hemoglobin levels. Demographics and medical histories were recorded. Factors associated with the presence of anemia were analysed by logistic regression. Results Among the 1948 patients, 75.8% were male. Median age was 40 years (range: 18–80 years). The overall prevalence of anemia among HIV-infected patients was 51.9% (51.5% among men, 53.2% among women). The prevalences of mild anemia, of moderate anemia, of severe anemia were 32.4%, 17.0%, and 2.5%, respectively. The prevalence of anemia was higher among ethnic minority patients than among the Han patients (70.9% versus 45.9%). The prevalence of anemia increased with increasing age (49.6%, 53.5% and 60.1% among patients who were 18–39, 40–59, and ≥60 years of age respectively) and with decreasing CD4 count (14.0%, 22.4%, 50.7%, and 74.6% among patients with CD4 count of ≥350, 200–349, 50–199, and <50 cells/mm3 respectively). The logistic regression analysis showed that older age, lower CD4 count and minority ethnicity were significantly associated with an increased risk of anemia. Conclusions Anemia is highly prevalent among Chinese adults with newly diagnosed HIV/AIDS, but severe anemia is less prevalent in this population. Older age, lower CD4 count and minority ethnicity are associated with an increased risk of anemia.

T-SPOT.TB in the Diagnosis of Active Tuberculosis Among HIV-Infected Patients with Advanced Immunodeficiency

We evaluated the performance of T-SPOT.TB (a commercial interferon gamma release assay) and its accuracy for the diagnosis of active tuberculosis (TB) among HIV-infected subjects with advanced immunodeficiency. In a clinical prospective study, we assessed the performance of T-SPOT.TB for the diagnosis of active TB in HIV-infected patients with CD4 cell counts below 350 cells/mm(3) who were naive to antiretroviral and anti-TB therapies. Results were available from 147 patients, of whom 38 (25.9%) had active TB. The majority (85%) of the participants were male, with a median age of 40 years and a median CD4 cell count of 77 cells/mm(3). T-SPOT.TB yielded 15 (10.2%) indeterminate results. The indeterminate results were not associated with CD4 cell counts. However, younger patients were more likely to have an indeterminate result (OR = 0.91 per unit increase in age, p = 0.007). After excluding the indeterminate results, the sensitivity of T-SPOT.TB for the diagnosis of active TB was 37.1% and the specificity was 88.7%. The sensitivity of the T-SPOT.TB was independent of the CD4 cell count. However, its specificity was higher when used for patients with CD4 cell counts <100 cells/mm(3) when compared to patients with CD4 cell counts ≥100 cells/mm(3) (97.9% vs. 79.6%, p = 0.008). T-SPOT.TB could not be used as a routine tool to screen for active TB among HIV-infected patients with advanced immunodeficiency because of its poor performance and low sensitivity. However, it may be used as an adjunctive tool to diagnose active TB in this population due to its high specificity.

Serological survey of viral hepatitis markers among newly diagnosed patients with HIV/AIDS in China

The aim of the study was to determine the seroprevalence and epidemiological features of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection among patients newly diagnosed with HIV/AIDS in China.

Spectrum of Opportunistic Infections and Risk Factors for In-Hospital Mortality of Admitted AIDS Patients in Shanghai.

AbstractTo investigate the frequency and the spectrum of major opportunistic infections (OIs), evaluate the major clinical factors associated with each specific OI, and identify the risk factors for in-hospital death among HIV patients in East China.A retrospective cohort study was made including all the HIV-infected patients who were admitted for the first time to the Shanghai Public Health Clinical Center during June 1, 2013 to June 1, 2015. The demographic and clinical data were collected. Comparison of continuous variables was analyzed by one-way ANOVA and rank sum test. Person &khgr;2 test and Fisher exact test were applied to analyze the categorical variables. A Cox proportional hazards regression model was used to determine the risk for the occurrence of in-hospital death.In total, 920 patients were enrolled with age of 41.59 ± 13.36 years and 91% male. Median CD4 was 34 (IQR, 13–94) cells/&mgr;L. Among these patients, 94.7% acquired OIs while the rest developed malignancies. Pneumocystis pneumonia and bacterial coinfection (42.1%) was found to be the most common OIs, followed by tuberculosis (31.4%), CMV (20.9%), Cryptococcosis (9.0%), and MAC infection (5.2%). Of the above 5 major OIs, CMV-infected patients had the lowest median CD4 cell count 22.50 (IQR, 7.50–82.00) while the patients with tuberculosis infection had the highest count 61.00 (IQR, 27.00–176.00). In-hospital death rate was 4.2 per 100 person-years among these patients. Of note, admitted patients with 2 types of OIs (2.20, 95% CI 1.39–3.48) and those patients who were 40-year old or older (1.75, 95% CI 1.10–2.78) had a higher risk of such death.Pneumocystis pneumonia and tuberculosis were still the leading causes for the admission of HIV-infected patients in East China, and these patients tended to have very low CD4 cell counts. It is believed that expanding the HIV screening test and pushing the infected ones get ART earlier is required for generating a more successful HIV management strategy.

Understanding the behavioral and social characteristics of VCT clients in a Shanghai hospital, China.

Abstract We conducted a cross-sectional survey in a hospital in Shanghai, China, to investigate the demographic and behavioral characteristics of clients seeking voluntary HIV counseling and testing (VCT). There were 1251 clients who participated in this study. The overall HIV seroprevalence among the clients was 4.96%. Among the study participants, 52.4% were aged 21–30 years, 77.9% were male, 53.5% were married, and 67.4% had attained the level of college education. People older than 30 years and those educated to below college level were more likely to be infected (P=0.001 and P<0.001, respectively). Most participants (83%) were motivated by sexual risk followed by blood transmission risk (9.6%). The HIV seroprevalences in these populations with risk of HIV transmission via sex and blood were 4.8% and 10%, respectively. People with prior VCT were more likely to be infected (P=0.001). These results indicate: (1) targeted intervention is needed to promote VCT uptake among people older than 30 years and educated to below college level; (2) VCT should be provided more frequently to people with a risk of blood transmission because of the high infection rate in this population; and (3) a negative test result may be a serious unintended consequence of VCT. Therefore, post-education emphasized on safer sex practices is needed.

Serum TRSUT Titer ≥1: 16 Is a Predictor for Neurosyphilis Among HIV-Infected Patients With Concurrent Syphilis and No Neurological Symptoms.

AbstractInvestigating the predictors for lumbar puncture to diagnose the asymptomatic neurosyphilis among HIV and syphilis co-infected patients in Shanghai, China.Respectively, screening the medical records from August 1, 2009 to June 30, 2015. Those HIV-infected patients with concurrent syphilis who had received lumbar puncture were selected and their clinical and demographic data were recorded. Participants comprised symptomatic and asymptomatic patients. The latter ones could be further divided into 3 groups: late syphilis, early syphilis with anti-syphilis treatment failure, and early syphilis with serum toludine red unheated serum test (TRUST) ≥1:32. Both syphilis stage and anti-syphilis treatment effect were defined by common criteria, and syphilis of unknown duration was considered as late syphilis. Asymptomatic neurosyphilis was defined as neurosyphilis without neurological symptoms such as headache, cognitive dysfunction, motor deficits, auditory or ophthalmic abnormalities, and stroke. Neurosyphilis was defined as reactive cerebrospinal fluid (CSF) TRUST and/or CSF white blood cell >20 cells/&mgr;L without other reasons. Mann–Whitney test and Fishers exact test were used for analyzing the difference between neurosyphilis and non-neurosyphilis group. Logistic regression test was performed to analyze the risk factors for neurosyphilis.In total, 170 participants were collected, and the rate of neurosyphilis was 32.35%. Among all the 105 participants without neurological symptoms, 80 patients were with late syphilis and 25 were with early syphilis. Among the early syphilis patients, 23 had a TRUST ≥1:32 and the other 2 experienced an anti-syphilis treatment failure. The differences of clinical and demographic variables between neurosyphilis and non-neurosyphilis group were not statistically significant except the serum TRUST titer (P < 0.01). From HIV/syphilis co-infected patients with or without neurological symptom, those who had neurological symptoms, CD4 <350 per &mgr;L and serological TRUST titer ≥1:16 were 4.9-fold (95% confidence interval [CI]: 2.37–10.31), 4.3-fold (95% CI: 1.17–15.78), and 4.1-fold (95% CI: 1.58–10.76), respectively, more likely to be diagnosed with neurosyphilis. Asymptomatic patients whose serum TRUST titer ≥1:16 were 8.48-fold (95% CI: 1.08–66.63) more likely to have asymptomatic neurosyphilis.Among asymptomatic HIV-infected patients with late syphilis or early syphilis experienced an anti-syphilis treatment failure, those who have a serum TRUST titer ≥1:16 are suggested to perform lumbar puncture in order to avoid delayed diagnosis and the occurrence of severe sequelae of syphilis.