中国系统性红斑狼疮伴发骨坏死相关因素的Meta分析

背景：系统性红斑狼疮是一种异质性疾病,除长期应用激素可引起骨坏死外,有研究指出临床表现的差异性也有可能是骨坏死的危险因素。目前国内外学者对在系统性红斑狼疮患者中发生骨坏死的致病因素存在不同观点。 目的：对国内系统性红斑狼疮患者并发骨坏死的危险因素进行系统分析。 方法：检索中国学术期刊全文数据库(CNKI)、中国生物医学文献数据库(CBMdisc)、万方数据库获得已公开发表的国内系统性红斑狼疮并发骨坏死相关危险因素的病例对照研究文献,筛选出符合评价标准的文献,采用RevMan 5.0及Stata软件进行Meta分析,并计算各危险因素的合并比值比及95%置信区间。 结果与结论：共纳入10篇病例对照研究,累计病例组332例、对照组986例。系统性红斑狼疮并发骨坏死的各危险因素的比值比及95%置信区间分别为：雷诺现象3.28(1.69-6.38),口腔溃疡2.95(2.13-4.09),肾脏受累1.21(0.83-1.74),血管炎因素5.64(2.84-11.21),高脂血症5.11(3.10-8.42),抗磷脂抗体2.32(1.49-3.61),关节受累2.02(1.33-3.07)。提示激素应用明确为系统性红斑狼疮并发骨坏死的独立危险因素,但并非惟一因素,血管炎、高脂血症、雷诺现象、口腔溃疡、抗磷脂抗体阳性及关节受累均为需要重视的国内系统性红斑狼疮患者并发骨坏死的危险因素。     

Low carotenoid concentration and the risk of HIV seroconversion in Pune, India

Low vitamin A and carotenoid levels could increase the risk of sexual HIV acquisition by altering the integrity of the genital epithelium or by immunologic dysfunction. We addressed this issue by measuring serum vitamin A and carotenoid levels in patients who were at risk of subsequent HIV infection. In a nested case-control study in individuals attending two sexually transmitted disease (STD) clinics in Pune, India, serum micronutrient levels were measured in 44 cases with documented HIV seroconversion (11 women and 33 men) and in STD patients matched for gender and length of follow-up with no subsequent HIV seroconversion (controls). STD patients in Pune had low vitamin A and carotenoid levels, and low serum beta-carotene levels were independently associated with an increased risk of subsequent HIV seroconversion. STD patients with beta-carotene levels less than 0.075 micromol/L were 21 times more likely to acquire HIV infection than those with higher levels (adjusted odds ratio = 21.1; p =.01). No such association was observed in case of other non-provitamin A carotenoids. This study reports the first evidence of an association between low serum provitamin A carotenoid levels and an increased risk for heterosexual HIV acquisition in STD patients in Pune, India.     

Virologic rebound on HAART in the context of low treatment adherence is associated with a low prevalence of antiretroviral drug resistance

The contributions of viral drug resistance, drug pharmacokinetics, and treatment adherence to failure of protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) have been explored in isolation. We examined the interactions between these factors. Patients on their first PI-based HAART combination for >6 months with plasma HIV viral load (VL) >1000 copies/mL ("viremic" group) were compared with patients with a stable VL <50 copies/mL ("nonviremic" group). Data were collected on adherence (measured electronically), PI plasma levels (sampled randomly, at trough and twice after an observed dose), viral genotype, and phenotype. Mean adherence was significantly lower in the viremic group (84.3% versus 100.1%; p =.005). In the viremic group, substitutions in HIV protease were detected most frequently in the following positions in subjects on indinavir (IDV): L10I/V (35.7%), M46I/L (35.7%), A71T/V (35.7%), V82A (42.9%); and for subjects on nelfinavir (NFV): D30N (50.0%), V77I (56.3%), N88D (37.5%). Phenotypic resistance was detected in 20% of isolates from patients on IDV and 42% on NFV. Lower adherence was associated with detection of fewer resistance substitutions (r = 0.52; p =.005) and less phenotypic resistance (rho = 0.56, p =.005). There were no differences between the groups in pharmacokinetics. However, in viremic subjects, lower postdose NFV levels were associated with higher resistance (rho = -0.61, p =.02).     

Randomized,controlled, 48-week study of switching stavudine and/or protease inhibitors to combivir/abacavir to prevent or reverse lipoatrophy in HIV-infected patients

OBJECTIVE: HIV-1 protease inhibitors (versus no protease inhibitors) and stavudine (versus zidovudine) are independently associated with a higher risk of lipoatrophy in HIV-infected patients. We sought to determine whether the revision of stavudine and/or protease inhibitor-containing regimens to combivir/abacavir would result in prevention and/or reversibility of lipoatrophy in HIV-1-infected patients. DESIGN: The investigation was a prospective, randomized, controlled, open-label study. SUBJECTS: The subjects included 37 HIV-1-infected individuals with stable undetectable HIV-1 loads who were taking a regimen containing either stavudine or zidovudine with lamivudine and a protease inhibitor. INTERVENTION: Subjects were randomized to continue therapy or switch stavudine to zidovudine and protease inhibitor to abacavir, such that the universal switch regimen was combivir (zidovudine/lamivudine) and abacavir. MAIN OUTCOME MEASURES: Total body, leg, and arm fat mass was measured at baseline, 24 weeks, and 48 weeks using whole-body dual-energy x-ray absorptiometry. Single-cut L4 computed tomography and assays of multiple metabolic parameters were also performed. RESULTS: There was an average gain in fat mass of 0.009 kg/(leg.mo) in switch patients versus a loss of 0.010 kg/(leg.mo) in controls (p =.04, on-treatment analysis) over 48 weeks. Significant arm fat restoration was observed in patients who switched regimens, with an average gain of 0.014 kg/(arm.mo) (p =.004), whereas controls did not have a significant change from baseline. Analyses of percentage changes in arm and leg fat masses showed similar findings. No significant effects on intraabdominal fat, blood lipid levels, glycemic indices, and lactate levels were detected, although most baseline mean values were normal in study subjects. Combivir/abacavir maintained virological control in all but one case, and three (13.6%) of 22 individuals had adverse reactions to abacavir therapy. CONCLUSIONS: A switch to combivir/abacavir therapy was associated with objective evidence of limb fat-sparing and fat restoration compared with continued treatment with stavudine and/or protease inhibitor.     

Association between insulin resistance and hepatitis C virus chronic infection in HIV-hepatitis C virus-coinfected patients undergoing antiretroviral therapy.

Insulin resistance (IR) in the context of highly active antiretroviral therapy (HAART) is becoming more common in HIV-infected patients. Patients with chronic hepatitis C virus (HCV) infection have an increased risk of IR and type 2 diabetes mellitus. A cross-sectional study was performed to investigate whether chronic HCV infection constitutes a risk factor for IR in HIV-HCV-coinfected patients undergoing HAART. Inclusion criteria were positive HCV viremia and a sustained increase of alanine aminotransferase of at least twice the normal value. A total of 29 HIV-HCV patients, 76 HIV patients, and 121 HCV controls were tested for IR and body mass index (BMI). IR was measured using the homeostasis model assessment. In HIV-HCV and HIV patients, fat redistribution and lipid profile were assessed. There was no significant difference in age, CD4 cell count, HIV viral load, or duration of HAART between the HIV-HCV and HIV groups. HIV-HCV patients and HCV controls had a significant increase in IR when compared with HIV patients (0.25 +/- 0.28 and 0.21 +/- 0.34 versus 0.04 +/- 0.37; p =.01 and p =.003, respectively). Lipoatrophy was observed more frequently in HIV-HCV patients in comparison with HIV patients (41% versus 14%; p =.003). In HIV-HCV patients, total cholesterol and triglyceride levels were significantly lower than in HIV patients. In multivariate analysis, IR, BMI, triglyceride levels, and peripheral fat wasting were the independent variables associated with HCV infection. Our findings suggest that chronic HCV infection is a significant factor associated with the development of metabolic abnormalities and with modifications in body composition in HIV patients receiving antiretroviral treatment.     

Electron beam computed tomography for assessment of coronary artery disease in HIV-infected men receiving antiretroviral therapy

Hyperlipidemia has been seen in patients receiving protease inhibitor-based antiretroviral therapy, prompting concern that such patients are at risk for accelerated coronary artery disease (CAD). To assess the risk of CAD in antiretroviral-treated HIV-infected men, we quantified coronary artery calcium (CAC), a sensitive and established marker of subclinical CAD, using electron beam computed tomography (EBCT) of coronary vessels. Sixty HIV-infected men who met the following criteria (cases) were enrolled in the study: age of 40 years or older; naive to antiretroviral therapy or use of a stable antiretroviral regimen for >or=6 months (mean duration, 25.9 months; 41 patients were receiving protease inhibitor therapy); and no known CAD or no use of lipid-lowering agents. EBCT-derived CAC scores, serum lipid levels, history of antiretroviral therapy, and risk factors for CAD were obtained. Each case was compared with three age-, sex-, and race-matched HIV-negative controls randomly selected from a database including >9000 patients who had undergone EBCT. We determined differences in the proportion of cases and controls with CAC scores of >0 (detectable calcium) and clinically significant CAC for age range. There were no statistically significant differences between the number of cases and controls with detectable CAC (33% and 39%, respectively) and clinically significant CAC (18% and 17%, respectively). This study suggests that the rate of coronary atherosclerosis among HIV-infected patients who receive short-term antiretroviral therapy with or without protease inhibitors is not higher than that among age-, sex-, and race-matched HIV-negative controls. These results need to be confirmed in larger long-term studies, with controls well matched for coronary risk factors.     

Predictive value of HIV-1 viral load on risk for opportunistic infection

OBJECTIVE: The relationship between HIV-1 viral load and the risk for opportunistic infection (OI) was examined in Adult AIDS Clinical Trial Group (AACTG) 722, a virology substudy of AACTG 323: a phase 4 randomized study designed to examine the use of chronic suppressive versus episodic fluconazole therapy. METHODS: The primary analysis used a case-control sampling scheme with two controls per "case" (subjects that developed an OI) matched by gender, age, and time on study. Forty-five cases and matched controls were identified and used in the analysis. RESULTS: Study 722 accrued 518 subjects between 5/97 and 11/99. Forty-five subjects developed serious OIs or refractory candidiasis. Median baseline CD4 count was 24 cell/mm3 for cases and 46 for controls (p =.003). Median viral load (VL) was 5.02 log10 copies/mL for cases and 4.08 for controls (p =.002). Multivariate analysis found four independent variables associated with time to OI: baseline VL and CD4 (RR = 2.2 per log increment and 6.0 per 50-cell increment, respectively), a one log increase in VL at any time (RR = 15), and history of an OI (RR = 5.2). CONCLUSIONS: VL and changes in VL were independently associated with risk of development of OIs in a prospective study and should be considered by clinicians when assessing patients for risk of OI.     

Acute retrovirus syndrome among prospectively identified homosexual men with incident HIV infection in Brazil. Projecto Praça Onze Study Group

BACKGROUND: Symptoms associated with HIV infection are common among HIV seroconverters, but the acute retroviral syndrome (ARS) is a diagnostic challenge because of the absence of a sensitive and specific case definition. We conducted an analysis of HIV seroconverters in Projeto Pra?a Onze, a HIVNET HIV seroincidence study among homosexual men in Rio de Janeiro. METHODS: Information from study subjects enrolled in Projeto Pra?a Onze who were documented HIV seroconverters were compared with nonseroconverters. At each semiannual study visit, participants were asked about HIV seroconversion symptoms and sexually transmitted diseases (STDs) during the preceding 6 months. All information was collected before the laboratory evaluation. A classification tree analysis was used to identify an ARS case definition, first using clinical information and then after including risk factor data for seroconversion in our cohort. RESULTS: As of July 1998, 674 volunteers were enrolled and 34 of these seroconverted; information was available for 33 of these. Among the seroconverters, 11 (34%) denied any symptoms, and 22 (66%) reported one or more symptoms, the most common of which were fever (25% of seroconverters versus 7% of nonseroconverters; p <.01), night sweats (9% versus 2%, respectively; p =.05), incapacitating disease (ID) for >/=3 days (27% versus 7%, respectively; p <.001), and weight loss of >/=2 kg (21% versus 9%, respectively; p =.05). STDs were more common in seroconverters (gonorrhea: 9% versus 1%, respectively; p <.01 and condyloma: 9% versus 3%, respectively; p =. 08). The first case definition was ID for >3 days, fever, pharyngitis, and myalgia (seroconverters, 3 of 32, versus nonseroconverters, 2 of 640). The second case definition was was ID for >3 days, anti-core hepatitis b-positive, and age <21 years (seroconverters: 6 of 32 versus nonseroconverters 4 of 640). The sensitivity and specificity for the first and second case definitions were: 9.4%, 99.4%, and 18.8%, 99.8%, respectively. CONCLUSIONS: Among HIV seroconverters, symptoms consistent with ARS were common. We were unable to identify a sensitive case definition that could be used as a screening tool. Although the clinical case definition was not validated, the specificity of our case definitions was high, suggesting that subjects within this HIV risk group who fulfill the case definition should be tested for HIV.     

Investigation of pre‐diagnostic virological markers for progressive multifocal leukoencephalopathy in human immunodeficiency virus‐infected patients

Progressive multifocal leukoencephalopathy (PML) is a severe neurological disorder due to JC virus (JCV) infection. Pre‐diagnostic biological markers and risk factors for PML are not well understood. We conducted a case–control study nested within the Multicenter AIDS Cohort Study to examine the association between JCV viruria and viremia and serum antibody to JCV capsids, in relation to subsequent PML diagnoses, 5 months to 12 years later. Other demographic and immunologic factors were also examined. The study population included 28 incident cases of PML, 26 matched HIV‐positive controls, and 50 HIV‐negative controls. Prevalence of JCV viruria was 37% in cases, 42% in HIV‐positive controls, and 28% in HIV‐negative controls (P = 0.43). Among persons with JCV viruria, persistent viruria was more common in cases (89%) than in HIV‐positive controls (33%) (P = 0.02). Presence of JCV viruria was not related to the time to PML diagnosis (OR: 1.03, 95% CI: 0.8–1.4); however, the urinary concentration of JCV DNA increased with proximity to the date of PML diagnosis in cases. JCV seropositivity did not differ between cases or controls (P = 0.42). Four cases tested JCV seronegative, including one case only 5 months prior to diagnosis with PML. JCV DNA was detected in the serum of one HIV‐positive control. Smoking was the only demographic variable analyzed associated with an increased risk for PML (MOR: 9.0, 95% CI: 1.2–394.5). The results suggest that persistent JCV viruria and increasing urinary concentration of JCV DNA may be predictive of PML for some patients. J. Med. Virol. 81:1140–1150, 2009. © 2009 Wiley‐Liss, Inc.     

Independent effects of reported sexually transmitted infections and sexual behavior on HIV-1 prevalence among adult women, men, and teenagers in rural Uganda

OBJECTIVE: To assess whether sexually transmitted infections (STIs) and sexual behavior are independently associated with HIV-1 among adult women, men, and teenagers in rural Uganda. DESIGN: Cross-sectional survey. METHODS: All adults (13 years and older) residing in 18 communities were invited to participate. HIV status was determined from serum samples and data collected during confidential interview. Independent effects of risk factors for HIV were estimated using adjusted odds ratios (ORs) with 95% confidence intervals (CIs) from logistic regression. RESULTS: Women reporting genital ulcers in the last 12 months were over twice as likely to be HIV positive after adjustment for sociodemographic factors and number of lifetime sexual partners (OR, 2.5; 95% CI, 1.9-3.4). Equivalent associations were stronger for men (OR, 3.2; 95% CI, 2.2-4.7) but weaker for teenagers (OR, 2.0, 95% CI, 0.5-8.7). Number of lifetime sexual partners was associated ( p <.05) with HIV status for women, men, and teenagers independently of reported genital ulcers. Teenagers reporting casual partners were over four times ( p <.001), and men reporting condom use almost twice ( p <.001), as likely to be HIV positive. Neither history of genital discharge nor other measures of sexual behavior were independently related to HIV status. CONCLUSION: Reported STIs and sexual behavior are independently associated with HIV in rural Uganda. Community-based interventions to reduce HIV should target both and should include teenagers.     

Physician-patient communication in HIV disease: the importance of patient, physician, and visit characteristics

BACKGROUND: Although previous work that considered a variety of chronic conditions has shown that higher quality physician-patient communication care is related to better health outcomes, the quality of physician-patient communication itself for patients with HIV disease has not been well studied. OBJECTIVE: To determine the relationship of patient, visit, physician, and physician practice characteristics to two measures of physician-patient communication for patients with HIV disease. DESIGN: Cross-sectional survey of physicians and patients. SETTING: Cohort study enrolling patients from throughout eastern Massachusetts. STUDY SUBJECTS: 264 patients with HIV disease and their their primary HIV physicians (n = 69). MEASUREMENTS: Two measures of physician-patient communication were used, a five-item general communication measure (Cronbach's alpha = 0.93), and a four-item HIV-specific communication measure that included items about alcohol, drug use, and sexual behaviors (Cronbach's alpha = 0.92). RESULTS: The mean age of patients was 39. 5 years, 24% patients were women, 31.1% were nonwhite, and 52% indicated same-sex contact as their principal HIV risk factor. The mean age of physicians was 39.1 years, 33.3% were female, 39.7% were specialists, and 25.0% self-identified as gay, lesbian, or bisexual. In multivariable models relating patient and visit characteristics to general communication, longer reported visit length (p<.0001), longer duration of the physician-patient relationship (p =.02), and female gender (p =.04) were significantly associated with better communication. The interaction of patient gender and visit length was also significant (p =.02); longer visit length was more strongly associated with better general communication for male than female patients. In similar models relating patient and visit characteristics to HIV-specific communication, longer visit length (p <.0001) and less advanced disease stage (p =.009) were associated with better communication. In multivariable models relating physician and practice characteristics to general communication no variables were significant. However, both female physician gender (p =.002) and gay/lesbian/bisexual sexual preference (p =.003) were significantly associated with better HIV-specific communication. CONCLUSIONS: In this study, female and homosexual physicians provided higher quality HIV-specific communication than male and heterosexual physicians. Better understanding the processes by which female and homosexual physicians achieve higher quality communication may help other physicians communicate more effectively. Health care providers and third-party payers should be aware that shorter visits may compromise physician-patient communication, and that this effect may be more consequential for male patients.     

HIV knowledge and risk behaviors among Pakistani and Afghani drug users in Quetta,Pakistan

Situated on the Pakistan-Afghan border, Quetta is home to growing numbers of Afghan refugees. We studied HIV knowledge and risk behaviors among Pakistani and Afghani drug users between July 2001 and November 2001. Of 959 drug users, all were male and the majority used heroin. Most were Pakistani (84.8%), 14.9% were Afghani, and 0.3% were Iranian. Relative to Pakistani drug users, a higher proportion of Afghanis reported no formal education, homelessness, and unemployment ( p <.001). Afghanis were more likely to have used an opiate as their first illicit drug (16% vs. 7%, p <.001), to have ever injected (18.8% vs. 12.3%, p =.04), to report needle sharing (72.2% vs. 48.2%, p =.08), or to report a drug user in their family ( p =.08). None of sexually active Afghanis had ever used a condom compared with 5.0% of the Pakistanis ( p =.01). Only 4.3% of Afghans had ever heard of HIV/AIDS compared with 18.3% of Pakistanis ( p <.001). Extremely low levels of HIV/AIDS awareness and high HIV risk behaviors were evident among drug users in Quetta, among whom Afghanis were especially vulnerable. Interventions to prevent transition to injection, needle exchange, and drug treatment are urgently required to prevent blood-borne infections.     

Immunoassay and molecular methods to investigate DNA methylation changes in peripheral blood mononuclear cells in HIV infected patients on cART

This study aimed to investigate the influence of antiretroviral therapy on methylation markers, in a group of HIV infected, heavily treated patients. Immune and molecular methods were used to investigate potential changes in methylation profile in DNA isolated from peripheral blood mononuclear cells collected from antiretroviral-experienced HIV infected patients and healthy controls. The percentage of 5-methylcytosine was inversely correlated with proviral DNA and active replication while DNMT1 (p = 0.01) and DNMT3A (p = 0.004) independently correlated with active viral replication. DNMT3A expression increased with total treatment duration (p = 0.03), number of antiretroviral drugs ever used (p = 0.003), and cumulative exposure to protease inhibitors (p = 0.02) even in currently HIV undetectable patients.     

Impact of selenium status on the pathogenesis of mycobacterial disease in HIV-1-infected drug users during the era of highly active antiretroviral therapy

The risk of mycobacterial disease is significantly increased in drug abusers as well as in immunocompromised HIV-1-infected individuals. The essential trace element selenium has an important function in maintaining immune processes and may, thus, have a critical role in clearance of mycobacteria. The impact of selenium status on the development of mycobacterial diseases in HIV-1-seropositive drug users was investigated over a 2-year period (1999-2001). Twelve cases of mycobacterial disease (tuberculosis, 9; infection due to atypical Mycobacterium species, 3) occurred; these 12 cases were compared with 32 controls with no history of respiratory infections who were matched on age, sex, and HIV status. Significant risk for development of mycobacterial disease was associated with a CD4 cell count of <200/mm 3, malnutrition, and selenium levels of 相似文献