广东省HIV/AIDS患者抗病毒治疗后基因型耐药分析

目的 总结广东省261例HIV/AIDS患者抗病毒治疗1年以上,病毒未被抑制者的耐药基因型特征.方法 采用实验室自建方法,进行HlV-1耐药基因型检测.构建系统进化树确定基因亚型,并通过斯坦福HIV耐药数据库在线序列分析,确定耐药突变位点及药物耐受情况.结果 共检测样本280份,成功获得261条完整序列.序列分析显示:HIV-1病毒株以CRF01 AE亚型(194/261,74.3％)为主;逆转录酶(RT)区耐药位点以M184I/V(108/170,63.5％)、Y181C/V(61/170,35.9％)、K103N/S(56/170,32.9％)和G190A/S(48/170,28.2％)为主;蛋白酶(PR)区未发现主要位点突变,次要耐药位点主要为L10I/V(21/170,12.4％)和A71T/V(13/170,7.6％);未产生针对蛋白酶抑制剂(PI)的耐药;常见核苷类逆转录酶抑制剂(NRTIs)拉米夫定(3TC)、恩曲他滨(FTC)的耐药率均为43.7％,高度耐药率均为42.1％;非核苷类逆转录酶抑制剂(NNRTIs)奈韦拉平(NVP)及依非韦伦(EFV)的耐药率均为56.3％,高度耐药率分别为54.8％(143/261)和35.2％(92/261).耐药率随着抗病毒治疗时间增长而增加,初始单一用药人群耐药率76.7％(23/30)高于初始联合用药人群耐药率54.5％(126/231).结论 广东省抗病毒治疗1年以上且病毒未抑制的HIV感染者NRTIs耐药以3TC、FTC为主,NNRTIs耐药以NVP、EFV为主.临床上应及早发现耐药更改方案以保护TDF作为二线药物的有效性;在抗病毒治疗开始时应尽量避免单一用药.     

Ambulatory care for HIV-infected patients: differences in outcomes between hospital-based units and private practices: analysis of the RESINA cohort

Background

The efficacy of highly active antiretroviral therapy (HAART) in the treatment of HIV infection is influenced by factors such as potency of applied drugs, adherence of the patient, and resistance-associated mutations. Up to now, there is insufficient data on the impact of the therapeutic setting.

Methods

Since 2001, the prospective multicenter RESINA study has examined the epidemiology of transmitted HIV drug resistance in Nordrhein-Westfalen, the largest federal state of Germany by population. Characteristics of patients treated in hospital-based outpatient units were compared to those of patients treated in medical practices. Longitudinal data of all participants are being followed in a cohort study.

Results

Overall, 1,591 patients were enrolled between 2001 and 2009 with follow-up until the end of 2010. Of these, 1,099 cases were treated in hospital-based units and 492 in private practices. Significant differences were found with respect to baseline characteristics. A higher rate of patients with advanced disease and non-European nationality were cared for in hospital units. Patients in medical practices were predominantly Caucasian men who have sex with men (MSM) harboring HIV-1 subtype B, with lower CDC stage and higher CD4 cell count. Median viral load was 68,828 c/mL in hospital-based units and 100,000 c/mL in private practices (P = 0.041). Only median age and rate of transmitted drug resistance were not significantly different. After 48 weeks, 81.9% of patients in hospital units and 85.9% in private practices had a viral load below the limit of detection (P = 0.12). A similar result was seen after 96 weeks (P = 0.54). Although the baseline CD4 cell count was different (189.5/μL in hospital units and 246.5/μL in private practices, P <0.001), a consistent and almost identical increase was determined in both groups.

Conclusions

The RESINA study covers a large HIV-infected patient cohort cared for in specialized facilities in Germany. Despite significant differences of patients’ baseline characteristics in hospital-based units compared to medical practices, we could not find significant differences in treatment outcome up to 2 years after the initiation of HAART.     

Periodontal status of HIV-infected patients undergoing antiretroviral therapy compared to HIV-therapy naive patients: a case control study

Background

Although severe oral opportunistic infections decreased with the implementation of highly active antiretroviral therapy, periodontitis is still a commonly described problem in patients infected with human immunodeficiency virus (HIV). The objective of the present investigation was to determine possible differences in periodontal parameters between antiretroviral treated and untreated patients.

Methods

The study population comprised 80 patients infected with HIV divided into two groups. The first group was receiving antiretroviral therapy while the second group was therapy naive. The following parameters were examined: probing pocket depth, gingival recession, clinical attachment level, papilla bleeding score, periodontal screening index and the index for decayed, missed and filled teeth. A questionnaire concerning oral hygiene, dental care and smoking habits was filled out by the patients.

Results

There were no significant differences regarding the periodontal parameters between the groups except in the clinical marker for inflammation, the papilla bleeding score, which was twice as high (P < 0.0001) in the antiretroviral untreated group (0.58 ± 0.40 versus 1.02 ± 0.59). The participants of this investigation generally showed a prevalence of periodontitis comparable to that in healthy subjects. The results of the questionnaire were comparable between the two groups.

Conclusion

There is no indication for advanced periodontal damage in HIV-infected versus non-infected patients in comparable age groups. Due to their immunodeficiency, HIV-infected patients should be monitored closely to prevent irreversible periodontal damage. Periodontal monitoring and early therapy is recommended independent of an indication for highly active antiretroviral therapy.     

Highly active antiretroviral therapy and cervical dysplasia in HIV-positive women in South Africa

Background

The risk of squamous intra-epithelial lesions (SIL) is higher in HIV-positive women. As these women begin to live longer due to highly active antiretroviral therapy (HAART), their risk of cervical cancer may increase. Few data exist regarding the effect of HAART on the incidence and progression of SIL in HIV-positive African women. The aim of this study was to evaluate the effect of HAART on the incidence and progression of SIL in HIV-positive women in South Africa.

Methods

A prospective observational study of HIV-seropositive women was conducted over 5 years in an HIV treatment clinic in Johannesburg, South Africa. The participants consisted of 601 women on and off HAART who had repeat Pap smears greater than 6 months apart. The effect of HAART use on incidence and progression rates of SIL was determined using multivariate Poisson regression to obtain incidence rate ratios (IRRs), adjusted for age, CD4 count and other potential confounders.

Results

Median follow-up time was 445 days (inter-quartile range 383, 671). The crude rate of incidence of any SIL was 15.9 episodes (95% confidence limit (CL) 12.7, 19.9) per 100 person-years; the crude rate of all progression of cervical dysplasia among women was 13.5 episodes (95% CL 11.3, 16.1) per 100 person-years. HAART use was associated with a robust reduction in the rate of incidence and progression of cervical lesions, adjusted IRR=0.55 (95% CL 0.37, 0.80). Sensitivity analyses confirmed this main association held for incidence and progression when they were considered separately, and that the result was not dependent on the length of HAART exposure.

Conclusion

HAART use was associated with a reduction in the rate of both incidence and progression of cervical lesions among HIV-positive women.     

Cryptoccocal meningitis and HIV in the era of HAART in Côte d'Ivoire

Objective

The authors had for aim to describe the management of cryptococcal meningitis in HIV infected adults, in Ivory Coast.

Patients and methods

A retrospective study was made from January 1, 2005 to December 31, 2008 on the files of consecutive hospitalized patients presenting with cryptococcal meningitis, at the Treichville University Hospital, Infectious and tropical diseases department (Abidjan). The socio-demographic, clinical, and biological aspects as well as the outcome were analyzed.

Results

Eighty patients presenting with cryptococcal meningitis, (2.6% of hospitalized patients) were included: 41 men (51.25%) and 39 women (48.75%); mean age: 40 years (range 26 to 58 years). The delay before consultation was 5.4 days, range 2–12 days). The mains symptoms were headache (83.7%), fever (63.7%), and consciousness disorders (60%). Meningo-encephalitis accounted for 75% of the clinical presentations; 54 patients (67.5%) were naive of antiretroviral treatment (mean CD4: 45/mm³ (range 5–103/mm³), while 26 (32.5%) had received antiretrovirals before presenting with cryptococcal meningitis (Nadir CD4 = 81/mm³). Amphotericin B relayed by fluconazole was prescribed to 86.2% of the patients, associated with a therapeutic lumbar puncture for 30 patients. The death rate was 41.2%.

Conclusion

In spite of antiretroviral treatment availability in Ivory Coast, cryptococcal meningitis remains frequent with a high death rate. This study stresses the importance of early management to improve the prognosis.     

超声心动图评价高效抗病毒疗法对艾滋病患者右室功能的影响

目的利用超声心动图技术对照评价接受高效抗逆转录病毒治疗(HAART)的艾滋病(AIDS)患者和未接受HAART治疗者的右室功能,分析评价目前国内AIDS治疗所采用的HAART方案是否对AIDS患者右室功能造成影响。方法对59例未接受HAART治疗的AIDS患者及52例接受HAART治疗的AIDS者行超声心动图检查,测量各项常规超声心动图参数,采集三尖瓣环位点组织多普勒(TDI)运动频谱,测量各位点的收缩期峰值速度(Vs)、舒张早期峰值速度(Ve)、舒张晚期峰值速度(Va),计算各位点Ve/Va值及右心平均V-s、-Ve、V-a和-Ve/V-a值。两组间进行对照分析。结果未治疗组和治疗组间常规超声心动图指标及三尖瓣环各位点TDI测值包括Vs、Ve、Va、Ve/Va。-Vs[(11.35±2.00)cm/s,(11.32±1.40)cm/s]、-Ve[(11.63±2.38)cm/s,(12.14±1.98)cm/s]、-Va[(11.18±2.78)cm/s,(11.02±2.54)cm/s]和V-e/-Va(1.10±0.37,1.15±0.28),差异无统计学意义。结论国内AIDS治疗采用的HAART治疗方案对AIDS患者右室功能未见明显影响。     

Triple positivity of HBsAg,anti-HCV antibody,and HIV and their influence on CD4+ lymphocyte levels in the highly HIV infected population of Abeokuta,Nigeria

BackgroundFew studies exist on hospital-based seroprevalence of triple positivity of HIV/HBV/HCV in Nigeria.ObjectivesThe study aimed at determining the triple positivity of HIV, HBsAg and HCV among HIV-infected individuals in Abeokuta, Nigeria and defining the influence of these triple infections on CD4+ counts of HIV-infected individuals as antiretroviral therapy improves in Nigeria.MethodsEnumeration of CD4+ levels in 183 HIV-infected persons was done with Partec Flow Cytometer. Seropositivity of HBsAg and anti-HCV antibody was detected with rapid kits.ResultsFrom the result obtained, significance variance (p<0.05) existed between HIV positive persons and persons who tested positive to HIV/HBV/HCV triple infection before and after the commencement of HAART. Of these infections, 31(16.9%) had HBV/HCV/HIV triple infection, while 152(83.1%) had HIV mono infection only, 56(30.6%) had HBV/HIV dual infection only and 43(23.5%) had HCV/HIV dual infection only. Significant variance (p<0.05) also existed between subjects with CD4 counts of <200 cells/µl, 200–499 cells/µl and >500 cells/µl. Highest seroprevalence of HIV (35.0%) was found in age groups 35–44 years and >65 years had the least (2.7%). Significant variance (p<0.05) also existed in the progression of CD4+ lymphocytes cells between subjects with persistent decrease (32.3%) in CD4+ lymphocytes cells and those with fluctuation in their CD4+ lymphocytes cells (12.9%) after the commencement of ART.ConclusionThe study further confirms that triple positivity of HIV/HBV/HCV infection is common in Abeokuta, Nigeria. Testing of these triple infections should be a big concern in the best choice and commencement of ART. Also, the study showed that consistent and prolonged use of HAART had a positive impact on the CD4 count of HIV-infected individuals.     

Role of cell signaling in poxvirus-mediated foreign gene expression in mammalian cells

Poxviruses have been extensively used as a promising vehicle to efficiently deliver a variety of antigens in mammalian hosts to induce immune responses against infectious diseases and cancer. Using recombinant vaccinia virus (VV) and canarypox virus (ALVAC) expressing enhanced green fluorescent protein (EGFP) or multiple HIV-1 gene products, we studied the role of four cellular signaling pathways, the phosphoinositide-3-OH kinase (PI3K), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK), and c-Jun N-terminal kinase (JNK), in poxvirus-mediated foreign gene expression in mammalian cells. In nonpermissive infection (human monocytes), activation of PI3K, ERK, p38 MAPK, and JNK was observed in both VV and ALVAC and blocking PI3K, p38 MAKP, and JNK pathways with their specific inhibitors significantly reduced viral and vaccine antigen gene expression. Whereas, blocking the ERK pathway had no significant effect. Among these cellular signaling pathways studied, PI3K was the most critical pathway involved in gene expression by VV- or ALVAC-infected monocytes. The important role of PI3K in poxvirus-mediated gene expression was further confirmed in mouse epidermal cells stably transfected with dominant-negative PI3K mutant, as poxvirus-mediated targeted gene expression was significantly decreased in these cells when compared with their parental cells. Signaling pathway activation influenced gene expression at the mRNA level rather than virus binding. In permissive mammalian cells, however, VV DNA copies were also significantly decreased in the absence of normal function of the PI3K pathway. Poxvirus-triggered activation of PI3K pathway could be completely abolished by atazanavir, a new generation of antiretroviral protease inhibitors (PIs). As a consequence, ALVAC-mediated EGFP or HIV-1 gag gene expression in infected primary human monocytes was significantly reduced in the presence of atazanavir. These findings implicate that antiretroviral therapy (ART), also known as highly active antiretroviral therapy (HAART), may negatively impact the efficacy of live poxvirus vector-based vaccines and should be carefully considered when administering such live vaccines to individuals on ART.     

Major reduction in AIDS-mortality inequalities after HAART: The importance of absolute differences in evaluating interventions

This study estimates the magnitude of inequalities in AIDS mortality in the period when highly active antiretroviral therapy (HAART) was introduced and after its widespread dissemination in the Region of Madrid, Spain. Two population cohorts were constructed by linking records from 1996 and 2001 population censuses with mortality registry records after initial and full implementation of HAART, respectively. Absolute and relative differences in AIDS mortality in people aged 20–49 years were estimated in each population cohort according to neighbourhood and individual socioeconomic position. The absolute difference in mortality between neighbourhoods with highest and lowest socioeconomic position (unemployment rate, per capita income) declined from about 30/100,000 person-years in the 1996 population cohort to 8/100,000 person-years in the 2001 population cohort. The absolute difference in mortality between individuals with the highest and lowest socioeconomic position fell from about 60/100,000 person-years in the first cohort to about 20/100,000 in the second. Relative differences in mortality by neighbourhood socioeconomic position and by individual education level also decreased in the 2001 cohort with respect to the 1996 cohort. Although relative differences by individual occupation increased, there was no evidence of a significant change. These findings show major reduction in absolute socioeconomic differences in AIDS mortality after HAART and indicate that the use of relative differences alone may be inadequate to fully evaluate the results of health interventions.