高效抗反转录病毒治疗双药简化方案的研究进展

高效抗反转录病毒治疗三联方案是治疗HIV感染的主流,然而,随着治疗人群扩大到所有HIV感染者,以及治疗时间延长,人们对高效、高依从性、低不良反应、低耐药及低治疗成本方案的需求日益增加,双药简化治疗成为个性化治疗的备选方案,一些方案已经被纳入国内外抗病毒治疗指南。本文对近年来双药简化方案的发展进行综述,为临床正确应用该方案提供依据。     

Asymptomatic serum cryptococcal antigenemia and early mortality during antiretroviral therapy in rural Uganda

OBJECTIVE: To evaluate the association between a positive serum cryptococcal antigen (CRAG) test at baseline and mortality during the first 12 weeks on antiretroviral therapy (ART). Cryptococcal meningitis is a leading cause of HIV-related mortality in Africa, but current guidelines do not advocate CRAG testing as a screening tool. METHODS: Between May 2003 and December 2004, we enrolled HIV-1 infected individuals into a study of ART monitoring in rural Uganda. CRAG testing was conducted retrospectively on stored pre-ART serum samples of participants whose baseline CD4 cell count was <100 cells/mul and who were without symptoms suggestive of disseminated cryptococcal disease at enrolment. RESULTS: Of 377 participants, 5.8% had serum CRAG titre >/=1:2. Of these, 23% died during follow-up. Controlling for CD4 cell count, HIV-1 viral load, anaemia, active tuberculosis and body mass index, relative risk of death during follow-up among those with asymptomatic cryptococcal antigenemia at baseline was 6.6 [95% confidence interval (CI) 1.86-23.61, P = 0.0036]. The population attributable risk for mortality associated with a positive CRAG at baseline was 18% (CI 2-33%), similar to that associated with active tuberculosis (19%, CI 1-36%). CONCLUSION: Asymptomatic cryptococcal antigenemia independently predicts death during the first 12 weeks of ART among individuals with advanced HIV disease in rural Uganda. Routine screening and provision of azole antifungal therapy prior to or simultaneous with the start of ART should be evaluated for the potential to prevent mortality in this population.     

HIV+ MALT lymphoma remission induced by highly active antiretroviral therapy alone

MALT lymphoma is usually described in association with Helicobacter pylori, HCV, HHV8, Campylobacter jejuni or in a setting of overreactive immunity. In HIV(+) patients, MALT lymphoma is most commonly described in children. We describe here an original case of HIV(+) MALT lymphoma with bronchial, conjuctival and laryngeal involvement for which a clinical and histopathological remission has been obtained with HAART alone. We conclude that HIV, as well as H. pylori, C. jejuni and HCV can target lymphogenesis in MALT lymphoma.     

Strong impact of highly active antiretroviral therapy on survival in patients with human immunodeficiency virus-associated Hodgkin's disease

Hodgkin's disease (HD) is the most common non-acquired immunodeficiency syndrome (AIDS)-defining malignancy in human immunodeficiency virus (HIV)-infected patients. We analysed the outcome of patients with HIV-associated HD (HIV-HD) with respect to the use and efficacy of highly active antiretroviral therapy (HAART) and other prognostic factors. To evaluate the effects of several variables on overall survival (OS), Kaplan-Meier statistics and extended Cox regression analysis were performed. Response to HAART was used as a time-dependent variable and was defined as an increase of >0.1 x 10(9) CD4 cells/l and/or at least one viral load <500 copies/ml during the first 2 years following diagnosis of HIV-HD. Fifty-seven patients with HIV-HD diagnosed between 1990 and 2002 were included in the study. In the Cox model, the only factors independently associated with OS were HAART response [relative hazard (RH) 0.19; 95% confidence interval (CI) 0.06-0.60], complete remission (RH 0.30, 95% CI 0.13-0.72), and age 相似文献   

Assessment of HIV antiretroviral therapy adherence by measuring drug concentrations in hair among children in rural Uganda

Current tools for measuring medication adherence have significant limitations, especially among pediatric populations. We conducted a prospective observational study to assess the use of antiretroviral (ARV) drug levels in hair for evaluating antiretroviral therapy (ART) adherence among HIV-infected children in rural Uganda. Three-day caregiver recall, 30-day visual analog scale (VAS), Medication Event Monitoring System (MEMS), and unannounced pill counts and liquid formulation weights (UPC) were collected monthly over a one-year period. Hair samples were collected quarterly and analyzed for nevirapine (NVP) levels, and plasma HIV RNA levels were collected every six months. Among children with at least one hair sample collected, we used univariable random intercept linear regression models to compare log transformed NVP concentrations with each adherence measure, and the child's age, sex, and CD4 count percentage (CD4%). One hundred and twenty-one children aged 2–10 years were enrolled in the study; 74 (61%) provided at least one hair sample, and the mean number of hair samples collected per child was 1.9 (standard deviation [SD] 1.0). Three-day caregiver recall, VAS, and MEMS were found to be positively associated with increasing NVP concentration in hair, although associations were not statistically significant. UPC was found to have a nonsignificant negative association with increasing hair NVP concentration. In conclusion, NVP drug concentrations in hair were found to have nonsignificant, although generally positive, associations with other adherence measures in a cohort of HIV-infected children in Uganda. Hair collection in this population proved challenging, suggesting the need for community education and buy-in with the introduction of novel methodologies.     

Access to antiretroviral therapy during excess black-water flooding in central Thailand

Excess black-water flooding in central Thailand resulted in closure of several healthcare facilities in the Fall of 2011. Persons living with human immunodeficiency virus (HIV) infection were presumably at risk for interruption of antiretroviral therapy (ART), with consequent treatment failure. We conducted a retrospective cohort study of ART use among patients in care at a Thai HIV clinic that closed due to excess flood water. Among 217 patients on ART who had clinic appointments within the one-month interval before the floods through the one-month interval after the clinic re-opened, seven (3%) reported non-sustained ART access. Non-sustained ART access was independently associated with prior low self-reported ART adherence (P<0.001) and less than six-months duration on the ART regimen (P=0.03). Advanced ART receipt or procurement at other flood-free healthcare facilities were strategies associated with ART access. During a flood disaster, identification and close monitoring of at-risk patients, patient–staff communication, flood preparedness plans, “HIV care access for all” policies, and collaboration among patients, healthcare providers and the government are relevant issues within preparedness plans to optimize ART access.     

Isoniazid preventive therapy-related adverse events among Malawian adults on antiretroviral therapy: A cohort study

Adverse events may be a cause of observed poor completion of isoniazid preventive therapy (IPT) among people living with HIV in high tuberculosis burden areas. Data on IPT-related adverse events (AE) from sub-Saharan Africa are scarce. We report IPT-related AEs, associated clinical characteristics, and IPT discontinuations in adults who were stable on antiretroviral therapy (ART) when they initiated IPT. Cohort study nested within a randomized, controlled, clinical trial of cotrimoxazole and chloroquine prophylaxis in Malawians aged ≥ 18 years and virologically suppressed on ART. Eight hundred sixty-nine patients were followed for a median of 6 months after IPT initiation. IPT relatedness of AEs was determined retrospectively with the World Health Organization case-causality tool. Frailty survival regression modeling identified factors associated with time to first probably IPT-related AE. The overall IPT-related AE incidence rate was 1.1/person year of observation. IPT relatedness was mostly uncertain and few AEs were severe. Most common were liver and hematological toxicities. Higher age increased risk of a probably IPT-related AE (aHR = 1.02; 95% CI 1.00–1.06; P = .06) and higher weight reduced this risk (aHR = 0.98; 95% CI 0.96–1.00; P = .03). Of 869 patients, 114 (13%) discontinued IPT and 94/114 (82%) discontinuations occurred at the time of a possibly or probably IPT-related AE. We observed a high incidence of mostly mild IPT-related AEs among individuals who were stable on ART. More than 1 in 8 persons discontinued IPT. These findings inform strategies to improve implementation of IPT in adults on ART, including close monitoring of groups at higher risk of IPT-related AEs.     

Pneumococcal pneumonia in HIV-infected patients by antiretroviral therapy periods

OBJECTIVE: To ascertain the relationship between periods of various antiretroviral therapies and the incidence of first community-acquired pneumococcal pneumonia (CAPP) among HIV-1 infected patients. METHODS: We analysed 4075 patients enrolled prospectively in the Lyon section of the French Hospital Database on HIV between 1993 and 2004, stratified into three groups. The first group (G1) included patients for whom enrolment and last follow-up were before the highly active antiretroviral therapy (HAART) period (beginning 1 July 1996); the second group (G2) comprised patients who were enrolled before HAART but had last follow-up in the HAART period; the third group (G3) included patients for whom both enrolment and last follow-up took place in the HAART period. RESULTS: Fifty-five CAPP episodes were identified. The incidence of CAPP per 1000 patient-years declined over time, from 10.6 to 1.5 and 2.5 in calendar periods G1, G2 and G3, respectively (P=0.004 for linear trend). Factors associated with a decreased risk of CAPP were lower age, baseline CD4 count >or=200 cells/microL and more recent years of enrolment, when HAART use became extensive (P<0.001). The use of intravenous drugs increased the risk of CAPP (P<0.001). CONCLUSIONS: There has been a significant reduction in the incidence of CAPP in HIV-1 infected patients since the advent of HAART.     

Highly active antiretroviral therapy improved persistent lamivudine‐resistant viremia in acute hepatitis B virus genotype Ae infection with coinfection of human immunodeficiency virus

A 57‐year‐old man developed acute hepatitis B virus (AHB), caused by HBV genotype Ae. Lamivudine (LAM) therapy was started at 8 months after the disease onset, because the infection was persistent, but not self‐limited. Despite LAM therapy, the hepatitis became chronic. Further, virological breakthrough developed due to the emergence of LAM‐resistant YMDD mutants at 11 months after LAM therapy. Adefovir dipivoxil (ADV) was combined with LAM against breakthrough hepatitis at 28 months after LAM therapy. Sequential genetic analysis revealed that rtL217R, a mutation potentially diminishing the ADV efficacy, was detected before and after the combination therapy. During the follow‐up period, the patient unexpectedly turned out coinfected with human immunodeficiency virus (HIV) by measuring anti‐HIV‐1 antibody. At that time, LAM‐resistant HIV mutation, M184V, had been already detected. We switched from the combination therapy with LAM plus ADV to highly active antiretroviral therapy (HAART), which included tenofovir disoproxil fumarate. HAART drastically improved LAM‐resistant viremia and breakthrough hepatitis as well as HIV viremia and CD4 counts. Even in Japan, HBV genotype and HIV coinfection should be determined early in the treatment of AHB, and early induction of nucleotide analogs should be taken into consideration, because the proportion of AHB patients with HBV genotype A and the number of patients horizontally coinfected with HBV and HIV are increasing.     

艾滋病抗病毒治疗新进展

艾滋病是影响人类健康的重要公共卫生问题。目前,治疗艾滋病的主要措施是终身进行抗反转录病毒治疗(antiretroviral therapy, ART)。随着科技的不断进步和公共卫生体系的不断完善,艾滋病已成为一种可以治疗但尚无法彻底治愈的"慢性疾病",但长期服药所带来的药物不良反应及耐药等问题也逐渐成为影响患者生存质量和预后的主要因素。因此,寻找更便捷的给药方式、更低的药物毒性、更强的病毒抑制效果和更高耐药屏障的抗病毒药物是目前ART研究领域的发展方向。近年来,新型的整合酶抑制剂、蛋白酶抑制剂、单片复合制剂、新作用机制药物以及简化治疗策略的应用体现了ART研究的新进展。本文结合国内外相关研究和指南,综述艾滋病ART药物的研究进展。     

Human immunodeficiency virus associated thrombotic thrombocytopenic purpura--favourable outcome with plasma exchange and prompt initiation of highly active antiretroviral therapy

Thrombotic thrombocytopenic purpura (TTP) is an acute prothrombotic disorder. Human immunodeficiency virus (HIV) is an identified precipitant. This study reviewed 30 episodes of HIV-associated TTP in 24 patients from the South-East England Apheresis units, over the last 10 years. All patients were heterosexual Black Africans. First presentation of TTP revealed a new diagnosis of HIV in eight patients. TTP relapse occurred on six occasions (in four patients) as a result of non-adherence to highly active antiretroviral therapy (HAART). Prompt initiation/re-initiation of HAART in parallel with plasma exchange (PEX)±steroid led to prompt remission. Adjunct immunomodulatory agents (e.g. Rituximab) were required in 10% of cases. Once-daily HAART regimens are recommended, being compatible with PEX requirement, maximizing drug exposure between PEX. High viral loads (>500,000 copies/ml) require more PEX to remission. ADAMTS13 activity was reduced (<5%) as detected by collagen-binding assay and anti-ADAMTS13 immunoglobulin G antibodies were raised in 80%. Continued HAART-adherence ensured a durable TTP remission with associated viral control resulting in no evidence of relapse. PEX and HAART are associated with replenishment of ADAMTS13 and viral suppression. More PEX is required in cases with higher viral loads. Continued HAART maintains remission. In a small proportion of cases, further immunomodulatory therapy may be required.     

艾滋病合并重度血小板减少临床特征分析

目的 报告艾滋病合并重度血小板减少患者3例,并结合文献搜索讨论其有效治疗方法,为进一步提高临床诊治提供经验.方法 回顾分析3例艾滋病合并重度血小板减少患者的临床资料,讨论其有效治疗方法.结果 3例患者临床表现主要为全身皮肤瘀点、瘀斑,其中2例伴发黏膜出血.3例患者中2例在出现血小板减少时未启动抗病毒治疗,另1例患者已行抗病毒治疗2年,但CD4+T淋巴细胞计数仍<200个/μl.3例患者均使用甲泼尼松龙联合强效抗病毒治疗,后续贯泼尼松龙巩固治疗.1例患者激素治疗无效,行脾切除术.经过治疗3例患者血小板均逐渐恢复并出院.结论 HIV相关性血小板减少的发生可能与HIV在体内持续活跃复制有关,早期以强效抗病毒治疗联合激素冲击疗法为首选方案,可明显改善患者生活质量及结局.     

The eldest of older adults living with HIV: response and adherence to highly active antiretroviral therapy

Objective

The study objective was to analyze the characteristics and the response to therapy in the eldest of the older adults living with human immunodeficiency virus.

Methods

The study included a cohort of patients with human immunodeficiency virus aged 55 years or more on initiating highly active antiretroviral therapy (HAART). Immunologic and virologic response, morbidity, and mortality were assessed. Patients were categorized as aged less than 65 years and 65 years or more.

Results

A total of 112 patients were included (82 patients aged < 65 years and 30 patients aged ≥ 65 years). There were no differences between the age groups in baseline characteristics, survival, and virologic response. There was a trend toward better adherence and a lower CD4+ cell increase after HAART in the older group.

Conclusion

A relationship was found between lower CD4+ cell increase after HAART and advanced age. We found the best adherence to treatment in the eldest of the older adults, and this has been shown to be the only protective independent factor related to virologic failure.     

Evidence of cytogenetic and molecular remission by allogeneic cells after immunosuppressive therapy alone

An immunosuppressive but not myeloablative regimen followed by HLA-matched donor mobilized haemopoietic stem cell transplantation was employed in two high-risk patients. The first patient had refractory anaemia with excess blasts (RAEB) and cytogenetic evidence of translocation 1;3(p36;q21). The second patient had Philadelphia-negative but p190 BCR-ABL chimaeric gene positive chronic myelogenous leukaemia in accelerated phase (AP-CML). The conditioning regimen consisted of fludarabine (30 mg/m²/d, days 1–3) with cyclophosphamide (300 mg/m²/d, days 1–3). Cyclosporine and methotrexate were employed for acute graft-versus-host disease (aGVHD) prophylaxis. In both cases the engraftment of donor cells was demonstrated by cytogenetics and short tandem repeat polymorphisms via PCR. Both patients are alive with normal cytogenetic (RAEB) and molecular (AP-CML) remissions, 100 and 150 d after allografting, respectively. In particular, in the AP-CML patient, the BCR-ABL became undetectable and the BCR-ABL/ABL ratio was <0.0001.     

Plasmablastic lymphoma of the small intestine: Case report and literature review

Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoproliferative disorder, which has been characterized by the World Health Organization as a new entity. Although PBL is most commonly seen in the oral cavity of human immunodeficiency virus (HIV)-positive patients, it can also be seen in extra-oral sites in immunocompromised patients who are HIV-negative. Here we present a rare case of PBL of the small intestine in a 55-year-old HIV-negative male. Histopathological examination of the excisional lesion showed a large cell lymphoma with plasmacytic differentiation diffusely infiltrating the small intestine and involving the surrounding organs. The neoplastic cells were diffusely positive for CD79a, CD138 and CD10 and partly positive for CD38 and epithelial membrane antigen. Approximately 80% of the tumor cells were positive for Ki-67. A monoclonal rearrangement of the kappa light chain gene was demonstrated. The patient died approximately 1.5 mo after diagnosis in spite of receiving two courses of the CHOP chemotherapy regimen. In a review of the literature, this is the first case report of PBL with initial presentation in the small intestine without HIV and Epstein-Barr virus infection, and a history of hepatitis B virus infection and radiotherapy probably led to the iatrogenic immunocompromised state.     

Ambulatory blood pressure profiles in a subset of HIV-positive patients pre and post antiretroviral therapy

South Africa has 5.6 million people living with HIV/AIDS and has the largest antiretroviral therapy (ART) programme globally, with more than two million people accessing ART.1 Although ART has significantly decreased the mortality rate from HIV infection, these individuals are now living longer and are at risk of developing metabolic (dyslipidaemia, lipodystrophy, dysglycaemia), cardiovascular and renal complications from ART and chronic exposure to HIV infection.2-7Chronic HIV and ART are associated with increased risk of developing hypertension.8 In studies of HIV-positive patients in high-income countries, hypertension prevalence ranges from 13 to 34%.9,10 However, data from low- and middle-income countries remain sparse.Nocturnal blood pressure (BP) is superior to daytime or office BP as a predictor of cardiovascular disease.11 Non-dipping is defined as an abnormal diurnal rhythm manifested by a blunted nocturnal decline in systolic BP (SBP).11 It is associated with more severe hypertensive target-organ damage (left ventricular hypertrophy, microalbuminuria and cerebrovascular disease) and is also a predictor of increased cardiovascular risk, both in hypertensive and normotensive populations.11Studies from high-income countries have shown an increased prevalence of non-dipping with HIV infection.9,12 However, the participants in these studies were largely white, middle-aged males. Since the majority of subjects with HIV infection in sub-Saharan Africa are young black females, it is not known whether the same relationship between dipping status and HIV infection would be found. In addition, there are data showing that black HIV-negative individuals have less nocturnal dipping compared to their white counterparts.5,13,14Therefore, the aims of this study were to document the prevalence of chronic kidney disease (CKD) and hypertension at baseline (ART naïve) in a healthy HIV-positive cohort, and to assess changes in these parameters after six months on ART. The characteristics of ambulatory blood pressure (ABP) in a subset of patients were to be recorded and compared to a control group of HIV-negative patients.     

Plasmablastic Lymphoma of the Small Intestine in an HIV- and EBV-negative Patient

Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoproliferative disorder that is strongly associated with immunodeficiency, most often with human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) infection, and that mainly occurs in the oral cavity. Although some clinical features can lead to a diagnosis, PBL in an extraoral site is difficult to suspect clinically in a patient who is HIV negative. The small intestine as a site of PBL has also been described very rarely. We herein present a rare case of PBL of the small intestine in an 85-year-old HIV- and EBV-negative male.     

Dynamics of plasma hepatitis B virus levels after highly active antiretroviral therapy in patients with HIV infection

BACKGROUND/AIMS: The optimal strategy to prescribe highly active antiretroviral therapy (HAART) in patients infected with both hepatitis B virus (HBV) and human immunodeficiency virus (HIV) remains unsettled. This study aimed to compare the HBV dynamics between HBeAg-positive and HBeAg-negative coinfected patients treated with lamivudine-containing HAART. METHODS: We retrospectively analyzed the serial changes of plasma HBV DNA levels in 24 HBsAg-positive HIV-infected patients who entered the HAART program. A polymerase chain reaction-based assay, capable of quantifying as few as 400 HBV copies/ml, was used. The median follow-up time was 18 months. RESULTS: HAART containing lamivudine 300 mg/day effectively suppressed plasma HBV-DNA to 10(-3)-10(-5)-fold of the baseline levels, but a multi-phasic decay of HBV DNA was observed. The later phases became flat, as a persistent residual HBV viremia, in eight of the studied 10 HBeAg-positive patients; in contrast, residual HBV viremia was not observed in the 10 HBeAg-negative patients studied (8/10 vs. 0/10, P=0.0007, Fisher's exact test). HAART without lamivudine did not suppress plasma HBV DNA levels in the remaining four patients. CONCLUSIONS: HAART containing lamivudine 300 mg/day effectively suppress HBV replication in HBeAg-negative HIV/HBV-coinfected patients. Nevertheless, residual HBV replication persisted in most HBeAg-positive coinfected patients.