高效抗反转录病毒治疗相关性脂肪代谢综合征

自1996年高效抗反转录病毒治疗(HAART)应用于临床以来,艾滋病的发病率和死亡率已经大大降低。但HAART治疗需长期或终身服药,因此,药物的毒副作用容易导致患者的依从性下降。其中脂肪代谢综合征就是HAART用药过程中的一个比较常见的远期不良反应之一。HAART药物中与脂肪代谢有关的主要是蛋白酶抑制剂(PIs)和核苷类逆转录酶抑制剂(NRTIs),可以引起各种代谢异常和内分泌紊乱综合征。其具体的发病机制目前尚不清楚。本文就脂肪代谢综合征的发病机制、检测及治疗进行了阐述。     

Interleukin-2 therapy restores CD8 cell non-cytotoxic anti-HIV responses in primary infection subjects receiving HAART

OBJECTIVE: To determine the effect of interleukin-2 (IL-2) therapy on immunologic and virologic responses in subjects with acute or recent HIV infection already receiving highly active antiretroviral therapy (HAART). METHODS: The effect of IL-2 therapy on immunologic and virologic responses was studied in 21 acutely infected individuals who had been receiving HAART for 48 weeks following acute or recent HIV infection. Nine subjects receiving no therapy served as controls. Viral loads, as well as CD4 and CD8 cell counts were monitored and the CD8 cell non-cytotoxic anti-HIV response (CNAR) was measured. RESULTS: IL-2 therapy led to significant increases in CD4 cell numbers (P = 0.005) that were maintained for 6 months after discontinuation of the IL-2 treatment. No effect of IL-2 was observed on viral loads or the CD8 cell numbers as compared to subjects receiving HAART alone. CNAR activity was restored among subjects receiving HAART and IL-2 whereas CNAR declined among those receiving HAART alone and in untreated infected subjects. The percentage of HAART subjects with CD8 cells showing at least 50% suppression of HIV replication increased significantly following IL-2 therapy (P = 0.02) and persisted for 6 months. CONCLUSIONS: In primary HIV infection administering IL-2 concomitant with HAART following 1 year of treatment with HAART gives a significant increase in CD4 cells and a previously unrecognized beneficial effect on the CD8 cell non-cytotoxic anti-HIV response.     

Healthcare use by varied highly active antiretroviral therapy (HAART) strata: HAART use, discontinuation, and naivety

OBJECTIVES: Prior reports have found a temporal association between the introduction of highly active antiretroviral therapy (HAART) and population rates of health service use among persons living with HIV. Our objective was to explore further the effect of HAART by comparing healthcare use among persons who use HAART and persons who discontinue HAART to that among HAART-naive and HIV-negative persons. METHODS: Longitudinal analyses of 1485 women with and at-risk for HIV who contributed data to the Women's Interagency HIV Study between April 1997 and March 2000. RESULTS: Compared with HAART-naive women, those using HAART had a higher probability of more than three primary care visits per 6 months [odds ratio (OR), 1.38; 95% confidence interval (CI), 1.16-1.65), a lower probability of more than one emergency room visit per 6 months (OR, 0.75; CI, 0.59-0.95), and a lower probability of more than one hospitalization per 6 months (OR, 0.67; CI, 0.51-0.88). Compared with HAART-naive women, women who had discontinued HAART had a higher frequency of primary care visits (OR, 1.57; CI, 1.26-1.97) but did not demonstrate a significant change in emergency room or hospital use. Modeling of a standardized population HIV-positive women without AIDS indicated hospitalization and emergency room use among HAART users was equivalent to that among HIV-negative women. CONCLUSIONS: HIV-positive HAART users (without AIDS) exhibited emergency room and hospitalization use patterns equivalent to those of HIV-negative women. Furthermore, the discontinuation of HAART was associated with a loss of the reduction in hospital use that was achieved with HAART.     

Mycobacterium xenopi osteomyelitis in a patient on highly active antiretroviral therapy (HAART)

Skeletal infections with atypical mycobacteria are a manifestation of advanced HIV disease, most patients having CD4 counts of less than 100 cells/mm(3). We report a case of Mycobacterium xenopi vertebral osteomyelitis in a patient on HAART with a CD4 count of 490 cells/mm(3) and viral load below the level of detection at the time of diagnosis.     

Effect of highly active antiretroviral therapy (HAART) on hypergammaglobulinemia in HIV infected patients

To investigate the mechanism of hypergammaglobulinemia in HIV infected patients, the effect of highly active antiretroviral therapy (HAART) on the hypergammaglobulinemia was analyzed. Involved in this study were 34 untreated, 21 HAART-effective (complete response) and 14 HAART-non-effective (partial response) patients. Serum levels of HIV-RNA and gammaglobulin and immunoglobulin (Ig) isotypes were measured. Mean HIV-RNA levels of untreated and partial response patients were 1.6 x 10(4) copies/ml and 0.4 x 10(4) copies/ml, respectively. HIV-RNA levels of all complete response patients were below 4.0 x 10(2) copies/ml. Mean gammaglobulin percentages of untreated, partial response and complete response patients were 24.4%, 21.8% and 17.9%, respectively (p < 0.01 in untreated vs complete response patients). Mean IgG levels in the three groups were 2,489 mg/dl, 1,947 mg/dl and 1,618 mg/dl, respectively (p < 0.001 in untreated vs complete response patients). IgA levels were high in some untreated patients and lower in complete response patients. IgE levels were increased in some untreated and partial response patients, but there was no significant difference among the three groups. These results suggested that the hypergammaglobulinemia found in HIV infected patients was associated with HIV replication. The activation mechanism might differ by Ig isotypes.     

Highly active antiretroviral therapy (HAART) in adults with tuberculosis: current status.

The overlapping epidemiology of human immunodeficiency virus (HIV) infection and tuberculosis (TB) and the catastrophic consequences of the interactions between the two epidemics have led to increased morbidity and mortality due to HIV-associated TB. While effective therapy is available for both conditions, there are major challenges in the concurrent treatment of HIV and TB co-infection. This review examines the interactions between HIV and TB infections and reviews the current status of highly active antiretroviral therapy (HAART) in patients with co-infection. Specific questions relating to optimal timing of concurrent HAART, challenges to concurrent HAART, optimal regimens and future considerations are discussed.     

Thymic output during initial highly active antiretroviral therapy (HAART) and during HAART supplementation with interleukin 2 and/or with HIV type 1 immunogen (Remune)

The thymic output of patients receiving highly active antiretroviral therapy (HAART) was assessed by sjTREC (signal joint T cell receptor rearrangement excision circle) analysis to determine the thymic contribution to CD4(+) T cell reconstitution during initial therapy and during interleukin 2 (IL-2) and/or Remune supplementation of HAART. Levels of sjTRECs were observed to decline dramatically after the first 4 weeks of HAART and then increased without significant associated changes in CD4(+) T cell counts. HAART supplementation with IL-2 was observed to lead to rapid increases in CD4(+) T cells that were accompanied by sjTREC decreases. No notable changes in CD4(+) T cell counts and sjTRECs were seen in patients receiving HAART supplemented with Remune alone. The results indicate CD4(+) T cell maintenance during initial treatment of HIV-1 with HAART and early CD4(+) T cell reconstitution of patients receiving IL-2 with HAART is largely due to thymus-independent mechanisms, with the thymus making a limited contribution.     

Revelations of HIV-infected patients treated with highly active antiretroviral therapy (HAART) in rural Uganda

The purpose of this qualitative study was to explore the psychosocial changes revealed by persons living with HIV/AIDS (PLWHA) in western Uganda as a result of the introduction of highly active antiretroviral therapy (HAART). Fourteen participants were interviewed on two occasions. Two focus groups discussions were also conducted. Patients experienced important personal benefits as a result of HAART and the resulting clinical improvement. These benefits included a restoration of hope, self-esteem and personal agency. Patients were also relieved of the great fear which they had about the conditions of their death. The financial and social struggles introduced by AIDS illness continued after the introduction of HAART. The conclusion is that the HAART programs should provide more holistic care to patients to address the persistent family issues identified in this study.     

Inpatient care of the HIV infected patient in the highly active antiretroviral therapy (HAART) era

The inpatient presentation of the HIV infected patient has changed over the years. From the early years when patients presented with accumulating opportunistic infections that led to an early demise to the HAART era with reports of dramatic decreases in opportunistic infections and improvements in life expectancy, the evolution of inpatient HIV care has been a challenge to the clinician. In the HAART era the presentation of the HIV inpatient has diversified and in many ways is more challenging than the management of the HIV inpatient in the pre-HAART era. We will discuss the changing dynamics of HIV inpatient care from socioeconomic changes to changes in the presentation and reasons for hospitalization.     

HAART对HIV感染者/AIDS病人短期生活质量影响研究

目的 探讨艾滋病病毒(HIV)感染者/艾滋病(AIDS)病人接受抗病毒治疗6个月时,生活质量有无变化.方法 给予安徽省两地40名HIV感染者/AIDS病人高效抗逆转录病毒治疗(HAART),应用病历报告表的形式收集参加治疗病人的人口学信息、流行病学、临床及实验室检查信息,同时采用MOS-HIV量表,对病人治疗前和治疗6个月时生活质量进行调查,对相关数据进行统计分析.结果 40名HIV感染者/AIDS病人平均年龄(42.2±8.8)岁(26～62岁),治疗前CD4平均为(197±41)个/μl(94～271),治疗6个月时体重平均增加(5.1±4.5)kg(t＝7.24,P＜0.01),CD4平均增加(122±109)个/μl(t＝7.07,P＜0.01).采用MOS-HIV量表评定,病人躯体状况及精神状况在治疗后均有显著改善;维度分析显示,在健康感知、认知功能、疼痛、精神健康、精力与劳累、健康压力、生活状况、健康的变化方面,治疗前后的差异有显著的统计学意义(P＜0.01).结论 抗病毒治疗6个月时病人CD4细胞计数明显升高、体重增加、生活质量改善,躯体及精神状况均有所提高.     

Highly active anti-retroviral therapy (HAART) prolongs time to treatment failure in Kaposi's sarcoma.

OBJECTIVE: To evaluate the impact of highly active antiretroviral therapy (HAART) on Kaposi's sarcoma. DESIGN: Retrospective study of patients who had received systemic or local treatment for AIDS-related Kaposi's sarcoma who subsequently commenced HAART. METHODS: Case note review to determine time to treatment failure for Kaposi's sarcoma before and after starting HAART. Time to treatment failure was calculated from the end of last therapy to the start of the next new treatment for Kaposi's sarcoma. RESULTS: The cohort contained 78 patients. Only 38% had good risk Kaposi's sarcoma (stage T0I0) at presentation. The median time to treatment failure before starting HAART was 0.5 years. Initial HAART therapy was three or more drugs including a protease inhibitor for 38 (49%), three or more drugs without a protease inhibitor for 27 (35%) and a two-drug protease combination for 13 (16%). The median follow-up after starting HAART was 12 months (range, 0.5-52 months) and anti-Kaposi's sarcoma treatment has been required for 24 (31%) patients. The median time to treatment failure for Kaposi's sarcoma from the start of HAART is 1.7 years. This is statistically longer than the time to treatment failure for the same cohort of patients before they started HAART (log rank chi2 = 16.5, P < 0.0001). The serum HIV RNA viral load (VL) at the time of Kaposi's sarcoma progression revealed virological failure of HAART (defined as VL > 5000 copies/ml) in 14 of 24 (58%) and good control (VL < 200 copies/ml) in five of 24 (21%). CONCLUSION: HAART is associated with prolonged time to treatment failure in Kaposi's sarcoma. Progression of Kaposi's sarcoma while on HAART is not necessarily associated with virological failure as determined by rising viral RNA titre.