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SCIENTIFIC AMERICAN 2000年第5期283卷 98-103页

作者： Ezzell, C

Most of the 35 million people infected with the AIDS virus live on the African continent,where drugs that can fight hiv are rare. Will the world let these people die?

关键词：艾滋病相关机会致病菌感染/药物疗法获得性免疫缺陷综合征/药物疗法非洲抗hiv药/经济学抗hiv药/治疗应用传染性疾病传播垂直国际合作病人依从贫困齐多夫定/经济学齐多夫定/治疗应用成年人女(雌)性人类男(雄)性妊娠

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Treatment intensification with abacavir in hiv-infected patients with at least 12 weeks previous lamivudine/zidovudine treatment

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ANTIVIRAL THERAPY 2001年第2期6卷 135-142页

作者： Rozenbaum, W Katlama, C Massip, P Bentata, M Zucman, D Delfraissy, JF Trepo, C David, F Lanier, ER Vavro, C Mamet, JP Hop Rothschild F-75571 Paris France Grp Hosp Pitie Salpetriere F-75634 Paris France Hop Purpan Toulouse France Hop Avicenne F-93009 Bobigny France Hop Foch Suresnes France Hop Kremlin Bicetre Paris France Hotel Dieu Serv Hepatogastroenterol Lyon France GlaxoWellcome Marly le Roi France Glaxo Wellcome Inc Res Triangle Pk NC 27709 USA

Objectives: To demonstrate that lamivudine and zidovudine, given separately (lamivudine/zidovudine) or as a single combination tablet (Combivir(TM)), had equivalent efficacy. To evaluate the safety and antiretroviral activity of intensification with abacavir in patients treated with lamivudine/zidovudine for greater than or equal to 12 weeks. Design: A 12-week, equivalence study of lamivudine/ zidovudine versus Combivir. Patients who completed this study could enter a 48-week, intensification study of Combivir plus abacavir. Methods: In the equivalence study, treatment-naive patients were assessed for hiv-1 RNA, CD4 cell count and genotype. The same assessments plus phenotype were made in the intensification study. Serious adverse events were recorded in the equivalence study and all adverse events in the intensification study. Results: Lamivudine/zidovudine (n=40) and Combivir (n=35) gave equivalent reductions in plasma hiv-1 RNA levels at week 12. An identical proportion of patients (74%) in each treatment group harboured virus with the M184V mutation after 12 weeks. Fifty-two patients entered the intensification study and 44 completed 48 weeks of treatment. At the time of intensification with abacavir, all 35 patients with evaluable isolates harboured hiv-1 containing M184V. Addition of abacavir to Combivir led to further decreases in plasma hiv-1 RNA and increases in CD4 cell counts compared with the start of intensification (P<0.001 at week 48). After 48 weeks of triple therapy, multi-nucleoside resistance mutations at codons 69 and 151 were not detected in any patients. All treatment regimens were generally well tolerated. Conclusion: Lamivudine/zidovudine and Combivir have equivalent antiretroviral activity over 12 weeks. Adding abacavir to Combivir can be a safe and effective therapeutic option for patients, including those harbouring virus with the M184V mutation.

关键词：投药口服抗hiv药/投药和剂量抗hiv药/治疗应用双脱氧核苷类/投药和剂量双脱氧核苷类/治疗应用用药计划表复方合剂药物疗法联合 hiv感染/血液 hiv感染/药物疗法 hiv-1/药物作用 hiv-1/遗传学 hiv-1/分离和提纯拉米夫定/投药和剂量 RNA 病毒/血液时间因素齐多夫定/投药和剂量青少年成年人女(雌)性人类男(雄)性中年人

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Progress against AIDS

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NATURE BIOTECHNOLOGY 2000年第4期18卷 466-467页

作者： Persidis, A RheoGene Charlottesville VA 22903 USA

Focuses on the progress in the development of drugs against AIDS and AIDS-related conditions. Issues related to the incidence and prevalence of AIDS; Several challenges faced by the people involved in preventing the d... 详细信息

关键词：获得性免疫缺陷综合征/药物疗法获得性免疫缺陷综合征/流行病学抗hiv药/治疗应用制药工业 hiv感染/药物疗法 hiv感染/流行病学发病率患病率美国人类

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Antiretroviral resistance during successful therapy of hiv type 1 infection

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 2000年第20期97卷 10948-10953页

作者： Martinez-Picado, J DePasquale, MP Kartsonis, N Hanna, GJ Wong, J Finzi, D Rosenberg, E Günthard, HF Sutton, L Savara, A Petropoulos, CJ Hellmann, N Walker, BD Richman, DD Siliciano, R D'Aquila, RT Massachusetts Gen Hosp Div Infect Dis Boston MA 02129 USA Massachusetts Gen Hosp AIDS Res Ctr Boston MA 02129 USA Harvard Univ Sch Med Boston MA 02129 USA Hosp Badalona Germans Trias & Pujol Fundacio irsiCaixa Badalona 08916 Spain Univ Calif San Diego Dept Med La Jolla CA 92093 USA Univ Calif San Diego Dept Pathol La Jolla CA 92093 USA San Diego Vet Affairs Healthcare Syst La Jolla CA 92093 USA Johns Hopkins Univ Sch Med Dept Med Baltimore MD 21205 USA ViroLog Inc San Francisco CA 94080 USA

hiv type 1 (hiv-1) drug resistance mutations were selected during antiretroviral therapy successfully suppressing plasma hiv-1 RNA to 50 copies/ml and virus env gene sequence changes. Each had received a suboptimal r... 详细信息

hiv type 1 (hiv-1) drug resistance mutations were selected during antiretroviral therapy successfully suppressing plasma hiv-1 RNA to <50 copies/ml. New resistant mutant subpopulations were identified by clonal sequencing analyses of viruses cultured from blood cells. Drug susceptibility tests showed that biological clones of virus with the mutations acquired during successful therapy had increased resistance. Each of the five subjects with new resistant mutants had evidence of some residual virus replication during highly active antiretroviral therapy (HAART). based on transient episodes of plasma hiv-1 RNA > 50 copies/ml and virus env gene sequence changes. Each had received a suboptimal regimen before starting HAART. Antiretroviral-resistant hiv-1 can be selected from residual virus replication during HAART in the absence of sustained rebound of plasma hiv-1 RNA.

关键词：抗hiv药/药理学抗hiv药/治疗应用抗药性微生物/遗传学 hiv感染/药物疗法 hiv感染/病毒学 hiv-1/药物作用 hiv-1/遗传学分子序列数据突变人类

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Can HCV affect the efficacy of anti-hiv treatment?

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ARChivES OF VIROLOGY 2000年第5期145卷 937-944页

作者： Filippini, P Coppola, N Scolastico, C Liorre, G Nocera, R Sagnelli, E Piccinino, F Univ Naples 2 Inst Infect Dis Sch Med I-80135 Naples Italy

To evaluate the impact of new antiretroviral combinations (HAART: Highly Active Anti Retroviral Therapy) on HCV replication and liver enzyme levels, we analysed the changes in HCV viremia and aminotransferase levels in hiv and HCV co-infected patients. Moreover, to evaluate the influence of HCV infection on the efficacy of HAART, we compared the virological, immunological and biochemical response to antiretroviral combinations in anti-hiv positive subjects with or without HCV infection. We enrolled eight consecutive outpatients with hiv-HCV coinfection and with indications for HAART (Group A). For each patient in group A, we selected an anti-hiv negative patient with indications for HAART, pair-matched for age, sex, risk factor for hiv infection, presumed duration of infection, number of CD4;cells, hiv viremia and treatment schedule (Group B). A statistically significant increase in CD4 in both groups was found at 1(st), 3(rd) and 6(th) month of antiretroviral therapy. A decrease in hiv-RNA in both groups was observed at 1(st) and 6th month of treatment. The percentage of patients with undetectable hiv-RNA at the 1(st) month was higher in Group B than in Group A (8/8 vs. 3/8, p = 0.025). Basal HCV-RNA viremia was very high in each case and no variations during treatment were observed. During therapy the aminotransferase levels slightly decreased in Group A and consistently increased in Group B. In Group A the differences were not significant to the statistical analysis in Group B the aminotransferase levels at 3(st) and 6(th) month were significantly higher than those observed at the baseline.

关键词：丙氨酸转氨酶/血液抗hiv药/投药和剂量抗hiv药/治疗应用天冬氨酸氨基转移酶类/血液 CD4淋巴细胞计数病例对照研究 DNA 病毒/血液 hiv感染/并发症 hiv感染/药物疗法 hiv感染/免疫学肝炎丙型/并发症肝炎丙型/酶学肝炎丙型/病毒学肝/药物作用肝/酶学病毒血症/药物疗法病毒复制/药物作用成年人女(雌)性人类男(雄)性中年人

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Antiretroviral therapy of hiv-1 infection: established treatment strategies and new therapeutic options

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CURRENT OPINION IN MICROBIOLOGY 2000年第5期3卷 508-514页

作者： Kaufmann, GR Cooper, DA Natl Ctr HIV Epidemiol & Clin Res Sydney NSW 2010 Australia

Recently, studies have shown that non-nucleoside reverse transcriptase inhibitors, such as efavirenz or nevirapine, in combination with two nucleoside analogues have an antiretroviral potency comparable to protease inhibitor containing regimens. Triple combination therapy that includes a non-nucleoside reverse transcriptase inhibitor can therefore be regarded as an effective alternative first-line treatment of hiv-1 infection.

关键词：抗hiv药/治疗应用抗逆转录病毒治疗高效 hiv感染/药物疗法 hiv蛋白酶抑制药/治疗应用 hiv-1 逆转录酶抑制剂/治疗应用挽救疗法人类

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A tale of two futures: hiv and antiretroviral therapy in San Francisco

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SCIENCE 2000年第5453期287卷 650-654页

作者： Blower, SM Gershengorn, HB Grant, RM Univ Calif San Francisco Dept Med San Francisco CA 94143 USA Univ Calif San Francisco Gladstone Inst Virol & Immunol San Francisco CA 94141 USA

The effect of antiretroviral therapy (ART) in preventing human immunodeficiency virus (hiv) infections and averting acquired immunodeficiency syndrome (AIDS) deaths in the San Francisco gay community over the next 10 years was predicted. A transmission model was coupled with a statistical approach that enabled inclusion of a high degree of uncertainty in the potential treatment effects of ART (in terms of infectivity and survival), increase in risky behavior, and rate of emergence of drug resistance. Increasing the usage of ART in San Francisco would decrease the AIDS death rate and could substantially reduce the incidence rate.

关键词：获得性免疫缺陷综合征/死亡率抗hiv药/治疗应用抗药性微生物药物疗法联合预测 hiv/药物作用 hiv感染/药物疗法 hiv感染/预防和控制 hiv感染/传播 hiv感染/病毒学同性恋模型生物学模型统计学蒙特卡罗法概率冒险旧金山/流行病学人类

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A double blind, randomized, placebo-controlled phase II study to assess the safety and efficacy of orally administered SP-303 for the symptomatic treatment of diarrhea in patients with AIDS

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AMERICAN JOURNAL OF GASTROENTEROLOGY 1999年第11期94卷 3267-3273页

作者： Holodniy, M Koch, J Mistal, M Schmidt, JM Khandwala, A Pennington, JE Porter, SB AIDS Res Ctr FACP VA Palo Alto Hlth Care Syst Palo Alto CA 94304 USA Stanford Univ Palo Alto CA 94304 USA Univ Calif San Francisco San Francisco CA 94143 USA

OBJECTIVE: The aim of this study was to investigate the safety and effectiveness of orally administered SP-303 in patients with AIDS and diarrhea. METHODS: This is a multicenter, phase II, randomized, double blind, placebo-controlled study. hiv-positive subjects with a history of a CD4 count <200 or an AIDS-defining illness were admitted to an inpatient study unit and screened for diarrhea defined as at least three abnormal (i.e., soft or watery) stools and >200 g of abnormal stool weight over a 24-h period. Subjects discontinued all antidiarrheal agents >24 h before enrollment. Stool samples were studied for routine pathogens. Subjects received 500 mg y.o. of SP-303 or placebo every 6 h for 96 h (4 days). Stool frequency and weights were recorded. Subjects were monitored for symptoms and side effects and were seen 1 wk later in follow-up. RESULTS: A total of 26 subjects received SP-303, and 25 received placebo. There were no significant demographic differences between treatment arms. A total of 41 subjects (80%) were receiving antiretroviral therapy and 39 subjects (77%) were receiving at least one protease inhibitor. Stool studies revealed no pathogens in 38 of 51 patients (94%). There were no serious adverse events or laboratory abnormalities. The SP-303 treatment group demonstrated a mean reduction from baseline stool weight of 451 g/24 h vel-sw 150 g/24 h with placebo on day 4 of treatment (p = 0.14), and a mean reduction in abnormal stool frequency of three abnormal stools in 24 h versus two in 24 h in the placebo group (p = 0.30). Daily measures analysis over 4 days of treatment demonstrated that SP-303 subjects had a significant reduction in stool weight (p = 0.008) and abnormal stool frequency (p = 0.04) when compared to placebo-treated subjects. CONCLUSIONS: SP-303 is safe and well tolerated. These results suggest that SP-303 may be effective in reducing stool weight and frequency in patients with AIDS and (C) 1999 by Am. Cell. of Gastroenterology.

关键词：获得性免疫缺陷综合征/并发症投药口服抗hiv药/治疗应用止泻药/投药和剂量止泻药/治疗应用抗病毒药/投药和剂量抗病毒药/治疗应用生物聚合物/治疗应用儿茶素/类似物和衍生物儿茶素/治疗应用腹泻/药物疗法腹泻/病毒学双盲法粪便随访研究 hiv蛋白酶抑制药/治疗应用安慰剂安全成年人女(雌)性人类男(雄)性中年人

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Experience with nevirapine in previously treated hiv-1-infected individuals

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ANTIVIRAL THERAPY 2000年第4期5卷 257-266页

作者： Wit, FWNM Univ Amsterdam Acad Med Ctr Dept Internal Med Natl AIDS Therapy Evaluat Ctr NL-1012 WX Amsterdam Netherlands

Objective: To assess the tolerability, virological, immunological and clinical effects of nevirapine in the setting of a compassionate use programme in pretreated hiv-infected individuals. Design: Retrospective observational cohort-study in 13 hiv-outpatient clinics in The Netherlands. Methods: Main outcome measures: plasma hiv-1 RNA levels;CD4 cell counts;incidence of new AIDS-defining diseases;multivariate analysis of predictors for virological success;incidence of skin rashes. Results: 187 hiv-infected individuals treated with nevirapine in the Nevirapine Named Patient Programme in The Netherlands were included. After 48 weeks, 38% of patients had an hiv-1 RNA level below 1000 copies/ml. In multivariate regression analysis, prior treatment with three or less nucleoside analogue reverse transcriptase inhibitors, and a higher baseline CD4 cell count was predictive of virological success. The median CD4 cell count remained stable over the 48 weeks. Eleven patients experienced a new AIDS-defining event. The total incidence of rash (including rash not leading to discontinuation of nevirapine) was 13.9 and 6.4% of the patients discontinued nevirapine because of rash. None of the 28 patients with undetectable hiv-1 RNA levels at baseline developed a rash. Conclusions: We conclude that nevirapine when used as part of salvage therapy is safe and most likely to give sustained suppression of hiv-1 in patients that have been less extensively pretreated. CD4 cell counts remained stable despite the low rate of virological success, this also occurred in patients not concurrently using protease inhibitors (PIs). The incidence of nevirapine-related rash in PI-pretreated patients and especially in patients with undetectable hiv-1 RNA levels at the start of nevirapine treatment, is considerably lower than previously reported for antiretroviral-naive patients.

关键词：抗hiv药/治疗应用 CD4淋巴细胞计数队列研究药物疗法联合 hiv感染/药物疗法 hiv感染/病毒学 hiv-1/生理学奈韦拉平/治疗应用 RNA 病毒/血液回顾性研究逆转录酶抑制剂/治疗应用挽救疗法成年人女(雌)性人类男(雄)性中年人

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Dissociation of hiv-1 from follicular dendritic cells during HAART: Mathematical analysis

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 1999年第26期96卷 14681-14686页

作者： Hlavacek, WS Wofsy, C Perelson, AS Univ Calif Los Alamos Natl Lab Div Theoret Los Alamos NM 87545 USA Univ New Mexico Dept Math & Stat Albuquerque NM 87131 USA

Follicular dendritic cells (FDC) provide a reservoir for hiv type 1 (hiv-1) that may reignite infection if highly active antiretroviral therapy (HAART) is withdrawn before virus on FDC is cleared. To estimate the treatment time required to eliminate hiv-1 on FDC, we develop deterministic and stochastic models for the reversible binding of hiv-1 to FDC via ligand-receptor interactions and examine the consequences of reducing the virus available for binding to FDC, Analysis of these models shows that the rate at which hiv-1 dissociates from FDC during HAART is biphasic, with an initial period of rapid decay followed by a period of slower exponential decay. The speed of the slower second stage of dissociation and the treatment time required to eradicate the FDC reservoir of hiv-1 are insensitive to the number of virions bound and their degree of attachment to FDC before treatment. In contrast, the expected time required for dissociation of an individual virion from FDC varies sensitively with the number of ligands attached to the virion that are available to interact with receptors on FDC. Although most virions may dissociate from FDC on the time scale of days to weeks, virions coupled to a higher-than-average number of ligands may persist on FDC for years. This result suggests that HAART may not be able to clear all hiv-1 trapped on FDC and that, even if clearance is possible, years of treatment will be required.

关键词：抗hiv药/治疗应用补体C3 树突细胞滤泡/病毒学 hiv-1/药物作用 hiv-1/免疫学模型理论受体补体3d 随机过程

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