青蒿素衍生物和某些天然化合物抗HIV-1活性的研究

对生活在发展中国家的90%以上的HIV感染者而言，现有FDA已批准的抗HIV药物的价格十分昂贵。中国也是发展中国家，但HIV感染者已遍布全国，其数量正急剧增长，这必将对生产力和国民经济建设产生严重影响。为预防艾滋病蔓延，我们在进行宣传教育的同时，务必研制开发有我国特色的、高效的、便宜的抗HIV药物。因此，我们在抗猴逆转录D型病毒（SRV1）活性研究基础上，对SM458等24个青蒿素衍生物进行了抗HIV-1活性的深入研究。同时，为充分利用我国丰富的自然资源，我们还研究了20个天然化合物和中草药配方。除应用MTT比色法外，我们还采用了另外3种体外抗HIV-1活性研究的实验，如合胞体形成抑制，间接免疫荧光法（IFA），p24半定量ELISA等。此外，我们还研究了SM458、SM486和肝龙与AZT的协同作用，并进一步重复了SM458和SM486抗SRV1活性的研究。结果表明：AZT的抗SRV1/HIV-1活性十分显著，SM458和SM486 也有较高的抗SRV1活性，其选择指数均接近100；但除了SM458较稳定地表现微弱的抗HIV-1活性外，其它23个青蒿素衍生物没有活性；为初步探索SM458和SM486抗SRV1/HIV-1活性差异的机理，我们进行细胞融合阻断实验，结果表明其作用靶点并非融合。由此说明：SRV1虽然与HIV-1同属灵长类逆传录病毒，但以SRV1进行的抗病毒研究结果，不能完全与抗HIV-1的活性相符合，必须以直接用HIV-1所做的研究为依据。令人鼓舞的是，肝龙表现稳定的抗HIV-1活性，值得进一步深入研究。而其它19个样品中，仅桑黄素、桑白皮和GE-II表现很微弱的活性，JK028和V1-1-Na有待确证。SM458、SM486和肝龙与AZT无协同作用。

The chemical resolution of racemic cis-2-hydroxymethyl-5(cytosine-1 '-yl)-1,3-oxathiolane (BCH-189)-one direct method to obtain lamivudine as anti-HIV and anti-HBV agent

Racemic cis-BCH-189 can be resolved to (-)-enantiomer (lamivudine) and (+)-enantiomer by esterification of cis-2-hydroxymethyl-5-(N-4(')-acetylcytosine-1'-yl)-1,3-oxathiolane and (+)-menthyl chloroformate in CH3CN with pyridine as base. The two diastereomers of ester were seperated by recrystallization in methanol at 0degreesC. Lamivudine was obtained by deprotection of (-)-diastereomer with high yield.

具有抗HIV病毒活性的杂多酸HPA－23与谷胱甘肽的作用

以谷胱甘肽作为病毒包络蛋白的模拟物，用ＮＭＲ方法研究了与具有抗爱滋病病毒活性杂多酸ＨＰＡ－２３的作用．对不同配比的ＨＰＡ－２３和谷胱甘肽混合物的１Ｈ和１８３ＷＮＭＲ谱研究结果表明，还原型和氧化型谷胱甘肽均以Ｃ末端ＣＯＯ－与ＨＰＡ－２３骨架的钨原子配位，还原型谷胱甘肽侧链上的巯基（ＳＨ）也参加配位．ＣＯＳＹ谱证明了ＳＨ配位为慢交换反应．早在七十年代初，人们就发现杂多酸具有抗病毒活性［１，２］．最近报道［ＮＨ４］１８［ＮａＳｂ９Ｗ２１Ｏ８８］·２４Ｈ２Ｏ（结构代号为ＨＰＡ－２３）具有很高的抗爱滋病病毒活性，在法国已进入临床应用［３］．但从分子水平研究杂多酸化合物抗病毒的机理．目前尚未见到国内外报道．而作为病毒可以广义地看作由一个蛋白外壳包裹，内部则为核酸．爱滋病病毒同样由两层蛋白所包裹，与宿主细胞发生吸附作用主要是通过外层包络蛋白（ＧＰ１２０）［４］，该蛋白的活性组份是一个由８个氨基酸组成的Ｔ（Ａｌａ－Ｓｅｒ－Ｔｈｒ－Ｔｈｒ－Ｔｈｒ－Ａｓｎ－Ｔｙｒ－Ｔｈｎ）肽段［５］．我们以容易得到的三肽一谷胱甘肽作为病毒包络蛋白的模拟物，用ＮＭＲ方法研究杂多酸ＨＰＡ－２３与它的作用．结果表明还原型和氧化型谷胱甘肽均以Ｃ末端Ｃ

H5N1 avian influenza re-emergence of Lake Communication Qinghai: phylogenetic and antigenic analyses of the newly isolated viruses and roles of migratory birds in virus circulation

Highly pathogenic avian influenza H5N1 virus has swept west across the globe and caused serious debates on the roles of migratory birds in virus circulation since the first large-scale outbreak in migratory birds of Lake Qinghai, 2005. In May 2006, another outbreak struck Lake Qinghai and six novel strains were isolated. To elucidate these QH06 viruses, the six isolates were subjected to whole-genome sequencing. Phylogenetic analyses show that QH06 viruses are derived from the lineages of Lake Qinghai, 2005. Five of the six novel isolates are adjacent to the strain A/Cygnus olor/Croatia/1/05, and the last one is related to the strain A/duck/Novosibirsk/ 02/05, an isolate of the flyway. Antigenic analyses suggest that QH06 and QH05 viruses are similar to each other. These findings implicate that QH06 viruses of Lake Qinghai may travel back via migratory birds, though not ruling out the possibility of local circulation of viruses of Lake Qinghai.

Toward a comprehensive care of HIV patients: Finding a strategy to detect depression in a Spanish HIV cohort

Depression is a common but frequently undiagnosed feature in individuals with HIV infection. To find a strategy to detect depression in a non-specialized clinical setting, the overall performance of the Hospital Anxiety and Depression Scale (HADS) and the depression identification questions proposed by the European AIDS Clinical Society (EACS) guidelines were assessed in a descriptive cross-sectional study of 113 patients with HIV infection. The clinician asked the two screening questions that were proposed under the EACS guidelines and requested patients to complete the HADS. A psychiatrist or psychologist administered semi-structured clinical interviews to yield psychiatric diagnoses of depression (gold standard). A receiver operating characteristic (ROC) analysis for the HADS-Depression (HADS-D) subscale indicated that the best sensitivity and specificity were obtained between the cut-off points of 5 and 8, and the ROC curve for the HADS-Total (HADS-T) indicated that the best cut-off points were between 12 and 14. There were no statistically significant differences in the correlations of the EACS (considering positive responses to one [A] or both questions [B]), the HADS-D ≥ 8 or the HADS-T ≥ 12 with the gold standard. The study concludes that both approaches (the two EACS questions and the HADS-D subscale) are appropriate depression-screening methods in HIV population. We believe that using the EACS-B and the HADS-D subscale in a two-step approach allows for rapid, assumable and accurate clinical diagnosis in non-psychiatric hospital settings.

HIV/AIDS and national security

McInnes, C., 'HIV/AIDS and national security', in: AIDS and Governance, N. Poku, A. Whiteside and B. Sandkjaer (eds.),(Aldershot: Ashgate, 2007), pp.93-111 RAE2008

A transcriptase reversa como alvo terapêutico em doenças retrovirais

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Ciências Farmacêuticas

Shifting the Burden of HIV/AIDS

As the economic burden of HIV/AIDS increases in sub-Saharan Africa, the allocation of the burden among levels and sectors of societies is changing. The private sector has greater scope than government, households, or NGOs to avoid the economic burden of AIDS, and a systematic shifting of the burden away from the private sector is underway. Common practices that shift the AIDS burden from businesses to households and government include pre-employment screening, reduced employee benefits, restructured employment contracts, outsourcing of less skilled jobs, selective retrenchments, and changes in production technologies. In South Africa, more than two thirds of large employers have reduced health care benefits or required larger contributions by employees. Most firms have replaced defined benefit retirement funds, which expose the firm to large annual costs but provide long-term support for families, with defined contribution funds, which eliminate firm risk but provide little to families of younger workers who die of AIDS. Contracting out of previously permanent jobs also shields firms from costs while leaving households and government to care for affected workers and their families. Many of these changes are responses to globalization and would have occurred in the absence of AIDS, but they are devastating for employees with HIV/AIDS. This paper argues that the shifting of the economic burden of AIDS is a predictable response by business to which a thoughtful public policy response is needed. Countries should make explicit decisions about each sector’s responsibilities if a socially desirable allocation is to be achieved.

Rationing Antiretroviral Therapy for HIV/AIDS in Africa: Efficiency, Equity, and Reality

Background: Rationing of access to antiretroviral therapy already exists in sub-Saharan Africa and will intensify as national treatment programs develop. The number of people who are medically eligible for therapy will far exceed the human, infrastructural, and financial resources available, making rationing of public treatment services inevitable. Methods: We identified 15 criteria by which antiretroviral therapy could be rationed in African countries and analyzed the resulting rationing systems across 5 domains: clinical effectiveness, implementation feasibility, cost, economic efficiency, and social equity. Findings: Rationing can be explicit or implicit. Access to treatment can be explicitly targeted to priority subpopulations such as mothers of newborns, skilled workers, students, or poor people. Explicit conditions can also be set that cause differential access, such as residence in a designated geographic area, co-payment, access to testing, or a demonstrated commitment to adhere to therapy. Implicit rationing on the basis of first-come, first-served or queuing will arise when no explicit system is enforced; implicit systems almost always allow a high degree of queue-jumping by the elite. There is a direct tradeoff between economic efficiency and social equity. Interpretation: Rationing is inevitable in most countries for some period of time. Without deliberate social policy decisions, implicit rationing systems that are neither efficient nor equitable will prevail. Governments that make deliberate choices, and then explain and defend those choices to their constituencies, are more likely to achieve a socially desirable outcome from the large investments now being made than are those that allow queuing and queue-jumping to dominate.

Treatment of HIV/AIDS at South Africa's Largest Employers: Myth and Reality

Background: In the past three years, many large employers in South Africa have announced publicly their intention of making antiretroviral treatment (ART) available to employees. Reports of the scope and success of these programs have been mostly anecdotal. This study surveyed the largest private sector employers in South Africa to determine the proportion of employees with access to ART through employer-sponsored HIV/AIDS treatment programs. Methods: All 64 private sector and parastatal employers in South Africa with more than 6,000 employees were identified and contacted. Those that agreed to participate were interviewed by telephone using a structured questionnaire. Results: 52 companies agreed to participate. Among these companies, 63% of employees had access to employer-sponsored care and treatment for HIV/AIDS. Access varied widely by sector, however. Approximately 27% of suspected HIV-positive employees were enrolled in HIV/AIDS disease management programs, or 4.4% of the workforce overall. Fewer than 4,000 employees in the entire sample were receiving antiretroviral therapy. In-house (employer) disease management programs and independent disease management programs achieved higher uptake of services than did medical aid schemes. Conclusions: Publicity by large employers about their treatment programs should be interpreted cautiously. While there is a high level of access to treatment, uptake of services is low and only a small fraction of employees medically eligible for antiretroviral therapy are receiving it.

The Private Sector and HIV/AIDS in Africa: Taking Stock of Six Years of Applied Research

Background: Until recently, little was known about the costs of the HIV/AIDS epidemic to businesses in Africa and business responses to the epidemic. This paper synthesizes the results of a set of studies conducted between 1999 and 2006 and draws conclusions about the role of the private sector in Africa’s response to AIDS. Methods: Detailed human resource, financial, and medical data were collected from 14 large private and parastatal companies in South Africa, Uganda, Kenya, Zambia, and Ethiopia. Surveys of small and medium-sized enterprises (SMEs) were conducted in South Africa, Kenya, and Zambia. Large companies’ responses or potential responses to the epidemic were investigated in South Africa, Uganda, Kenya, Zambia, and Rwanda. Results: Among the large companies, estimated workforce HIV prevalence ranged from 5%¬37%. The average cost per employee lost to AIDS varied from 0.5-5.6 times the average annual compensation of the employee affected. Labor cost increases as a result of AIDS were estimated at anywhere from 0.6%-10.8% but exceeded 3% at only 2 of 14 companies. Treatment of eligible employees with ART at a cost of $360/patient/year was shown to have positive financial returns for most but not all companies. Uptake of employer-provided testing and treatment services varied widely. Among SMEs, HIV prevalence in the workforce was estimated at 10%-26%. SME managers consistently reported low AIDS-related employee attrition, little concern about the impacts of AIDS on their companies, and relatively little interest in taking action, and fewer than half had ever discussed AIDS with their senior staff. AIDS was estimated to increase the average operating costs of small tourism companies in Zambia by less than 1%; labor cost increases in other sectors were probably smaller. Conclusions: Although there was wide variation among the firms studied, clear patterns emerged that will permit some prediction of impacts and responses in the future.

How Much Does It Cost to Provide Antiretroviral Therapy for HIV/AIDS in Africa?

Background: Many African countries are rapidly expanding HIV/AIDS treatment programs. Empirical information on the cost of delivering antiretroviral therapy (ART) for HIV/AIDS is needed for program planning and budgeting. Methods: We searched published and gray sources for estimates of the cost of providing ART in service delivery (non-research) settings in sub-Saharan Africa. Estimates were included if they were based on primary local data for input prices. Results: 17 eligible cost estimates were found. Of these, 10 were from South Africa. The cost per patient per year ranged from $396 to $2,761. It averaged approximately $850/patient/year in countries outside South Africa and $1,700/patient/year in South Africa. The most recent estimates for South Africa averaged $1,200/patient/year. Specific cost items included in the average cost per patient per year varied, making comparison across studies problematic. All estimates included the cost of antiretroviral drugs and laboratory tests, but many excluded the cost of inpatient care, treatment of opportunistic infections, and/or clinic infrastructure. Antiretroviral drugs comprised an average of one third of the cost of treatment in South Africa and one half to three quarters of the cost in other countries. Conclusions: There is very little empirical information available about the cost of providing antiretroviral therapy in non-research settings in Africa. Methods for estimating costs are inconsistent, and many estimates combine data drawn from disparate sources. Cost analysis should become a routine part of operational research on the treatment rollout in Africa.