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国立国際医療センターACC(リサーチレジデント) 畢秀瓊


1. About the basic science
In the era of antiretroviral therapy (HAART), we are still facing such a lot of difficulties such as the pathogenesis of HIV/AIDS, the eradication of HIV virus, the new treatment and vaccine development etc. in AIDS filed. This is the deepest impression of the 15th International AIDS Conference.

In his special plenary session, Dr. Fauci gave a thorough and clear outline of the pathogenic mechanism of HIV disease: HIV is the key point. It infects the immune cells and simultaneously activates them. This stimulation causes the immune activation and gives a positive feedback to the replication of HIV. HIV infection and the immune activation then lead to a depletion and dysfunction of the immune cells, aberrant lymphocyte turnover. He mentioned that the HIV envelope modulates PBMC gene expression that is associated with virus replication and secretion of cytokines involved in immune activation but the induction of gene expression requires coordinate signaling through CD4 and the respective co-receptor, so HIV envelope-induced cell signaling may play an important role in the propagation of virus replication and the state of aberrant immune activation. He also introduced that the HIV-viremic patients manifest a dichotomy of expression of NK cell receptor: inhibitory receptors are maintained or increased while activating receptors are decreased. NK cells from viremic patients express increased levels of Fas on their surface and the CD56dim/CD16+ subset respond to sFasL with increased apoptosis. However, this disease cycle could be interrupted or even stopped if HIV replication is blocked. The goal is mainly dependent on antiretroviral therapy. This is just the theme of the Conference?Access for All.

Although treatment by HAART can control the HIV viral load to less than 50 copies/ml in plasma, to eradicate HIV including the integrated provirus is a very difficult task because the latent HV reservoir remains. Some research reported that HIV DNA (mainly integrated) could be detected in patients after prolonged virus suppression although the level became lower than that without HAART because the unintegrated DNA decayed rapidly after treatment started.

Targeting various targets related HIV infection or human hosts such as fusion, viral gene transactivation as new approaches to therapy were reported. PRO140, a humanized monoclonal antibody to CCR5 and a novel CCR5 antagonist, 873140, showed anti-HIV activity. PLO2438, a CXCR4 interfering compound showed an antiviral potency in fusion-based infections in in vitro study. Another HIV entry inhibitor called NSC13778 and several analogs appeared to inhibit HIV infection by targeting the gp120-binding domain of host CD4. SiRNA showed a potential of new treatment for HIV because of its advantages such as more inhibition effectiveness, possibility to target multiple points in viral replication cycle and any part of viral genome, high sequence specificity and ability of targeting drug-resistance viruses, etc. However, rapid occurrence of resistance because the sequence is short may be the barrier for its use.

The presentations on innate immune response including CD8+ T cells and NK cells provided insights into other important for viral control. The replication capacity of virus differs among three groups of HIV. Even in the same subtype M, different virus showed different fitness. This may give some explain on the progress of AIDS. On the other hand, among the nonpregressors, some characteristics of the host including HLA B57, B58, B27 or B51, high CD8+ T cells response, etc. were reported. Thus, both HIV factors and host factors and the interaction between them are important for understanding, treating and preventing the disease.

Since its discovery, HIV vaccine has been attempted. But till now, there is no satisfactory one available. The main hurdle may be the less effectiveness of vaccine candidates and large numbers of HIV types and HIV always mutates. So it seems that there still are a lot difficulties should be overcome for vaccine research and treatment.

2. About my presentation

I gave a poster presentation on Tuesday. CD4+ T cell count is one of the important surrogate markers on monitoring HAART. However, flow cytometry, the reference method for enumerating CD4 count in developed countries, is an expensive and complex technique. It is difficult for resource limited settings. We modified Dynabeads method to enumerate the CD4 count and presented at the Conference. Our modified protocol made the method cheap, simple with enough accuracy. By using our protocol, the cost for one sample is less than 3 US$, and no need high-tech equipment. Thus, we believe our method can be used as good alternative tool to flow cytometry for enumerating CD4 count in resource limited situations.

3. Plan
While brought back precious information and references from the symposiums, oral presentations, poster presentations and poster exhibitions, I also felt that there are still a lot of issues about HIV disease we do not know and need to be studied, and there are still a lot of people could not access to HAART. Therefore, I hope to continue my research related to clinical field in the future.

4. Impression

This is the first time to attend International AIDS Conference. The first impression is that there are so many people including leaders, scientists, doctors, nurses, patients and famous actors and actress in the meeting. Everyone seemed so busy because they must move a long way to the meeting room where they are interested. The second impression is that there were too many symposiums and oral presentations in different meeting rooms at the same time, so I wished I could separate myself to go any room I wanted to. The third impression is the conference covered almost all fields of AIDS including basic science, clinical science, social issues, leaderships and so on. The forth is that there was not only a place to get new information, but also a place to meet old friends. I should say attending the 15th International AIDS Conference was an unforgettable experience for me. Here I would like to express my appreciation to Japanese Foundation for AIDS Prevention for giving me this treasure opportunity.