Journal of human virology最新文献

Objectives: To describe the prevalence of genotypic resistance mutations, including single and multidrug resistance (MDR) to reverse transcriptase (RT) and protease (PR) inhibitors in treated and untreated patients from two geographical areas in Spain (Madrid and Galicia).

Study design/methods: Resistance mutations to RT inhibitors were studied by line probe assay (LiPA) or by automated sequencing in 468 patients (Madrid, 268; Galicia, 200), and resistance mutations to PR inhibitors were studied by automated sequencing in 295 patients (Madrid, 85; Galicia, 210).

Results: The proportion of resistance mutations in treated and untreated patients results were higher by the LiPA method than by sequencing. By sequencing, we detected resistance mutations to nucleoside analogue RT (NRT) inhibitors and NRT inhibitors plus nonnucleoside RT (NNRT) inhibitors in 35.4% and 17.2% of treated patients, respectively. We also detected MDR to zidovudine plus lamivudine in 13.9% of treated patients from Galicia, in 1.7% from Madrid (p < 0.001), and in 1.5% of untreated patients from Galicia. Also, we detected MDR to NRT inhibitors in 3.8% and to NNRT inhibitors in 9.1%. We found resistance mutations to PR inhibitors in 38.1% of treated patients and in 0.9% of untreated patients.

Conclusions: These findings reinforce the usefulness of testing for resistance mutations in some cases to evaluate their prevalence in a given population and in the follow-up of treated patients.

Despite the fact that vaccines are successful at preventing disease as well as cost-effective, many factors prevent their uptake. These factors are different for different regions. In the United States and Europe, several factors have been identified. The first of these factors is complacency. Both patients and parents lack the knowledge of disease. In addition, physicians are often apathetic about vaccines. There is a lack of training in public health and preventive medicine in that the mind-set of physicians is not directed toward prevention but rather toward treatment. Younger physicians are often less aware of disease controlled by vaccines than their older colleagues are because they have not seen them. One of the paradoxes of vaccines is that success leads to decreased use. Despite the Vaccine for Children's Program, which has provided ample funding for the purchase of vaccines, there are limits on funding for people, facilities, and systematized approaches to maintaining high levels of immunizations. Finally, and perhaps most important, there is fear, real and unfounded. Additionally, in many developing countries there is a lack of focus on preventive medicine, including immunization, as well as limited funding available. Reasonable steps can be taken to overcome these obstacles.

The genome, the structural and regulatory proteins of HIV-1, as well as the clinical course of the disease it induces are well studied. Despite this knowledge, it is still unknown how the virus induces AIDS. The disease is characterized by opportunistic infections based on a generalized and nonspecific immunosuppression. I present evidence indicating that the immunosuppressive domain of gp41 of HIV may be causually involved in the induction and progression of AIDS.

The sciences of vaccinology and immunology were created only two centuries ago by Jenner's scientific studies of prevention of smallpox through inoculation with cowpox virus. This rudimentary beginning was expanded greatly by the giants of late 19th- and early 20th-century biomedical sciences. The period from 1930 to 1950 was a transitional era, with the introduction of chick embryos and minced tissues for propagating viruses and rickettsiae in vitro for vaccines. Modern vaccinology began about 1950 as a continuum following notable advances made during the 1940s and World War II. Its pursuit has been based largely on breakthroughs in cell culture, bacterial polysaccharide chemistry, molecular biology, and immunology which have yielded many live and killed viral and bacterial vaccines plus the recombinant-expressed hepatitis B vaccine. The present paper was presented as a lecture given at a Meeting of the Institute of Human Virology entitled A Symposium on HIV-AIDS and Cancer Biology, Baltimore, Maryland, on August 30, 1999 and recounts, by invitation, more than 55 years of vaccine research from the venue of personal experience and attainment by the author. The paper is intentionally brief and truncated with focus only on highlights and limited referencing. Detailed recounting and referencing are given elsewhere in text references 1 and 2. This narration will have achieved its purpose if it provides a background of understanding and guidelines that will assist others who seek to engage in creation of new vaccines.

Countries in both the developed and developing world are expected to experience an unprecedented growth in the number of their elderly and decline in the number of their youth. This extraordinarily rapid aging of the world's population is a phenomenon without precedence in human history. Additionally, there is an increasing gap between the rich and poor both among and within nations. Both trends will not only constitute the primary health issues of the first decades of the 21st century but will also profoundly alter the world's economic, political, and social landscapes.

The field of AIDS vaccine development is in flux. Important new findings were reported in 1999 that led to a rethinking of AIDS vaccine strategies. We have been given the challenging task of providing an overview. Rather than attempting to provide a comprehensive summary, we will restrict our discussion to a few major topics, and we ask for understanding if we can only highlight.

Although initial anti-ENV vaccines have failed, better results may be obtained with "non-ENV" vaccines capable of inducing cell-mediated responses and perhaps mucosal reactions. A turning point in AIDS vaccine research has been reached in that there are three precise questions to answer: 1. Are the protections obtained in monkeys significant and reproducible and could they be made more frequent? 2. Can more frequent, polyepitopic, and long-lasting cell-mediated responses in human subjects be obtained? 3. Is it possible to induce significant mucosal responses? The decision as to whether phase III trials must be launched will depend on answers to these questions. It may be possible to organize international AIDS vaccine research so that these answers could be obtained in 3 to 4 years, but this would require a frank acceleration of the present endeavors.

Key public policies that have contributed to the rise of modern medical research in the 20th Century are reviewed, focusing especially on the United States and the post-World War II period. Drawing on this history, the question is posed: "Are these policies sufficient to insure vigorous medical research in the 21st Century?" Although radical policy changes are not needed, several proposals for policy and medical research portfolio redirection are offered, including a rebalancing of public supported research in all fields of science that contribute to medical advances. Medical research must also invest in a national and international information infrastructure that will allow the linking of researchers, clinical experimenters, practicing physicians, and the public in ways heretofore not imagined. Medical researchers must be leaders and advocates for the whole research enterprise in the 21st Century.