New York City health officials announced on February 11, 2005 that a patient rapidly developed full-blown AIDS shortly after being diagnosed with a rare, drug-resistant strain of HIV-1. The New York City Department of Health issued an alert to all hospitals and doctors and a press conference was held to announce the emergence of an aggressive HIV-1 strain that may be difficult to treat and that appears to trigger rapid progression to AIDS. Is the panic justified?

The two phenomena of rapid disease progression and multi-drug resistance, which are combined in the aggressive HIV-1 strain, are not unique. HIV-1 causes a persistent infection and this virus is generally not a fast killer. Within the Amsterdam Cohort Studies on HIV-AIDS, it takes on average 8.3 years from the time a person is first infected with HIV-1 for AIDS to develop, and another 17 months from AIDS to death [ 1 ]. However, the length of the incubation period varies from 2 months to more than 20 years. Cases where it takes much shorter are not uncommon (rapid-progressors), and likewise there is a significant group of socalled long-term non-progressors [ 2 - 5 ]. There seems uncertainty about the actual date of infection of the New York individual, such that AIDS may actually not have developed within 2 to 3 months, but rather within 20 months, which makes this case less exotic. Transmission of a drug-resistant HIV-1 variant is not uncommon either [ 6 , 7 ]. The number of cases have remained relatively small, but may be on the rise due to an increase in therapy failures [ 8 ]. The New York virus appeared resistant to three classes of antivirals (the Reverse Transcriptase inhibitors; nucleoside and non-nucleoside drugs, as well as Protease inhibitors), but this is not unexpected either in the era of combination-therapy in which therapy failure will usually mean the emergence of multi-drug resistant HIV-1 variants. Drug-resistant HIV-1 variants usually have reduced replication capacity compared to a wild-type virus due to the mutations in the Reverse Transcriptase and Protease enzymes [ 9 ]. This loss in replication fitness may be even larger for a multi-drug resistant virus [ 10 ]. How does this relate to the aggressive disease course? More research is needed to resolve this issue. First, it is not always true that the acquisition of drug-resistance mutations causes a fitness loss. Even in case a loss is apparent, the virus may select compensatory changes over time, and the end result may in fact be a virus variant with increased replication fitness [ 11 ]. Second, one can only link a particular pathogenicity phenotype to a virus strain when a distinct disease pattern is seen in multiple infected persons. When an isolated case is discussed, it is equally possible that the particular disease pattern is not due to the virus, but rather due to a special property of the infected human host. Person-to-person variation in the immune system or other factors that interact with HIV-1 (receptors, innate immune factors etc) can greatly influence disease progression [ 12 ]. Overall, this case seems relatively rare but not necessarily alarming. Increased attention is not necessarily bad, but press conferences should be reserved for situations when a cluster of such transmissions is apparent. The current hype about super aggressive HIV-1 strains seems unfounded.

The two phenomena of rapid disease progression and multi-drug resistance, which are combined in the aggressive HIV-1 strain, are not unique. HIV-1 causes a persistent infection and this virus is generally not a fast killer. Within the Amsterdam Cohort Studies on HIV-AIDS, it takes on average 8.3 years from the time a person is first infected with HIV-1 for AIDS to develop, and another 17 months from AIDS to death [ 1 ]. However, the length of the incubation period varies from 2 months to more than 20 years. Cases where it takes much shorter are not uncommon (rapid-progressors), and likewise there is a significant group of socalled long-term non-progressors [ 2 - 5 ]. There seems uncertainty about the actual date of infection of the New York individual, such that AIDS may actually not have developed within 2 to 3 months, but rather within 20 months, which makes this case less exotic. Transmission of a drug-resistant HIV-1 variant is not uncommon either [ 6 , 7 ]. The number of cases have remained relatively small, but may be on the rise due to an increase in therapy failures [ 8 ]. The New York virus appeared resistant to three classes of antivirals (the Reverse Transcriptase inhibitors; nucleoside and non-nucleoside drugs, as well as Protease inhibitors), but this is not unexpected either in the era of combination-therapy in which therapy failure will usually mean the emergence of multi-drug resistant HIV-1 variants.Drug-resistant HIV-1 variants usually have reduced replication capacity compared to a wild-type virus due to the mutations in the Reverse Transcriptase and Protease enzymes [ 9 ]. This loss in replication fitness may be even larger for a multi-drug resistant virus [ 10 ]. How does this relate to the aggressive disease course? More research is needed to resolve this issue. First, it is not always true that the acquisition of drug-resistance mutations causes a fitness loss. Even in case a loss is apparent, the virus may select compensatory changes over time, and the end result may in fact be a virus variant with increased replication fitness [ 11 ]. Second, one can only link a particular pathogenicity phenotype to a virus strain when a distinct disease pattern is seen in multiple infected persons. When an isolated case is discussed, it is equally possible that the particular disease pattern is not due to the virus, but rather due to a special property of the infected human host. Person-to-person variation in the immune system or other factors that interact with HIV-1 (receptors, innate immune factors etc) can greatly influence disease progression [ 12 ].Overall, this case seems relatively rare but not necessarily alarming. Increased attention is not necessarily bad, but press conferences should be reserved for situations when a cluster of such transmissions is apparent. The current hype about super aggressive HIV-1 strains seems unfounded.Competing interests The author(s) declare that they have no competing interests
Competing interests
The author(s) declare that they have no competing interests


Why does the world need a new medical journal? In this first editorial the  PLoS Medicine  Editors set out their vision for the journalPLoS Medicine

Today the possibilities for a medical journal are almost limitless. The first medical journals reflected the needs of a closed group of doctors. But medicine, its place in the world, and the dissemination of information have changed utterly. So in starting afresh, what should a new medical journal retain, and what should it ditch?Most obviously, we should throw out the old way of disseminating information. In today's electronic age, it is no more difficult, and it is only minimally more costly, to provide access to one million people than it is to one person. So the revolutionary idea of anyone being able to read any article is possible. This idea—open access—which completely challenges the old subscription-based publishing model, is the driving force behind the launch of  PLoS Medicine . You can download and distribute articles without restrictions (feel free to make a thousand copies, translate articles into other languages, put articles into books—just give the author proper credit).PLoS MedicineWe have also changed the way we involve the academic community in our journal. Our large global editorial board reflects the diversity of medicine today and is intimately involved in what we do. In particular, members of the editorial board are a crucial part of our peer review process. As academic editors they, along with a senior editor at the journal, take research papers through the peer review process in a way that we believe provides the most constructive and fair review. We are delighted that members of our editorial board have also shown their support for our journal by submitting papers to us, even before we launched.What will we publish? The research article on malaria in this issue reflects our priority of publishing papers on diseases that take the greatest toll on health globally. But we will also publish papers reporting a substantial advance in any specialty, whether that advance is in public health, such as the paper on the global burden of disease; drug effects, such as the paper on the effect of HIV drugs on lipids; or the molecular understanding of disease, such as the paper dissecting out the immune responses in lung disease caused by smoking.A good general medical journal should also be a place where the global medical community can discuss together what matters to them. The magazine section of  PLoS Medicine  will be devoted to comment, lively debate, and diverse opinions, in particular giving neglected voices and diseases a place in the limelight. In this issue's magazine section you will see articles from five continents that cover a huge range of topics, from basic sciences (such as the pathology of emphysema) to global public health (such as palliative care in developing countries). You will find diverse opinions—for example, on whether President Bush is helping or hindering Africa's progress towards tackling HIV, and on whether health professionals should routinely screen women for domestic violence (tell us what you think by taking our poll at  www.plosmedicine.org ). And you'll find case-based learning materials on meningitis linked to an online video and an online quiz.PLoS MedicineThe revolutionary idea of anyone being able to read any article is possible.The revolutionary idea of anyone being able to read any article is possible.Interpretation of results is an essential part of a medical journal's job. Although we expect that many of our readers will be doctors, we hope readers will range from patients wanting to learn about the latest research on their illness, to teachers wanting to use an article in the classroom, to policymakers. Hence, we have several levels of comment on original research. Perspectives, written by an expert, are aimed at readers who are already familiar with the topic. Synopses, written by  PLoS Medicine 's professional editors, should provide any health professional with a quick introduction to an article. Patient summaries provide a starting point for patients to assess the relevance to them of a research paper.PLoS MedicineWe have decided not to be part of the cycle of dependency that has formed between journals and the pharmaceutical industry, an industry that focuses overwhelmingly on the most profitable drugs, thus sidelining many of the world's health problems. Medical journals have allowed their interests to become aligned with those of the pharmaceutical industry by printing advertisements for drugs, publishing trials designed by drug companies' marketing departments, and making profits on reprints used as marketing tools.  PLoS Medicine  will not accept advertisements for pharmaceutical products or medical devices. Our open-access license allows free distribution of articles, so PLoS cannot benefit from exclusive reprint sales. And we consider as the lowest priority for publication papers that are simply aimed at increasing a drug's market share without obvious benefit to patients.PLoS MedicineWe will aim to have the highest levels of transparency in our published papers. We require authors to tell us of any possible competing interests; we in turn will tell readers about them.But, information flow should not be just one-way. Our editorial doors (or at least our E-mail boxes) are always open. We want your feedback on the journal: send us an E-mail or submit an eLetter about any article in the journal, take part in our polls, contribute ideas for the magazine section and submit original research.  PLoS Medicine  is a journal for the global medical community; we invite you to join in.PLoS Medicine


If you need to know anything  basic  about Biostatistics and Epidemiology, this book  belongs  in your library! Unlike most science and technology books – which, I have concluded after nearly 42 years in this business, tend to be written less to teach and communicate information than to impress the reader with how much the  author  knows about the subject matter – this one, refreshingly and quite successfully, ensures that the  reader  comes away with a better understanding of the topics of Biostatistics and Epidemiology, as a result of the authors' genuine desire to convey information in a clear, concise, relevant, understandable, and very readable way.basicbelongsauthorreaderIn nine Chapters and nine Appendices, spanning 243 pages (which include ample references and suggested further readings), the indexed material covers a wide range of fundamental principles that form the basis for such subjects as: (1) The Scientific Method; (2) Probability Theory; (3) Statistics; (4) Epidemiology; (5) Screening Methods and Techniques; (6) Clinical Trials; (7) Quality of Life; (8) Genetics; and (9) Biomedical Ethics. A unique feature of the way the book is written, is that individual Chapters can be read out-of-sequence with no loss of continuity. The reader can skip around, omit certain sections, and still glean what he or she needs to know without feeling cheated. That's not easy to do, but this author does it well.I found the material to be written at a very comfortable cognitive level – aimed mainly at medical, upper-level-college, and graduate students – and sequenced in a logical manner, thus making it easy to follow and totally user-friendly. The author has a special talent for reducing complicated concepts to an easily understandable level. For example the Appendix dealing with Genetic Principles gives the best introductory synopsis of this topic that I have seen anywhere; and the "middle Chapters" that address "Mostly About" – Statistics (Chapter 3), Epidemiology (Chapter 4), Screening (Chapter 5), Clinical Trials (Chapter 6), Quality of Life (Chapter 7), and Epidemiology (Chapter 8), are gems!.What are especially nice are the many relevant, easy-to-understand and practical examples, that the author judiciously and effectively intersperses with the theoretical background material; and, the Chapter Summaries that conclude most of them. There is a very well-balanced give-and-take between theory and practice. I also liked the wonderful (sometimes witty) little parables and anecdotes that give the book a charming personality. In all, I would offer my compliments to the author for a "job well done!"