Comprehensive Sites

Of the Web sites in this category (table 1), HIV InSite, Medscape, and the Johns Hopkins AIDS Service provide the most original content. Each of these sites has authoritative, well-written reviews of HIV-related meetings and recently published papers, daily news summaries, continuing medical education (CME) courses, HIV-related drug summaries, and links to key Web publications.

HIV InSite is the most comprehensive of the sites. It provides full-text access to The AIDS Knowledge Base [4], a custom search interface to both the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO) surveillance data sets (through the link Statistics), and an independently researched HIV clinical trials database (at the link Trials Search). Additional useful features include clinical case discussions, a page devoted to the International AIDS Society and its excellent journal Topics in HIV Medicine, and a biweekly electronic newsletter that alerts subscribers to new information on the site.

Johns Hopkins AIDS Service Web site provides full-text access to the manual Medical Management of HIV Infection [5]. In addition, it contains expert responses to questions sent in by both patients and clinicians. Some of the material is reproduced in the Hopkins HIV Report bimonthly newsletter for HIV practitioners, which can also be accessed from the site.

Medscape is a commercial site supported by advertising and grants from pharmaceutical manufacturers of antiretroviral agents. It is most useful for its same-day conference summaries, its Quick Guide to Antiretrovirals, a section that allows for rapid screening for pharmacokinetic drug interactions, and a Medication Daily Scheduler. Medscape also contains material from The AIDS Reader, a publication designed to review clinical issues commonly faced by physicians treating HIV-infected patients.

The Journal of the American Medical Association Web site has well-written news and reviews and provides on-line CME courses. The International Association of Physicians in AIDS Care (IAPAC) site contains news and conference reviews as well as provocative, well-written editorials. The IAPAC site also maintains a comprehensive list of upcoming conferences. HIVandhepatitis.com provides news, well-written reviews, and Webcasts. The Physicians' Research Network Web site features timely reviews written by the site's editorial faculty members.

Journals

Clinical HIV studies are generally published in one of the leading medical journals or in one of the infectious diseases or HIV/AIDS journals. However, studies of HIV-related complications may appear in a wide variety of subspecialty medical journals. Scientific studies are generally published in leading journals devoted to specific scientific disciplines (e.g., virology, biochemistry, structural biology, or immunology) or in the HIV/AIDS journals. On-line availability of full-text versions of many of the journals with important HIV-related publications should dramatically improve the ability of physicians and researchers to remain current with regard to knowledge about HIV.

Table 2 lists the majority of available HIV/AIDS journals and describes the on-line availability of their articles. The National Library of Medicine (NLM) provides links to the Web sites of ∼700 journals that provide full-text articles on-line. Most of the journals that provide full-text articles require a paid subscription.

Scientific Meetings

As noted in the introduction, the state of urgency that exists in the field of HIV practice and research makes up-to-date knowledge of meeting abstracts and presentations particularly important. However, few people can attend even a small proportion of the HIV-related meetings held around the world. In the past, scientific results presented at such meetings often spread by word of mouth—a potentially unreliable method of data-sharing—but coverage of these meetings on the Web has improved this situation dramatically.

Web sites covering some of the most important HIV-related meetings are listed in table 3. Several of these are exemplary for their content. For example, beginning last year, the Web site of the annual Conference on Retroviruses and Opportunistic Infections made available meeting abstracts and posters. Many of the oral presentations are also available as Webcasts. In addition, the comprehensive sites discussed above often have valuable editorials summarizing the salient points of recent meetings.

Clinical Guidelines, Textbooks, and other Reference Materials

The US Department of Health and Human Services (DHHS), together with the Henry J. Kaiser Family Foundation, has convened a number of expert panels to provide up-to-date guidelines that address many fundamental aspects of the clinical management of HIV infection. These guidelines are well-written and authoritative and provide sufficient background information and references to ensure readers' thorough understanding. The guidelines are often published in journals, particularly the Morbidity and Mortality Weekly Report, but the most up-to-date versions (“living documents”) are available from the HIV/AIDS Treatment Information Service (HIV ATIS; figure 1 and table 4).

Additional general information on HIV infection can be found in The AIDS Knowledge Base [4] at HIV InSite and in the Johns Hopkins University manual Medical Management of HIV Infection [5], which is focused on the diagnosis and treatment of HIV infection and more closely resembles the DHHS guidelines. The AIDS Knowledge Base [4] is a comprehensive textbook that includes continually updated chapters on HIV pathogenesis and clinical syndromes as well as information on diagnosis and treatment.

Both of these references have excellent chapters on HIV drug complications and drug interactions—information that is essential for even the most expert clinician. If these chapters do not address the specific drug interaction or drug side effect of interest, some of the additional sites listed in table 4 may be helpful. For example, Medscape has a program that allows users to select a particular multidrug regimen and receive feedback on potential interactions between the drugs. PDR.net and RxList are free sites that provide the most comprehensive information on HIV- and non-HIV—related drugs, including the texts of package inserts.

The National HIV Telephone Consultation Service (“Warmline”) offers health care providers up-to-the-minute clinical information and case consultation. The Warmline is staffed by clinicians experienced in HIV-related care and is accessible on weekdays. The National Clinicians' Post-Exposure Prophylaxis Hotline (PEPline) offers clinicians around-the-clock advice on managing their own occupational exposures to HIV, hepatitis virus, and other bloodborne pathogens. Detailed information about these services can be found on their Web sites (table 4).

Because HIV-related problems cannot be evaluated independently from a patient's other medical problems, we have listed several other on-line references for the clinician in table 4. Medical Matrix is devoted to posting, annotating, and continuously updating full-content clinical medicine resources. The site contains a list of on-line textbooks, including both books that are free and those requiring a paid subscription. Finally, there are an increasing number of general medical information sites that provide access to multiple medical texts for paid subscribers.

Government Sites

Table 5 lists 4 United States government sites and the WHO—Joint United Nations Programme on AIDS (UNAIDS) site. The home page of the National Institutes of Allergy and Infectious Diseases (NIAID) provides information about its funding programs, which includes links to its Centers for AIDS Research, AIDS Clinical Trials Group sites, CPCRA, HIVNET, and vaccine evaluation programs. It also includes a resource guide for the development of AIDS therapies, as well as access to a few AIDS-related data sets. Finally, the page also provides links to many National Institutes of Health (NIH)-sponsored projects.

The CDC Web site gives access to the Morbidity and Mortality Weekly Report, HIV surveillance data, prevention research, and guidelines on a variety of other topics, including HIV testing. The CDC National Prevention Information Network contains >10,000 publications for patients and health-care providers.

Access to the bulk of the Adult AIDS Clinical Trials Group (ACTG) Web site is accessible only to researchers at one of the ∼25 AIDS Clinical Trial Units. It contains detailed descriptions of ACTG protocols, including executive summaries that are released after studies are completed but before the results are published. The ACTG site also contains useful technical data (e.g., the ACTG Virology Manual), frequently updated drug information, and a comprehensive members directory.

The HIV-related Web site of the US Food and Drug Administration (FDA) contains a large amount of data derived from presentations made by pharmaceutical and diagnostic companies, as well as the deliberations of advisory groups. Although this information is often difficult to access, the NIH AIDS Clinical Trials Information Service (ACTIS) provides a specialized search engine for FDA documents (use the Search Site page).

The UNAIDS consists of WHO and 6 other international organizations, including UNICEF, UNESCO, and WORLD Bank. The WHO-UNAIDS Web site contains the most complete data on HIV global epidemiology, including country-specific data. It also contains monographs on HIV vaccine and prevention strategies.

Research Databases

Research databases are listed in table 6. MEDLINE, AIDSLINE, AIDSDRUGS, and AIDSTRIALS are databases of the NLM. MEDLINE contains bibliographic citations and author abstracts from >4000 biomedical journals published throughout the world. AIDSLINE currently provides no significant advantage over MEDLINE; in addition to MEDLINE references, its only other sources are material from the 12th International AIDS Conference and articles from out-of-date, non—peer-reviewed publications. PubMed is the NLM's search service that provides access to MEDLINE. PubMed's users should note the tools named Limits, History, and Clipboard and the MeSH Browser, which will allow them to perform their searches optimally. AIDSDRUGS, and AIDSTRIALS contain information about experimental HIV drugs and ongoing and completed HIV clinical trials.

GenBank is an annotated collection of all publicly available DNA sequences maintained by the NIH. As of January 2000, it contained >5 million sequence records and >6 billion nucleotides [6]. GenBank, the European Molecular Biology Laboratory, and the DNA DataBank of Japan exchange data daily and together make up the International Nucleotide Sequence Database Collaboration. These primary sequence databases (figure 2) contain sequence data for tens of thousands of genes, but because they rely on passive reporting they are often missing important unpublished sequence data sets.

The Protein Data Bank (PDB) is the international repository for the processing and distribution of 3-dimensional macromolecular structure data primarily determined by x-ray crystallography and nuclear magnetic resonance [7]. The National Center for Biotechnology Information has created an integrated information-retrieval system entitled Entrez, which is based on links between MEDLINE, GenBank, and PDB entries [8].

The HIV Sequence Database (Los Alamos Database) maintained at Los Alamos National Laboratories is a publicly available, curated database of HIV sequences. It has the following goals: (1) collecting, curating, and annotating HIV and simian immunodeficiency virus (SIV) sequence data; (2) providing users with curated sequence alignments; (3) providing software tools for analyzing HIV sequence data; (4) performing meta-analyses and combined analyses of published sequence data; and (5) publishing its data and analyses in a yearly printed publication, the HIV Sequence Compendium [9]. The Los Alamos Database contains a large number of software tools and unique research reviews, which makes it an essential site for researchers in many disciplines. Its companion database, the HIV Molecular Immunology Database, contains an annotated, searchable collection of HIV-1 cytotoxic and helper T-cell epitopes and antibody binding sites. The Los Alamos Database also maintains a list of published drug-resistance mutations and references that can be browsed (with use of the compendium) or searched [10].

The HIV RT (reverse transcriptase) and Protease Sequence Database at Stanford University is an interactive database designed for researchers studying evolutionary and drug-related HIV RT and protease sequence variation [11]. The database links HIV RT and protease sequences to the drug-treatment histories of the individuals from whom sequenced isolates were obtained and to drug susceptibility data, if available. Users can retrieve sets of sequences that meet specific criteria, such as those having a particular mutation, or that occur during a specified treatment regimen. The Web site also has an HIV RT and protease sequence analysis program created for laboratories that perform genotypic HIV resistance tests.

The Division of AIDS at the NIAID has established the Database for Anti-HIV Compounds. It contains chemical structures and biological data acquired by continuous surveillance of primary literature sources. The database Web site is divided into sections on the virus life cycle, viral targets, cellular targets, and anti-HIV drugs. The HIV Protease Database was created by the Program in Structural Biology at the National Cancer Institute. It contains an archive of experimentally determined HIV and SIV structures, including some which are not in the PDB. It also contains a variety of tools for structure analysis.

Since 1988, the AIDS Reagent Program funded by the NIH has provided the research community with state-of-the-art bio-logical and chemical materials for the study of HIV and related opportunistic infections. More than 1670 reagents are available to registered users. The on-line catalog includes antibodies, cell lines, HIV isolates, opportunistic pathogens, and DNA and peptide reagents.

EuroSIDA is a prospective observational cohort study of 8500 patients in 20 European countries. This site contains information important to study participants, as well as some of the study's published results [12]. The Cochrane Collaborative Review Group on HIV Infection and AIDS publishes peer-reviewed systematic reviews on the prevention and treatment of HIV infection.

Clinical Trials Sites

ACTIS allows users to search the NLM databases, AIDS-TRIALS, and AIDSDRUGS. The ACTIS site (table 7) also contains the AIDS Clinical Trials Results Database, which contains references to journal articles presenting the interim or final results of HIV/AIDS-related clinical trials. It also contains links to the majority of the ACTG clinical sites, to the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) community-based clinical trials network, and to sites doing preclinical and clinical work on HIV vaccines.

AMFAR, the AIDS Treatment Data Network, and HIV InSite Trials Search also allow users to search a clinical trials database. The HIV InSite database is independently researched and may contain protocols that are not in the ACTIS database. Search results include a list of the names of trials meeting the search criteria, brief summaries of the trials, and links to more detailed information about the trials. Each of the clinical trials Web sites also provides useful information about pharmaceutical company and State Drug Assistance programs, as well as expanded-access protocols of experimental drugs. The results of a search may differ between sites, and it is safest to search several until you are familiar with the different search parameters on each of these clinical trials sites.

The Canadian HIV Trials Network site contains a road map to ongoing and completed clinical trials in Canada. The Initio Trial site provides access to information on a large multicenter European study that is currently enrolling patients to compare different initial treatment protocols for previously untreated, HIV-infected individuals.

Patient-Oriented Sites

There are several excellent patient-oriented sites for lay readers that provide well-written reviews of HIV infection and its treatment (table 8). These sites also play an essential role in helping HIV-infected persons navigate the complex maze of health care in the United States in their efforts to obtain state-of-the-art medical and social services.

Aidsmap is a British site produced by the National AIDS Manual in collaboration with the British HIV Association and St. Stephen's AIDS Trust. It is both comprehensive and well-organized and has authoritative summaries of HIV that are written for lay persons but are also valuable to health professionals. The HIV ATIS, Project Inform, and Bulletin of Experimental Treatments for AIDS (BETA) sites contain excellent educational material. Materials on these sites are often more up-to-date than material on some of the larger sites belonging to this category. These sites also do a better job at distinguishing didactic material from editorial opinion.

Aegis began in 1990 as the HIV/AIDS bulletin board service (BBS). It now contains >100,000 on-line documents and links thousands of bulletin boards worldwide. Aegis contains extensive coverage of news via wire services, newspapers, patient-oriented newsletters, and physician-oriented review journals such as AIDS Weekly Plus, Hopkins HIV Report, and the IAPAC Journal.

The “Insight from Experts” section is one of the strong points of the site named The Body. Users can post questions for one of several experts on topics such as HIV treatment, viral load and resistance testing, opportunistic infections, and lipodystrophy. The answers are usually direct yet appropriately conservative, considering the nature of the physician-patient interaction.

The National AIDS Treatment Advocacy Project (NATAP) Web site contains extensive summaries and sophisticated discussions of data presented at recent meetings. It is primarily targeted toward physicians and patients who are already very knowledgeable about HIV treatment.

Specialized Sites

Specialized sites (table 9) include CancerNet and OncoLink, which provide rich sources of information on HIV-related malignancies for both patients and physicians. HIVandhepatitis.com provides news items related to HIV, hepatitis C, and hepatitis B. It contains well-written reviews and editorials and background information on clinical issues pertaining to hepatitis B, hepatitis C, and coinfection with HIV. HIVresistance.com, contains a growing list of short, informal yet expertly written reviews of issues related to HIV drug resistance. The test information section contains up-to-date information regarding HIV drug resistance assay development, regulatory status, reimbursement status, and referral information for resistance testing.

Many of the Web sites described in this article have sections devoted to HIV in women. Two of these are listed in table 9, but a more complete list can be found at http://HIVInSite.ucsf.edu/topics/women. The NIH maintains a site devoted to research on acute HIV infection. AIDSimaging is a site which publishes clinical, radiographic, and microscopic images of many of HIV's complications. Although many of the Web sites described in this article have sections devoted to lipodystrophy, we have not identified medical sites focusing primarily on the complications of anti-HIV therapy.