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11 February 2009 (Reuters Health [Deborah Mitchel])—Beginning treatment with combination antiretroviral therapy (ART) at higher CD4+ cell counts than normally recommended reduces the mortality rate in HIV-infected patients, the results of 2 large clinical trials indicate. The findings were presented at the 16th Conference on Retroviruses and Opportunistic Infection (CROI 2009). Dr. Mari Kitahata of the University of Washington, Seattle, reported on the results of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), a collection of observational studies in Canada and the U.S. that included 9174 HIV-infected patients. The participants were antiretroviral naive, had no signs of AIDS, had CD4+ counts greater than 500 cells per mi-cro-li-ter, and began treatment between 1996 and 2006. The investigators compared the relative hazard of death of those who began therapy immediately (29%) at a median CD4+ count of 674 cells per microliter with those who deferred treatment (71%), beginning at a median CD4+ count of 390 cells per microliter. Patients who began treatment with CD4+ counts below 350 cells per microliter were excluded. Data were available for 25,337 person-years of follow-up. “The absolute risk of mortality was significantly higher in the deferred treatment group,” Dr. Kitahata reported. Patients in the treatment-deferral group were 36% more likely to die compared with those who began treatment earlier. Meanwhile, Dr. Jonathan Sterne of the University of Bristol, UK, presented the findings of his group, the “When To Start Consortium,” which evaluated the data from 15 prospective cohort studies in North America and Europe that include 24,444 patients and 81,071 person-years of follow-up. At study entry, all of the patients were antiretroviral-naive, did not have AIDS, had CD4+ counts of less than 500 cells per microliter, did not have a history of drug use, and began ART after 1997. “Deferring treatment until CD4+ count range [was] 251 to 350 cells per microliter was associated with higher rates of AIDS and death, compared with starting in the range [of] 351 to 450 cells per microliter,” according to Dr. Sterne and colleagues. Although both studies attempted to control for confounders, “only randomized controlled trials can deal with both measured and unmeasured confounding factors,” Dr. Sterne told conference participants. 11 February 2009 (Reuters Health [Deborah Mitchell])—For HIV-infected patients who are on combination antiretroviral therapy (ART), adjunctive treatment with synthetic interleukin 2 (IL-2) increases the number of CD4+ cells but does not reduce the risk of HIV-related opportunistic diseases or mortality. The results of 2 large international clinical trials, presented at the 16th Conference on Retroviruses and Opportunistic Infection (CROI 2009), appear to close the book on using IL-2 to treat HIV infection. “In both studies, the volunteers who received IL-2 and antiretrovirals experienced notable, sustained increases in CD4+ T cells counts, as expected,” Dr. Anthony S. Fauci, Director of the US National Institute of Allergy and Infectious Diseases (NIAID), commented in a NIH statement. “Unfortunately, these increases did not translate into reduced risks of HIV-associated opportunistic diseases or death when compared with the risks in volunteers who were taking only antiretrovirals.” The 2 phase III trials, ESPRIT and SILCAAT, enrolled more than 5500 HIV-infected patients in 26 countries who were randomized to ART plus injections of synthetic IL-2 (Proleukin) over several 5-day cycles or to ART alone. To investigate the possibly different effect that IL-2 might have at different stages of HIV infection, the ESPRIT study enrolled patients with early-stage infection (CD4+ counts of 300 or more cells per microliter), while the SILCAAT study enrolled patients with more advanced disease (CD4+ counts between 50 and 299 cells per microliter). The ESPRIT (Evaluation of Subcutaneous Proleukin in a Randomized International Trial) study was presented by Dr. Marcelo Losso of Hospital JM Ramos Mejia in Buenos Aire, Argentina. It included 4111 adults. The SILCAAT (Subcutaneous, Recombinant, Human Interleukin-2 in HIV-Infected Patients with Low CD4+ Counts under Active Antiretroviral Therapy) trial was presented by Dr. Yves Levy of Hopital Henri Mondor in Creteil, France. It included 1695 adults. In the ESPRIT and the SILCAAT studies, the patients' CD4+ counts increased by an average of 169 and 59 cells per microliter, respectively, but as stated, there were no differences in outcome between the treatment groups and the control groups. 17 February 2009 (Reuters Health)—The AIDS virus became the top deadly infectious disease in China last year for the first time, killing 6,897 people in the first 9 months of 2008, the official news agency Xinhua said. The number of people infected with the HIV/AIDS virus doubled during that period, Xinhua said, citing a report posted on the Ministry of Health website. Xinhua said there were a total of 264,302 HIV/AIDS cases by the end of September last year and 34,864 people have died of the disease so far. United Nations figures estimate that 700,000 people in China were HIV positive by the end of 2007. Xinhua said tuberculosis was the second biggest killer in the first 9 months of last year, while rabies ranked third, followed by hepatitis and infant tetanus. Editor' comment. To put the severity of the HIV problem in context, China has an estimated 4.5 million cases of people with tuberculosis, the second largest number of tuberculosis cases in the world after that of India, and almost 10% of cases are resistant to the most-effective first-line drugs. Yet, HIV killed more Chinese than tuberculosis. (D.K.) 13 February 2009 (Reuters Health)—A compound isolated from the ocean sponge Agelas conifera demonstrates very strong anti-biofilm activity as well as the ability to make antibiotics more effective, according to research presented in a symposium at the annual meeting of the American Association for the Advancement of Science in Chicago. “About 80% of the hard coral in the Caribbean is dead,” presenter Dr. Peter Moeller said in an interview with Reuters Health. “But we came upon a sponge that was pristine, healthy and thriving, in an otherwise bleak and dead world.” The compound ageliferin was found to be responsible for the ability of A. conifera to protect itself from spoilage. Dr. Moeller's team identified small molecule derivatives that retained the activity of the parent compound, and subsequently synthesized them in the lab. “We found that these compounds can do incredible things—they disperse existing bacterial biofilms and inhibit their subsequent production,” Dr. Moeller said. In addition, when these compounds were combined with current generation antibiotics, resistant bacteria were re-sensitized to the drugs' antibacterial effects. “We tried this with a number of human pathogens known to be antibiotic resistant,” including methicillin resistant Staphylococcus aureus, Acinetobacter baumanii, Pseudomonas aeruginosa, Vibrio vulnificus, Haemophilus influenza, and Bordetella pertussis, Dr. Moeller commented, “and in every case we saw the same phenomenon.” Because these agents can be easily incorporated into a wide variety of manufactured materials, he predicts that ageliferin derivatives will find wide application in medical devices, such as stents, central catheters, and prosthetic limbs “to obviate the number of secondary infections, most of which are biofilm based.” Once cleared for direct human use, the compounds hold promise for extending the usefulness of antibiotics to which microorganisms are currently resistant. They are also likely to have direct application in conditions such as cystic fibrosis, in which patients are prone to lung infection with biofilm-forming Pseudomonas aeruginosa. The research by Dr. Moeller and associates at the National Oceanic and Atmospheric Administration's Hollings Marine Laboratory in Charleston, South Carolina, was conducted in collaboration with scientists at the Medical University of South Carolina and North Carolina State University. Editor' comment. According to other reports, after sophisticated toxicity screening, the compound thus far shows no toxic effects, making the possible systemic use a reality. (D.K.) 12 February 2009 (Reuters Health)—From 2000 to 2006, the rate of reported coccidioidomycosis cases has increased steadily in California, according to findings released in the Morbidity and Mortality Weekly Report. In 2007, a slight drop in cases occurred, but the rate is still the highest it has been in the state since 1995. According to the new report, cases of coccidioidomycosis, a reportable disease in California, averaged about 2.5 per 100,000 population annually from 1995 to 2000. Between 2000 and 2006, however, the rate more than tripled, from 2.4 to 8.0 per 100,000 population. In terms of reducing coccidioidomycosis cases, the report notes that “options for environmental control of coccidioidomycosis are limited, and no safe, effective vaccine for the disease exists currently. Developing such a vaccine appears to be the best option for preventing disease in those persons at risk for coccidioidomycosis.” Source: Morb Mortal Wkly Rep CDC Surveill Summ 2009;& 58:105–9.

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