More than 30 million people are currently infected with the human immunodeficiency virus (HIV), the cause of acquired immunodeficiency syndrome (AIDS). HIV slowly destroys immune system cells (including CD4 cells). Without treatment, the immune system loses the ability to fight off infections by other disease-causing organisms and HIV-positive people then develop so-called opportunistic infections, Kaposi sarcoma (a skin cancer), or non-Hodgkin lymphoma (a cancer of the lymph nodes) that determine the diagnosis of AIDS. Although HIV-positive people used to die within 10 years of infection on average, the development in 1996 of combination antiretroviral therapy (cART; cocktails of powerful antiretroviral drugs) means that, at least for people living in developed countries, HIV/AIDS is now a chronic, treatable condition.
The number of CD4 cells in the blood is a strong predictor of the likelihood of AIDS or death in untreated HIV-positive individuals and in people starting cART. Current guidelines recommend, therefore, that cART is started in HIV-positive patients without symptoms when their CD4 cell count drops below a specified cutoff level (typically 350 cells/ml.) In addition, several guidelines suggest that clinicians should also consider cART in symptom-free HIV-positive patients with a CD4 cell count above the cutoff level if their CD4 cell count has rapidly declined. However, it is not actually known whether the rate of CD4 cell decline before initiating cART is related to a patient’s outcome, so should clinicians consider this measurement when deciding whether to initiate cART?
A team lead by Marcel Wolbers (formerly at the Basel Institute for Clinical Epidemiology and Biostatistics (CEB), Switzerland, now biostatistician at OUCRU Vietnam) and Heiner C. Bucher (CEB) investigated this question based on data from CASCADE (Concerted Action on SeroConversion to AIDS and Death in Europe), a large collaborative study of 23 groups of HIV-positive individuals. The results have just been published in Plos Medicine.
The researchers found that individual CD4 cell count decline does not improve the prediction of future AIDS events or deaths in HIV-positive patients with a CD4 cell count above 350 cells/ml. They conclude that knowledge of the current CD4 cell count and an assessment of established risk factors are sufficient when deciding whether to initiate cART in asymptomatic HIV patients. Moreover, they found that that the rate of CD4 cell decline in individual patients is highly variable over time. Consequently, a rate measured at one time cannot be used to reliably predict a patient’s future CD4 cell count.
See the Plos Medicine website for the whole article:
http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1000239





2010 promises to be a landmark year for dengue research in Viet Nam. In collaboration with Roche Plc and the Hospital for Tropical Diseases, we will conduct the first ever clinical trial of a small molecule anti-viral drug to treat adult patients with dengue. Although this is the first trial of its kind in dengue, we expect many more to follow as anti-viral drug development for dengue accelerates in the public and private sectors. Separately, a randomised controlled trial of methyl-prednisolone (a corticosteroid drug) in children will complete enrolment at the Hospital for Tropical Diseases. This trial will answer whether methyl-prednisolone is safe to use in dengue patients, and might tell us if early interruption of the host immune response to dengue virus infection can improve clinical outcomes. These two trials will give us critical information on the prospects for anti-viral or immunodulatory therapies in the management of dengue as well as provide important insights into pathogenesis.