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The Royal Statistical Society Medical Section meeting, from 2pm to 5pm on Tuesday June 26, will be on the topic of HIV/AIDS. The meeting will take place at the RSS headquarters on Errol Street (for directions see www.rss.org.uk). The speakers, titles and abstracts are as follows: Dr Fiona Lampe (UCL Department Of Primary Care And Population Sciences) An overview of HIV natural history and the effect of antiretroviral therapy. It is estimated that about 40 million people are living with HIV worldwide and about 64 thousand people are infected in the UK. In the absence of effective treatment, HIV attacks the immune system, causing depletion of CD4 T-lymphocytes, which eventually results in development of opportunistic infections and greatly increased risk of death. The prognosis of HIV infection changed dramatically with the introduction of triple combination antiretroviral treatment (ART) in the mid 1990s. Combination ART is now the standard of care in industrialised countries, and its use has resulted in striking declines in rates of AIDS events and death among HIV-infected individuals. The short-term outcome of ART has continued to improve in recent years, although factors such as long-term durability of drug regimens, drug toxicity, and multiple drug resistance are potential threats to continued treatment success. This talk will outline trends in the HIV epidemic in the UK, describe the main surrogate markers of HIV, and present data from observational cohort studies of HIV clinic populations on the prognosis of untreated and treated infection. Some implications for HIV research will be discussed. Dr Liz Bailes (Institute of Genetics, University of Nottingham) The Origins of HIV In the absence of morphological data molecular sequence analysis has been used to characterise HIV and uncover its evolutionary origins. Molecular phylogenetics has allowed us to answer questions about the source of HIV and how often and where it has been transmitted to humans. There are two distinct AIDS viruses in humans, HIV-1 and HIV-2, each further subdivided into multiple groups. These human viruses fall within the radiation of primate lentiviruses; the other members of this genus are simian immunodeficiency viruses, SIVs, found in more than 30 species of African primates. HIV-2 is divided into eight groups. Six of these have been found only in single individuals but two, groups A and B, are epidemic in West Africa. The HIV-2 groups are each the result of independent cross-species transmissions of virus from a West African monkey, the sooty mangabey. SIVs isolated from wild sooty mangabeys cluster geographically in phylogenetic trees. The closest simian virus relatives of HIV-2 groups A and B come from monkeys in Côte d'Ivoire and so this is the likely source of epidemic HIV-2. The three HIV-1 groups are M, the cause of the AIDS pandemic, and N and O, which are largely confined to Cameroon and Gabon. These three groups are each the result of separate cross-species transmissions of a chimpanzee virus into humans. Chimpanzee viruses from Cameroon also show phylogeographical structure, leading to the conclusion that the origins of HIV-1 groups M and N were most likely in south east and south central Cameroon, respectively. Where the cross-species transmission leading to HIV-1 group O occurred is not yet known. To date nearest relative of HIV-1 group O is SIV found in gorillas, but it is not yet possible to distinguish whether the cross-species transmission leading to HIV-1 group O was from a gorilla or a chimpanzee. Once a virus has crossed the species barrier it will adapt to its new host. Comparison of HIV-1 gene sequences with those of chimpanzee viruses revealed one site conserved in chimpanzee viruses but different in HIV-1. This amino acid change, from methionine to arginine in the gag-encoded matrix protein, is required for efficient replication in human cells, which is compelling evidence for its being a viral adaptation to its human host. Dr Sarah Walker (MRC Clinical Trials Unit, London) When are factorial designs not the answer? experience from the DART Trial of strategies for antiretroviral therapy in Africa Factorial designs have a number of advantages and disadvantages, but may be particularly useful in a new indication or population where there are many more questions than would be feasible to address in separate trials. The Development of AntiRetroviral Therapy (DART) Trial in HIV-infected adults in Uganda and Zimbabwe is an example where for good reasons three factorial randomisations were included in one design, one a period of time after trial entry (conceptually the same as co-enrollment). Subsequent events highlighted particular problems with inclusion of this co-enrollment-like partial factorial randomisation. Possible statistical analysis methods are discussed and briefly compared in a simulation study. The talks will be preceded by the Medical Section's AGM at 2pm.