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.