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.
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