final program.qxd - Parallels Plesk Panel

OP 2.1
Research Priorities in HIV : Epidemiology
Amanda Mocroft, HIV Research Unit, Dept Primary Care and Population Sciences, Royal
Free and University College Medical School, Rowland Hill St, London, NW3 2PF. UK.
The widespread introduction of combination antiretroviral therapy (cART) to Europe during
1996 has led to a remarkable decline in new AIDS defining illnesses and deaths. Clinical
trials of new antiretroviral therapies concentrate on the short term virologic or
immunologic response to cART, and there are few trials considering longer-term
outcomes. Typically, clinical progression is now considered within the setting of large,
often collaborative, observational studies, which can introduce considerable bias when
comparing antiretrovirals. This is because there will be both unmeasured and unknown
confounders influencing the choice of treatment, which may affect the outcome.
Observational studies have however contributed enormously to research, have provided
important input into HIV treatment guidelines, and have been used to both help in the
design and running of randomised clinical trials.
There remain many questions to be answered in the cART era, and these can be
focussed into the continuing morbidity and mortality observed, the development of
resistance and adverse events. Will the efficacy of cART continue in all patients, and if not,
what determines why some patients do not seem to experience the same benefits from
cART as others? Clearly, patients who die in the cART era die from a much wider range
of causes than seen before, and the epidemiology of deaths in HIV has become much
more complicated. cART cannot reduce the risk of deaths which are truly unrelated to HIV
infection, but it is uncertain to what extent causes of death are related to HIV or
associated immunodeficiency. Serious adverse events, such as pancreatitis or chronic
kidney disease, may only become apparent after the long-term follow-up of a large
number of patients, which is not normally possible within the setting of a randomised
clinical trial. In such circumstances, well conducted observational studies can provide
important information of both the expected frequency of serious adverse events, and
determine which patient groups have the greatest risk of such toxicities. There is an
increasing group of patients who have been exposed to all available classes of
antiretrovirals, have multi-drug resistance and have failed all regimens. These patients are
typically not included in randomised trials, which concentrate on antiretroviral naïve
patients with the best chance of virologic success but have the greatest risk of clinical
progression. Is this patient group likely to continue increasing, and if so, which group of
patients are at greatest risk, and how likely are they to develop AIDS or die?
“ Focusing FIRST on PEOPLE “ 36 w w w . i s h e i d . c o m