Serious Fatal and Non-fatal Non-AIDS-defining Illnesses in Europe
Amanda Mocroft*1, P Reiss2, J Gasiorowski3, B Ledergerber4, A Chiesi5, J Gatell6, A Rakhmanova7, M Johnson8, O Kirk9, J Lundgren9,10, and the EuroSIDA Study Group
1Royal Free and Univ Coll Med Sch, London, UK; 2Academisch Medisch Centrum bij de Universiteit van Amsterdam, Amsterdam, The Netherlands; 3Med Univ, Wroclaw, Poland; 4Univ Hosp, Zurich, Switzerland; 5Inst Superiore di Sanita, Rome, Italy; 6Hosp Clin i Provincial, Barcelona, Spain; 7Medical Academy Botkin Hospital, St Petersburg, Russia; 8Royal Free Hosp, London, UK; 9Copenhagen HIV Program, Panum Institute, Copenhagen, Denmark; and 10Centre for Viral Disease KMA, Rigshospitalet, Copenhagen, Denmark
Background: There is a perception that diseases thought to be non-HIV related
are becoming increasingly common, but little is known about the incidence and
risk factors for serious non-AIDS-defining illnesses.
incidence after January 1, 2002 was calculated of non-AIDS-defining illnesses
(malignancies, end-stage renal disease, liver failure [grade III/IV hepatic
encephalopathy, death from liver-related disease], pancreatitis, cardiovascular
disease [acute myocardial infarction or stroke; CVD]) and AIDS-defining
illnesses. Poisson regression was used to investigate factors associated with
non-AIDS-defining illnesses and AIDS-defining illnesses.
10341 patients, 684 were diagnosed with a non-AIDS-defining illnesses
(incidence 16.5 per 1000 person-years of follow-up; 95%CI 15.3 to 17.7); 316
patients (46.5%) died. In comparison, the incidence of AIDS-defining illnesses
(641 diagnoses; 219 deaths, 34.5%) was 15.5 of 1000 person-years of follow-up
(14.3 to 16.7). The most common non-AIDS-defining illnesses were malignancy
(255, 36.5%), CVD (209, 29.9%), and liver failure (136, 19.5%). The incidence
of non-AIDS-defining illnesses was markedly lower at higher current CD4 counts
and was similar to, or exceeded the incidence of AIDS-defining illnesses at all
current CD4 counts ≥100/mm3 (see the figure). The table shows
the adjusted incidence rate ratios for developing a non-AIDS-defining illnesses
or an AIDS-defining illnesses. Having diabetes or hypertension or being a
current smoker all significantly increased the incidence of non-AIDS-defining
illnesses. A patient with a current (i.e. latest) CD4 count twice the level of
a comparable patient had a 23% lower incidence of a non-AIDS-defining
Conclusions: Non-AIDS-defining illnesses were more common than AIDS-defining
illnesses in the combination ART era, have considerable mortality, and should
be routinely reported in clinical trials and observational studies. The risk
factor profile for non-AIDS-defining illnesses was diverse with multiple
potentially modifiable immunodeficiency and lifestyle-related risk factors.
Evidence on the influence of modifying these factors on the risk of non-AIDS-defining
illness is an important but unmet research need.