New definitions of both late HIV diagnosis and diagnosis with advanced HIV disease have been proposed by UK investigators.
In an article published in the online edition of AIDS, the researchers suggest that patients who have a CD4 cell count below 350 cells/mm3 – the current threshold for starting HIV treatment – at the time of their HIV diagnosis should be defined as having a late diagnosis.
The presence at diagnosis of factors associated with a high risk of death within three months – a CD4 cell count below 200 cells/mm3 or an AIDS-defining illness – should, the investigators propose, be described as presentation with “advanced HIV disease”.
Large numbers of European patients have their HIV diagnosed late. This contributes to much of the remaining HIV-related mortality seen in the region.
Earlier diagnosis of HIV would therefore help cut rates of HIV-related illness and death. It is also possible that it would have public health benefits as well, as individuals with untreated, advanced HIV infection have higher viral loads and are more infectious.
But definitions of late diagnosis vary. Investigators from the UK Collaborative HIV Cohort (UK CHIC) therefore looked at the characteristics of 15,774 patients seen between 1996 and 2006 to identify “a definition that can reliably identify a high proportion of individuals who will die shortly after their HIV diagnosis”.
Overall, 10% of patients had a CD4 cell count below 50 cells/mm3 at the time of diagnosis, and a further 17% of individuals had a CD4 cell count below 200 cells/mm3 at diagnosis. However, the researchers note that there were no CD4 cell count measurements for 14% of patients at the time of diagnosis.
Just under 10% of patients had an AIDS-defining illness at the time of their HIV diagnosis. In 2.4% of individuals this illness was moderate or severe and posed a significant risk of death.
Most patients (78%) with a CD4 cell count below 50 cells/mm3 also had an AIDS-defining illness at diagnosis. Furthermore, 46% of patients with a more serious AIDS-defining illness had a CD4 cell count below 200 cells/mm3, with 79% of patients with this category of illness having a CD4 cell count below 50 cells/mm3.
A total of 206 (1.3%) of patients died within three months of their HIV diagnosis.
However, higher mortality rates were seen among patients in each of the categories identified by the investigators.
Individuals with a CD4 cell count below 200 cells/mm3 had a mortality rate of 3%, and 5% of patients with a CD4 cell count below 50 cells/mm3 at diagnosis died within three months.
Moreover, 6% of those with an AIDS diagnosis died within this period, as did 10% of individuals with a potentially life-threatening AIDS-defining condition.
But the investigators found that 45% of patients died without having their CD4 cell count measured.
Because of this, using CD4 cell count alone did not identify all patients dying within three months of diagnosis. Only a third of individuals who had a CD4 cell count below 50 cells/mm3 and 51% of those with a CD4 cell count below 200 cells/mm3 would have been identified if CD4 cell criteria alone were used.
Similarly, a reliance on clinical criteria would only have identified 43% of those dying within three months who had AIDS at diagnosis and 18% of those with a more severe AIDS-defining illness at this time.
However, combining CD4 cell counts and clinical characteristics proved a more reliable guide, enabling the identification of over two-thirds of patients who died.
“We propose that any individual who presents with either a CD4 cell count below 200 cells/mm3 or a clinical AIDS event is defined as presenting with advanced HIV disease”, write the investigators.
In addition they suggest that patients diagnosed with a CD4 cell count below 350 cells/mm3, or who develop an AIDS-defining illness within a month of diagnosis should be classified as having their HIV diagnosed late.
The investigators caution that a reliance on CD4 cell counts alone would not identify a substantial number of patients who have advanced HIV disease and a high risk of death at the time of their diagnosis. They write, “these patients may present and die without having their CD4 cell count measured”.
They hope that their proposed definitions will facilitate cross-country comparisons and help identify patients with a high risk of advanced disease at the time of their HIV diagnosis.
The UK Collaborative Cohort (UK CHIC) Steering Committee. Late diagnosis in the HAART era: proposed common definitions and associations with mortality. AIDS 24 (advance online publication), 2010.