AIDS-defining illnesses remains elevated even when the CD4 cell count is between
500 and 749 cells/mm3, European research published in Clinical Infectious Diseases shows.
“We found an
increased rate of new ADIs [AIDS-defining illnesses] at a current CD4 count of
500-749 cells/mm3 compared to 750-999 cells/mm3 or higher
but no evidence of any association between CD4 count and incidence of new ADIs
within 750-999 cells/mm3, or > 1000 cells/mm3,” write
The authors also
found that “the incidence of new ADIs at higher CD4 counts was extremely low.”
antiretroviral therapy, most people living with HIV in richer countries now have
a normal life expectancy. The risk of most AIDS-defining illness is highest
when CD4 cell count falls to below 200 cells/mm3. All HIV treatment
guidelines recommend that people with this level of immune suppression should
take antiretroviral therapy.
However, there are
few data on the incidence in the era of modern HIV therapy of AIDS-defining
illnesses at higher CD4 cell counts.
the Collaboration of Observational HIV Epidemiological Research Europe (COHERE)
study therefore designed research with the aim of describing the incidence of new
AIDS-defining illness among people with CD4 cell counts above 200 cells/mm3.
They also wanted to establish the incidence of AIDS events at CD4 cell counts
above 500 cells/mm3.
care between 1998 and 2010 with a CD4 cell count above 200 cells/mm3
were eligible for inclusion in the study. These individuals were placed into
different CD4 cell categories: 200-349 cells/mm3; 350-499 cells/mm3;
500-749 cells/mm3; 750-1000 cells/mm3; and above 1000 cells/mm3.
A total of 207,539 individuals were included in the study and contributed over 1,154,800
person-years of follow-up. A total of 12,135 new AIDS-defining events were
The most common
were oesophageal candidiasis (13%), Kaposi's sarcoma (11%) and pulmonary
Median CD4 cell
count at the time of diagnosis with a new AIDS-defining illness ranged from 314
cells/mm3 among the 127 patients diagnosed with MAI to 416 cells/mm3
among the approximately 780 patients with recurrent herpes.
Overall, 5632 new
AIDS-defining illnesses were diagnosed in patients with a CD4 cell count in the
200-349 cell/mm3 group and a further 3319 were among patients with a
CD4 cell count between 350-499 cells/mm3. Only 1000 diagnoses
involved people with a current CD4 cell count above 750 cells/mm3.
The incidence of
new AIDS events was 21 per 1000 person-years of follow-up among patients with a
CD4 cell count between 200-349 cells/mm3, 10.2 per 1000 person-years
of follow-up for individuals with a CD4 cell count between 350-499 cells/mm3,
and 6.4 per 1000 person-years for those with a CD4 cell count between 500-749
cells/mm3. This compared to a rate of just 4.7 per 1000 person-years
of follow-up among those with a CD4 cell count above between 750-999 cells/mm3,
with the rate falling to 4.1 per 1000 person-years for those with a CD4 cell
count above 1000 cells/mm3.
with the development of a new AIDS-defining illness when current CD4 cell count
was above 500 cells/mm3 included a CD4 cell count below 750 cells/mm3
(p < 0.001), injecting drug use (male, p = 0.009; female, p < 0.001), a
current viral load above 10,000 copies/ml (p < 0.001), older age (each
additional ten years, p < 0.001) and a previous history of AIDS (p <
patients with a CD4 cell count between 750-999 cells/mm3,
individuals in the 500-749 cells/mm3 had a significantly higher rate
of new AIDS events (aIRR = 1.20; 95% CI, 1.10-1.32; p < 0.001).
Each 50 cell/mm3
reduction in CD4 cell count for patients in the 500-749 cell/mm3
category increased the risk of a new AIDS event by a significant 6% (p <
0.001). The risk of AIDS was uniformly low for patients in the 750-999 cell/mm3
stratum and did not differ according to precise CD4 cell count.
A CD4 cell count
above 1000 cells/mm3 was not associated with any further reduction
in the risk of AIDS.
also found that patients with a current CD4 cell count between 500-749 cells/mm3
had a higher risk of developing a new AIDS illness even if they had an
undetectable viral load.
between a CD4 cell count between 500-749 cells/mm3 and an increased
risk of AIDS was stronger for cancer-associated diagnoses (aIRR = 1.52; 95% CI,
1.25-1.86) than non-malignant AIDS illnesses (aIRR = 1.12; 95% CI, 1.01-1.25).
“Despite the low
rate of new ADIs at current CD4 counts >500 cells/mm3, the
rate was increased by 20% when compared to those with a current CD4 count of
750-999 cells/mm3, whereas there was no further significant
reductions in ADIs at higher CD4 counts,” conclude the authors. “These results
were similar in those with viral suppression.” They believe “persons with HIV
infection are not fully immune reconstituted until the CD4 count increases to