Starting HIV therapy with a CD4 cell count above 500
cells/mm3 has only minimal additional benefits compared to
initiating therapy with a CD4 cell count in the region of 350-500 cells/mm3,
Australian investigators report in the online edition of the Journal of Acquired Immune Deficiency
The study was restricted to patients with started
antiretroviral treatment when their CD4 cell count was above 350 cells/mm3.
Patients with CD4 cell counts between 350-500 cells/mm3
rapidly achieved increases to above 500 cells/mm3. Moreover, 72
months after the commencement of treatment, patients had broadly comparable CD4
cell counts, regardless of their immune status at baseline.
Starting treatment at higher CD4 cell counts had clinical
benefits, but overall these were modest.
The study will inform the ongoing debate about the best time
to start antiretroviral therapy.
Individuals who start treatment before their CD4 cell count
falls below 350 cells/mm3 are known to have a lower risk of illness
and death from both HIV-related and some non-HIV-related diseases. However, the
benefits of therapy at higher CD4 cell counts are unclear. Some doctors believe
that the threshold for initiating therapy should be 500 cells/mm3.
A large randomised clinical trial called the START study is
currently examining this question, but its results are not expected for a number of years. Therefore
Australian investigators performed an observational study involving 432
individuals who started HIV therapy when their CD4 cell count was above 350
The patients were stratified into three groups on the basis
of their baseline CD4 cell count (350-500; 501-650; above 650 cells/mm3),
and were followed for 72 months, with investigators monitoring changes in CD4
cell counts between the three groups.
Using data obtained from other large studies, the
investigators calculated the impact of baseline CD4 cell strata on the risk of
progression to AIDS or death.
After twelve months of HIV therapy, mean CD4 cell counts had
increased to above 500 cells/mm3 for patients in all baseline CD4
cell strata (means 596, 717, and 881 cells/mm3 respectively).
“Patients who commenced treatment with a baseline CD4 cell
count 351-500 cells/mm3, typically and rapidly…achieved and
maintained a CD4 cell count greater than 500 cells/mm3,” comment the
After 72 months of therapy, mean CD4 cell counts were
broadly comparable regardless of baseline CD4 cell strata (689, 746 and 742
The investigators then turned their attention to the impact of
baseline CD4 cell count on the risk of death or AIDS.
Using data from another study, the investigators estimated
that patients who started treatment when their CD4 cell count was above 650 cells/mm3
had a projected 8% reduction in mortality over 72 months compared to
individuals who initiated therapy when their CD4 cell count was in the region
of 350-500 cells/mm3, an absolute risk reduction of 0.33 per 1000
Comparison with patients in the 500-650 cells/mm3
strata showed that individuals with a CD4 cell count above 650 cells/mm3
had a 4% reduction in their risk of death over six years, an absolute reduction
of 0.16 per 1000 person years.
Extrapolation of data from two other studies showed that
patients who started therapy with a CD4 cell count above 650 cells/mm3
reduced their risk of progressing to AIDS or death by 14% compared to
individuals who initiated therapy with a CD4 cell count between 350-500
“Our results shows that potentially, initiating cART
(combination antiretroviral therapy) at CD4 cell counts >650 cells/mm3
could yield the prevention of hundreds or thousands or AIDS events or
illnesses,” write the authors.
They conclude, “our analysis suggests that patients who
start cART at CD4 counts >650 cells/mm3 have better preserved
immune function, but only to a relatively modest degree…furthermore the extent
to which this might be expected to result in better clinical outcomes we show
to be uncertain.”