Patients whose CD4 cell count does not recover despite
achieving virologic control with HIV therapy require continued medical
attention, results of a large European study presented to the recent
International AIDS Society conference in Rome show.
Researchers found that individuals whose CD4 count failed to
increase above 200 cells/mm3 were significantly more likely to
experience a new AIDS-defining event or die than patients with more robust CD4
cell count increases.
“In virologically suppressed patients, lack of increase in
CD4 cell count is relevant for prognosis and poorer outcome,” comment the
Encouragingly, the research also suggested that patients
whose CD4 cell count increases to above 500 cells/mm3 have an
excellent long-term prognosis.
Modern HIV therapy is potent, easy to take and generally
causes only mild side-effects. The goal of treatment is suppression of viral
load below 50 copies/ml, and over 90% of patients can achieve this outcome
within a year of starting antiretroviral treatment.
In most patients, suppression of viral load is accompanied
by a gradual increase in CD4 cell count. Long-term HIV therapy can result in
the restoration of CD4 cell count to normal levels.
However, despite having a successful virologic response to treatment,
CD4 cell count fails to increase in some patients.
Investigators from the Collaboration of Observational HIV
Epidemiology in Europe (COHERE) wished to determine the prognostic implications
of poorer CD4 cell increases in patients whose viral load was suppressed.
A total of 66,147 individuals were included in their
research. All experienced a fall in their viral load to undetectable levels
after starting antiretroviral therapy. Their average age was 37 years, 73% were
men, 26% had a prior AIDS diagnosis and 14% had a history of injecting drug
Median CD4 cell count at the time HIV therapy was started
was high – 396 cells/mm3, and the patients had a baseline viral load
of 4.6 log10 copies/ml.
When viral load was first suppressed below 50 copies/ml, 34%
of patients had a CD4 cell count above 500 cells/mm3, 25% had a
count between 350 and 500 cells/mm3, 26% a count of between 200 and 350
cells/mm3, and 16% had a CD4 cell count below 200 cells/mm3,
including 1% with a count beneath the dangerously low level of 50 cells/mm3
– a factor well known to be associated with a poor prognosis.
There were few new AIDS events or deaths among patients whose
CD4 cell count was above 500 cells/mm3 (5 per 1000 patient-years).
Events were also rare for patients in the 350 to 500 cells/mm3 and 200 to 350 cells/mm3 strata (7.9 and 12.0 per 1000 patient-years
However, incidence was markedly higher for patients with a
CD4 cell count below 200 cells/mm3 (30.5 per 1000 patient-years),
especially so for those with a CD4 cell count beneath 50 cells/mm3
(94.9 per 1000 patient-years).
The investigators plotted the impact of CD4 cell count on
The prognosis for patients with virologic suppression and a
CD4 cell count above 500 cells/mm3 was excellent. The investigators
calculated that they had a 95% probability of survival and avoidance of AIDS.
Projected outcome for patients with a well-controlled viral
load and CD4 cell counts between 500-350 or 200-350 cells/mm3 were
also good, with event-free survival projected for approximately 90%.
However, at lower CD4 cell counts the chance of remaining
alive and AIDS-free were significantly poorer. The projected event-free
survival rate for patients with a CD4 cell count beneath 200 cells/mm3
was in the region of 65%.
There was also robust evidence that the time to an event was
significantly shorter for patients whose CD4 cell count did not increase above
200 cells/mm3 despite virological suppression (HR = 0.21, 95% CI, 0.19-0.24
vs. HR = 0.92, 95% 0.90-0.94 for patients with a CD4 cell count above 200
“In virologically suppressed patients an increase in CD4
cells reduces the risk of AIDS or death,” comment the investigators, “lack of
increase in CD4 cell is relevant for prognosis and poorer outcome.”