The level of a patient’s CD4 cell count shortly after
infection with HIV can predict the extent of immune recovery after the
initiation of antiretroviral therapy, investigators from the US military report
in the online edition of the Journal of
Acquired Immune Deficiency Syndromes.
“The baseline CD4+ T cell count observed during
the early stages of HIV infection is a strong predictor of CD4+ T
cell count attained after HAART [highly active antiretroviral therapy],”
comment the authors.
They believe that their findings have implications for HIV
care, especially the current debate about the best time to initiate therapy
with antiretroviral drugs: “Our results indicate that it may be clinically
useful to consider the baseline CD4+ T cell count as an approximate
guideline for targeting the post-HAART recovery.”
CD4 cell count is used as a guide to help doctors and
patients decide when to start HIV therapy. Current US guidelines recommend that
an individual should start treatment when their CD4 cell count is around 500
cells/mm3.
Initiation of therapy at higher CD4 cell counts has been
shown to reduce the risk of both HIV-related and non-HIV-related illnesses.
Moreover, the timing of therapy can also have an impact on immune recovery. Patients
who wait to start HIV treatment until their CD4 cell count is in the region of
200 cells/mm3 are less likely to achieve the same levels of immune
restoration as patients with initiate therapy at higher CD4 cell counts.
However, the relationship between CD4 cell count in the
period shortly after infection with HIV (baseline) and subsequent improvements
in immune function after the commencements of antiretroviral treatment is
unknown.
Therefore researchers from the US military’s HIV Natural
History Study undertook a longitudinal study to assess the impact of immune
function soon after HIV seroconversion, as well as the lowest ever, or nadir,
CD4 cell count on immune restoration two years after the initiation of HIV
therapy.
A total of 1084 HIV-positive US military personnel who
received care between 1996 and 2008 were included in the study. These
individuals were regularly tested for HIV, and the median period between a
negative and positive HIV antibody test was 1.37 years.
At the time of their diagnosis the patients had a median CD4
cell count of 470 cells/mm3.
Median nadir CD4 cell count was 311 cells/mm3.
All the patients started antiretroviral therapy and 93% achieved virological
control. Two years after starting
HIV therapy the patients’ median CD4 cell count had increased to 577 cells/mm3.
A strong relationship was found between a lower baseline CD4
cell count and poorer immune recovery during HIV therapy.
Patients with a first ever CD4 cell count below 500 cells/mm3
were over three times more likely than individuals with higher baseline CD4
cell counts to have an average CD4 cell count below 500 cells/mm3
over two years after starting HIV therapy (odds ratio [OR] = 3.19; 95% CI,
2.27-4.49).
Further analysis showed that the relationship between CD4
cell count soon after infection with HIV and CD4 cell count after two years of
treatment was largely independent of nadir CD4 cell count, and that baseline
CD4 cell count accounted for between 50-74% of subsequent immune recovery.
Nevertheless, nadir CD4 cell count was important. During HIV
therapy the highest CD4 cell counts were seen in patients who had a baseline
CD4 cell count above 700 cells/mm3 and a nadir CD4 cell count of at
least 200 cells/mm3.
In multivariate analysis a significant relationship was
identified between a higher first ever CD4 cell count and CD4 cell gain during
treatment (p < 0.001). However, a lower nadir CD4 cell count
was associated with poorer improvements in immune function (p < 0.001).
However, the investigators observed that for “a given nadir
CD4 count, a higher baseline CD4+ T cell count was associated with a
larger gain after HAART.”
There was also a relationship between the extent of CD4 cell
decline prior to the initiation of therapy and subsequent recovery during HIV
treatment.
Patients whose nadir CD4 cell count was at least 60% of the
baseline value when they started HIV therapy were significantly more likely to
experience reconstitution of their CD4 cell count to that recorded soon after
infection.
“We developed a novel marker, the nadir/baseline ratio as
one with a high degree of association with future course of immune
reconstitution after HAART,” write the authors.
“This finding further implies that a) it may be useful to
have a knowledge of baseline CD4+ T cell count as close to seroconversion
as feasible; and b) if the CD4+ T cell count falls below 60% of this
value, the situation is less likely to yield a robust immune reconstitution
even if viral load suppression is achieved.”
The investigators add that their findings are “in line with
the view that early HIV-diagnosis and HAART initiation can be beneficial.
Second, our study implies that knowledge of the baseline CD4+ T cell
count may provide a clinician with a realistic therapeutic goal for CD4
recovery following HAART.”