Uncontrolled HIV replication is associated with an increased
risk of AIDS for patients with a CD4 cell count above 350 cells/mm3,
European investigators report in the online edition of AIDS. The researchers also found patients with a viral load above
500 copies/ml had an increased risk of serious non-AIDS related illnesses, but
only after they had adjusted their results to take account of confounding
“In HIV-positive individuals with a CD4 cell count > 350
cells/mm3 we observed an association with uncontrolled viral
replication and a higher incidence of fatal and non-fatal AIDS events and a
slightly increased incidence of fatal and non-fatal non-AIDS events,” comment
the investigators. “The higher incidence of AIDS events was observed in…both
crude and adjusted analysis. However, the increased incidence of non-AIDS
events was only apparent after adjustment.”
European HIV treatment guidelines currently recommend that
patients should initiate antiretroviral therapy when their CD4 cell count is in
the region of 350 cells/mm3. Initiating treatment at this time,
rather than waiting until later, reduces the risk of developing AIDS-related
illnesses as well as some serious non-HIV-related illnesses such as
Uncontrolled HIV replication is known to cause immune
stimulation and inflammation. However, the impact of viral load on disease
progression in patients with higher CD4 cell counts has received little
Therefore investigators from the EuroSIDA cohort study
analysed the risk of developing an AIDS-defining illness or a serious
non-AIDS-defining event in patients with a CD4 cell count above 350 cells/mm3
according to their viral load.
The patients were divided into three viral load strata:
Low – below 500 copies/ml.
Intermediate – between 500 copies/ml and 9999
High – above 10,000 copies/ml.
A total of 11,492 patients who received care after 1997 were
included in the analysis investigating the relationship between viral load and
the risk of AIDS-related events. For the non-AIDS event analysis, 10,869
patients who were seen after 2001 were included.
Most of the patients (82%) had a viral load below 500
copies/ml, with 11% having an intermediate viral load and 7% a viral load above
10,000 copies/ml. A total of 90% of patients with a low viral load were taking
HIV therapy, compared to 61% of individuals with an intermediate viral load and
36% of those with a high viral load.
Overall, 354 AIDS events were reported, and the overall
incidence was 0.68 events per 100 person years of follow-up.
Initial analysis showed that the incidence of AIDS-related
illnesses was 0.53 per 100 person years for patients with a low viral load,
increasing to 0.90 per 100 person years for those with an intermediate viral
load and 2.12 per 100 person years for individuals with a high viral load.
The relationship between both an intermediate and a high
viral load and an increased risk of progression to AIDS remained significant
after results were adjusted for potentially confounding factors (p = 0.03 and p
< 0.001 respectively).
“The association we found between viral replication and the
incidence of AIDS events appears to be almost linear and was independent of
current CD4 cell count,” comment the investigators.
There were 572 non-AIDS-related events. These included 208
(36%) cardiovascular events and 204 (36%) non-AIDS-related malignancies. The
overall incidence of serious non-AIDS-related illnesses was 1.31 per 100 person
years of follow-up.
Incidence was 1.28 per 100 person years of follow-up for
patients with a viral load below 500 copies/ml, compared to 1.52 per 100 person
years for individuals with an intermediate viral load and 1.38 per 100 person
years for those with a higher viral load.
The investigators adjusted these results to take account of factors
such as HIV risk group, region, hepatitis co-infection, diabetes, high blood
pressure, a previous AIDS
diagnosis and use of HIV therapy.
These adjusted results showed that compared to individuals
with a low viral load, patients with intermediate viraemia were 61% more likely
to develop a serious non-HIV-related illness (IRR = 1.61; 95% CI, 1.21-2.14; 0
= 0.001), and those with a viral load above 10,000 copies were 66% more likely
to experience such an event (IRR = 1.66; 95% CI, 1.17-2.34; p = 0.004).
Further analysis showed that a viral load between 500 and
9999 copies/ml was associated with a significant increase in the risk of
cardiovascular disease (p = 0.03).
However, the investigators comment: “A larger study with
longer follow-up would be needed to analyse the association between each
specific non-AIDS events and viral replication further.”
The investigators then looked at the risk of AIDS and
non-AIDS events according to CD4 cell count. Compared to individuals with a CD4
cell count between 350 and 499 cells/mm3, patients with a CD4 cell
count above 500 cells/mm3 had a non-significant reduction in their
risk of both AIDS-related and non-AIDS-related events.
conclusion,” write the investigators, “in HIV-positive individuals with a CD4
cell count > 350 cells/mm3, an increased incidence of AIDS and a
slightly increased incidence of non-AIDS was found in those with uncontrolled