A low CD4 cell
count is associated with increased mortality risk, even if people are taking
virologically effective HIV therapy, an international team of investigators
report in the online edition of Clinical
Infectious Diseases. People with incomplete CD4 count recovery – a count
below 200 cells/mm3 – despite
three years of treatment with virologic suppression had a more than two-fold
increase in their mortality risk compared to people with more robust immune
older age, transmission via male heterosexual sex or IDU [injecting drug use],
lower CD4 count at start of the suppressed period and longer time from
initiation of cART [combination antiretroviral therapy] to start of the virally
suppressed period as risk factors for incomplete CD4 cell recovery,” write the
They believe their
findings underline the importance of earlier HIV diagnosis and the prompt
initiation of therapy. The investigators also urge that patients with
incomplete CD4 count recovery should be closely monitored for certain diseases,
including hepatitis and non-HIV-related cancers.
antiretroviral therapy is very effective at suppressing viral load. This
control of HIV replication allows the immune system to strengthen and CD4 count
to increase. People with virologic and
immunologic responses to HIV therapy now have a normal life expectancy.
However, it is
well known that a significant proportion of people taking anti-HIV drugs do
not have a robust increase in their CD4 count, even though treatment is
controlling viral load. The clinical consequences of this discordant response
to treatment are unclear.
Europe and North America therefore designed a study to elucidate the factors
associated with an incomplete CD4 response to HIV therapy in people with
long-term virologic suppression. They also compared mortality rates according
to CD4 count and analysed the relationship between incomplete immune recovery
and specific causes of death.
population comprised 5550 patients enrolled in 53 cohorts across Europe and
North America. All the participants had a CD4 count below 200 cells/mm3
when they started HIV therapy. They were followed for a median of 3.4 years.
The majority (85%)
achieved an increase in their CD4 cell count to above 200 cells/mm3
after three years of viral suppression.
Risk factors for
incomplete CD4 count recovery were older age, HIV transmission risk group
(heterosexual males and injecting drug users), a viral load below 100,000
copies/ml at the start of therapy, lower CD4 count at baseline, and longer interval between initiation of
treatment and suppression of viral load.
A total of 175
(3%) participants died. The mortality rate was 8% among people with incomplete
CD4 count recovery compared to 2% among individuals whose CD4 count increased
to 200 cells/mm3. Therefore individuals who did not attain a CD4
count of 200 cells/mm3 despite long-term virologic suppression, had a
significantly increased mortality risk compared to people with an immunologic
response to treatment (aHR = 2.6; 95% CI, 1.86-3.81).
five-year mortality rate was 12% among participants with a CD4 cell count below 200
cells/mm3 after three years of suppression. This compared to a 2%
rate among participants with CD4 counts above 500 cells/mm3.
As regards causes
of death, the investigators found that incomplete immune recovery was
associated not only with an increased risk of all-cause mortality (aHR = 2.75;
95% CI, 1.71-3.70), but also of non-AIDS-related mortality (aHR = 2.61; 95% CI,
1.61-4.23), hepatitis-related death (aHR = 6.76; 95% CI, 1.93-23.74) and
mortality related to non-AIDS-defining cancers (aHR= 2.89; 95% CI,
“Since 15% of
treated HIV-positive patients have a CD4 count < 200 cells/mm3
after long-term viral suppression, prognosis of such patients is a major
concern,” write the authors.
underline the importance of the early diagnosis of HIV and treatment with cART
before patients have a low CD4 count,” the investigators conclude. “Virally
suppressed patients with low CD4 counts should be monitored closely for diseases
not conventionally considered HIV-related, especially non-AIDS cancers and