Mortality rates are higher amongst
HIV-positive patients with a CD4 cell count above 350
cells/mm3 who are not taking antiretroviral treatment
than those in the general population, an analysis published in the
Over 40,000 patients in Europe and North
America were included in the study. When compared to HIV-negative individuals
of the same sex, those with HIV had a higher twelve-month mortality
rate. The risk of death fell as a CD4 cell count increased, and was lowest
amongst gay men.
“Death rates in ART [antiretroviral
therapy]-naive people with HIV who have CD4 counts greater than 350 tend to be
higher than in the general population of industrialised countries.” The
investigators attribute the especially high risks of death observed for HIV-positive
injecting drug users and heterosexuals to “socioeconomic and lifestyle
Mortality rates were lower for patients
with a CD4 cell count above 500 cells/mm3
especially for those with a count above 700 cells/mm3
– a finding which is likely to contribute to the
ongoing debate about the best time to start antiretroviral treatment.
Indeed, the international team of
investigators undertook the study because they wished to address a
“fundamental” question about the possible benefits of starting HIV therapy at a
CD4 cell count above the currently recommended 350 cells/mm3:
“are ART-naïve patient with CD4 cell counts greater than 350…at higher risk of
death than the general population?”
They therefore pooled data from 23 cohort
studies in Europe and North America. Their analysis included 40, 830 patients
who had at least one CD4 cell count above 350 cells/mm3 when
HIV therapy naive. These individuals contributed a total of 80, 682 person
years of follow-up.
A total of 419 (1%) individuals died,
giving an overall mortality rate of 5.2 per 1000 person years. Of these deaths
61 (15%) were categorised as AIDS-related, 188 (45%) as non-AIDS-related, and
the cause was unrecorded for 170 deaths (41%).
The risk of death was higher for patients
with HIV than for the general population. However, the magnitude differed
according to HIV-risk group. It was only modestly elevated for gay and other
men who have sex with men (standardised mortality ratio [SMR] = 1.30; 95% CI:
1.06 to 1.58), but was notably higher for heterosexuals (SMR = 2.95; 95% CI:
2.28 to 3.73), and was especially elevated for injecting drug users (SMR = 9.37;
95% CI: 8.13 to 6.53).
Analysis was then restricted to the
patients with HIV, and the investigators compared the twelve-month death rate
of that recorded in patients in different CD4 cell strata (350-499; 500-699;
and above 700 cell/mm3).
An adjusted analysis that took into account
potentially confounding factors showed that, compared to those with a CD4 cell
count between 350-499 cells/mm3, the mortality rate was
23% lower amongst patients with CD4 cell counts in the 500 to 699
cells/mm3 strata, and 34% lower for those with CD4 cell
counts above 700 cells/mm3. A series of sensitivity analyses did not
substantially affect these results.
“These data suggest that people with HIV who
have not taken ART and have CD4 count greater than 350
cells/mm3, have a raised risk of death compared with the
general uninfected population, although the increase seems to be small,”
conclude the investigators.
They add, “because ART might reduce the
risk of death in such patients, these findings support the need for continuing
studies (such as the START trial and the further exploration of existing
observational databases) of the risks and benefits of starting ART at CD4
counts greater than 350”.