Recently
updated U.S.
and European
HIV treatment guidelines recommend that patients should start antiretroviral
therapy when their CD4 cell count falls below 350 cells/mm3. But there is increasing
evidence that earlier therapy may be beneficial.
Colored
scanning electron micrograph of a T4 cell (green) infected with HIV (red).
The
investigators aimed to determine whether treatment-naive patients with a high
CD4 cell count are at increased risk of death compared with the HIV negative general
population, and whether there are trends in mortality according to CD4 count and
viral load in this group.
The analysis included 46,400 individuals from
23 cohorts in developed countries (5 North American, 18 European) who collectively
contributed 237,553 CD4 cell measurements and 98,527 person-years of follow-up.
About 75% were male, just over half were men who have sex
with men (MSM), 21% were heterosexual, 21% were injection drug users (IDUs),
and 5% were in another or an unknown risk group.
Comparing the HIV positive
groups with the general population, the researchers calculated country-, age-,
and sex-specific standardized mortality ratios (SMR), stratifying by HIV risk
group. Reported results were from a sensitivity analysis of all patients with
a pre-treatment CD4 cell count above 350 cells/mm3 before January 2005, which
they suggested mitigated the effect of late reporting of deaths. Results
•
The median CD4 count during the follow-up
period was high, above 550 cells/mm3.
•
38% of the data were from patients with a
CD4 count in the 350-500 cells/mm3 range, 35% from those with 500-700 cells/mm3,
and 28% with greater than 700 cells/mm3.
•
During follow-up, 487 individuals (1.04%)
died due to any cause, or 4.9 per 1000 person-years.
•
16% of the deaths were due to AIDS-related
cause, 48% were non-AIDS-related, and the remainder were unknown.
•
The overall mortality rate for HIV positive
individuals was higher than that of the general population, but the difference
varied by risk group:
•
Marginally higher for MSM (SMR 1.37);
•
3 times higher for all heterosexual men and
women (SMR 3.04);
•
10 times greater for IDUs (SMR 10.21).
•
The risk of death increased with lower CD4
cell counts and higher viral loads, as is the case for patients with CD4 counts
below 350 cells/mm3.
•
A small proportion of patients died due to
AIDS-related causes despite having a CD4 count above 350 cells/mm3.
The
higher mortality rate for HIV positive IDUs was not unexpected, even with high
CD4 counts, due to other risk factors for death in this group. However, the researchers
concluded, the significantly higher mortality rate among heterosexual men and
women, as well as the slight increase among MSM, suggests that HIV infection is
associated with excess mortality even in the absence of seriously compromised
immunity.
In
a related plenary presentation (abstract 8), Dr. Andrew Phillips of the
Royal Free Hospital in London gave an overview of recent data indicating that
HIV infection may contribute to so-called "non-AIDS-related" conditions,
and that starting antiretroviral treatment with a CD4 cell count above 350 cells/mm3
appears to be associated with better outcomes.
"We need to be looking
at whether antiretroviral therapy should be initiated earlier, in patients with
CD4 cell counts above 500," he suggested.
Adding weight to this recommendation,
researchers studying the Johns Hopkins HIV Clinical Cohort presented a poster
(abstract 963) showing that HAART reduced the risk of illness due to non-infectious
causes - including cardiovascular, liver, lung, and kidney disease, cancer, and
neuropsychological conditions -- at all CD4 levels.
While the non-infectious
morbidity rate dropped by nearly 50% for patients with a CD4 count below 200 cells/mm3,
it still fell by 30% for those with more than 350 cells/mm3. The risk of both
infectious and non-infectious illness declines among patients taking antiretroviral
therapy. These researchers, too, concluded that, "Early (CD4 > 350) use
of HAART may be indicated to
decrease this risk."
02/22/08
References
R Lodwick,
K Porter, C Sabin, and others. Age- and Sex-specific Death Rates in ART-naïve
Patients with CD4 Count above 350 cells/mm3 Compared with the General Population.
15th Conference on Retroviruses and Opportunistic Infections (CROI 2008). Boston,
MA. February 3-6, 2008. Abstract 141.
HAART
Decreases Risk of Death Even in People with CD4 Counts above 350 Cells/mm3
Results
