In
the first study (abstract
351), German researchers looked at changes in CD4 cell counts in 3 groups:
•
Untreated elite controllers with undetectable
plasma HIV RNA (< 50 copies/mL)(n = 8);
•
Untreated "medium controllers" with
viral load between 50 and 5000 copies/mL (n = 13);
•
HAART-treated patients with HIV RNA < 50
copies/mL after 3 or more years on therapy (n = 20).
Participants
were followed for a minimum of 1 year and had at least 3 CD4 cell measurements
available.
Results
•
CD4 cell counts were not significantly different
in the 3 groups at study entry (742, 512, and 567 cells/mm3, respectively).
•
7 of the 8 elite controllers (88%) and 9 of
the 13 medium controllers (69%) experienced decreasing CD4 counts over median
follow-up periods of 5 and 3 years, respectively.
•
Calculated median annual CD4 count declines
were 42 cells/mm3 in the elite controllers and 15 cells/mm3 in the medium controllers.
•
The HAART-treated controls subjects, by contrast,
experienced an annual increase of 30 cells/mm3.
•
Fewer elite controllers had normal CD4 cell
values (within the 95% confidence interval of age- and sex-adjusted normal values)
at the end of the observation period than at study entry (4 vs 7 patients).
•
Conversely, more treated control patients
had normal CD4 counts at the end of follow-up than at baseline (15 vs 9 patients).
•
CD8 T-cell changes were not significantly
different across the 3 groups.
"[T]hese
results suggest that even in elite controllers of HIV replication, CD4 T-cell
counts may decrease with long-term follow-up," the investigators concluded.
"Stable or increasing CD4 cells in the controls on HAART support the view
that this decrease is directly or indirectly related to HIV replication."
Based
on these findings, they added, "There could indeed be no 'harmless' level
of HIV replication."
Atherosclerosis
In
the second study (abstract
951), Steven Deeks and colleagues at the University of California at San
Francisco and San Francisco General Hospital assessed the development of atherosclerosis
(hardening of the arteries due to loss of elasticity and plaque build-up) in HIV
positive individuals.
Specifically, they measured blood lipid levels and
carotid intima-media thickness (IMT), or thickness of the lining of the carotid
arteries that supply blood to the brain, in 28 untreated HIV controllers with
undetectable viral load (< 75 copies/mL), 87 untreated individuals with detectable
HIV RNA, HAART-treated HIV positive patients with detectable (n = 92) and undetectable
(n = 180) viral load, and 93 HIV negative control subjects. Most participants
(about 85%) were men and the median age was about 47 years.
Results
•
Median LDL ("bad") and HDL ("good")
cholesterol, triglyceride, and glucose levels were similar across groups.
•
Median IMT measurements were as follows:
•
HIV negative control subjects: 0.73 mm; •
Untreated patients with detectable viral load:
0.84 mm; •
Untreated controllers: 0.87 mm; •
Treated patients with detectable viral load:
0.90 mm; •
Treated patients with suppressed viral load:
0.96 mm.
•
Median IMT was higher in each of the 4 HIV-infected
subgroups compared with HIV negtaive control subjects.
•
These differences remained statistically significant
after controlling for traditional cardiovascular risk factors such as family history,
smoking, diabetes, and high blood pressure.
•
After adjusting for these risk factors, untreated
controllers had a 0.14 mm higher IMT than HIV negative subjects.
•
Among the treated patients, longer during
of antiretroviral therapy overall, and longer treatment with PIs and with NRTIs,
independently predicted higher IMT.
"After
adjustment for traditional risk factors, both HIV infection and duration of exposure
to protease inhibitors were independently associated with higher levels of subclinical
atherosclerosis," the researchers concluded.
They added that, "The
treatment-independent effect of HIV infection on IMT appeared to be due to factors
other than HIV replication or advanced immunodeficiency, as evidenced by high
IMT in our HIV controllers."
Taken together, these 2 studies suggest
that even well-controlled HIV infection can have a variety of detrimental effects.
Some of these (e.g., CD4 cell decline) may be improved with early antiretroviral
therapy, but others may persist despite treatment.
CD4
Cell Loss and Accelerated Atherosclerosis Occur Even in HIV Positive "Elite Controllers"
with Undetectable Viral Load
CD4
Cell Loss
Results
In
the second study (
