The long-term benefits of starting antiretroviral therapy during
primary HIV-1 infection have still not been confirmed. While some
studies suggest it lowers viral set-point and preserves immune
function, others find no long-term advantages, suggesting that delaying
therapy until HIV-1 RNA and CD4 cell counts reach a predetermined
threshold is the best way to manage patients. The results of two recent
studies presented at the 14th Annual Retroviral Conference this week
highlight the need to clarify this issue.
In the first study, Dr. Radjin Steingrover from the University of
Amsterdam reported his group's findings for 332 patients with
laboratory evidence of primary HIV-1 infection. Sixty-four started
highly active antiretroviral therapy within 180 days of seroconversion.
Thirty-two of these patients subsequently stopped treatment. The
remaining patients delayed treatment.
A viral set-point was reached 7 weeks after seroconversion or
interruption of treatment. Compared with the untreated patients, the
viral set-point was 0.6 log copies/mL lower in those who interrupted
early treatment (p < 0.001), Dr. Steingrover reported.
This lowering of viral set-point following early treatment, he
concluded, "indicates there are long-term clinical benefits to be
gained" from this treatment strategy. No differences in CD4 cell counts
were seen between the early and delayed treatment groups.
Symptoms during primary infection were also not associated with increased time to AIDS or death.
A factor that biased the results, Dr. Steingrover added, was that
primary infection patients with high viral loads, known to be
associated with a poor prognosis, were more likely to receive early
treatment.
When asked how he would manage patients with primary infection, he
said patients presenting with severe symptoms, requiring
hospitalization, should probably start treatment immediately, whereas
those with mild or no symptoms can probably wait until changes in HIV-1
load and CD4 counts begin.
Contradictory results were obtained in the second study, in which
early treatment appeared to have no effect on viral set-point. However,
a beneficial effect on CD4 cell counts was noted.
Using a different approach, Dr. Christine Koegl of MUC, Munich, and
colleagues are following 200 patients with primary HIV-1 infection
enrolled in one of two large ongoing trials. One hundred forty-four
subjects began treatment immediately and 56 delayed treatment. So far,
the team has followed the patients for a median of 27 months, Dr. Koegl
said.
When 100 patients stopped therapy after 9.5 months, viral load was
below detection in 82% and the median CD4 count was 799 cells per
microliter.
However, 12 months after treatment was stopped, the median viral
load was up to 38,056 copies/mL compared with 52,880 copies/mL in the
untreated patients. Median CD4 values were 538 cells per microliter in
patients who had been treated compared with 525 cells per microliter in
the untreated group.
"On the other hand, we have three patients (in the early treatment
group) who are still undetectable," Dr. Koegl said. These patients
appear to have benefited from early treatment, "but we don't know why,"
she added.
Overall, Dr. Koegl concludes that early treatment has no significant
effect on viral load 12 months after treatment is stopped. However,
compared with baseline values, the untreated patients had a median
decline in CD4 count of 87 cells per microliter, whereas the treated
patients had an increase of 60 cells per microliter, suggesting a
beneficial immunologic effect.
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