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Early treatment of primary HIV infections may lower viral load set point
Another study found that viral load set point was not affected by early treatment.
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LOS ANGELES — HIV viral load set points were significantly lower seven weeks after interruption of early highly active antiretroviral therapy in a Dutch study. But researchers in Germany tentatively concluded that early treatment did not affect viral load set points but may have an advantage in increasing CD4 count.
Researchers from both studies presented data at the 14th Conference on Retroviruses and Opportunistic Infections, held here.
Researchers from both studies agreed that clinical trials are necessary to provide definitive answers to treatment timing questions for highly active antiretroviral therapy (HAART) and to reach conclusions on how treatment choices based on infection phasing could effect CD4 counts in the long term, short term and when treatment is interrupted.
“As physicians, we are struggling with the question of whether or not to treat the acute patients presented to us,” said Radjin Steingrover, MD, of the University of Amsterdam Academic Medical Center. “We are still lacking a randomized trial with clinical outcomes, so we have to make do with the data we have.”
Immune gains made by study participants were noted with caution because studies have yet to indicate whether benefits will be progressively sustained.
“Early treatment is a benefit for CD4 cell counts; for how long, I don’t know,” said Christine Koegl, MD, a researcher from MUC Research GmbH in Munich.
Viral set points decrease
In the Dutch study, researchers analyzed data from people with primary HIV infection (n=332) from two cohorts, which included participants from all HIV treatment centers in the Netherlands. The initiation of HAART was classified as early when patients began the regimen within 180 days of seroconversion. Sixty-four participants were treated with early HAART, and 32 participants stopped early HAART.
CD4 counts and viral set points (plasma HIV RNA) were compared in untreated patients and patients who interrupted early treatments. In early treatment patients, viral set points were reached seven weeks after seroconversion or treatment interruption. Viral set points were also 0.6 log copies/mL lower after interrupting early treatment than in untreated patients (P<.001). After the seven-week period, the difference decreased by 0.003 logs per week. No differences in decline of CD4 cell counts were detected between the two groups.
Although researchers found viral set points in treated patients were significantly lower at seven weeks after early HAART was stopped, viral set points did increase over time.
“In early treatment, we did find an initial lowering of viral set point, indicating that in the long term there may be a clinical benefit to be gained,” Steingrover said.
Viral set points unchanged
In the German study, two national cohorts were used. Early treatment arm population data was taken from Prime-DAG, a study started in July 2001. Ac-DAG, a 2003 study of people who were not treated for primary HIV infection, data were used for the non-treatment arm. The study population included 200 people (191 men) from 42 centers. Median observation was 27 months. CD4 counts and viral load in untreated participants 12 months after seroconversion (n=56) were compared with CD4 counts and viral load in treated participants (n=144) 12 months after they stopped treatment.
At baseline, median viral load was 240,000 copies/mL in patients without treatment and 500,001 copies/mL in treated patients (P<.001). One hundred of the treated patients stopped treatment after a median 9.5 months. At this time, viral load was below detection in 82% of participants, and median CD4 count was 799 mcL. At 12 months after treatment stopped (n=44), median viral load was 38,056 copies/mL, and there was a median CD4 increase of 60 mcL from baseline. Viral load was below detection in two participants.
In 37 untreated participants, median viral load was 52,880 copies/mL, and median antibodies CD4 count was 525 mcL, with a median decrease of -87 mcL 12 months after seroconversion.
Although early treatment did not change viral load set point, treated patients had an immune benefit as median CD4 counts increased vs. seroconversion.
There was a significant difference in viral load of treated participants six months after treatment was stopped and untreated participants; however, the difference was no longer present between the two groups six months later, according to the study.
“In our cohort, we have no effect on viral set point, but on the other hand we have three patients who are still below detection, so some patients had a benefit but we don’t know why,” Koegl said.
Clear pathways to optimal care for people with early HIV infection are inconclusive. The current clinical practice is to treat infection when confronted with severe symptomatic disease that requires hospitalization, according to Steingrover.
“If symptoms are mild or absent, we tend to wait and see how the patient does in terms of CD4 and viral load,” Steingrover said. – by Kirsten H. Ellis
For more information:
- Steingrover R, Bezemer D, Fernandez-Garcia E, et al. Early treatment of primary HIV-1 infection lowers the viral set point. Presented at: The 14th Conference on Retroviruses and Opportunistic Infections; Feb. 25-28, 2007; Los Angeles.
- Koegl C, Wolf E, Jessen H, et al. No benefit from early treatment in primary HIV-infection? Presented at: The 14th Conference on Retroviruses and Opportunistic Infections; Feb. 25-28, 2007; Los Angeles.