By Liz Highleyman

Since the advent of potent combination antiretroviral therapy in the mid-1990s, researchers have debated the value of early treatment during the first months after seroconversion. Proponents of the "hit early, hit hard" philosophy suggested that starting therapy at the earliest stages of HIV disease could lower the viral "set point," or level of viral load stabilization.

But as the long-term toxicities of therapy became more apparent, many experts favored delaying therapy until there was evidence of disease progression or immunological decline. Current U.S. DHHS federal HIV treatment guidelines recommend starting therapy in asymptomatic patients when the CD4 cell count falls below 350 cells/mm3.

The optimal time to start therapy remains controversial due to conflicting data, as illustrated by 2 studies presented last week at the 14th Conference on Retroviruses and Opportunistic Infections in Los Angeles.

Early Treatment Lowers HIV Set-point

In the first study, Dutch researchers looked at patients with primary HIV infection (defined as a negative or indeterminate Western Blot test plus detectable HIV RNA or p24 antigen, or a negative HIV test followed by a positve test within 180 days) in the Amsterdam Cohort Study and the Athena cohort. Subjects were classified based on whether or not they started antiretroviral therapy within 6 months after seroconversion.

Results

• Out of 332 patients with primary HIV infection, 64 started HAART early, and 32 of these then stopped antiretroviral therapy.

• There were no significant differences in progression to AIDS or death between asymptomatic and symptomatic patients.

• The viral set point was reached 7 weeks after seroconversion or treatment interruption.

• The set point was 0.6 log copies/mL lower in patients who started treatment early then interrupted therapy, compared with those who never started early HAART (P < 0.001).

• There was no difference in the rate of CD4 cell decline between untreated patients and those who started then interrupted therapy.

"Compared to untreated patients, the viral set point is significantly lower at 7 weeks after interruption of early HAART, but increases over time," the researchers concluded. "The CD4 decline is unaffected by early HAART."

Academic Med Ctr, Univ of Amsterdam, The Netherlands; Natl Antiretroviral Therapy Evaluation Ctr, Amsterdam, The Netherlands; Intl Antiviral Therapy Evaluation Ctr, Amsterdam, The Netherlands; HIV Monitoring Fndn, Amsterdam, The Netherlands; Municipal Hlth Svc, Amsterdam, The Netherlands; and Leiden Univ Med Ctr, The Netherlands.

No Benefit from Early Therapy

In the second study, German researchers analyzed patients from 2 national cohorts, Prime-DAG (early treatment) and Ac-DAG (non-treatment of primary HIV infection).

Results

• Out of 200 patients with primary HIV infection, 144 started treatment immediately and 56 patients remained untreated.

• Untreated subjects had a lower median first viral load measurement and a higher median CD4 count than those who started therapy.

• Among untreated patients, 12 months after seroconversion, the median viral load was 52,880 copies/mL and the median CD4 count was 525 cells/mm3.

• 100 of the 144 treated patients stopped therapy after a median time of 9.5 months.

• At the time of stopping, 82% had an undetectable HIV viral load and the median CD4 count was 799 cells/mm3.

• 12 months after stopping, the median viral load was 38,056 copies/mL, 2 patients still had undetectable viral load, and the median CD4 count was 538 cells/mm3.

• There was a 60 cells/mm3 increase relative to baseline among treated patients after interruption of therapy, compared with a 87 cells/mm3 decrease among untreated subjects (P = 0.01)

"In this relatively large cohort of acute, primary infected HIV patients, early treatment did not change the viral load set point," the researchers concluded. "However, there was an advantage with regard to immune function."

MUC Res, Munich, Germany; Private Practice, Berlin, Germany; Practice St Georg, Hamburg, Germany; HIV Outpatient Practice Kaiserdamm, Berlin, Germany; DAGNAE eV, Aachen, Germany; HIV Res and Clin Care Ctr Munich, Germany

03/09/07

References

R Steingrover, D Bezemer, E Fernandez Garcia, et al. Early Treatment of Primary HIV-1 Infection Lowers the Viral Set Point. 14th Conference on Retroviruses and Opportunistic Infections (CROI). Los Angeles. February 25-28, 2007. Abstract 124LB (oral).

C Koegl, E Wolf, H Jessen, and others (for the Prime-DAG and Ac-DAG Study Group). No Benefit from Early Treatment in Primary HIV-Infection? 14th CROI. Abstract 125LB (oral).

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