569 
The Role of Hydroxyurea in Enhancing the Virological Control Achieved through Structured Treatment Interruption in Primary HIV Infection: Final Results from a Randomized Clinical Trial
Mark Bloch*1, D Smith2, P Grey2, D Quan1, R McFarlane3, R Finlayson4, T Kelleher2, J Zaunders2, K Petoumenos2, K Irvine2, M Law2, A Carr5, J Kaldor2, and D Cooper2
1Holdsworth House Gen Practice, Sydney, Australia; 2Natl Ctr in HIV Epidemiology and Clin Res, Univ of New South Wales, Sydney, Australia; 3407 Doctors, Darlinghurst, Australia; 4Taylor Square Private Clin, Darlinghurst, Australia; and 5St Vincent's Hosp, Darlinghurst, Australia
Background: Structured treatment interruptions (STI) have
been postulated to improve virological control in PHI by stimulating HIV specific T-lymphocyte
immunity. Durable virological control may be enhanced
using hydroxyurea, an immuno-modulator
that suppresses T-lymphocyte activation.
Methods: To determine whether virological
control could be enhanced through the addition of hydroxyurea
to an STI regimen commenced during
primary infection, consecutive volunteers who consented were screened for
eligibility and randomized to receive a standardized ARV regimen: (800 mg indinavir twice a day, ritonavir
100 mg twice a day, 400 mg didanosine once a day, and
150 mg lamivudine twice a day) with or without hydroxyurea 500 mg twice a day in an open-label clinical trial.
Initial ARV therapy was administered for as long as 12 months followed by up to
3 STI. Timing of re-initiation of ARV after each interruption was determined by
virological rebound to > 5000 RNA copies/mL. The primary endpoint was virological
control (HIV RNA consistently < 5000 copies/mL) at
2 years after initiation of ARV.
Results: We randomized 68 patients, 35 to ARV + hydroxyurea and 33 to ARV alone. All were men, median age
of 35.5 years, with a history of homosexual contact. Therapy was commenced
during acute primary infection (< 4 bands on Western blot) in 42.7% and
during early (positive Western blot with negative HIV antibody test within
previous 6 months) in the remainder. Median baseline HIV RNA was log 5.73 copies/mL and median CD4 T
lymphocyte 517 copies/mL. There was no significant
difference in the extent of virological control
between those receiving and not receiving hydroxyurea,
with respectively 9 (25.7%) and 9 (27.3%) successfully suppressed in each
group, a difference of 1.6% (95% confidence interval—19.4% to 22.6%, p = 0.88). Virological
control was achieved by 11 of 59 (19%) after one STI, 1/41 (2%) of those
remaining after 2 STI, and 6/36 (17%) after the third STI. Serious adverse
events were recorded for 9 of 35 (25.7%) of patients using hydroxyurea
and 3 of 33 (9%) in the ARV only group.
Conclusions:
Hydroxyurea
was not found to be beneficial when used in association with STI in PHI .
However, it contributed substantially to the number of serious adverse events
recorded during treatment.
Keywords: PRIMARY HIV INFECTION; TREATMENT INTERRUPTION; HYDROXYUREA
