124LB
Early Treatment of Primary HIV-1 Infection Lowers the Viral Set Point
Radjin Steingrover*1,2,3, Radjin Steingrover*1,2,3, Radjin Steingrover*1,2,3, D Bezemer4,5, D Bezemer4,5, E Fernandez Garcia3, F Kroon6, F de Wolf4, M Prins5, J Lange1,2,3, J Lange1,2,3, J Lange1,2,3, and J Prins1
1Academic Med Ctr, Univ of Amsterdam, The Netherlands; 2Natl Antiretroviral Therapy Evaluation Ctr, Amsterdam, The Netherlands; 3Intl Antiviral Therapy Evaluation Ctr, Amsterdam, The Netherlands; 4HIV Monitoring Fndn, Amsterdam, The Netherlands; 5Municipal Hlth Svc, Amsterdam, The Netherlands; and 6Leiden Univ Med Ctr, The Netherlands
Background: Data are conflicting whether initiation of HAART within
6 months after HIV seroconversion influences the viral set point or the slope
of CD4+ count decline after discontinuation of treatment. Available
studies are retrospective, and most patients in these studies have been
identified based on symptoms, which may affect the generalizability of the
results.
Methods: We
searched 2 large cohorts—the Amsterdam Cohort Study and the Athena cohort
(comprising all patients from the Dutch HIV treatment centers)—for patients
with evidence of primary HIV infection (PHI). A combination of a negative or
indeterminate Western Blot in the presence of p24 or viral RNA, or a negative
HIV screening test within 180 days preceding the first positive HIV test were
accepted as evidence of PHI. The initiation of HAART was classified as early or
deferred when the time from seroconversion to start was less or more than 180
days from seroconversion. Time to AIDS or death was analyzed using Cox’
regression. Determinants of early versus deferred treatment were analyzed using
logistic regression. CD4 count decline and viral setpoint (plasma HIV RNA) were
compared between untreated patients and those interrupting early treatment
using linear mixed models. For the viral load, a biphasic model was fitted that
allowed for initial non-linear dynamics. The slopes of CD4 counts became linear
after taking the natural logarithm.
Results: Of 332 patients who met the inclusion
criteria, 64 were treated with early HAART; 32 patients stopped early HAART. In
the HAART era, no significant differences in prognosis (AIDS or death) were
present between asymptomatic and symptomatic patients. Independent predictors
of early initiation of HAART were the presence of negative or developing serology
and a higher plasma viral load. The viral set point was reached 7 weeks after
seroconversion or treatment interruption and was 0.6 log copies/mL lower after
interrupting early treatment than in untreated patients (p
<0.001). Hereafter, the difference decreased with 0.003 log/week. There was
no difference in CD4+ T-cell decline between untreated patients and
patients after treatment interruption.
Conclusions: Compared to untreated patients, the viral set
point is significantly lower at 7 weeks after interruption of early HAART, but
increases over time. The CD4 decline is unaffected by early HAART. Randomized
studies are needed to assess the clinical benefit of the lower viral setpoint.
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